Alan Cassels

The easiest ADR (adverse drug reaction) to avoid is the second one, not the first one. CLOSE TO A DECADE AGO Vancouver resident Johanna Trimble took a seaplane trip to Victoria for an important mission and she brought one important thing. A story. And that story has made all the difference. She travelled that day with two Vancouver emergency room physicians, who invited her along to a meeting with officials at the BC Ministry of Health. The trio’s goal was to try to convince officials at the Pharmaceutical Services Division that BC had a very big, but very solvable problem on its hands. It concerned adverse drug events (ADEs), drug reactions that can be serious enough to cause hospitalizations, serious illness and sometimes death. Johanna was unwittingly thrust into the position of witnessing the care of both her elderly mother-in-law, and her stepmother who were prescribed drugs and hospitalized due to adverse drug reactions. Equipped with both the wisdom to question a drug and the determination to question the doctors, in both cases she managed to get the culprit pills stopped. You’d think that would be the end of the story, but in both cases, the offending drug was represcribed by a different doctor, in a different clinic, and wham, back to the emergency room for a repeat episode. A doctor from a different mold Emergency room physician Dr Corinne Hohl has seen her share of people showing up in the emergency department suffering the effects of prescribed drugs. Adverse drug events are a leading cause of emergency department visits and unplanned hospital admissions. Shockingly, of those in the emergency department because of an adverse drug event, 29 percent are there because they are having a repeat adverse reaction to the same drug (or drug class) that had brought them to the ED previously. Dr Hohl accompanied Johanna on that trip to Victoria, and she speaks with the kind of verve and enthusiasm of someone who’s out to change the world. She recounted an incident that made its mark on her. An elderly woman was admitted to her emergency room in Vancouver General with subdural hematoma—a fairly serious head injury—related to a fall. The patient was taking fairly high doses of fentanyl patches, which were likely the cause of the fall. After being hospitalized for weeks, the patient was slowly switched off the fentanyl to a safer drug. Not long after, the same woman appeared in her emergency room after another fall, this time with multiple rib fractures. “And guess what?” she told me. “She was on the fentanyl again. Basically back on the drug that had previously been related to her fall.” Dr Hohl had been working on how to get a handle on this problem for several years before that meeting with the Ministry. “They thought we were going to show up on the phone but we showed up in their offices in person and their jaws were on the floor.” Her request was concise: she wanted a very simple change to PharmaNet, BC’s comprehensive province-wide drug data system that tracks every prescribed drug in the province. Why not modify it so that it would allow physicians and pharmacists working in hospitals to enter any drug-related ADEs on the patients’ chart? She reasoned that if that information, like an allergy, for example, was a routine part of a patients’ medical record, then the problem of repeat ADEs could be eliminated overnight. “We did all kinds of modelling, to show them how expensive and serious the issue of repeat adverse drug events was. In my presentation I compared it to the opioid epidemic and I showed them how many people died from this problem that is being completely ignored,” she said. Not to be outdone by the enormity of the problem, she also made a promise: “I told them I was going to design a solution for them that was unique across the world.” It helped immensely that Johanna was there—just a regular BC citizen who has seen this problem firsthand, twice. Her story probably helped convince the Ministry of Health officials that change needed to happen. After all, how many BC seniors are on the receiving end of an avoidable prescription mistake that could be fatal? The meeting was probably the inflection point that is now slowly reducing the problem of repeat ADEs in BC. But as Dr Corinne Hohl found out, big system or cultural changes in medicine don’t happen overnight. Research money and pizza From the time that Dr Hohl recognized the problem of repeat ADEs, until some (not all) hospitals began acting on the information from BC PharmaNet, eight years had passed. The delays were understandable but frustrating. Once she got over the bureaucratic hurdles that stymie all but the most determined, Dr Hohl saw that making software changes to a large and impossibly complex computer data system was no walk in the park. And then there’s what is known as the “human factor”—the culture of medicine would need clinicians, nurses, doctors and pharmacists to recognize, record and later seek out any ADEs that are in a patient’s chart. What fuelled her work to make headway on an impossibly complicated task came down to research money and pizza. Many times smart clinicians working in our medical system will see a problem that needs a solution, yet they hit the brick wall of their colleagues or administrators asking “where’s the evidence?” Inertia is easier, and if you don’t have a study to back up what you’re proposing, you better go get one. Dr Hohl went to the research world, getting grants from various sources including the Canadian Institutes of Health Research (CIHR), which helped pay for a gold-standard study, a randomized controlled trial (RCT), and allowed her to tap into the expertise of people on the front lines. A system like this needed a user-friendly interface for physicians and pharmacists, so that meant a kind of “action-research” approach. She worked tirelessly with Ellen Balka, a communications specialist and qualitative researcher at SFU, who helped her dig deep into the principles of behaviour change. This also meant constantly going back to those in clinical practice. “We really needed to bring in that expertise to figure out how clinicians think, work out the details of proper drop-down menus, data standards, and so on,” said Hohl. “We kept buying pizza for the pharmacists. They told us, change this, make this like this, and so on. All those sorts of design features were exceedingly important.” The software application Hohl and her team created is called ActionADE, designed to enable front line clinicians to document adverse drug events by communicating to a central medication dispensing database. Dr Hohl’s system is not province-wide yet, but it has been implemented in nine acute care hospitals already. It still needs ongoing investment to upgrade software and pay for staff, mostly pharmacists, to enter the data into patient records. At the end of the day she has shifted the culture, reminding her colleagues of the enormity of potential adverse drug events, and the need to make sure peoples’ medications are as safe as they can be. All this is part of the growing patient safety movement, where adverse drug events are better known, and many people are becoming aware that tracking and recording them can be lifesaving. Johanna Trimble doesn’t mind being “the voice of the patient” when it comes to speaking truth to power. And she’s darned good at it, becoming one of our province’s most vocal patient safety advocates. About ActionADE she says, “in the absence of such a system, it all comes down to the family. The family has to remember the drug information and these side effects, because nobody else is. The family is the continuity. If the family doesn’t know they have to do that, then somebody might die.” Luckily now in BC, the family is going to get some help in this area. Alan Cassels is a researcher and writer about pharmaceutical policy issues. He lives in Victoria. A webinar discussing Dr Hohl’s research is posted at the website of the Therapeutics Initiative.

Are we headed to dangerous levels of overdiagnosis by interpreting a test in a way that labels people as sick and infectious when they may be neither? EIGHT MONTHS INTO THE PANDEMIC, here are some BC numbers to think about: 5,071,000: Population of BC (est. 2019) 38,471: Typical number of BC deaths in a single year (2019) 132: Number of BC deaths, on average, everyday. (est. 2019) 274: Number of days between Jan. 15 and Oct. 14, 2020 36,168: Estimated number of total deaths in BC between Jan 15 and Oct 14, 2020 250: Number of deaths in BC attributed to COVID-19 up to Oct 14, 2020 0.69: Percentage of total BC deaths over 8 months possibly due to COVID 10,836: Number of “laboratory confirmed” cases of COVID up to Oct 16, 2020 691,741: Number of SARS-CoV-2 tests Jan. 15– Oct 13, 2020 1.82%: Proportion of COVID-19 tests in BC showing as “positive.” As COVID’s daily data dump lands on our heads, shaped by scorekeeping, commentary and predictions, it’s pretty easy to get lost in the numbers and what to make of a nasty pathogen circulating in our communities. What stands out from these numbers? An extremely low likelihood of death by COVID-19 in BC. Certainly lower than any annual toll of the flu. Certainly lower than the numbers of people who have died from cancers, heart attacks, overdoses, suicides and the myriad of other things that take life every single day. If you take 2019 as an average, 132 people per day die in BC, from all causes. That was the last full year without a pandemic virus. With less than one person per day dying of COVID in BC, one is tempted to ask if we’re making a mountain out of a molehill. I’m increasingly surprised by the general subservience of the populace and the absence of thoughtful dissent against emergency measures that are undoubtedly causing all kinds of other suffering, wreaking long-term havoc on our society, our livelihoods and our economy. People are quick to point at our numbers and say what a wonderful job BC public health people are doing, keeping COVID cases down and deaths by COVID at a minimum. We are an obedient lot and so listen to Dr Bonnie, among others, who reminds us to limit contact, wear masks, and control the virus by widespread testing, even if some people have reported how hard the tests are to get. Yet, if it is true that the SARS-CoV-2 causes the respiratory disease COVID-19, how much effort has been put into ensuring the virus test is done properly, evaluated thoroughly and adequately interpreted? Basically, can we trust the test? What is it about the test? Kary Mullis won the Nobel Prize in chemistry 1993 for inventing the PCR (Polymerase Chain Reaction) test, the test that is now being used to ascertain whether or not a person has COVID-19. His test eventually became the standard test that drew the definitive link between the HIV virus and AIDS. Ironically, Mullis himself was at the forefront arguing that PCR should not be used as a tool to diagnose the disease. Why? Because even if it could identify the presence of a virus, that detection did not mean the virus was capable of infecting other cells. An eccentric and vocal iconoclast, with a penchant for dropping acid, Mullis went to his grave last year continuing to decry his test being misused to diagnose HIV. Like many jurisdictions in the world, BC employs RT-PCR to test for COVID. It uses an enzyme called reverse transcriptase to take a piece of RNA (ribonucleic acid) which comes from a swab deep inside the patient’s nose. Adding viral enzymes to the RNA converts it into DNA through what is called Polymerase Chain Reaction. The DNA is turned into billions of copies and a fluorescent signal is added, which, after being run through numerous cycles of heating and cooling, can be detected. This amplification allows the needle in the haystack to be seen. Here’s where things get interesting: The “Ct” or cycle threshold is the number of cycles needed to see the fluorescent signal. So how many cycles of heating and cooling do you need to determine a definitive “positive” or “negative” result? If you don’t detect the virus after a few dozen cycles does that mean the patient is negative? What if you do more than 30 which many molecular biologists say is like trying to squeeze blood from a stone? There may be detectable virus in that highly cycled sample but it is so small and so dead it’ll never be able to infect others. I put some questions about BC’s Ct cutoff to a spokesperson from the BC-CDC and here’s what she wrote back: “The cycle threshold number used to diagnose COVID-19 may vary based on the test used but we typically use a cutoff of 35 cycles.” She added that other targets (the RDRP and E gene) and certain assays “use cutoffs of 40 or even more cycles.” I’m no expert, but I wondered: Shouldn’t they have a constant Ct—because changing it can dramatically change the number of positives? It also makes me wonder that if BC uses a Ct of 35 and Ontario (whose Ct, I’m told, is set at 38) then can this alone explain why BC has a much lower level of positive cases? If some countries set the Ct at 20 (very low) and others set it at 40 (absurdly high), how can one even compare levels of positivity between jurisdictions? This really matters. I consulted a molecular biologist (who asked me to withhold her name as she works as a provincial government biologist) who said that we have to be very cautious in interpreting these tests because the reverse transcriptase enzyme has poor efficiency in converting RNA to DNA. She told me that if we do over 30 to 35 cycles “we can’t culture a live virus from the sample.” Basically, she added, “a high cycle threshold means we’re finding meaningless fragments that say nothing about the infectivity of the patient.” This is an expert who uses the RT-PCR test everyday in her work doing forensic science, so I trust she knows its limitations. She was quite forthright in saying that possibly as many as 90 percent of those testing positive for COVID-19 are probably not infectious. Which is to say they may have had “fragments” of the virus, but they couldn’t possibly spread the virus to anyone else. Is a “positive” test really positive? Where this is heading is a dangerous level of overdiagnosis. Other commentators have said the rate of false positives might be 50-80 percent. More testing and more false positives would help explain why deaths and hospitalizations aren’t rising on the same trajectory. It’s because some new “cases” are unlikely infectious or indicative of ill health. Again a “positive test” is about declaring a person “infected and infectious” but what follows from that? If we were to say maybe half of those 11,000 people in BC testing “positive”—and therefore have been subject to quarantines, social isolation and stigma—then that’s an awful lot of people who have been unfairly labelled and isolated with a disease they couldn’t possibly transfer to others. Maybe this comes down to a question of what we value. Is it better to have a non-sick person incorrectly labelled as sick (a false positive) than to have a sick person labelled as not sick (a false negative)? I can understand the BC CDC’s position, because it’s based on the greatest fear of all, the boogeyman of underdiagnosis. The CDC spokesperson explained it to me this way: “setting the detection threshold too low seems appealing until one misses that early case that can transmit infections to multiple people.” The implication here: we can’t be too careful. However, with screening people for disease you will always have overdiagnosis and underdiagnosis, and careful testing tries to eliminate the possibilities of both false positives and false negatives. It would seem to me that we are likely doing a serious disservice—to society and our economy—by interpreting a test in a way that labels people as sick and infectious when they may be neither. Alan Cassels is a drug policy researcher and author in Victoria. He is the author of Seeking Sickness: Medical Screening and the Misguided Hunt for Disease.

The science is thin whereas the symbolism is strong. ONE OF THE MORE FASCINATING THINGS that COVID-19 has brought us is a lot of pandemic-related discourse around masks. Wearing a mask seems like a fairly simple, non-invasive and inexpensive intervention to prevent the spread of a virus. Yet the virulence of arguments made on both sides of the issue is so forceful, and, at times, self-confident, it’s worth digging into the evidence to see what lessons we might find partly because I am a firm believer in the adage that all technology bites back. I’ll wear a mask when I’m sanding, or when exposed to smoke or dust during a renovation, or when I need to conceal my identity, such as at a costume party or when robbing a bank. Wearing a mask in a crowded place, like a store or a train, while the coronavirus still circulates seems reasonable. Yet in Victoria you see people wearing masks walking alone down the street, riding a bicycle, or even driving alone in a car. Sheesh. Even if there is some theoretical benefit to masking up in some situations, in the process have we lost our common sense? Like many things related to healthcare we think that if a little of something is good, then a lot is better. And we’re probably being misled. Wearing a mask in a crowded space during the pandemic seems reasonable. But is there evidence that it makes a difference? Weakness of the evidence base An alert Focus reader from Duncan sent us links to a handful of studies asserting the case that “mandating masks has not kept death rates down anywhere.” The 15 studies he used to support this provocative statement examined health professionals in medical settings over about a 45-year period and he claimed the results have been consistent: “masks are useless in preventing the spread of disease and, if anything, are unsanitary objects that themselves spread bacteria and viruses.” Often in medicine, reasonable-sounding recommendations, when poked, reveal an evidence base that is weak or non-existent. A review of the literature from 2015 of mask wearing in surgery confirmed that there’s very little evidence that “facemasks protect either patient or surgeon from infectious contamination.” Just last month researchers Tom Jefferson and Carl Heneghan at the Centre for Evidence Based Medicine in Oxford wrote that in the past three months there have been 15 evidence reviews on masks, but there is still not a single published trial on the effectiveness of masks for COVID-19. Let’s not forget that lack of evidence for effectiveness does not mean the contrary is true, that there is evidence for their ineffectiveness. What seems most true is that we simply don’t know. Is it possible to extrapolate from other situations, such as studying the spread of other infectious agents, such as the flu virus? In May, an article from the US Centres for Disease Control and Prevention looked at 14 randomized trials of non-drug measures to prevent the spread of the flu. Focusing just on face masks, they found 10 randomized trials of the effects of masks in reducing flu virus infections in the community and found “no significant reduction in influenza transmission with the use of face masks.” Shifting public health recommendations Earlier in the pandemic, the World Health Organization (WHO) reflected this evidence base, saying that “there is no direct evidence (from studies on COVID-19 and in healthy people in the community) on the effectiveness of universal masking of healthy people in the community to prevent infection with respiratory viruses, including COVID-19.” The WHO went on to state that since the community prevalence of COVID-19 is so low (such as here on Vancouver Island) “even if facemasks are assumed to be effective, the difference in infection rates between using facemasks and not using facemasks would be small.” The numbers, if true, are startling: “Assuming that 20 percent of people infectious with SARS-CoV-2 do not have symptoms, and assuming a risk reduction of 40 percent for wearing facemasks, 200,000 people would need to wear facemasks to prevent one new infection per week in the current epidemiological situation.” Even when the evidence case in support of masking shows a pretty small yield, the battle for and against mask wearing remains strong. Spend any time on social media and you’re sure to ingest a powerful dose of pro and anti-mask sentiment. Sidestepping the most vociferous of conspiracy theories, you’ll find those vigorously opposed to lockdowns and physical distancing measures are apoplectic about mandatory mask orders. On the other hand, people in Victoria, whether driven by fear, altruism or simply enacting the spirit of “let’s do what Bonnie asks” can be spotted masked up in the most preposterous of low-risk situations (such as being alone in a car). You can’t overlook the symbolism of masks, the wearing of which can be like a talisman, assert virtue and personal support for “doing whatever” to flatten the curve. Alternatively, not wearing one asserts the opposite: that no one is going to restrict my god-given freedom to do whatever the hell I like. Stanford scientists on COVID-19 mask guidelines Things began to shift in June when the WHO revised their guidelines, after apparently reviewing new information from researchers at Stanford and elsewhere. Claiming that wearing cloth coverings over nose and mouth can prevent the spread of the virus, the WHO guidelines shifted to say that when in close contact with others in crowded areas, with people over 60 or those with underlying health conditions, people should wear medical masks, such as surgical masks, in public. This recommendation might pass the test of common sense, noting that masks are just another form of “source control” to prevent the spread of respiratory droplets from infected people. Yet are there any harms in mandating masks? The Stanford researchers quickly discounted a number of arguments put forth that mask wearing can be harmful—curiously presenting no research to support that position—and concluded with a boilerplate platitude: as societies open up more, we need to protect vulnerable people around us and therefore it’s our duty to do what we can. What if we are all wrong about masks? One of the arguments against masks says that wearing face masks can adversely affect attitudes towards social distancing. Which is to say you’re more comfortable sitting or standing closer to someone else when wearing a mask, a case of risk compensation, similar to the argument that people wearing seat belts are more likely to drive recklessly. Certainly people with respiratory problems like asthma can find mask-wearing very problematic. Then there is the bigger picture about the virus and what is the ultimate effect of hand washing, social isolation and masking policies. Increasingly there is more heft in the discussion of herd immunity, absent a vaccine, and that we’re never going to get through the pandemic until enough of us have been exposed and developed some immunity. Others wonder how high the herd immunity threshold must be before we all basically develop some level of natural protection from the virus. It’s the most crucial unanswered question in this whole pandemic thing. Let’s say herd immunity is at 20 percent. That means about 1 in 5 people are immune. If it was this low, the number of people infected would just keep going down. The problem, of course, is that we have no idea where that number is, and whether, ultimately, all our efforts at social distancing and wearing masks are going to make a whit of difference. Then there is the big question of how long immunity lasts once people have been exposed to COVID-19 and developed some antibodies. No one knows how long antibodies last or how “protected” one is by previous exposure. We think that wearing a mask is protecting our loved ones, but we may be doing so with a price—prolonging the amount of time we’ll need to get to the other side of this pandemic. At the end of the day, no one would argue against an urgent need for scientists to deeply understand COVID-19 and herd immunity before we go overboard with more stringent mask-wearing public policies. Heneghan and Jefferson of the Centre for Evidence Based Medicine in Oxford also write that “masks are a symbol for society—[implying that] you are protected. The evidence says you may not be.” They conclude that in this kind of uncertainty, society has a deep responsibility to study the use of masks thoroughly. This can happen a number of ways, especially by examining the many “natural experiments” in different mask and distancing policies around the globe. The key is to refuse to jump to premature conclusions such as that tighter masking policies are nothing but beneficial. Only when public health officials are brave and willing to have their preconceptions challenged, can society arrive at a truer understanding of what behaviours are beneficial and which are harmful. Masking might seem like common sense for many people and only time and good research will uncover whether we are being mislead. Alan Cassels is a drug policy researcher and lives in Victoria.

