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.