Many people have stopped seeking medical attention during the pandemic out of fear of catching the virus at a doctor's office or clinic. As a result, fewer people may die from adverse drug reactions to prescription medicine. WHEN YOU WITHHOLD MEDICINE, people die, right? Well, not quite. We are currently living in a massive medical experiment that may reveal a number of surprises. Down the road, as researchers look back and parse through what happened in the year 2020, they will undoubtedly discover a goldmine of evidence of the impact of the pandemic—both the good and the bad. We know that things won’t be the same in many dimensions of our lives, and we may discover things that make us fundamentally rethink much of what we do in medicine. Despite all the hardship, anxiety, and economic impact inflicted on the world by the COVID pandemic, there may be some silver linings. One particular area of interest is the ceasing of the delivery of medical interventions. Undoubtedly many types of harm have been inflicted by imposed lockdowns, shutting hospital beds, cutting off of elective surgeries, isolating elderly people from their loved ones, and the general heightened level of fear imposed by social distancing rules. The fact that people have been generally fearful of going near any doctor or health facility may have prevented them from accessing important healthcare. At the same time, not going to the doctor on a massive scale will allow researchers to examine the full effects of stopping medical delivery and possibly uncover unexpected benefits. This is not the first time stopping medical delivery has been studied. Much has been studied about the impact of doctor strikes over the last 40 years, and the results generally point in the same direction: when doctors strike, fewer people die. A systematic review of five doctor strikes between 1976 and 2012 found that patient mortality either stayed the same or fell. It didn’t—as one might expect—increase. How does one explain this? One of the key answers is iatrogenesis, which is harm that is inflicted by the medical system itself—so that any medical activity, including tests, drugs, scans, and hospital stays, can involve harm. Less contact with the medical system, less avoidable death. At least that’s the theory. Currently there are many voices delivering dire warnings about the pandemic’s effects on the health of the population, beyond the risk of the virus. Other voices, perhaps more muted, include some who suggest there could even be some general health improvements. I talked to my friend Dr Eddy Lang, an emergency room physician from Calgary and a member of the Canadian Task Force on Preventive Health Care. He told me: “Some signals are suggesting increased mortality in countries hard hit by the virus, but it is unclear if this is uncounted COVID deaths or collateral damage, as others claim.” We know that, for example, during doctor strikes the kinds of hospital infections and other complications associated with surgery go way down. Some patients who might have mild heart conditions will avoid the hospital, where they may avoid the stent or other bypass surgery they’d get in normal times. This might be a good thing as there is some evidence that we are doing too many of these cardiac interventions in low-risk patients. In mid-July Dr Lang and colleagues published a piece in the British Medical Journal which echoed these thoughts and called for rigorous studies to investigate the effects of reduced healthcare. It noted that “looking beyond the crisis, our collective learning about the effects of the large falls in healthcare use can help inform and intensify efforts to reduce unnecessary care. This in turn can prevent avoidable harm to patients, enhance healthcare equity, and improve the sustainability of health systems everywhere.” What about drugs? If reductions in physician office visits mean that patients aren’t getting new prescriptions, or renewals of existing prescriptions, three things could happen: Their health may worsen, it may stay the same, or, possibly, it might improve. In those serious cases, such as when a person with asthma avoids getting a puffer prescription refilled or a diabetes patient avoids renewing their insulin prescription—this kind of avoidance could turn fatal. But for many conditions, a drug holiday might be very good for you. Dr Lang reminded me that many prescriptions for antibiotics, for example, are unneeded and often cause more harm than good. For longer-term drug use, people who take drugs in a class called proton pump inhibitors (PPIs) including Losec, Pariet, or Pantaloc, which are prescribed mostly for heartburn, might see their health improve if they slowly weaned themselves off the pills. A study published last year examined over 200,000 US veterans who took PPIs and found that long-term therapy with these drugs, with other things being equal, increases the risk of death. Adverse drug reactions (ADRs) associated with many commonly used prescriptions, are a real thing. As well, as Dr Lang points out: “The trials that looked at these drugs actively avoided recruiting frail folks with co-morbidities.” What this means is that older and more frail people are likely at even more risk. Being injured or hospitalized because of a medication reaction is commonplace and some estimates say as many as 220,000 Canadians suffer ADRs per year in Canada, of which about 10 percent, or 22,000, are fatal. “Not to mention the thousands of avoidable hospitalizations,” adds Dr Lang. Obviously if the harm exceeds the benefit of any medication, stopping it might be the right and healthy thing to do. ADRs are often overlooked and underreported, but if you broke down the estimated ADRS by province, BC alone would have about 2,860 ADR deaths per year, or about 8 deaths per day due to what are regular, normal prescribed drugs. As of mid-July in BC, we’ve had about 190 COVID deaths in the last 120 days, or about 1.5 per day. So you could look at it this way: If people stopped taking drugs that were causing excessive ADRs, that act alone could potentially save up to five times more lives than we are losing to the virus. In the future, stopping certain medications could be a lot more “normal” than it currently is. Some of the major chronic conditions like high cholesterol, type 2 diabetes or high blood pressure, result in a lot of long-term drug use, but probably not as much as you’d think. Many people naturally stop taking their drugs for whatever reason, or get to the point where they’d rather not live with the hassle or expense. Drugs for type 2 diabetes are almost universally prescribed to alter blood sugars, yet for most people any change in your numbers brought on by these drugs don’t automatically translate into a longer or healthier life. Even the guidelines (which are underwritten by the drug industry) advise that the most important step in helping type 2 diabetics is altering diet and exercise patterns—before you ever consider taking a drug. But what about high blood pressure? Stopping medications has always been difficult because clinicians and patients worry that stopping a drug will worsen their health. But what about drugs for high blood pressure? Well, even here there is growing evidence that stopping antihypertensive drugs (drugs to lower blood pressure) may not be bad for you, especially if you’ve never had a heart attack and are not afflicted by cardiac issues. Dr Lang reminds me that “elders have a higher risk of ADRs and may not benefit at all from a lower blood pressure.” A recent systematic review by Cochrane agreed with him. It looked at six studies with over 1000 healthy patients over 50 and found that those who stopped their high blood pressure pills did as well (in terms of heart attacks and deaths) as those who continued. This review was rated as “low certainty” of evidence, so it is not the last word on the question. What it did show is that there is no evidence of increased risk if older people without established heart disease stop taking their antihypertensive medications. The implications of this itself could be huge. Let’s not downplay the seriousness of hypertension, which is considered a risk factor for strokes, heart attacks, and chronic kidney disease. At the same time, you would only want to be taking these drugs if you were sure they are reducing your overall risks, instead of just altering your numbers. But as Eddy Lang notes: “Knowing for sure is almost impossible. Best you could hope for is a decent chance of benefit.” In any event, it’s certainly worth a discussion with your doctor. Stopping medications, for older people who face the many problems that often come with too many drugs, is becoming more and more mainstream. There are a number of groups who are actively concerned with overprescribing and working to reduce the harm of too much medicine.The Canadian Deprescribing Network, and Choosing Wisely Canada are two such organizations. As a researcher I’m particularly hopeful that this pandemic will prove to be an opportunity to discover which medical treatments or drugs we could use less of. It’s a natural experiment that is happening around the world. With some good international collaboration and good data on how we have faired with less medicine and less medication, we might learn some valuable lessons. Alan Cassels lives in Victoria where he studies and writes about pharmaceuticals. He works for UBC but the opinions represented here are his own.

Vaccines often seem to be in their own special, sacred category of pharmaceuticals, yet the science is often far from settled. THERE’S NEVER BEEN A VACCINE FOR A HUMAN CORONAVIRUS and yet a vaccine for SARS-CoV-2 seems to be the holy grail we’re all waiting for. If so, we could be in for a very long wait. Vaccine development is tricky and the kind of immunity that most would find acceptable—protecting against excess deaths and sickness—may never be achieved. There has never been an effective vaccine for a coronavirus, so to think we’ll develop one within 12-18 months, as experts are saying, seems farfetched. Any shortcuts taken to approve a vaccine may compromise safety and effectiveness for speed. We may all hope and pray for a vaccine, but it would be most preferable if we had a vaccine that worked. And it’s worth noting, that all technology bites back. Sometimes fatally. Before the pandemic, a friend, an expert who is writing a book on vaccine safety, thought I might have some thoughts on where we are going on vaccines and whether vaccine mandates might be used. He sent me a list of questions, which I answered and now have adjusted in light of COVID-19. 1. What have you learned about vaccines, their effectiveness against infectious diseases, and the risks they might pose for some individuals? I have learned a lot from the scientific literature and working with colleagues who study the safety of drugs. In the drug world, often experts will assert the “facts” of a drug’s safety are solid and unassailable, but we later find out we were mislead. In fact, if I had one universal thing to say it would be that expressing certitude concerning effectiveness or safety of a drug or vaccine is a naïve position. Those who are honest about the science will often say that proper and unbiased research to establish a true picture of safety is often not done. People need some level of comfort that they are making the right choices for themselves or their children. In this vein, the benefits of the six basic childhood vaccines (combined in the DPT—diphtheria, pertussis, and tetanus—and MMR—measles, mumps, rubella—vaccines) likely exceed the harms and can improve population health. Have some people been harmed by these vaccines? Yes. It’s very unhelpful to label people who have legitimate concerns about vaccine harms as “anti-vaxx” and disregard them. It is delusional to think vaccines only have benefits and no harms. 2. Do you believe vaccines are an important component of modern medicine? Please provide examples to illustrate your opinion. Nobody would ever say all drugs are important, but many will claim that “all vaccines are important.” For some vaccines, it’s not yet established if they are important or not. Asking people to “vote” on whether they’d get a COVID-19 vaccine (if it is ever produced) is stupid. Like any drug, the right answer is, it depends. On my list of “possibly useless” or “not yet proven to be beneficial” vaccines, I’d put shots for rotavirus, pneumonia, flu, chicken pox and HPV (human papilloma virus). Some people might benefit from a flu shot, but in a healthy population the benefit is vanishingly small. Despite the hype over the HPV, the first mass vaccination to prevent cervical cancer, it hasn’t shown any lifesaving benefits yet. And chicken pox? Meh. Most kids challenged by chicken pox will have a few days off school and be rewarded with lifetime immunity. Not a bad deal, huh? 3. Do you have concerns about vaccine adverse effects? Which ones in particular, if any? Indeed. For some vaccines we don’t know the magnitude of adverse effects, the type of person who might be at higher risk if immunized, whether the recommended vaccine schedule itself causes adverse effects, or even if medically-trained people can properly diagnose a vaccine-related adverse effect. Rare yet nasty immune-system harms have been linked to some vaccines. There are several medical clinics in Europe designed to help girls suffering the adverse effects of the HPV vaccine. Have these families cooked up a conspiracy against HPV vaccine manufacturers? Unlikely. Again, labelling vaccine-injured people as “anti-vaxx” isn’t helpful. It’s a much more mature conversation if you can accept that people are sometimes helped and sometimes hurt by vaccines. 4. Do you feel that on this subject the science is settled? Do you feel that the same claim can be made about any other branch of science or hypothesis/theory? No. No. No. Nothing is settled. Proclaiming “the science is settled” on the usefulness and safety of vaccines is the biggest barrier to producing quality, independent science. The scrutiny of any COVID-19 vaccine is going to be intense and before any mass immunization plans come together we need solid proof the real benefits exceed the harms. This may come as a shock to people but many prescription drugs swallowed by millions of us every day are either not proven in quality trials, have proof of harm, or haven’t been proven either way. A Health Canada stamp of approval is no guarantee that we can fully trust the science underlying that approval. Scientific debates over the value of some drugs and some vaccines are frequently “unsettled” and, frankly, unsettling. 5. What do you feel the role of the pharmaceutical industry is, if any, in controlling the discussion about vaccines in general? Like any big business or monopoly industry, the goal is to maintain and increase shareholder value. Pharma companies, which make both drugs and vaccines, have only one main legal requirement: to maximize shareholder value. Over the last 25 years I have seen how the pharmaceutical industry has used its prestige, power and financial might to purchase a central role in the practice of medicine. It holds inordinate power over how we think about sickness and medicine, a kind of “cultural hegemony” where the beliefs and explanations, perceptions, values and mores of a society have been imposed by a ruling class manipulating the culture of that society (rephrased from Wikipedia). Let’s be clear about one thing: The drug industry doesn’t just manufacture products, it manufactures consent about its products. Can our public health people work in a healthy alliance with the hegemony of the pharmaceutical industry? Will trustworthy, independent, evidence-based assessments of a new COVID-19 vaccine prevail? In our haste for a vaccine will we continue to live in this strange dual world where many of us are deeply and appropriately skeptical of the pharmaceutical industry’s hegemonic power in medicine, yet somehow blindly believe that vaccines are in a special, sacred category? 6. What is your opinion about the need for “vaccine mandates”? Why? Mandates are about forcing people to accept a medical treatment when they may not want it, for whatever reason. They are seen as a way to put pressure on vaccine-hesitant people, through regulations and laws. Problem is, mandates can be ineffective because they are likely to backfire. Mandating the injection of a chemical into someone’s body is unlikely to achieve the objective of increased immunization rates. Thankfully Dr Bonnie Henry, our Provincial Health Officer, doesn’t think a mandate is necessary. She told CTV news “we have no mandatory immunization in the province and I do not expect we will have mandatory COVID-19 immunization.” 7. Do you have any concerns about such mandates for civil or natural rights? Absolutely I’m concerned about legislating vaccines. The biggest problem with forced vaccines is that Canada has no compensation system for people who are vaccine-injured. Would it be good policy to order everyone to drive a car but tell them they can’t buy car insurance? If you are injured and medically damaged for the rest of your life, tough luck. Too bad sucker. You’re on your own. I would be very concerned if our politicians relied on a hastily developed and launched COVID-19 vaccine policy that could ultimately harm people. What if it produces antibodies but people get sick anyways? Or worse, healthy people become injured by a vaccine designed to help them? Lockdowns might drive people crazy, but an uninformed public might push hard for a mandatory immunization policy. Before even thinking of a mandate, public health people will need hard evidence that there is a vaccine that is rigorously scrutinized, proven effective and safe. This is a very, very tall order… Alan Cassels is a pharmaceutical policy researcher and lives in Victoria.

FIFTEEN YEARS AGO while writing our book Selling Sickness, Ray Moynihan and I probed deeply into the pharmaceutical industry’s involvement in the development and marketing of a little known condition called “social phobia.” Apparently, some people are so nervous in social situations that they rarely leave their house. Public speaking? Definitely out of the question for social phobics. While the extreme form of that condition could certainly be debilitating for some, with the financial might of one of the world’s biggest pharmaceutical companies, and the FDA approval for paroxetine (Paxil) to treat this new condition, “social anxiety disorder” (SAD) became a multi-billion dollar market almost overnight. With some of the slickest, award-winning drug marketing ever seen, the poster tagline behind Paxil read: “Imagine being allergic to people.” The ad didn’t even mention the name of the drug. Why? Because they were just marketing the condition, and they had (at that time) the only pill approved to treat it. The whole fascinating tale, complete with celebrity spokespeople, athletes on the payroll, and fake patient groups promoting the disease, was textbook bamboozlement, selling consumers and prescribers a company-sponsored version of “abnormal” mental health. Enter the pandemic, an unprecedented time of worry, where stress, fear and anxiety among a locked-down population become the perfect petri dish to spawn new customers of psychiatric drugs of all sorts. A report from the US pharmacy management company Express Scripts said that the number of prescriptions filled per week for antidepressant, anti-anxiety and anti-insomnia medications “increased 21 percent between February 16 and March 15.” The kicker here? Three quarters of these were for new prescriptions. The Council for Evidence-Based Psychiatry (CEP) in the UK reported that 20 percent of the adult population in the UK were taking antidepressants. They are worried that “reframing situational distress as a psychiatric condition” could lead to speculative, pre-emptive prescribing. That is, getting a script “just in case.” Suffice to say a whole lot more of us might be coping with their lock-down situation with the help of a new drug, an adventure that may not end when the pandemic has run its course. If you’re anxious, does that mean you’re sick? There are many things wrong with this picture. First of all, feeling anxious towards situations out of one’s control is normal. Feeling a sense of loss and worry given the rapid way in which society is being reshaped by the pandemic? Also normal. People need social interaction and the support of their families and peers, something which social distancing makes more difficult. Yet a pharmaceutical lifebuoy may not be the answer for most. The history of “selling” depression, which put generations of people on antidepressants, is built on a false narrative of “chemical imbalance” where wonky brain chemistry is blamed for your sorrow and thus tweaking your neurotransmitters fixes it. If it were only so simple. Today, most thoughtful psychiatrists have largely discarded the chemical imbalance theory, yet patients come to them for chemical help. Undoubtedly media saturation, and the infodemic of minute-by-minute death numbers due to COVID-19, adds to the stress of pandemic-induced isolation and disruption. Media reports claiming we’ve got a full blown “mental health crisis” on our hands—whether true or not—likely means that careful and cautious prescribing gives way to an epidemic of people taking antidepressants and anti-anxiety drugs. KIM WITCZAK BECAME A FIERCE DRUG SAFETY ADVOCATE 15 years ago, after her husband Woody took his own life after being prescribed Zoloft, a widely-prescribed SSRI antidepressant (this class of drugs include Prozac and Paxil). Well-versed on the dangers of antidepressants, Kim is one of the most coherent voices on the dangers of psychiatric drugs and sits as a patient representative on the US FDA’s Psychopharmacologic Advisory Committee. Advocates like Witczak have influenced regulators about drug warnings and in fact her testimony and others in front of the FDA on the risk of suicide related to SSRI depressants forced the US FDA to put black box warnings on those drugs. (See www.woodymatters.com) Kim Witczak I contacted her at her home in Minneapolis to talk about the impact of COVID on mental health. “So many lives have been greatly damaged or impacted by the economic toll on families,” she said, adding, “drugs are going to be thrown at people.” “People need to be informed…Pills are not a quick fix, but I fear they will be the easiest way to deal with mass mental health issues of society,” said Witczak. What adds fuel to this fire is the fact that telemedicine in both Canada and the US are loosening the requirements and making it a lot easier to prescribe a range of drugs. Witczak is concerned that many patients aren’t going to have needed conversations around the immediate and long-term harms including addition and withdrawal effects related to psychiatric drugs. “These are serious, mind-altering drugs that have real risks,” she told me. “It is normal to be struggling with intense emotions like anxiety, fear, sadness, anger given this global pandemic and no one having a clue what the future holds. But is it really mental illness? People should pause and think twice before quickly resorting to a pill.” There are effective alternatives to drugs including counselling, cognitive behavioural therapy, mindfulness-based stress reduction and “exposure therapy” which can effectively reduce anxiety without the potential problems that come with any drug. The normal advice about reducing stress applies even more: getting exercise, eating properly and getting out into nature. My lay advice would add one thing: stop squirrelling away with social media or reading the news all the time. The world might be crazy but you don’t have to be. Some people are questioning this premise that we’re facing a massive mental health crisis and noting that there is a flip side to all of this. George Monbiot, writing in the UK’s Guardian, noted that the pandemic is causing a global outpouring of community action—people getting to know and look after their elderly neighbours, volunteers delivering food for healthcare workers and first responders, kids building healthcare visors on their home 3D printers and so on. Maybe the inherent altruism of people is emerging as a way to deal with the pandemic’s stresses? But back to the selling of social anxiety. In surveys people often say they fear public speaking more than they fear death. But is being afraid of speaking in public a “disease?” Is the fear of death? Maybe imagining the worse makes us all eager to reach for any lifebuoy at hand. But for those of us who are well aware of the dangers of prescription drugs, we just want to make sure that what keeps you afloat is buoyant, and not another anchor. At the end of the day it’s OK to feel anxious. Our world is changing. What would be really bad is if the short-term solutions turn into much worse long-term problems. Alan Cassels studies pharmaceutical policy and works at UBC. His book Seeking Sickness: Medical Screening and the Misguided Hunt for Diseases is available from bookstores and libraries. You can follow him on twitter @akecassels.

March 5, 2020 Thoughts around overdiagnosis after a visit to a medical specialist. A FASCINATING STUDY was published last month in Australia. It may not have got much press here in Victoria, but confirmed a lot of what the world is learning about overdiagnosis. That study, carried out by Paul Glasziou and colleagues, compared the year 1982 to 2012, analyzing changes in lifetime risks for prostate, breast, renal, thyroid cancers and melanoma. They concluded that 18 percent of all cancers diagnosed in Australian women (11,000 diagnoses each year), and 24 percent of those in men (18,000 each year) are overdiagnosed cancers. Screening programs (for cancers and other things) look for signs of disease detected in healthy people. Often those signs are just “prediseases,” benign signs which never go on to be lethal. Predisease is what might be diagnosed when a screening result isn’t quite normal, but is below the threshold of true disease. It is considered a potential precursor to a disease which may or may not be worrisome. The seriousness of “false positives” is also gaining worldwide attention, as this Australian study demonstrated. I wrote about the problems of overdiagnosis in my 2012 book Seeking Sickness and made the same case, where in condition after condition which involves some kind of medical screening, there is always overdiagnosis. There’s both benefits and harm in screening healthy people. It’s worthwhile if it finds signs of potential disease that will stop you getting a more serious disease. It can, however, lead to anxiety and often substantial medical activity, including biopsies, more screening, more procedures, surgery, radiation, and prescription drugs. Often all this anxiety and medical activity never actually extends the quality or quantity of your life. Here’s a scene that happened when I was partway through writing that book: I am in the chair at the optometrist, as he was about to blow a puff of air into my eyeball, checking for eyeball pressure. It dawned on me: “This is a screening test!” This is how I described it: “Things look different when you’re sitting in the chair, playing the role of the trusting patient. It was like I had two angels sitting on my shoulders. One was whispering in one ear: ‘What’s the big deal? It was just a puff of air to the eyes. C’mon.” On the other shoulder, the naysayer angel, armed with a pitchfork, was jabbing me in the ear: “Are you nuts? Do you have any idea what this screening test will lead to? False positives. False negatives. Overdiagnosis. Downstream effects. Worry. Anxiety. Depression. Say no!’” I was being overdramatic, yet I wrote that I learned a vital lesson: if you are about to face a health professional offering you a screening test, you need to have already done your research. Doing it afterward is getting things backward. The air-puff test showed normal eye pressure, but what if it didn’t? Thankfully, I didn’t find out. That experience became my operating axiom of why people need to go into medical screening test with their “eyes wide open.” Fast-forward eight years, and it was time for another trip to the optometrist. To get my eyes checked, maybe see if I needed a new eyeglass prescription. But darned if this didn’t turn out to be another “teachable moment,” this time with a much more potentially serious intervention. My optometrist said he saw something unusual in one of my eyes. He said I had a suspected case of narrow-angle glaucoma, a condition that could lead to an acute eye emergency and the potential loss of sight. That opened my eyes. He referred me to an ophthalmologist. The first trip to the ophthalmologist was just for a few tests and pictures of my eyes, collecting data. I was invited to watch a video of the doctor explaining the procedure he would offer, a quick operation called a laser peripheral iridotomy (LPI). Perfectly safe, right? But… Let’s be clear. I am a healthy patient, normal eyeball pressure, and a normal optic nerve. No history of eye disease and no family history either. I was what the literature called a PACS, which stands for “primary angle closure suspect.” I don’t have disease—I have the younger sister, predisease. I found an excellent paper by Dr H. George Tanaka, an ophthalmologist in Arkansas whose 2018 Review of Ophthalmology study gives considerable detail about the pros and cons of such a procedure. I learned quickly this was no slam-dunk, and I was right to be cautious. I tracked him down and arranged a phone interview. The main thing I learned is that for people without symptoms or family history of other types of eye diseases, there is no way to know how many PACS patients go on to have an “acute episode” that involves losing your eyesight. Is it one in ten, or one in ten thousand? We don’t know. He admitted that “unfortunately, we don’t have any good evidence for how to manage a PACS patient, and that we don’t know how many PACS patients go on to develop more serious eye problems.” For the sake of everyone in Victoria who (at a certain age) may well be diagnosed with suspected angle-closure glaucoma, there are a few things to know about the LPI surgery being offered. Angle- closure glaucoma can be an aggressive disease, probably the leading cause of glaucoma blindness in the world, and it is one of the few emergencies in ophthalmology. But as Dr Tanaka wrote: “We don’t actually know how many future angle-closure attacks we’re preventing by performing LPIs. That’s why we can’t say to a patient with narrow angles, ‘Mrs Smith, your risk of going blind is X percent (or your risk of getting glaucoma is Y percent), but the odds will improve by this much if I perform this procedure.’ We don’t have the numbers to support that.” It’s the conclusion that bothers me: “so we just treat everybody.” Clearly, this is textbook overdiagnosis: finding “predisease” in normal people, who are then given the impression they are now living under a dark cloud. The research suggests the LPI may delay or prevent primary-angle glaucoma. Luckily, the LPI is fairly benign. This operation used to be major surgery, but now is a couple of minutes in the clinic, with minimal risks of infection or bleeding. As for the cons, sometimes things go sideways. Sometimes patients get extra spots of light in their vision—dysphotopsias—which won’t go away. And believe it or not, some research says the LPI can accelerate cataract development, as well as make you more predisposed to getting a condition called posterior synechiae, making future cataract surgery more difficult. For me, saying no to the procedure was a no-brainer. If I had higher risks, a personal or family history of eye disease, high eyeball pressure, or if I was going to be hiking in the outback for months at a time where getting emergency medical care was difficult, my decision might have been different. But the doc was not impressed. I really liked the ophthalmologist. He was a very nice gentleman. He explained things well, but at the same time, I could tell he was taken aback when I refused the procedure. Perhaps he’s not used to patients doing a deep dive into the literature on the potential benefits and harms of surgical procedures. He pressed me, eventually turning up his hands and saying: “Oh well, I just want to tell you the risks, but you’re on your own,” later adding, “well, you’re the ticking time bomb.” Luckily I have a thick skin, though if you had taken my blood pressure at the time it, would have been through the roof. Not only does his comment not reflect the real research, it’s the height of insensitivity to call a patient a “ticking time bomb.” No one deserves to be intentionally frightened into getting an elective procedure, especially one with many unknowns and potential harms. As an aside, if the average person knew how much these doctors make by five minutes of lasering your eyes, they would be astounded (all in, close to $400 per eye—$116.76 for the actual few minutes of surgery, $35 for the office visit, $96 for the consultation, $60.42 for “orthooptic evaluation,” with likely extra charges for the photography of the eyes, etc. ). I found in the MSP bluebook that this ophthalmologist billed MSP $749,000 last year. Later, when I calmed down, I reflected on the “ticking time bomb” comment. Listen, dear reader. Like everyone on the planet, you could live another five minutes or another fifty years. We are all ticking time bombs, more or less. We are all “prediseased” and suffering from “predeath.” Being called a “ticking time bomb” made me angry but also sad for all the patients who are worried, who crave the trusted advice of a health professional, but then get bullied into procedures (or drugs) that they would rather not have. When I was in the navy, we had a principle: if you don’t know where you are, stop the ship. All signs of disease have uncertainties, and all surgeries and drugs have potential harms and potential benefits. Any honest health professional will tell you those uncertainties. When you don’t know where you are, don’t keep sailing. Alan Cassels studies pharmaceutical policy and works at UBC. His book Seeking Sickness: Medical Screening and the Misguided Hunt for Diseases is available from bookstores and libraries. You can follow him on twitter @akecassels.

September 2015 Vancouver Island’s aging baby boomers, coupled with stretched budgets and operating rooms, have created a perfect storm for timely access to needed joint surgery. SIXTY-EIGHT-YEAR-OLD Nancy Tienhaara, who works in marketing for a Victoria software company, felt she needed a new knee but couldn’t get it. The pain, she recalls, was unbearable and X-rays showed there was very little cartilage in her knees. Walking was difficult and painful. After seven weeks of waiting, she finally got in to see an orthopaedic surgeon. But she didn’t hear what she wanted to hear: She wasn’t a good candidate for surgery—her pain and immobility were not yet severe enough. Disgusted with the system and driven by pain and desperation, she did what some Canadians do when they’re forced to play the waiting game—she left the country. Tienhaara travelled to Phoenix, Arizona and shelled out $22,000 US for knee replacement surgery. While that isn’t an option for most of us, Tienhaara felt compelled to find the money: “If I had not done so, I would be in a wheelchair today.” Vancouver Island residents waiting for a new hip or knee, in pain and misery, tell stories that are compelling, even heart-wrenching. When I called him at his home at the end of July, Rob Brown, a retired actuary in Colwood, had just returned home from the hospital the day before with a new hip. His year of immobility waiting for a hip replacement was like “being placed under house arrest,” he told me. Ask anyone who has had to wait for a joint replacement and you will hear the same urgent advice: “Get on that list as fast as possible.” The message couldn’t be clearer: Since you could be waiting in agony for a very, very long time, you’d be a fool not to act quickly. But how reliable is that advice? And does acting fast guarantee earlier treatment? Outside of emergency procedures, if you think you need a new knee or a new hip, how is your level of pain and immobility prioritised among other patients who are waiting? These questions are not trivial. In fact, they lie at the heart of the sustainability of our health care system because how we manage waitlists for joint surgery is an issue—due to demand and the costs involved—that has the power to make or break Canada’s public healthcare system as we know it. Canada spends almost a billion dollars a year for hip and knee surgery, and waitlists for those surgeries are among the hottest and most political aspects of Canada’s healthcare system. In BC, over half a million publicly-funded surgical procedures are performed every year, of which almost 80 percent are day procedures. Hip and knee replacements currently require a stay in a hospital for about three days. Another statistic to note is that more than half of all surgeries done every year in BC are emergency or unscheduled procedures and therefore do not appear on any surgery wait time list which juggles the line-up for new hips and knees. In Canada, a federal benchmark for “the maximum amount of time that clinical evidence shows is appropriate to wait for a particular procedure” is set at 26 weeks for both hip and knee replacement. Problem is, you’d be hard pressed to find anywhere in the country that comes close to the benchmarks. Some jurisdictions, including Victoria, miss the benchmarks by miles. Norm Peters is executive director of surgical services and heart health at Island Health. He oversees surgery for the two main hospitals in Victoria and the Nanaimo Regional General Hospital. He is responsible for quality and strategic planning for the other five community hospitals across the island. Peters openly admits that people in Victoria face one of the longest waiting games in the province. Even though Island Health has introduced a number of measures to address waitlists for hips and knees—aiming to perform 500 to 550 more of those surgeries this year—he doesn’t mince words about our waiting list: “We have the unfortunate distinction of being the worst performing in BC.” If you live in Victoria and your orthopaedic surgeon suggests you are a candidate for a new joint, you might get your surgery in a year, as Rob Brown did. Or it might take longer. The waiting game Wait times have been studied extensively. Despite the endless analyses, along with programs created to reduce those waitlists, and money poured in to relieve the problem, the lists keep growing. Demographics play a big role (more later). But there are also more mundane communication issues at the bottom of the quagmire. Often physicians and specialists operate in silos, impervious to what their next-door neighbour is doing. Patients are motivated and moved by anecdotes, and believe surgery is vital, and always the solution. None of us have any idea whether the excruciating stories we hear about patients waiting reflect a general reality or are just egregious outliers. The criteria for being on a list are determined by an assessment from an orthopaedic surgeon who will scrutinize X-rays, and will assess your state of pain and mobility. Is the pain keeping you awake at night? Do you need heavy-duty meds to keep pain under control? How well can you get around? What is your overall health like? Some patients, like Nancy Tienhaara, will be told they’re not yet candidates. Others might be deemed at such risk of becoming disabled they would be placed in a higher priority. As to how long each person will wait, as they say, “it all depends.” Everyone likes to talk about “the list” and, in fact, whole conversations can happen without people realizing there are several types of lists. Going from pain in your hip to being fully recovered from a replacement hip after a two-hour operation and a three-day hospital stay involves at least four waits. Wait One is the time from when your doctor refers you to the specialist until you are sitting in front of the orthopaedic surgeon. Wait Two is the time from when the specialist agrees you need surgery and books it—known as the decision date—to the date you actually get it. The other types of waits are the access to diagnostics, maybe an X-ray or other diagnostic test, and then the wait for recovery. The waits of most concern to patients are the first two and they happen to be the ones where there is the best reporting. According to Neeta Das McMurty, a member of Canada’s Evidence Network who compiled a consumer backgrounder on surgical wait times, the numbers often don’t reflect reality. For example, sometimes there are patients who are put on multiple waiting lists. She writes, “One study found that up to one-third of patients should have been removed from the list because the patient has already had the procedure done elsewhere, was already admitted into hospital as an emergency case, no longer wants the procedure, or it is not medically necessary.” Sometimes the patient dies while on the list (from other causes) or has asked to reschedule their surgery for a more convenient time. Others might argue, saying there should be more patients on the list and that people are being cruelly turned away from getting on the first rung. Clearly, managing a waitlist demands heavy-duty coordination. Norm Peters points me in the direction of the BC Surgical Wait Times website (https://swt.hlth.gov.bc.ca) where you can go online, choose a surgical procedure, and look at the types of waits you might expect. For example, as of July 31, 2015, there were 956 people on Vancouver Island (out of 3302 in all of BC) waiting for a new hip. Of these, 468 people were waiting to be treated at Greater Victoria hospitals. Of the 11 doctors listed for Victoria, two had less than 5 patients waiting and one had 149 patients waiting. Each doctor has a different number of patients waiting for a number of reasons. In this system patients can choose which doctor they’d like to see, some only work part-time, and so on. The two key metrics represented are “50 percent received services within X weeks” and “90 percent received services within X weeks.” You will find that according to these data, half the people on the BC waitlist (in the previous three months) got their hip replaced within 19 weeks after their “decision date” and 90 percent of them got it within 52 weeks. This compares to 34 weeks and 59 weeks respectively for Vancouver Island, about the same as it is for Greater Victoria Hospitals. There still might be a lot of grumbling about how long one has to wait, but the advantage here, at least for BC, is that these statistics are fully transparent for anyone to see. Compared to other jurisdictions, this is huge progress. A local attempt at triage If you live in Victoria, you’ll be, like Nancy Tienhaara and Rob Brown, sent to Rebalance, (www.rebalancemd.com) which is basically a one-stop shop. Physiotherapist Stefan Fletcher and orthopaedic surgeon Patrick McAllister started Rebalance four years ago, eager to do something about the chaotic nature of Victoria’s current wait system: impenetrable lists, overworked physicians, and underserved patients. Fletcher is the CEO of Rebalance, and he has an air of calm about him, dressed in a polo shirt and shorts when he greets me in his spanking new 11,000-square-foot facility in the Uptown Centre. Though Rebalance is a private company, there’s something unique about it beyond the chic glass and steel décor and video monitors adorning the walls. This doesn’t look like any public health facility you’ve ever seen in Canada, but it is public in one important way: The services offered here are covered by our Medical Services Plan. Generally you don’t need anything but your Care Card and a doctor’s referral to get service here. It feels ultra-modern and efficient, an ambience very different from the one-doctor, one-office silos we’re used to. This place reflects the group’s team approach where doctors, nurses, physiotherapists, and patient navigators are all in the same place, working towards the same goal: streamlining the journey. Fletcher comes out to greet me at reception, then steers me into his office to discuss the issue of wait times. We get down to business. The tour, he promises, comes later. He says that prior to Rebalance there was a “huge amount of ignorance around waitlists…[with] no knowledge, no markers, no transparency, and no tracking.” The creation of his company, he says, was “driven by physicians,” essentially Victoria’s orthopaedic surgeons who wanted a more rational, patient-centred model to help people waiting interminably (and sometimes needlessly) just for a firm answer to the first question: “Do I need surgery or not?” “It used to be nine months to two years to even see an orthopaedic surgeon,” he tells me, “and now it’s four to six weeks. Our goal,” he says, “is to get the right person to the right place at the right time.” Is this triage, I ask? “Absolutely. It’s 100 percent triage,” he says. The acronym they use is FAAST which stands for “first available appropriate specialist treatment.” The emphasis there is on “appropriate.” “Basically, this is the whole conservative journey,” he continues. “Get them in early. If you can, try A, B, C, D, and E. And if those fail, come back and see us.” Those other things are mainly exercise, weight loss, and pain-relieving drugs. Maintaining flexibility and strengthening the muscles that support the joints are both considered important. The percentage of people who consult an orthopaedic surgeon who go on to have surgery—Fletcher calls this the “hit rate”—is only about 30 percent. The other 70 percent might need help—perhaps from physiotherapy or other forms of preparation including proper diagnostics such as X-rays—but they aren’t yet candidates for surgery. Fletcher says that at least half the patients who come and see his clinic “have other things they need to happen” before they have surgery and this includes weight loss and consultations with other specialists to correct other health problems. Patients who have manageable joint pain should obviously try to avoid or delay surgery as long as possible. Recovery from surgery can take a long time and the procedure itself can involve complications. Plus there is no real guarantee how long a new joint will last. Some say you might get 10-15 years out of a new hip but then that may mean “revision surgery” down the road, which is much more complex. Rebalance has a contract with Island Health for physiotherapy, Fletcher says, “to optimize patients pre op and to deliver post op physio after joint replacement surgery.” Rebalance’s nurses and navigators coordinate information, manage the intake, and arrange education—stuff that allows the surgeon to focus on what they do best. According to Fletcher, the satisfaction of both the patients and the physicians is “through the roof.” He explains that patient satisfaction levels are a lot higher because people don’t have to wait as long (Wait Time One) to actually get their health complaint seen. And those who do need surgery more urgently can get in there quicker, too. Fletcher uses his hands to explain “unravelling the nut of wait times.” He says: “What we have is this great big funnel coming in, and so the accessibility to the system is greater. We have squeezed the Wait One,” he tells me, moving his hands closer together, “yet Wait Time Two,” he says, spreading his hands far apart, “well, it’s a lot bigger.” When Rebalance got going four years ago there were about 1200 people on the Wait Two list for knee and hip surgeries; now it’s about 3000. Fletcher believes it’s because more people are being seen by surgeons. This means, he points out, that "those patients not needing surgery are also being addressed where before they were not being seen as easily.” With the Wait Two list so long, however, it means a lot of people like Rob Brown waiting for up to a year for a new hip. How does this compare to other places, I wonder? Fletcher calls the triage systems in other places “a pile of faxes,” explaining, “The surgeon comes in and says, give me the 10 on the bottom.” At Rebalance, the triage is continuous, and if your situation changes, so too can your place in line. Despite the Province maintaining the waitlist website, access to a surgeon is still a considerable barrier in other communities, Fletcher tells me: “In Kelowna it’s nine months just to get an appointment. It’s a mess. Vancouver it’s two years—unless you want to pay privately. We are 100 percent in the public system.” Bottlenecks and other realities So Canadians are still waiting, and on Vancouver Island, they may wait more than a year after a surgeon has made a decision that surgery is the best option for them. According to a study on wait times by the Organization for Economic Co-operation and Development (OECD), there are typically three key strategies to reduce waiting times: More money, enforced wait times, and better triaging. In 2003 a federal agreement in Canada committed $5.5 billion over 10 years to the Wait Time Reduction Fund to reduce wait times for cataract removal, hip and knee replacements, diagnostic imaging, cardiac bypass surgery and cancer radiation therapy. In 2011, the Canadian Institute for Health Information (CIHI) showed that there were reported improvements for three years, as the money helped clear the backlogs, but there is insufficient data to determine if the improvements were sustained. Wait time guarantees set a maximum wait time for certain procedures, putting pressure on system managers and physicians to provide care within a target time frame. These are helpful, but not a long-term solution. The most hopeful strategy is what the OECD called “clinical prioritisation tools”—which is about managing and triaging patients based on need. These tools have been shown to be the best and most sustainable of the approaches. A study published eight years ago by the Canadian Centre for Policy Alternatives analyzed waitlist reduction projects across Canada and found that better management of waitlists requires two major things: Firstly, physicians needed to go from working on their own to working in teams and, secondly, the accountability for waitlist management had to be transferred from individual surgeons to health authorities working with groups of surgeons and other health professionals. These principles essentially underpin what Rebalance has done in Victoria. A strategy document prepared by the BC Ministry of Health, “Setting Priorities for the BC Health System,” admits how difficult it is to make progress. “Despite the attention paid to surgical waitlists and increases in volumes of elective surgeries, BC’s wait times for many procedures have not declined and performance is either stagnant or slipping. For example, the average wait time for the top 20 surgical procedures declined slightly from 2009 to 2010, but has remained mostly the same since then.” For everywhere in Canada, how long you wait depends on many factors: your medical status (your pain levels, your mobility, whether you’ve got other health conditions, etc), which specialist you get referred to, how busy he or she is, and whether that specialist has good access to operating rooms. The overall drivers of demand, however, are largely determined by demographics. On that front, Norm Peters calls it the perfect storm. “We [on Vancouver Island] have two of the three oldest communities in BC. We have a healthy and active population so people wear out their knees.” But it’s not just older, active people wearing out their joints. Peters blames growing levels of obesity as well for an increase in the demand for hips and knees. The Canadian Community Health Survey shows the numbers of obese people in Canada rose more than 25 percent between 2000 and 2011. So demand is definitely on the rise. Looking at the “supply side,” we can’t blame lengthy waitlists on a lack of orthopaedic specialists. I think my jaw might have dropped when Rebalance’s Fletcher told me there were more than 130 unemployed orthopaedic surgeons in Canada. According to Peters, the major bottleneck is access to operating rooms. Fletcher described the practical dimensions of that bottleneck, noting the demand for anaesthetists, staff, nurses, and hospital time. He produced a graph that showed big drops in the number of procedures done in July and August when many people are on vacation, and November and December because of Christmas. Getting surgery depends on many people, not just surgeons, and it’s hard to get them to operate on you when they’re lying on a beach or eating turkey. But beyond people, it’s money. Obviously buying more dedicated hospital time at these off-peak periods could help reduce Wait Time Two; everyone agrees that to get that down, the Province needs to put more money into the back end. Still, Fletcher was optimistic about the future. In April, Island Health issued a Request for Proposal (RFP) for a “surgical services partner to carry out between 3000 and 4000 day procedures per year over a five-year contract term.” These will certainly reduce the pressure on waitlists by taking some other surgeries out of public operating rooms, and perhaps help reduce the backlog for joint surgery, but more innovations are needed. Fletcher saw other possibilities, too: a dedicated joint unit, where hips and knees could be done either in a hospital or a day care clinic in less than the required three-day stay. That seems sensible to me. The right patients, with the right home supports in place, may not need a full three-day stay after their surgery. “We could profoundly influence the wait times in the public system for surgery,” Fletcher suggested. “If we can crack that nut, and continue to keep our eye on the ball at the front—entry level system—then we have cracked the nut of orthopaedics in Canada.” I wondered about patients like Nancy Tienhaara who don’t think they can wait. She feels there are serious downsides to waiting, and a report from the Alberta Bone and Joint Institute backs her up. The report says that patients waiting longer than three months have more pain and less mobility, and there is often pain in the opposite joint for patients who wait longer than six months. It established 14 weeks as the Wait Two target. Tienhaara notes, “Intolerable pain is the criterion provided by many doctors for agreeing to surgery for a patient. Because I did not have constant high levels of pain, I was rejected at Rebalance.” Because pain is subjective, and experienced by everyone differently, perhaps this is why triaging patients is particularly difficult. Fletcher admitted he often has to deal with people complaining of not getting treatment soon enough, or at all. I told him the story of Nancy Tienhaara and he was sympathetic. “We deal with that all the time,” he said. One patient pleaded with him, in tears, saying she would lose her job if she didn’t get to see an orthopaedic surgeon. He is as responsive as he can be. After all, any system has to make allowances for urgent special cases. He found a slot and put her in in two days. It’s not as subjective as it seems though. Obviously there is a human element in managing waitlists. Clearly these are very difficult issues, but I get the feeling that at least here in Victoria, there is a sense of progress and hope. We don’t want a society that leaves people suffering and in pain when surgery could fix it. We want a system that is responsive enough so that they don’t have to travel to Arizona for a new joint. At the same time, we want a sustainable healthcare system where the most urgent care is going to those with the most urgent need. Better management of the lists is the first step. More money to deal with the mounting lists is clearly the second step. But beyond this we citizens have to remember that there are many other kinds of high-value, life-saving treatments such as those for cancer and heart disease that we still need to fund. There’s a limit on the supply of money in the healthcare system, but there shouldn’t be a limit on how we innovate while keeping that system public and accessible for those in need. Alan Cassels is a health policy researcher affiliated with the Faculty of Human and Social Development at the University of Victoria, and the author of Seeking Sickness: Medical Screening and the Misguided Hunt for Disease (Greystone, 2012), and the 2005 book Selling Sickness.

October 2013 Are we ready for the consequences of a province-wide colon screening program? THE SIGN ON THE FRONT OF THE PODIUM said it all: “Screening Saves Lives.” It was April of this year and Health Minister Margaret MacDiarmid was speaking at a very important event. After a three-year pilot study in several communities around BC, she was announcing the official start of the new Provincial Colon Screening Program which was going to be unrolled on Vancouver Island this summer, before moving on to the rest of the province. As she was announcing that program, few might have predicted the controversies that lay ahead; a summer where front page headlines were saying people who needed colonoscopies were facing massive line-ups and long waits for referrals to gastroenterologists. The new Health Minister Terry Lake had to face reporters to explain how they would fix things. Some might say these were just growing pains for a province that has been somewhat slow in introducing a colon cancer screening program (at least six other provinces have already established their programs), yet screening large numbers of healthy people in the name of prevention is undoubtedly a complicated matter, both medically and politically. The praiseworthy goal is to reduce the rate at which British Columbians die from colon cancer—the third most lethal type of cancer in Canada—and BC’s program seems on the surface well-designed, but its implementation is not without its problems. Within months of the program beginning on Vancouver Island, referrals to the island’s gastroenterologists, experts in assessing and treating people with a range of stomach and digestive problems, tripled. The ensuing waitlists for colonoscopies generated those headlines and the perception was set: People were being denied a lifesaving procedure. BC’s program asks people to take a low-tech screening test before moving on to more complex, invasive and expensive tests, like the colonoscopy. The FIT (Fecal Immunochemical Test—essentially a take-home poop test) is offered free to all eligible BC residents between 50 and 74 years old. If you have a positive test (evidence of blood in the stool) you are eligible for a colonoscopy, which, done every ten years, is considered equivalent to the FIT every 1-2 years in terms of its ability to prevent or detect colon cancer at an early stage. For people thought to be at higher risk because of their family history or a previous history of polyps, they can skip the FIT test and jump straight to a publicly-funded colonoscopy. The simple fecal test costs our health care system only $35 per person to administer. It is an appropriate first-line screening tool as it can detect blood in the stool which might be an early sign of colon cancer. But there may be other reasons why there is blood in your stool: for example, hernias, ulcers, anal fissures. Sometimes even eating very rare meat can create a false positive. So, like any screening test, the problem of a false-positive result is always there. A colonoscopy involves a long flexible scope, threaded through the anus and up into the colon to look for signs of bowel disease. If any signs of precancerous growth such as polyps are found, they can be removed. It is believed by most medical authorities that finding and removing these polyps can reduce the risk of colon cancer. Currently, a typical Canadian faces a lifetime risk of a colon cancer death of about four percent. If a simple inexpensive FIT can improve those odds, it seems a reasonable and appropriate thing to do. However, like all screening programs, colon screening is imperfect. There is much medical conjecture and debate about the relative values of FIT versus colonoscopy. Colonoscopies can find polyps and remove them, but they can also miss things. Also, at least a third of healthy people between ages 50 and 75 will have colon polyps. And here’s what you’re not likely to hear: Most of us will die with—but not because of—colon polyps. Vancouver gastroenterologist Jennifer Telford is enthusiastic about colon screening. She was involved in piloting the screening program in BC and says it’s entirely appropriate that the stool test should precede a colonoscopy. She estimated that if we gave the FIT to 10,000 eligible BC residents, 8.5 percent, or 850 would go on to be recommended for a colonoscopy. Of those 850, about 34 cancers would be detected and about a third would have an advance neoplasia, or advanced polyps. These can be removed during the procedure. “Colonoscopy is a great test and I love doing it,” says Dr Telford. Certainly removing polyps must be a satisfying enterprise because of the perceived benefit to patients. Dr Telford estimates that “75 to 80 percent of colon cancers come from precancerous polyps.” But does a polyp automatically mean a death sentence? Not at all—only about 2.5 polyps in a thousand will progress to cancer. There is much medical debate around how fast even “precancerous” colonic polyps will go on to develop into full blown cancers; estimates range from 10 to 25 years. Admittedly, finding things that could be precursors to cancer and then leaving them alone is very hard to do. Hunting down and removing polyps seems relatively easy to do and lucrative for those doing it. But before fully embracing the program, we need to understand the problems colonoscopies themselves can cause both individuals and the health care system. Volume clogging care In early August, the Times Colonist reported that a young Oak Bay High graduate had sued VIHA for not arranging an early-enough colonoscopy when he had serious symptoms (blood in his stool, a swollen abdomen and fever) that needed investigating. He was told by physicians that a diagnostic colonoscopy was necessary to determine if it was Crohn’s disease or perhaps a carcinoid tumour—something that can be fatal if not detected early. But the 19-year-old got stuck in the four-month-long queue with everyone else getting a screening colonoscopy. (He has now had this test.) Consumer advocate Wendy Armstrong of Edmonton isn’t surprised to see these sorts of delays now happening in BC. She has been monitoring the expansion of various screening programs for decades and what concerns her—watching how colonoscopies have been so eagerly promoted, sought and delivered in Alberta—is how the attention of gastroenterologists is consumed by, among other things, all the polyp chasing. She tells me the story of a young man in Alberta, suffering a flare-up of Crohn’s, who was told he had an eight-month wait before he could get a colonoscopy. The problem, in Wendy’s estimation, is how busy the specialists can become “looking further at people with suspicious fecal tests.” Unlike BC’s program—which requires the FIT first—Alberta publicly funds first-line colonoscopy screening. The growing numbers of colonoscopies performed in Alberta in the last few years has been staggering. In 2007, Alberta Health paid for 54,000 colonoscopies, yet by 2012 that number had increased to just over 107,000, a 100 percent rise in a province whose population grew just over 10 percent. This is, perhaps, why Calgary has been given the ignominious title of the “Colonoscopy Capital of Canada.” The experience in Alberta is relevant because when you introduce a test that goes on to occupy the energies of the specialists, they may have even less time to treat genuinely sick people. With all the screening through colonoscopies, Wendy Armstrong says she has seen firsthand the “difficulty for people with debilitating symptoms of bowel disease—such as Crohn’s or colitis or even people showing clinical symptoms of possible cancer—to get timely and appropriate care.” After all, the time and availability of gastroenterologists are limited. Unpredictable demand, unknown costs BC’s program seems more rational than Alberta’s, yet with both provinces, access to specialists is related to the issue of unpredictable demand. When you offer a screening program, how many people will bite? When I inquired earlier this spring, health authorities on Vancouver Island could give few precise details on the forthcoming screening program, such as the numbers to be screened, how many lives would be saved and the overall cost of the program. A 2010 UBC study suggested a cost of about $70 million per 100,000 individuals (in BC there are 1.345 million people between the ages of 50 and 74). But calculations are not simple. Besides factoring in possible savings from earlier detection of cancer—which will take many years, maybe decades, to be realized—there are many other unknown factors: How many people will submit to screening? How many positives will be found? How many physicians will refer their patients to a colonoscopy without a positive FIT? And we can’t forget the costs associated with medical procedures needed to fix people who are injured by a colonoscopy. The BC Cancer Agency’s Angela Wilson told me by email that “FIT use in the first three months of availability has been [25 percent] higher than expected. Patients with positive FIT would be referred to colonoscopy; therefore colonoscopy referrals have been higher than anticipated as well.” Wilson also said that “the Ministry of Health has estimated the annual program cost to be $10 million,” though those costs could be much higher. There are many things which might drive (or reduce) demand for colonoscopies. One of the things that drives consumer demand for screening is the celebrity factor. When TV personality Katie Couric had her colonoscopy done live on the Today Show, there was a 20 percent spike in colonoscopies in the US. Celebrity endorsements might be the last place one should go for health information, but knowing someone who has died from colon cancer (or believing one’s life had been saved because of a polyp removal) surely contributes to the demand for colonoscopies. What does the evidence say about the difference between the FIT test and colonoscopies? Dr James Allison, a gastroenterologist and clinical professor of medicine at University of California, San Francisco says BC’s colon screening program seems “conservative and appropriate.” He has written extensively on the lack of evidence to support the popularity of colonoscopies, telling me that there is “no proof from randomized controlled trials that colonoscopy every 10 years is superior to FIT every year in decreasing colorectal cancer incidence and mortality.” In other words, the colonoscopy is not any more “lifesaving” than having the poop test every year or two. So how effective is the fecal test? Like many screening programs, many of us have to be screened in order for one person to benefit. Dr James Penston, a UK gastroenterologist, criticizes colorectal screening as “being sold to the general public on the grounds that it saves lives. But there’s no evidence for this claim.” He points to a large 10-year study in the UK of colon cancer screening using the fecal occult blood test. In the control group (those not screened) the death rate for colorectal cancer was 0.8 percent. It was 0.7 percent in the screened group. This 0.1 percent difference translates into a one-in-a-thousand benefit. A new study published in the prestigious New England Journal of Medicine in late September looked at 30 years of follow-up for more than 46,000 people undergoing annual or biennial fecal blood screening for colon cancer. Those undergoing screening were less likely to die from colon cancer (by about 6 in 1,000), but overall death rates in screened and unscreened populations were the same. So the Minister's sign that “Screening saves lives,” at least in this case, isn’t proven by the evidence. Perhaps more important, how many will be given colonoscopies that lead to bleeding, hospitalization, perforation and, occasionally, death? Unfortunately, we won’t know the answers and hence the overall outcome until the program has been in place for a very long time. Overdiagnosis, overtreatment and harm In the last few years even the most-studied and widely-used screening programs (for breast and prostate cancer, for instance) have faced evidence-based arguments about whether they were doing more harm than good. The main issue has been the possibility of overdiagnosis. In the case of colon cancer, because most of us will have polyps and very few of us will die from them, screening is also liable to result in overdiagnosis and overtreatment. If and when polyps are found, people may live under a dark cloud, with a “pre-cancerous” label for the rest of their lives. They will certainly be more frequently reminded of their colon health because they will receive many future invitations for follow-up colonoscopies. There is some evidence that depression and suicide is higher among those who submit to screening programs. Dr Gilbert Welch, author of the book Overdiagnosed: Making People Sick in the Pursuit of Health, knows well the downsides of screening. In an article he wrote for the New York Times last year he said that “screening the apparently healthy potentially saves a few lives…but it definitely drags many others into the system needlessly—into needless appointments, needless tests, needless drugs and needless operations…” He argues that the process of screening doesn’t promote health but rather promotes disease. “People suffer from more anxiety about their health, from drug side effects, from complications of surgery. A few die. And remember: These people felt fine when they entered the health care system.” In addition to the psychological effects of screening, the downsides to an actual screening colonoscopy can include the side effects of ingesting the bowel preparation (including bloating, gas, stomach pain, feeling very hungry and dehydrated), as well as cardiac arrhythmias, and other metabolic disturbances, and even neurological damage. When Deb Novak, a 56-year old native of Edmonton agreed to have a screening colonoscopy, like many people she was seeking an ounce of prevention. When Novak arrived for the procedure, the clinic was crowded with others waiting for their colonoscopies. Despite the mild sedation she found the colonoscopy painful and at one point a searing pain caused her to scream out and struggle to jump off the table. When the procedure was over the doctor said they had found a single mushroom-like polyp and removed it. That should have been the end of the story. But it wasn’t. She spent most of that night vomiting and in severe pain. A late-night ambulance ride back to the hospital and a near 12-hour, agony-filled wait in the emergency room left her feeling abandoned and bitter. She said that it appeared the screening program “had no back-up plan for a return in the case of a perforation emergency.” During the emergency operation to repair a seven-centimetre perforation of her bowel, Novak thought to herself, “I think I’m going to die.” She had to rely on a colostomy appliance for a year before they could repair her torn intestine. While only a small proportion of colonoscopy procedures turn out as horrendous as Deb Novak’s, colonoscopies for some people can be fatal. Studies show a .5 percent risk of serious medical complications from colonoscopy—one person in 200. There’s also the opposite possibility, that a patient will get stamped with a clean bill of health after a colonoscopy when the scope missed something. This is common “even among expert examiners who know that they are being scrutinized,” said one study. In fact, as Deb Novak tells me, the doctors doing the emergency repair to her perforated colon found a polyp that had been missed during the original colonoscopy. Inflating the demand For some diseases of the digestive system, such as Crohn’s and colitis, getting a close-up view of a colon with a colonoscopy can be an incredibly valuable tool. After all, these are people who have clear symptoms of pre-existing bowel diseases and a diagnostic colonoscopy is a great way to find out more about their condition. But when used purely as a screening method, it’s worth reminding ourselves of the financial incentives shaping who gets screened, how often, and for what purpose. Physicians in BC don’t make a ton of money doing a colonoscopy (MSP pays them $230.62 for a colonoscopy or $344.79 if a polyp is removed), but when you add all the additional costs—the anaesthetist’s time, the nurse, equipment and admin costs—the bill to the tax-funded system could be as much as $1000. And of course if you have complications, bleeding or perforations, it’s back to the hospital for even more medical interventions and costly treatment. In the private sector, a screening colonoscopy can be bought for $1600 at a place like the False Creek Healthcare Centre in Vancouver. When I called inquiring about the program, I was told that I’d be in good hands because “all the doctors are gastroenterologists who work in the public system.” There are a limited number of gastroenterologists in the province. If they can get (or their private facility can get) $1600 for a colonoscopy for 20-30 minutes of work, and only $344 for removing a polyp in the public system, guess where most of them are going to work? That’s exactly what they found happened in Alberta. This understandably results in more stress on the public system, making delays more likely for those who are suffering symptoms that require a scope to help determine their cause. Wendy Armstrong, who is a past president and current researcher for the Consumers Association of Alberta, was an official intervener in a recent public inquiry in Alberta examining alleged preferential access in the public healthcare system. The inquiry found that some private patients were getting booked for screening colonoscopies in weeks or months in private clinics while others waited two to three years to get the procedure in the public system. It also found that some patients were being recalled for follow-up colonoscopies more frequently than recommended by current guidelines. In Wendy’s opinion, the potential for inflating demand for colonoscopies (inside and outside the public system) was huge and that the wait-time problems and frustrations that we are seeing in BC are entirely predictable. She told me, “what came through loud and clear was that doctors in these boutique clinics are shopping for ‘healthy users.’” By overscreening healthy, better-paying private clients, the sick and the more needy (those with real symptoms) will inevitably get shunted to the back of the line, or stuck in the line with everyone else, like that poor Oak Bay student. There is a name for this: It’s called the “inverse care law,” which can be re-tweaked here to be the “inverse screening law”—which is to say, the availability of a service, in this case screening, is in inverse proportion to its need. Spending $10 million or more of public health dollars every year to avoid a fatal disease seems on the surface like the right thing to do, but we always have to ask: What kind of overall impact will this screening program have? Will other important public healthcare services or programs be cut or clawed back to pay for the growing costs of this program? Have they been already? And are there better, perhaps more efficient ways to reduce the burden of colon cancer? We know, for example, that better diets (less meat and processed food), more exercise, not smoking—the usual triumvirate of better health advice—is crucial to help us all live longer and healthier lives. Want to reduce your risk of colon cancer? Eat more vegetables and ride your bike (as well as talk to your doctor about your family risk and how you might benefit from colon cancer screening). From my perspective as a researcher, we need better evaluation of existing screening programs to estimate the benefits; better predictions so we can estimate the burden of the program on the gastronenterology profession; and better information so that people go into screening knowing what to expect—both the potential benefits and potential harm—so they can opt out if they don’t like the odds presented to them. At the end of the day, well-informed citizens, not physicians or the government, should determine if they want to submit to a colon screening program around which there are many questions and unknowns. Alan Cassels is the author of Seeking Sickness: Medical Screening and the Misguided Hunt for Disease and he has worked for the last 18 years as an administrator, researcher and consultant on research and evaluation projects supported by the provincial and federal governments.

March 2013 Health researcher Alan Cassels explores the context—and theories—surrounding the unprecedented and unexplained destruction of independent drug evaluation in BC. WHEN I MET ROBERT BROWN FOR COFFEE a couple of years ago he had something to show me. It was a sample of a new drug called Pradax (dabigatran) that his doctor had given him. It was the first in a new class of drugs prescribed for people with atrial fibrillation (AF), a relatively common condition that can increase one’s risk of having a stroke. The standard script for AF is warfarin, a widely used blood-thinning drug. I didn’t want to worry him but in the course of our coffee I asked if he was aware of the drug safety controversies surrounding Pradax. It was an innocuous question but when the 64-year-old retired professor of statistics and actuarial science called me a few weeks later, he was outraged. He told me: “The drug was marketed as cutting a person’s risk of stroke in half,” and, he added, “If my risk of having a stroke to start with is about one percent, the daily dabigatran would reduce it to 0.5 percent.” Then he wondered: If the benefits are that small, how high are the rates for potential harm? He told me he consulted Dr Google and found what I knew was out there: reports of “serious bleeding events” as a result of taking the drug. That, too, can happen with warfarin. The difference is, unlike warfarin, there is no antidote to stop the bleeding with dabigatran. Dabigatran is just one of the drugs that was being evaluated when a wave of firings at the BC Ministry of Health last spring shut down a variety of drug safety investigations that involved BC citizens. I was thinking of Robert when I called the BC Ministry of Health last month to ask a few questions about certain drugs covered under our public drug program. I calculated that the $1.2 billion spent annually on drugs under BC PharmaCare translates to about 75 cents a day—or $274 per year—from every single person in BC (4.4 million people). This pays for pharmaceuticals for BC citizens who are eligible for drug coverage. I have had a long-time interest in public and private drug plans, and have studied how evidence-based medicine is applied in the real world. Having written books about the pharmaceutical industry, I have more than a passing interest in drug safety and so I had a lot of questions to ask the Ministry. I didn’t want to burden the staff there, so I decided to keep things simple. I pared my list of questions down to three, all related to drugs whose reviews were affected by the events of last spring: On May 23, 2012, the anti-coagulant drug dabigatran (Pradax) became covered by BC PharmaCare. Since that date, how many BC citizens taking this drug have bled to death? On September 30, 2011, BC PharmaCare started paying for drugs to help people stop smoking. Since that date, how many BC citizens taking varenicline (Champix) have committed suicide or had a cardiovascular event (heart attack or stroke)? Since February 23, 2011, when a national drug safety study was launched, how many women in British Columbia taking the acne drug isotretinoin (Accutane) delivered a baby with birth defects? Easy questions, right? The ministry spokesperson replied promptly when I phoned with these questions—by giving me some options for finding their answers. I could either search Health Canada’s Vigilance Adverse Reaction Online Database (a voluntary reporting system capturing less than 10 percent of adverse events); I could ask the drug companies who make the drugs for the data (uh, yeah); I could look at published research (there is none on my questions, I’ve looked); or I could submit a request to PopData BC. This group coordinates requests for PharmaNet data adjudicated by the Data Stewardship Committee at the Ministry of Health. That committee’s members include people with financial ties to the pharmaceutical industry. I wasn’t interested in starting my own research project; I just wanted answers to my questions. “Incredible,” said Janet Currie who took a look at the Ministry’s non-answers to me. Janet is a local consultant, an expert in adverse drug reactions and one of the contributors to www.psychmedaware.org, a website that tries to educate people about the dangers of psychiatric drugs. She said: “What they are saying is that they have no idea about the risks of these drugs. They’re telling you to just go out and find out yourself from data you know is lousy or you wouldn’t have access to. And even I know that these drugs have a profile of being dangerous.” The reason the non-answers worry me is because it likely means these three drugs, and many more, which could cause death and birth defects, are essentially unmonitored in BC. I know enough about drug evaluation in BC to know the problem is not one of technological capacity. British Columbia is one of the few provinces in the country that has a computerized database, BC PharmaNet, which tracks all of your prescriptions, silently and securely. With our unique personal health numbers, which we carry on our journey through the health care system, the pharmacy, the doctor’s office, and the hospital, finding links between drug A or drug B and your risk of dying should be straightforward. But you need people with specialized skills—in epidemiology, clinical medicine, database analysis and the ability to separate truth from artifact in the data. You also need another key component: people with the ability and the integrity to call a spade a spade. You need people who can do independent evaluations who are allowed to say, without interference from drug makers or governments, that deaths are due to, or conversely not due to, drug A or B. But with the fired researchers and the de-funding of the Therapeutics Initiative, we don’t have those people working on our behalf anymore. Every second of every day, someone in BC, like Robert Brown, is swallowing a drug like dabigatran, isotretinoin or varenicline, yet the BC Ministry of Health can’t tell us the degree to which the drug may be killing some of them. These three drugs have relatively small markets. They are the canaries in the coal mine, so to speak. If the Ministry can’t tell us who is dying from these drugs, then it is even more worrisome to think of the much more commonplace drugs like statins (known to cause diabetes, muscle breakdown and kidney failure) or heartburn drugs (likely causing C-difficile, colitis, pneumonia and heart attacks) which are also almost completely unmonitored. Creating “the right environment” On June 19, 2012, the BC Minister of Health was a long way from Victoria. Mike de Jong was in Boston at the BIO International Convention, a massive conference that bills itself as “The Event for Global Biotechnology.” He was in fine company, rubbing shoulders with many of the drug makers and deal takers among the world’s biotechnology elite. Past speakers at the BIO International include George W. Bush, Bill Clinton, Tony Blair, and Sir Elton John, among others. Among the 16,505-strong attendance list of medical academics, drug company executives and government officials from 65 countries, Mr de Jong did not have a passive role. He was there with an announcement to make, armed with a very expensive bit of bait. In Boston he told the crowd that his government was putting up $39 million in new money towards pharmaceutical research, bragging that “British Columbia is recognized as a leader in life sciences research in part because of our government’s support.” Twenty-nine million of that money was going to the newly-established Centre for Drug Research and Development (CDRD) which recently moved into a brand-spanking-new 35,000-square-foot glittering glass office building at UBC, known as the Pharmaceutical Sciences Building. The extra $29 million is on top of a previous investment of $25 million in the Centre. Ten million in new money went to Genome BC. The Faculty of Pharmaceutical Sciences has deserved a new building for a long time and this certainly reflects the world’s growing demand for pharmacists and UBC’s willingness to produce them. But the folks at CDRD are there not just to tap into UBC’s brain trust; they intend to turn molecules into money. Their website says: “Our mandate is to de-risk discoveries stemming from publicly-funded health research and transform them into viable investment opportunities for the private sector.” While funding to support start-ups and smaller companies doing essential bench research is laudable, the downstream purpose of this money is to attract the big pharma companies like GlaxoSmithKline, Pfizer, Eli Lilly, and Schering-Plough, all fine upstanding corporate citizens. Or maybe not. According to a recent analysis by the consumer group US Public Citizen, “the drug industry has now become the biggest defrauder of the [US] federal government.” In the last 20 years these four companies alone have been collectively fined $10.5 billion for criminal wrongdoing in the US, including withholding safety data and promoting drugs for use beyond their licensed conditions. No one can argue about the importance of bringing new drugs to market. Mike de Jong told the Globe and Mail what was really happening: “We decided some time ago that if we were smart and provided the right environment, that eventually national and international agencies would begin to take advantage.” “The right environment.” Mark those words. The obvious reason for excitement around the new money was best described by Karimah Es Sabar, the president of the Centre for Drug Research and Development, who effused that the investment will translate “academic health research into viable investment opportunities for the private sector, and ultimately into new therapies for patients.” At the same time as de Jong was in Boston, back home in BC Dr Margaret MacDiarmid, the then-Minister of Labour, Citizens’ Services and Open Government, added a few words at a sister event held at the CDRD: “Investments in research and development are necessary to keep on the cutting-edge of life sciences here in British Columbia. The funding we are announcing today will ensure that these two organizations continue to innovate and add value to health care in the province.” “Innovate and add value.” Remember those words. After all, who could be against your tax dollars innovating and adding value, especially in the “right” environment? As the champagne was flowing in Boston and Vancouver over the promise of high-paying research jobs and lifesaving drugs emerging from innovative BC labs, another innovation was underway which would change the complexion of BC’s drug evaluation world. Possibly forever. Seven fired, two lawsuits, one dead A year ago this month, March 28, 2012, to be exact, BC’s Office of the Auditor General told the BC Ministry of Health about a complaint someone made about the way contracts were being awarded and how research was being conducted within the Ministry’s Pharmaceutical Services Division (PSD). PSD is in charge of paying for medications for BC citizens, medications that cost about $100 million per month (the equivalent of one Johnson Street bridge, every month). The drug budget is the fastest growing, and possibly the most controversial area of the ministry. There’s always been a bitter struggle between governments who want to appropriately contain costs and ensure safety, and drug companies whose corporate mission is all about expanding sales through whatever legal means possible. At the time, there was a small evaluation unit within PSD—a staff of half a dozen economists and data analysts plus one position shared by two academic researchers, for facilitating drug evaluations by outside researchers. These weren’t lightweight researchers: both had PhDs, one was a world-leading Harvard trained epidemiologist and the other a health economist. The unit’s job was to help design and sponsor evaluations to determine if drugs paid for by BC PharmaCare were effective and safe. In the course of this work the evaluations might show that some medications are ineffective or worse: they might sometimes kill or injure people. When poring through drug data to find dangers, you need sophisticated methods to see the difference between observed and expected deaths. It is this difference that indicates causation, which can allow you to say “this type of drug probably caused this type of death.” The Ministry of Health started investigating the complaint in April 2012 by conducting staff interviews and reviewing contracts. As the summer started the net widened. People both within the Ministry and outside, including researchers at the University of British Columbia’s Therapeutic Initiative (TI) and the University of Victoria were drawn into the investigation. Ministry letters were sent out by a then-brand-new Assistant Deputy Minister Barbara Walman who was new to the field of pharmaceuticals, and employees were brought in for questioning. No one could say what was going on; there were few details to share. As the chill started to filter through the Ministry, staff, employees and researchers were told an investigation was underway and they were warned to talk to no one. What was going on? The Ministry said the formal investigation was initiated to “examine financial controls, contracting, data management and employee/contractor relationships.” Then a handful of employees were sent letters saying they were suspended without pay, but not told the specific reasons why. Other researchers had their data access suspended. Contractors were fired and contracts cancelled. In June, while the BC Minister of Health was announcing nearly $40 million in drug research money in Boston, his staff back in Victoria were carrying out what some called a “Kafkaesque” series of interrogations. People were on trial, not knowing the charges, or who was doing the accusing. All drug safety evaluations carried out by the Therapeutics Initiative (TI) were halted. Funded by the provincial government, the TI has been providing an independent voice on pharmaceuticals since the mid 1990s and has gained an international reputation for its meticulous and thorough drug reviews. Conspiracy theories started to take shape: Maybe the pharmaceutical industry’s hostility to drug cost-containment and evidence-based policies were dealing out their final blow before an election. Industry pressure, including a task force stacked with members almost all of whom had ties to the pharmaceutical industry, has repeatedly tried to shut down the Therapeutics Initiative. Now maybe this was the smokescreen to kill it once and for all. Something was up. But what? In early September, the day after her appointment as Minister of Health, Margaret MacDiarmid and her Deputy Minister Graham Whitmarsh called a press conference in the Legislature. They announced that four employees had already been fired and three more were suspended without pay. Two others were fired later. The seventh in the unit has sued for constructive dismissal. One of the fired employees, a coop student, had three days left in his term. He wasn’t able to complete his PhD—an evaluation of smoking cessation drugs, like varenicline—because the government cut off his access to data. And he’ll never complete it. He’s dead. (His death is still under investigation by the coroner.) Some of the fired employees are working through their unions to address their grievances or have brought suits against the government. In news reports, vague and confusing references were made to privacy concerns, inappropriate conduct, and potential conflicts of interests. The minister was “deeply troubled” and let it be known that the cops had been called, saying: “The Ministry provided the Royal Canadian Mounted Police with the interim review of this investigation in August 2012.” The health minister stated: “We take all allegations of this nature very seriously. I have instructed the Ministry to continue to take whatever steps are necessary to respond to these matters thoroughly. We must ensure confidence is maintained in the integrity of the public service to execute its responsibilities in a manner that meets the high standards of conduct expected by the public.” “Confidence…Integrity…High standards of conduct…” Mark those words. As the months rolled by, no one could say what was happening. No one knew, and/or no one would talk. After all, there was an investigation underway and the RCMP were involved. If this was about data breaches you might understand the Ministry’s heavy-handed position. But there was absolutely no precedent for this. There have been other data breaches in the past and no one was fired. Things must be serious. Very serious. Dabigatran was one of the drugs the Therapeutics Initiative evaluators were assessing as part of a cross-Canada drug safety study, but because their data access was cut off, any final national analysis of the drug will not include the experience of BC patients. This is the drug that the retired actuary, Robert Brown, was prescribed. Halting access to PharmaNet data means that his doctor and thousands of physicians in BC will be no closer to learning about dabigatran’s “real world” safety record in this province. The Ministry’s broad approach has halted studies involving Alzheimer’s drugs, smoking cessation drugs, atypical antipsychotics, and drugs for attention-deficit disorder. A program to inform physicians by giving them evidence-based information on drug therapy for cholesterol, blood pressure, and bacterial infections was also halted after it had been proven to save money and improve prescribing. At the end of the day, with these evaluations killed, BC physicians, and their patients prescribed dabigatran, isotretinoin or varenicline, or any of the dozen or so drugs currently carrying serious safety concerns, will be that much more left in the dark. Despite intense media curiosity, secrecy continues to be the order of the day. When I asked for confirmation of the people doing the investigation, the Ministry spokesperson wrote: “We have not and will not confirm any of the individuals involved in this investigation.” The health minister won’t even say when the nightmare is going to be over for the fired staff and the contractors who depend on evaluating Ministry data. She said: “We are unable to provide a specific timeline,” and made assurances the Ministry was working hard to wrap up the investigation “as quickly and expediently as possible.” Hmm. Quickly and expediently? It’s now been a year since the complaint was made. Staff at 1515 Blanshard (headquarters of the Ministry of Health) have been silenced, and insiders have told me that everyone is left wondering who will next be thrown under the bus. The Health Ministry is a major employer in Victoria and there are many people inside that big white building with a story to tell, but will those stories ever emerge with employees muzzled by fear? Government employees are sworn to uphold Standards of Conduct as explained by a policy statement which clearly states: “Employees have a duty to report any situation relevant to the BC Public Service that they believe contravenes the law, misuses public funds or assets, or represents a danger to public health and safety or a significant danger to the environment.” [Italics added] The people I know still working in the Ministry are intelligent, educated, and ethical. There are PharmaCare staffers who are well-aware that the Ministry is paying for drugs, like dabigatran, that could be increasing the rate of deaths compared to patients taking warfarin. They are ethical people with a sense of purpose who probably cringe at the thought of the minister of health and her inexperienced staff firing or shunning those whose alleged transgressions could never merit the swiftness or lethality of the guillotine applied. We don’t know what they did to warrant such a drastic step, but we do know one thing: Killing the mechanisms of independent drug safety evaluation represents a clear and present danger to public health and safety. Keystone Kops or pharma puppets? Thus far everyone involved in this curious investigation has remained anonymous, but this is a government town. We know who is doing what. The investigation is headed by the current Deputy Minister Graham Whitmarsh. He’s the one who signed the letters firing people and apparently the investigators brief him weekly. Pharmaceutical Services Division’s ADM is Barbara Walman and Lindsay Kislock is the ADM in charge of data access; both neck- deep in this one. Members of the investigation team included Sarah Brownlee from the Public Service Agency, Wendy Taylor, executive director of Information Management and Knowledge Services, Dale Samsonoff from Human Resources, Ted Boomer, director of the Ministry’s Accounting Operations Branch, and Manjit Sidhue from Finance and Corporate Services. Apparently Taylor runs the show and leaves no one wondering who is in charge. Some will say these bureaucrats were only doing their jobs. But who defined those jobs? Who is ordering the investigation and pursuing the firings? Of course, the biggest question of all is who most gains from carrying out a coup of this magnitude? Some have called this the last gasp of a government intent on killing any independent drug evaluation in BC. Is killing off the Therapeutics Initiative a going-away gift to the government’s many industry-friendly backers? (Pharmaceutical firms are among the larger donors to the BC Liberals.) Maybe seven fired employees are just part of the price you have to pay to keep the pharmaceutical industry investments flowing to BC, and to prevent any future drug safety evaluators from affecting the bottom line. The stench of conspiracy hangs heavy over the Ministry of Health and it’s going to take a long time to clear the air. Being a government town there are a lot of theories swirling around. The two dominant ones are the Keystone Kops theory and the Pharma-puppet theory. The KK theory—imagine five cops trying to get a ladder through a doorway sideways—portends that the people carrying out the investigation are rank amateurs who got a sniff of wrongdoing and went off cocksure, in a ready-fire-aim sort of way. The minister, the deputy, and the assistant deputy are all relatively new to the Ministry of health, as is the lead interrogator Wendy Taylor. This theory suggests that the bureaucrats running the show are simply floundering in their own inexperience, not just unwilling—but unable—to explain to anyone what the heck is going on. Then there’s the second theory, the Pharma-puppet theory which insinuates a motive. In developing BC’s home-grown pharmaceutical industry, measures of all sorts need to be taken to get rid of barriers, and independent drug evaluations are seen by some as a distinct barrier. Drug safety? Maybe not such a priority when the government is so busy “de-risking” investment in BC’s drug development machinery and trying to lure large pharmaceutical companies to our shores. Meanwhile people continue to dutifully swallow their daily prescriptions for dabigatran, varenicline and isotretinoin, their statins and their alzheimer’s drugs, while a large part of BC’s drug safety evaluation machinery shows no pulse. Bigger questions remain: Who is working the strings behind the scenes seeing that drug monitoring activities are halted, experts fired and important programs cancelled? And further, why such enormous delays in getting drug monitoring restarted? Maybe when the minister starts talking and we know all the facts it’ll become clearer, but at the moment fired employees are calling this a gross miscarriage of justice, and it is hard for anyone to imagine what crimes would have necessitated such a massive, anaphylactic reaction in the bureaucracy. When will the Ministry start to restore the reputations and the livelihoods of the innocent contractors and data evaluation people caught in the crossfire? So many questions remain that people are already saying a public inquiry is essential. But until then, back to my three questions. Let’s start there, shall we? Because finding those answers, as I have said, should be easy. Alan Cassels is the author of Seeking Sickness: Medical Screening and the Misguided Hunt for Disease and he has worked for the last 18 years as an administrator, researcher and consultant on research and evaluation projects supported by the provincial and federal governments. None of his earnings come from any of the interrupted evaluation studies mentioned in this article.

Thoughts around overdiagnosis after a visit to a medical specialist. A FASCINATING STUDY was published last month in Australia. It may not have got much press here in Victoria, but confirmed a lot of what the world is learning about overdiagnosis. That study, carried out by Paul Glasziou and colleagues, compared the year 1982 to 2012, analyzing changes in lifetime risks for prostate, breast, renal, thyroid cancers and melanoma. They concluded that 18 percent of all cancers diagnosed in Australian women (11,000 diagnoses each year), and 24 percent of those in men (18,000 each year) are overdiagnosed cancers. Screening programs (for cancers and other things) look for signs of disease detected in healthy people. Often those signs are just “prediseases,” benign signs which never go on to be lethal. Predisease is what might be diagnosed when a screening result isn’t quite normal, but is below the threshold of true disease. It is considered a potential precursor to a disease which may or may not be worrisome. The seriousness of “false positives” is also gaining worldwide attention, as this Australian study demonstrated. I wrote about the problems of overdiagnosis in my 2012 book Seeking Sickness and made the same case, where in condition after condition which involves some kind of medical screening, there is always overdiagnosis. There’s both benefits and harm in screening healthy people. It’s worthwhile if it finds signs of potential disease that will stop you getting a more serious disease. It can, however, lead to anxiety and often substantial medical activity, including biopsies, more screening, more procedures, surgery, radiation, and prescription drugs. Often all this anxiety and medical activity never actually extends the quality or quantity of your life. Here’s a scene that happened when I was partway through writing that book: I am in the chair at the optometrist, as he was about to blow a puff of air into my eyeball, checking for eyeball pressure. It dawned on me: “This is a screening test!” This is how I described it: “Things look different when you’re sitting in the chair, playing the role of the trusting patient. It was like I had two angels sitting on my shoulders. One was whispering in one ear: ‘What’s the big deal? It was just a puff of air to the eyes. C’mon.” On the other shoulder, the naysayer angel, armed with a pitchfork, was jabbing me in the ear: “Are you nuts? Do you have any idea what this screening test will lead to? False positives. False negatives. Overdiagnosis. Downstream effects. Worry. Anxiety. Depression. Say no!’” I was being overdramatic, yet I wrote that I learned a vital lesson: if you are about to face a health professional offering you a screening test, you need to have already done your research. Doing it afterward is getting things backward. The air-puff test showed normal eye pressure, but what if it didn’t? Thankfully, I didn’t find out. That experience became my operating axiom of why people need to go into medical screening test with their “eyes wide open.” Fast-forward eight years, and it was time for another trip to the optometrist. To get my eyes checked, maybe see if I needed a new eyeglass prescription. But darned if this didn’t turn out to be another “teachable moment,” this time with a much more potentially serious intervention. My optometrist said he saw something unusual in one of my eyes. He said I had a suspected case of narrow-angle glaucoma, a condition that could lead to an acute eye emergency and the potential loss of sight. That opened my eyes. He referred me to an ophthalmologist. The first trip to the ophthalmologist was just for a few tests and pictures of my eyes, collecting data. I was invited to watch a video of the doctor explaining the procedure he would offer, a quick operation called a laser peripheral iridotomy (LPI). Perfectly safe, right? But… Let’s be clear. I am a healthy patient, normal eyeball pressure, and a normal optic nerve. No history of eye disease and no family history either. I was what the literature called a PACS, which stands for “primary angle closure suspect.” I don’t have disease—I have the younger sister, predisease. I found an excellent paper by Dr H. George Tanaka, an ophthalmologist in Arkansas whose 2018 Review of Ophthalmology study gives considerable detail about the pros and cons of such a procedure. I learned quickly this was no slam-dunk, and I was right to be cautious. I tracked him down and arranged a phone interview. The main thing I learned is that for people without symptoms or family history of other types of eye diseases, there is no way to know how many PACS patients go on to have an “acute episode” that involves losing your eyesight. Is it one in ten, or one in ten thousand? We don’t know. He admitted that “unfortunately, we don’t have any good evidence for how to manage a PACS patient, and that we don’t know how many PACS patients go on to develop more serious eye problems.” For the sake of everyone in Victoria who (at a certain age) may well be diagnosed with suspected angle-closure glaucoma, there are a few things to know about the LPI surgery being offered. Angle- closure glaucoma can be an aggressive disease, probably the leading cause of glaucoma blindness in the world, and it is one of the few emergencies in ophthalmology. But as Dr Tanaka wrote: “We don’t actually know how many future angle-closure attacks we’re preventing by performing LPIs. That’s why we can’t say to a patient with narrow angles, ‘Mrs Smith, your risk of going blind is X percent (or your risk of getting glaucoma is Y percent), but the odds will improve by this much if I perform this procedure.’ We don’t have the numbers to support that.” It’s the conclusion that bothers me: “so we just treat everybody.” Clearly, this is textbook overdiagnosis: finding “predisease” in normal people, who are then given the impression they are now living under a dark cloud. The research suggests the LPI may delay or prevent primary-angle glaucoma. Luckily, the LPI is fairly benign. This operation used to be major surgery, but now is a couple of minutes in the clinic, with minimal risks of infection or bleeding. As for the cons, sometimes things go sideways. Sometimes patients get extra spots of light in their vision—dysphotopsias—which won’t go away. And believe it or not, some research says the LPI can accelerate cataract development, as well as make you more predisposed to getting a condition called posterior synechiae, making future cataract surgery more difficult. For me, saying no to the procedure was a no-brainer. If I had higher risks, a personal or family history of eye disease, high eyeball pressure, or if I was going to be hiking in the outback for months at a time where getting emergency medical care was difficult, my decision might have been different. But the doc was not impressed. I really liked the ophthalmologist. He was a very nice gentleman. He explained things well, but at the same time, I could tell he was taken aback when I refused the procedure. Perhaps he’s not used to patients doing a deep dive into the literature on the potential benefits and harms of surgical procedures. He pressed me, eventually turning up his hands and saying: “Oh well, I just want to tell you the risks, but you’re on your own,” later adding, “well, you’re the ticking time bomb.” Luckily I have a thick skin, though if you had taken my blood pressure at the time it, would have been through the roof. Not only does his comment not reflect the real research, it’s the height of insensitivity to call a patient a “ticking time bomb.” No one deserves to be intentionally frightened into getting an elective procedure, especially one with many unknowns and potential harms. As an aside, if the average person knew how much these doctors make by five minutes of lasering your eyes, they would be astounded (all in, close to $400 per eye—$116.76 for the actual few minutes of surgery, $35 for the office visit, $96 for the consultation, $60.42 for “orthooptic evaluation,” with likely extra charges for the photography of the eyes, etc. ). I found in the MSP bluebook that this ophthalmologist billed MSP $749,000 last year. Later, when I calmed down, I reflected on the “ticking time bomb” comment. Listen, dear reader. Like everyone on the planet, you could live another five minutes or another fifty years. We are all ticking time bombs, more or less. We are all “prediseased” and suffering from “predeath.” Being called a “ticking time bomb” made me angry but also sad for all the patients who are worried, who crave the trusted advice of a health professional, but then get bullied into procedures (or drugs) that they would rather not have. When I was in the navy, we had a principle: if you don’t know where you are, stop the ship. All signs of disease have uncertainties, and all surgeries and drugs have potential harms and potential benefits. Any honest health professional will tell you those uncertainties. When you don’t know where you are, don’t keep sailing. Alan Cassels studies pharmaceutical policy and works at UBC. His book Seeking Sickness: Medical Screening and the Misguided Hunt for Diseases is available from bookstores and libraries. You can follow him on twitter @akecassels.

What’s happening in the world of antipsychotics might keep you awake at night. WHY DOES IT SEEM LIKE everyone has an antipsychotic story they want to tell me? For Victoria resident Roedy Green, his troubles hit a peak when he found he couldn’t haul himself out of a bathtub. He felt things had already begun going seriously sideways after a series of falls, then the 71-year-old computer programmer found that he was constantly sleeping—sometimes for up to 20 hours a day—which made Roedy feel like he was losing his grip on life. In addition to starting to feel demented, the final straw was the loss of muscle strength while trying to exit the bathtub. He and his housemate Geneva Hagen began to search for answers. This Victoria pair discovered that in addition to many other pills he was taking to manage his HIV, diabetes and bipolar disorder, Roedy was being prescribed an antipsychotic—supposedly to help him sleep. Ironically, insomnia was one problem that he had never had, and what he needed was to stay more alert. The drug quetiapine (also sold under the brand name Seroquel) is widely used to promote sleep, though that is not an approved use. It is formally approved by Health Canada to treat major depressive disorder, schizophrenia, and episodes of mania associated with bipolar disorder, but is often used in low doses for insomnia. When the doctor asked, “So how are you doing on the Seroquel?” Roedy and Geneva were shocked. They hadn’t realized that a previous visit had resulted in a prescription for this antipsychotic. Apparently doctors at the geriatric clinic had misunderstood his complaint. “With Seroquel he was just a zombie,” Geneva told me. “He was sleeping 18-20 hours a day. He couldn’t get anything done. It was like having a potted plant.” THE INDISCRIMINATE USE OF ANTIPSYCHOTICS is likely one of the biggest pharmaceutical scandals of our time, centred around one of the most expensive and inappropriately used drug classes in modern society. The problems of antipsychotics being used to treat sleep problems have been on the radar of the medical establishment for many years. Even though antipsychotics like quetiapine are not approved to treat insomnia, they are often prescribed for that purpose. Some have blamed the growing use of antipsychotics on the recognition that other pills used for sleeping and anxiety—the benzodiazepines—are addictive and, over time, ineffective, but that is only part of the explanation. What often comes up is the issue of “management” in long-term care. People with dementia can often become agitated and aggressive, and therefore antipsychotics seem helpful, especially in dealing with someone who can be physically abusive to staff or other residents. In low doses, antipsychotics can be very sedating. Plus they come with a whole host of adverse effects, including a kind of unpleasant agitated restlessness called akathisia, and tardive dyskinesia, quirky movements and tremors that can be mistaken for Parkinson’s disease. The weight gain and diabetes associated with antipsychotics are also legendary. A Victoria psychiatrist once told me the story of prescribing an antipsychotic to a new patient. By his next visit a month later, the psychiatrist couldn’t recognize the patient, due to the ballooning weight he’d gained. SINCE 2003, there have been many regulatory actions against quetiapine and other “atypical” antipsychotics, which include drugs like olanzapine and risperidone, both in Canada and the US. Warnings from the FDA and Health Canada have included increased risk of diabetes symptoms, of death in elderly people with dementia, increased blood pressure in children and adolescents, arrhythmia (heartbeat rhythm abnormalities), sleep apnea (which can cause breaks in breathing or very shallow breathing during sleep), excessive sleepiness, low blood pressure upon sitting up or standing (postural hypotension), and problems with balance, effects that increase the risk of falls. In 2010, Quetiapine’s manufacturer agreed to pay a US $520 million fine over allegations of promoting off-label (unapproved) uses, such as for anger management, dementia and insomnia. A report commissioned by the BC Ministry of Health in 2011 said that 50.3 percent of all residential care patients in BC “were prescribed an antipsychotic between April 2010 to June 2011.” Since then, this problem has been the subject of numerous reports and guidelines trying to tackle the issue, with limited success. In 2015, the BC Seniors Advocate Isobel Mackenzie identified the continued overuse of antipsychotics and antidepressants in residential care as worrisome, noting that while only four percent of BC seniors in long-term care have a diagnosed psychiatric disorder, 34 percent of them were prescribed antipsychotics. According to the Alzheimer’s Society of Canada, about one-third of Canadian residents in long-term care are prescribed antipsychotic medications, despite the fact that professional geriatric societies have long warned against the use of these drugs in the elderly, especially those with dementia. THE PRESCRIBING OF ANTIPSYCHOTICS is not only controversial but expensive. BC Pharmacare lists quetiapine as the tenth most expensive drug on the Pharmacare formulary, paying over $16 million in 2017/2018 for the drug. Three of the top 20 drugs in BC Pharmacare’s list of most costly drugs are antipsychotics. Nationally, antipsychotics prescribed for non-seniors were the third highest public drug expenditure of all drug classes (fifth highest for seniors). In Canada this drug class consumes about $600 million in annual public expenditure. Last year Mackenzie slammed the Province again for making very little headway in reducing the use of antipsychotic medications in BC’s seniors. While numbers have decreased slightly in recent years, compared to other provinces, she complained that BC had made little headway in 2018. In that year, a quarter of BC seniors living in long-term care were still getting an antipsychotic medication without a supporting diagnosis, which is to say, they may be getting them for off-label uses. Physicians know that the elderly need much more delicate prescribing, partly because as we age, our bodies change, and the ability to metabolize drugs is also reduced. Kidney function often diminishes with age, and without appropriately clearing drugs from your body, drugs can build up in your system, causing other problems. Geneva told me that on the antipsychotic, Roedy became so impaired and disoriented that “we were both worried about dementia.” “What made you think that the problem might be due to the drug?” I asked. Geneva said there were two things: A friend had warned her several months earlier that many local patients are being prescribed Seroquel for sleep, and had advised her to avoid it. When she heard Roedy’s psychiatrist mention Seroquel, she remembered this warning and realized that something was amiss. “The bubble-pack had listed only the generic name quetiapine, but not its purpose,” she said. Questioning that drug and immediately withdrawing it, they both believe, had Roedy back to normal within a few days. His scores on cognitive function tests improved dramatically. “I’m not very social,” says Geneva, “yet since this happened I have had three other people tell me they are regularly using Seroquel for sleep.” She adds that none of those people seem very functional. The stories of patients prescribed drugs, often without awareness of their purpose, are endless, and the concept of “informed consent” seems to not apply. Many of us are too shy to question the safety and appropriateness of what is being prescribed, not wanting to be a prickly patient in a world where primary care doctors are a scarce commodity. As well, many busy physicians may not know, nor have the time to lay out the possible complications of an antipsychotic prescription. But often they’ll respond if asked. The inappropriate use of drugs such as quetiapine could be costing society immensely—not just in cost for the drugs themselves, but also in the rate of falls, broken bones, head injuries, drug-induced diabetes, motor vehicle accidents, and commitments to long-term care facilities. The wrong prescription drugs can be as dangerous as street drugs. But it doesn’t have to be that way. Roedy Green, who was losing his ability to function, was halted in his spiralling downhill by questioning the drugs he was being prescribed. Asking questions and questioning answers can often help change the course of one’s treatment. The medical world is slowly starting to wake up to the dire harms related to antipsychotics, and turning to safer, more effective ways to help people sleep. Doctors know that managing insomnia needs to focus on education and encouraging good sleep hygiene. The other issue too is that maybe our obsession with getting eight hours of uninterrupted sleep every night is downright harmful. Drugs, if needed, should only be used for the shortest possible time in exceptional cases. Now it’s important for patients to insist on this. This is true for antipsychotics, and almost every other drug you may be offered. Alan Cassels is a drug policy researcher and works at UBC.

Psychiatrist Dr Joanna Moncrieff says “often there are better ways to deal with things” than taking drugs. IT IS ONLY AFTER AFEW SECONDS into my conversation with Dr Joanna Moncrieff, a psychiatrist based in London, UK, when her fresh perspective on psychiatry strikes me. “I think mental illnesses are more like aspects of our personality than they are illnesses that come over us. People can struggle with their feelings and behaviour, but usually they can learn ways to manage and deal with them. Sometimes that might involve taking drugs, but often there are better ways to deal with things.” The British psychiatrist is a leading figure in what is known, broadly speaking, as the critical psychiatry movement. As the author of several books including The Myth of the Chemical Cure, Dr Moncrieff is a prominent critic of the modern “psychopharmacological” approach to treating mental health challenges. Dr Joanna Moncrief She is in Vancouver next month as the keynote speaker at a conference for BC physicians and pharmacists, and agreed to speak with me in advance of her trip. Our wide-ranging discussion delved into how society uses an array of psychiatric drugs including antipsychotics, drugs for ADHD, and antidepressants. It is the latter class of drugs—antidepressants—that I want to focus on, particularly because I want to try to understand one simple fact: why are so many of us taking them? A study released this August found that 8.8 percent of Canadians between the ages of 40 and 79 took an antidepressant in the last month. In the US, that number is 15.4 percent. When you tease apart the utilization data on these drugs, you find women are twice as likely as men to be on an antidepressant. In British Columbia, close to 20 percent of women between ages 19 and 55 are taking an antidepressant. Canadian data from 2016 found that 60 percent of seniors in long-term care are on antidepressants (compared with 19 percent of seniors living in the community). With a bit of census data and some quick math, I roughly calculate that in Greater Victoria alone, there are close to 30,000 women under 65 who are taking an antidepressant. Let’s be clear, depression can be serious and debilitating, and there should be no stigma associated with taking an antidepressant or on any drug that is helpful; yet at the same time, these kinds of statistics raise many questions. If one in five women in Victoria are on an antidepressant, why? Is depression really as widespread as the drug stats might indicate? Does this really indicate that a lot of people are medically sick and receiving an effective treatment, or are we medicalizing the ordinary difficulties of life? To be fair, antidepressants are prescribed for a variety of things, including anxiety, obsessive compulsive behaviour, premenstrual symptoms, and panic disorder, among others. But most of their use would likely be linked to persistent sadness and hopelessness. I asked Dr Moncrieff how we arrived at this point. She quickly pointed to a number of factors, particularly that taking mood-altering drugs is not a new phenomenon. For nearly half a century, women especially have been plied with drugs such as benzodiazepines or barbiturates for anxiety and depression. One way to explain this, she said, is that “women might be more likely to internalize their distress. Men are more likely to get angry and drink. Men are likely to blame outwardly.” As for the statistics, she’s as astonished as I am: “It’s extraordinary, isn’t it? It’s an indicator of a number of factors—there are a pool of people whose lives are miserable, who go to the doctor looking for a solution; years ago they would have been put on a benzo, or a barbiturate, and so on.” She noted some people do seek a chemical solution to their problems—but, she added, “this view reflects the huge marketing efforts that happened in the 1990s.” This coincided with the first Selective Serotonin Reuptake Inhibitor (SSRI) type of antidepressant, Prozac, coming into use. In her estimation, when it became apparent that benzodiazepines like Ativan, Valium or Xanax “were being handed out like sweets, that’s when the drug industry came up with this idea of the chemical imbalance, in association with launching the new SSRI antidepressants.” Prozac was followed by other drugs intended to alter serotonin in the brain, like Zoloft, Paxil, Effexor and others. The “chemical imbalance” theory is one of the biggest controversies in psychiatry; it is often hauled out to explain a person’s depressed mood, and how a drug which tweaks the level of serotonin in the brain might actually help. The problem is that there is little, if any, proof to support such a theory. “The evidence for a link between serotonin and mental illness is all over the place,” said Dr Moncrieff. “The idea that psychiatric drugs are tweaking some underlying abnormality is completely misleading,” yet this hasn’t stopped these drugs from becoming the mainstay treatment for depression. The automatic prescribing of antidepressants, in Moncrieff’s opinion, is fraught with problems. “If you tell a person going through depression that they need a drug, you are giving them a message that they are biologically abnormal. Not only are drugs chemicals that interfere with normal biological responses,” she says, “the ‘chemical imbalance’ idea is also disabling. It often ends up with the patient trying one, then another, then another different drug. They just end up being on a cocktail, because none of them actually work,” she said. While some sorts of psychiatric drugs can help some people some of the time, Moncrieff believes other factors are likely leading to society’s over-reliance on antidepressants. As Jiddu Krishnamurti famously said: “It is no measure of health to be well-adjusted to a profoundly sick society.” There is no shortage of adverse societal influences causing many of us to feel anguish and despair. Dr Moncrieff’s UK perspective includes “things such as austerity, following the financial crash in 2008—and a general income drop in the last few years—that has likely created a genuine large amount of distress and misery.” And let’s not forget more recently that her country has been dealing with the deep uncertainty caused by Brexit, undoubtedly adding anxiety to peoples’ lives. While it might be understandable why so many people are initially put on antidepressants, the question arises, how come so many people stay on them for the long haul? Part of this has to do with dependence. As Joanna Moncrieff says, “Some antidepressants are very difficult to get off—many people don’t realize they have withdrawal symptoms. They try to stop, and they think they have a relapse, and it confirms their status as a patient.” Moncrieff agreed the very mention of “withdrawal symptoms” associated with SSRIs is controversial. Earlier this year, a newsletter produced for BC doctors and pharmacists by the Therapeutics Initiative was attacked by a vocal Vancouver psychiatrist who dismissed the seriousness of the withdrawal effects of SSRI antidepressants. Yet the notion of dependency is gaining traction. Moncrieff cited a recent high-profile example published earlier this year in the medical journal The Lancet. Author Mark Horowitz wrote: “All classes of drug that are prescribed to treat depression are associated with withdrawal syndromes. SSRI withdrawal syndrome occurs often and can be severe, and might compel patients to recommence their medication.” Patients have reported such symptoms as nausea, headache, dizziness, chills, body aches, paresthesias, insomnia, electric-shock-like sensations, panic attacks, dramatic mood swings, suicidal thoughts, and exhaustion. Horowitz’s coauthor, David Taylor, the director of pharmacy and pathology at a London hospital, described his own withdrawal from Effexor as a “strange and frightening and torturous” experience that lasted six weeks in a recent New Yorker article. Instead of denying the existence of withdrawal symptoms, these two authors make a strong case for tapering antidepressants very slowly. Among the known side effects of antidepressants are those affecting sexual function. Dr David Healy, a psychiatrist from Wales, runs a website that tracks the effects of SSRI antidepressants (RxISK.org) and other drugs. For many years, he has been collecting data from real-world patients who reported losing their sexual function even after stopping their antidepressant. Healy has used these data to petition the European Medicines Agency to put a warning about persistent sexual dysfunction on these drugs. Moncrieff, who is very familiar with this literature, reminded me that often the studies on antidepressants are simply too short to detect the effects such as long-term sexual dysfunction. In terms of SSRIs’ effectiveness on depression, Moncrieff said, “sometimes [patients] feel better, sometimes they don’t.” With her own patients, she said, “I couldn’t convince myself that antidepressants were having any significant effect. Some have said they’re basically active placebos.” A large meta-analysis (a summary of a large number of studies in the same area) published last year was reported extensively in the media with the message “antidepressants do work!” But Dr Moncrieff found many flaws. “They looked at response rates which inflate the actual effects, [whereas] if the results are looked at in the usual way, the analysis showed a very small and clinically irrelevant effect.” Moreover, she pointed out, in this meta-analysis, “an awful lot of those studies were withdrawal studies.” They studied people who were on antidepressants, comparing those who continued on their regimen to those who were switched to a placebo. So instead of measuring the effects of the SSRIs, they were finding that those switched to the placebo were doing worse—probably because they were suffering withdrawal symptoms. Moncrieff has a different approach to mental illness and its treatments than many other physicians. She spends a lot of time helping patients get off psychiatric drugs, but also trying to avoid putting patients on them in the first place. She told me most cases of depression “are responses to things that happen in people’s lives—and we need to figure out ways to help people to manage or address their problems—it’s dealing with the causes.” She mentioned a number of options—CBT (cognitive behavioural therapy), exercise, and mindfulness training, among them—that enable people to manage their mood or anxiety in a non-drug way. When a patient says, “I’ve done all those things and nothing works,” she recommends physicians discuss with those patients the evidence on antidepressants, how there is little to support their effectiveness, as well as the pros and cons of medication. She said that if antidepressant medication is prescribed, it should be viewed as a short-term measure, one which needs constant review and a willingness to stop. This is the evidence-based message she’ll be bringing to BC doctors in Vancouver on October 5 at a conference sponsored by the Therapeutics Initiative (see www.ti.ubc.ca). Alan Cassels is a drug policy researcher in Victoria.

“Floxxed” patients are calling for better consumer drug information. APRIL GOODMAN had an appendix attack in 2015 and ended up in the hospital. Her appendix surgery wasn’t without its drama, but it was the drug that was prescribed afterwards that still haunts her to this day. Speaking to me from her home in New Westminster, she tells me she was prescribed an antibiotic called ciprofloxacin (Cipro), one of a number of fluoroquinolone antibiotics (these are drugs that end in floxacin). “No one—neither the doctor who prescribed it, nor the pharmacist who dispensed it mentioned a thing about the drug,” she said. She didn’t think anything about the drug’s safety either, until about a year and a half later when one of her back teeth broke. “When I read that Cipro has caused dental problems, such as teeth breaking off at the gumline, and further dental problems, which can continue indefinitely, I was quite alarmed.” What she uncovered in the course of several years of research is a truly astounding story of the floxacins, a widely popular class of drugs, wreaking devastation on an alarming number of people. She pointed me in the direction of a website, www.ciproispoison.com, where I learned a new word: “floxxed,” referring to a state of suffering from one or more of a long list of adverse effects related to this class of drugs. It seems mind-numbing that a drug you might take for less than two weeks to deal with an infection could cause long-term, and for some, irreversible adverse effects. This has taken a long time to acknowledge. April certainly wasn’t the first person to contact me about damages suffered due to fluoroquinolones. Over the last decade, I’ve had at least four different people write to tell me a tale of something truly horrendous, such as tendon rupture or retinal detachment, after taking a fluoroquinolone. Her concerns are echoed by official documents put out by various drug agencies in Canada. A 2017 report issued by CADTH (the Canadian Agency for Drugs Technology in Health) said this: “The use of systemic [taken by mouth or by injection] fluoroquinolones is associated with serious adverse events, [including] effects on the central and peripheral nervous system, hypersensitivity, myasthenia gravis exacerbation [a chronic autoimmune disease], phototoxicity, QT prolongation [a heart rhythm disorder], and tendon rupture. Rarely, some of these adverse events have the potential to lead to persistent disabilities.” Probably one of the more known risks of fluoroquinolones is its effect on tendons, which can sometimes become inflamed or even rupture. Health Canada warns that “rare cases of disabling and persistent serious adverse reactions including tendinopathy, peripheral neuropathy, and central nervous system disorders have been reported to Health Canada for fluoroquinolones.” In the glib, somewhat bureaucratic way they issue drug safety warnings, Health Canada helpfully reminds health professionals of the patently obvious: “Consider the potential for disabling and persistent serious adverse events when choosing to prescribe a fluoroquinolone. Avoid fluoroquinolones in patients who have previously experienced serious adverse reactions associated with them. Stop fluoroquinolone treatment if a patient reports any serious adverse reaction.” While there is growing public alarm at the overprescribing of antibiotics, fluoroquinolones can be effective if used properly. But they can also be terribly misused. WorstPills, an independent drug bulletin produced in the US, is direct and forceful in discussing the overprescribing of antibiotics in the US. It reports that “despite congressional hearings and numerous academic studies on this issue, it has become the general consensus that 40 to 60 percent of all antibiotics in this country are misprescribed. New studies continue to confirm the fact that a large proportion of antibiotic prescribing for both children and adults continues to be inappropriate.” WorstPills singles out the fluoroquinolones as “one of the biggest-selling and most overprescribed classes of drugs in the United States,” noting that these drugs should only be used for those allergic to alternatives or those with an infection resistant to other antibiotics. The problem here is typical of drug therapy—using the wrong drugs in the wrong patients and using fluoroquinolones for colds, sore throats, and bladder infections. How poorly they are used was captured in a 2003 study carried out in two American academic medical centres. The researchers looked at 100 patients who were prescribed a fluoroquinolone in an emergency room. Of those patients, 81 received a fluoroquinolone for an inappropriate indication (a use not officially approved by the regulator). Of those 81, half of the prescriptions were “judged inappropriate because another agent was considered first line.” Worse yet, for a third of those 100, there was no documented evidence that an infection was even present. In British Columbia, since the year 2000, when more than 150,000 patients were prescribed a fluoroquinolone, that number steadily increased until about 2010 when Health Canada started issuing the first of its warnings. Numerous programs have been launched to try to stem the inappropriate prescribing of antibiotics, including the public education campaign Do Bugs Need Drugs (www.dobugsneeddrugs.org). We are seeing that the number of patients who are prescribed fluoroquinolone antibiotics in BC has been steadily dropping since 2010. Yet even last year, almost 200,000 BC patients were dispensed a fluoroquinolone. THE WARNINGS AROUND fluoroquinolones continue to mount ever since the USFDA, in 2011, required that fluoroquinolone antibiotics must be dispensed with a Medication Guide, which is essentially a consumer-oriented operator’s guide to your drug. While the FDA has the authority to order that Medication Guides be distributed in pharmacies (and given out to patients who are getting new scripts or refills), no such authority exists in Canada. The safety information Canadians receive on most prescribed drugs is almost certainly inadequate, as April Goodman learned the hard way. For anyone prescribed a new drug, an important question might be: “is there a Health Canada warning on this drug?” Before new medicines hit the market, each country’s regulatory agency must first approve them for use, often based on limited safety evidence. After a drug enters general use, other safety issues can become apparent, including rarer or longer-term effects, prompting regulators to issue safety advisories on how to avoid or manage these risks. Barbara Mintzes, a researcher originally from Vancouver but now working in the Faculty of Pharmacy at the University of Sydney, is studying drug safety advisories issued by regulators around the world. She is running an international study looking at drug advisories, and discussed her study with me in Victoria last month. In a research letter she published in JAMA Internal Medicine, she looked at, in total, 1441 drug safety advisories issued in four countries—Canada, Australia, the US and UK—over a 10-year period, covering 680 drug safety concerns. Sadly, Canada didn’t fare too well. “Between 2007 and 2016, Canada’s drug regulator, Health Canada, issued safety warnings only about half the time related to issues identified by regulators in Australia, the US and UK,” said Barbara. “It’s concerning that all countries, including Canada, were seriously deficient in how they communicated emerging health risks of medicines.” She added that there were nine fluoroquinolone warnings for the study period (from 2007 to 2016 inclusive), in all four countries: four from Canada, four from the US, one in Australia, and zero in the UK. “Clearly if a drug has a safety advisory issued in one country, the same drug sold in another country should also come with similar warnings,” said Associate Professor Mintzes. “Overall, we found that regulators in these four nations were only consistent in the decision to warn 10 percent of the time.” According to research from the Canadian Institute for Health Information, from 2006 to 2011, emergency department visits and hospital admissions due to Adverse Drug Reactions (ADRs) among seniors in Canada cost an estimated $35.7 million. Much of this is preventable. For Barbara Mintzes, the prescription is clear: “We would like to see much more attention paid to ensuring that doctors and patients are informed of new evidence of harmful side effects of medicines, and what to do to prevent them.” April Goodman heartily agrees with that sentiment. If there’s one thing I’ve discovered after looking closely at drug safety for over two decades, it’s that people who have been through a drug disaster often become the most knowledgeable educators about the issue. These citizen experts can and do help educate the people around them to the dangers that could come via a simple pill. April Goodman, who has become extremely knowledgeable about fluoroquinolones, is a good example. She told me, “You have to be the CEO of your own health.” As for possible damages to teeth, she’s disappointed that neither Health Canada nor the US FDA has added that specific warning to the labels for these drugs. She has collected numerous articles warning of the potential for dental harm. “Many people, even young ones, are losing their teeth and get dentures after this Cipro harm.” With all the dangers she’s become aware of, she thinks that it might be time to pull the plug on this entire class of drugs. “I don’t think this is something that should be still on the market now.” Alan Cassels studies and writes about pharmaceuticals. He currently works at UBC.

Are broken bones “hiding in plain sight” of heartburn meds? LAST YEAR MORE THAN 30,000 people in Greater Victoria took a pill from a class of drugs called Proton Pump Inhibitors (PPIs). This class includes drugs like omeprazole (Losec), esomeprazole (Nexium), rabeprazole (Pariet) or pantoprazole (Pantaloc). They are effective weapons in the fight against the scourge of modern heartburn, or what doctors call Gastro-esophageal Reflux Disease (GERD). Among the most popular and highest-selling of any drug class in the history of the world, PPIs have been an enormous success story both for the companies that make them, and the tens of millions of people around the world who swallow them every day. For many people, PPIs effectively suppress stomach acid in a way that makes the burning discomfort in your throat a long-forgotten memory. They work through blocking an enzyme in the wall of the stomach that produces acid. PPI is often a physician’s first choice of drug when a patient shows up complaining about heartburn. And did I say they were popular? In BC, nearly half a million people filled a PPI prescription last year, and in some parts of Canada, up to a third of the over-65 population may be chronically—that is, daily—swallowing a PPI. All of this comes with a hefty cost. At one point, British Columbians (through Pharmacare, extended health insurance and out-of-pocket payments) were spending $100 million every year on PPIs. That financial toll has dropped in recent years (down to about $60 million) due to PPIs coming off patent, allowing generic companies to sell cheaper versions of these drugs. Clearly, the massive consumption of even an effective drug raises many questions, the first being: Is there really an epidemic of heartburn in Canada? Is it wise to jump straight to a pill when there are several non-drug ways to prevent heartburn? If you really do need a drug, why this one? And lastly, if these drugs effectively relieve short-term heartburn, are they also safe if taken for months or years on end? Remember, stomach acid plays a key role in digestion. Because so many people take them, even if adverse effects are considered rare—occurring somewhere between one in 1,000 to one in 10,000 patients—the toll of injury could indeed be quite large. And many, many people will take them longer than the 4-8 weeks recommended for treating heartburn. The first PPI came on the market 30 years ago, and now there are six different ones available. I was drawn to research on the newest drug in this class, a product called dexlansoprazole (Dexilant), because of a question of rare but potential serious adverse effects. On PPIs in general, the medical literature contains no shortage of warning signals, which tells me that long-term chemical alteration of human stomach acid may be wreaking havoc on other body systems, raising rates of C. difficile infections, pneumonia and even possibly gastric cancers. There are numerous precautions listed in the Canadian dexlansoprazole product monograph, but I was drawn to the bottom of page four which read: “Several published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.” (Italics added.) Because patent-protected drugs are the newest and most widely promoted, I suspect that dexlansoprazole (still sold under patent) is the kind of drug that doctors in BC are currently stocking in their sample cupboards. NOAH NATHAN worked for Takeda, a pharmaceutical company, when it launched dexlansoprazole in 2009, under the brand name Kapidex (which was changed to Dexilant a year later). He was among the first salespeople in America to promote it. Speaking to me from his home in Ellicott City, just outside of Baltimore, Maryland, he told me he loved his job as a pharma sales rep. To keep the sales reps happy, he said, “the company treated us really well and spared no expense.” He had a company car and an expense account. During his 15-year career at Takeda, he was often among the top 10 percent in sales, and won awards including an all-expenses-paid trip to Australia. Whistleblower Noah Nathan His sales area was in Virginia, just outside of Washington, DC and his days would consist of driving around, making calls on doctors including gastroenterologists, ENTs (Ear, Nose Throat) specialists, and rheumatologists, pitching his company’s drugs, including Dexilant. In the course of his work, he fed a lot of physicians and their staff. “I really went for the comfort food,” he said, “rotisserie chicken, meatloaf with potatoes and gravy, that sort of thing.” He explained that the food might win him a valuable minute or two to talk up his products. Getting that face-time was crucial: “There’s such a big difference in prescribing, between those [doctors] who see us sales reps and those who don’t.” Yet over time, all of this delivery of food, samples, and information was starting to give Nathan indigestion. There was something about dexlansoprazole that didn’t exactly go down easy with him. He worried about the side effects and the dosages. When dexlansoprazole came to the market, Nathan explained, it came in two dose sizes—30mg and 60mg. The company tried to get a 90mg dose approved, but it was turned down. As a sales rep, however, it was only the higher 60mg tablet being promoted. All the sales materials were built around the 60mg dose. In fact, Noah explained, the newer company reps often didn’t even know about the 30mg dose, and many doctors in the field didn’t either. Currently in North America, more than 90 percent of the prescriptions for dexlansoprazole are in the higher 60mg doses. When dexlansoprazole was being reviewed by the US FDA to determine whether the drug should be allowed on the market, two FDA reviewers didn’t like the look of it. In their judgment, one of the reviewers wrote that not only was there no additional benefit of dexlansoprazole over the other five PPIs already on the US market, but that the evidence showed a higher incidence of fracture/injury-related adverse events with dexlansoprazole compared to other drugs. To grant the company marketing approval, the FDA required the company to carry out a “post-marketing clinical trial.” Basically, the FDA allowed dexlansoprazole on the market as long as Takeda promised to produce additional safety data, which was due to the FDA in December 2011. Over seven years later, no results have been posted to the FDA website. Nathan became an unexpected whistleblower and later an author. In his self-published book, Heartburn, Broken Bones, and the False Claims Act: Nathan v. Takeda Pharmaceuticals—Why You Should Care About the Case You Never Heard Of, he estimates that half a million Americans are taking 60mg doses of dexlansoprazole. The court case that he launched in 2009, and which ended in 2014, was premised on the issue that the company was likely promoting the drug “off label” for the higher dose, possibly putting patients at risk for fractures and other complications related to high dose PPIs. Promoting a drug for unapproved uses is illegal in the US, yet quite hard to prove, even if you’re someone like Noah Nathan with insider knowledge on how the company worked. After gathering further data (including wearing a wire to record company meetings) his case was rejected. His case probably wasn’t as solid as it needed to be to pass the court’s strict standards, but as he told me, had he been in a different state, things could have looked a lot differently. He said that “the courts ruled against me, while potentially putting American patients at risk.” Over those five years, Nathan lost his marriage, his job, and the case that could have strengthened safety precautions for other patients. Admittedly he was outgunned, facing off against some of the biggest law firms money could buy. I asked him if it was worth it, and he was quick to admit “being a whistleblower is hard,” but he’s more worried about the overall issues for public health. It’s possible that Nathan vs. Takeda might set a dangerous precedent, making it harder for other whistleblowers to succeed. Ultimately, he thinks that justice will eventually be done: “public opinion will eventually catch up,” he said, “when the lawsuits start piling up and people are suing for bone fractures related to the drug.” He adds, “for sure, there are broken bones out there, hiding in plain sight.” The lesson here is a precautionary one—that effective drugs in the short term can often wreak havoc in the long term. Taking any new drug is often a gamble, and the statement in the product monograph to “use the lowest dose for the shortest period of time” is an axiom that stands the test of time not only for PPIs, but for almost all drugs. Victoria resident Alan Cassels has spent 25 years researching and writing about pharmaceuticals. He currently works at UBC.

The government doesn’t pay for it yet, but the pressure from Big Pharma is on. IN THE FALL OF 2016 a new flu vaccine became available in Canada, promising to provide much better protection for senior citizens. Known as a high-dose trivalent inactivated vaccine (HD-TIIV) and sold under the brand name Fluzone, the vaccine was promoted as a weapons-grade tool in the fight against the flu among our most vulnerable population—seniors. We were told it contained four times as much antigen compared to standard-dose quadrivalent inactivated vaccine (QIV), for the three strains the vaccines share in common. While this is not the first time I’ve tried to inform Focus readers about campaigns to shape our thinking about diseases and drugs, or questioned whether the best available evidence supports mass influenza vaccination, the high dose of propaganda floating around this flu season seems particularly noxious. The drama hinges on a key question: Would millions of dollars more—either from BC taxpayers or the pockets of seniors themselves—make any real difference to the annual burden of influenza? The so-called “awareness-raising” (mostly by industry) around this new flu vaccine is not only exposing all of us to the scariest of statistics around the flu, but seniors’ groups, doctors and pharmacists have been even more intensely targeted. “Seniors are at high-risk for the most severe consequences of flu, including hospitalization and death,” we are told in ads and public service announcements, adding that “up to 91 percent of flu-related deaths occur in those 65 years of age and older.” Repeated public health appeals to get the flu shot seem to be singling out older people and their weaker immune defenses, but for me this targeting raises a contentious question: If the flu is so bad, how many people die of it every year? The Public Health Agency of Canada, which runs the FluWatch program, says they get, on average, 23,000 lab-confirmed cases of influenza reported to them each year. Acknowledging that the “burden of influenza can vary from year to year,” they estimate that in Canada there are an average of 12,200 hospitalizations related to influenza, and approximately 3,500 flu deaths every year. These are projections, based on modelling, but that 3,500 number gets repeated ad nauseum. But is it true? Two months ago, a CBC story reported actual FluWatch data that said Canada had 302 flu deaths last year. In whose interest is it to exaggerate these numbers? I guess it only matters when you thoughtfully consider what game is going on. As every marketer knows, you don’t sell the steak, you sell the sizzle. Big Pharma is happy to have the projections and estimates sound dramatically scary, even if they are as much as ten times inflated from reality. In Canada, a national body called the National Advisory Committee on Immunizations, or NACI, said that Canadians over 65 should be offered this high-dose flu vaccine on the basis of “good evidence of better efficacy compared to standard-dose” flu vaccines. They suggested that older people suffer from “immunosenescence”—a waning immune system as they age—and hence older people are at greater risk of severe illness from the flu. This apparent need for stronger stuff buttresses the case that an “extra strong” vaccine is needed to protect our seniors. NACI’s Canadian Immunization Guide said that Canadian provinces “may use any of the four influenza vaccines available for use in adults aged 65 years and older: standard-dose TIIV, the HD-TIIV, adjuvanted TIIV, and QIV (quadrivalent influenza vaccine).” However, the organization also recommended “at an individual level, the HD-TIIV should be offered over standard-dose TIIV to persons 65 years and older because of the expectation of higher effectiveness.” This means it’s better, right? Others aren’t so sure. The BC Centres for Disease Control looked closely at the science behind the vaccine and said additional studies were needed to confirm whether the HD-TIIV vaccine’s effects are consistent “across seasons and vaccine strains.” They also said they didn’t know if the vaccine “warrants preferential recommendation and public funding over other available options.” The new high-dose vaccine costs about $80-$90 per shot, about five times as much as a standard flu shot. Saying yes to the vaccine would cost BC taxpayers millions more than we already spend. This would be money well spent if it saved more lives and kept more people out of the hospital, but…let’s dig into the numbers. The pivotal trial of HD-TIIV enrolled more than 30,000 people comparing it to standard-dose TIIV. The results? The HD-TIIV reduced the risk of influenza by 24 percent. It sounds pretty impressive, but what does that number really mean? The study, carried out in seniors who lived in their own homes, found 1.9 percent of those getting the standard-dose vaccine developed the flu, versus 1.4 percent who got the high-dose vaccine. While it’s a 24 percent drop to go from 1.9 to 1.4, it’s also a 0.5 percent difference (1.9 percent subtract 1.4 percent = 0.5 percent). This means that half a percent of seniors were saved from the flu. The CDC concludes that “an additional 200 such individuals would need to be immunized with the high-dose product to prevent 1 additional case of influenza.” Also, one person in 4,000 vaccinated would avoid a hospitalization. The high-dose vaccine showed no effect on deaths. So if you trust the study, the HD-TIIV vaccine increases grandma’s chances of avoiding the flu by 1 in 200. The converse of this is that 199 of every 200 people vaccinated with the HD-TIIV will see no benefit. The researchers’ conclusion and recommendation to the Ministry of Health speaks volumes: “the strength of the evidence and anticipated incremental benefit of HD-TIIV relative to standard dose TIIV is not commensurate with the additional 5-fold cost...” As of press time, the BC Ministry of Health seems to agree. It does not cover the HD-TIIV, likely because it costs five times as much but doesn’t help 199 of the 200 people who get it. My back-of-the-envelope math says that for $16,000, the high-dose flu shot will help prevent one additional flu case in seniors; it would cost $320,000 to prevent one hospitalization (that’s just for the vaccine, not for administration costs). And there is no evidence the high-dose vaccine saves lives. For drug companies in Canada, however, the big enchilada in sales is provincial coverage. If their drug or vaccine isn’t covered by the provincial government, their profits will be smaller, and they will have to rely on people paying out of their own pockets or having private insurance. Among Canada’s 13 provinces and territories, only Ontario funds the HD-TIIV for all adults aged 65 and older. Saskatchewan, Manitoba, Nova Scotia, P.E.I. and Northwest Territories cover it for seniors in care facilities. BC does neither. But the pressure is on. Over the last year I became aware of at least four different Canadian seniors’ organizations who have been lobbied by the company promoting the high-dose vaccine. The company offers conference speakers, workshops and webinars to “educate” seniors about the threat of influenza and the benefits of various vaccines. The punchline: You deserve the best, so lobby your government to pay for this vaccine! (The BC Liberal Opposition introduced legislation in October to cover costs of the high-dose drug for seniors.) These promotions have the veneer of being public-spirited and helpful, especially when the companies propose their own speakers to educate senior’s groups, offering free sessions on the dangers of influenza and so on. Putting vulnerable seniors into the cross hairs of big Pharma’s direct marketing tactics doesn’t please everyone. One member of a seniors’ organization based in Vancouver (who asked that his name not be used) was blunt with me: “Sanofi, the third-largest drug corporation in the world, has generously provided expensive restaurant meals and delivered their sales pitch to retired teachers’ groups in BC as part of promoting their new and very costly flu vaccine.” He added that “BC seniors cannot easily access independent information about the efficacy of new drugs, and neither can family doctors for that matter, so some seniors are now lobbying their provincial government to cover them. Constant TV advertisements marketing these new vaccines reinforce a message of fear and the need for urgent preventative action.” Also jumping on this bandwagon are a variety of national patient and seniors groups “partnering” with the vaccine makers to sponsor flu awareness campaigns. There is evidence that the marketing to health professionals is also in full action mode, and the way this works is usually through the digestive system. The manufacturer will sponsor a dinner at a nice local restaurant and invite community pharmacists or local GPs to attend a dinner lecture. They’ll either feature their own “Key Opinion Leader” or work with a local GP or pharmacist to deliver the goods with a company-provided slide deck. Don’t be shocked, this is Drug Marketing 101, and a time-worn way for the company to make sure our doctors and pharmacists buy into their version of this lifesaving vaccine. All this is perfectly legal, of course, despite the fact the doctors and pharmacists I know become somewhat red-faced when I ask them what they think of their colleagues being wined and dined with company presentations and other pharma-funded schmoozing. What can we do about this? I’d recommend a much higher dose of skepticism among the public and our health professionals as a partial antidote. We need to be reminded that we allow this kind of sneaky marketing and flu-mongering at our peril. But here’s my big worry: Maybe the growing distrust that many Canadians feel around flu propaganda will lead to a greater public reaction, causing fewer and fewer people to trust what they are being told about the value of other vaccines. Alan Cassels is a Victoria-based drug policy researcher and author whose motto is “We need clean, clear health information as urgently as we need clean, clear water.” He works for UBC’s Therapeutics Initiative but the opinions represented here are his and his alone. Follow him on twitter @akecassels.