Thank you very much for this opportunity to contribute to your study of Bill C-17
I'm going to focus today on why I think amendments to the bill are needed to address openness and transparency of clinical trials data and the decisions surrounding the approval of drugs by Health Canada.
I became interested in the transparency of safety and efficacy data almost 20 years ago while working as a research fellow on a phase four clinical trial. The manufacturer who sponsored our study selected the positive results from our database, ignoring the not-so-positive cases in order to argue for inclusion of that drug into the provincial formulary. I was appalled at the manipulation and wondered how mediocre drugs get approved in the first place given their cost to our health care system.
Between 2001 and 2006, I conducted extensive anthropological research at Health Canada's regulatory authorities. I was observing drug evaluations, regulatory activities, and decision-making. Also, I participated in progressive licensing consultations with Health Canada and I chaired their expert advisory committee on the special access program.
Concerns and recommendations that our committee made in 2008 about the role and fit of regulatory modernization were never made public and several apply to the recommendations for Bill C-17.
In 2004, Health Canada received the Code of Silence award from the Canadian Association of Journalists as the most secretive government department for denying access to drug databases that could harm or kill Canadians. The CAJ charged that commercial interests trumped Canadians' health. Regulatory capture, a term that gets used by all sides to accuse a regulatory authority of favouring the interests of one stakeholder over another, can happen in any sector. It's non-partisan.
The ability of Health Canada's regulatory evaluators and independent reviewers to do their job is challenged when assessing partial and incomplete data. I do not wish to criticize the dedicated work carried on by Health Canada's regulators. They work under considerable structural and financial constraints. Hiring just a few more evaluators in 2004 and 2005—while I was doing my research there—enabled the directorates to move out of years of backlog.
Improvements in recent years have made Health Canada's activities and reports more readily accessible. But these still remain weak instruments, lacking important details about the research design and methodologies, data, critical appraisal, and the assessment that would ensure unbiased results and analyses. While Health Canada's reviewers use many mechanisms to arrive at their decisions, including bilateral consultations with the sponsor and ongoing clarification of their questioning during reviews, I suggested there remains an essential role for independent appraisal that requires open access to the clinical trial data and to Health Canada's decision-making.
As a case in point, Health Canada's assessment of the stem cell therapy Prochymal left more questions than answers. In 2012, Canada became the first country to conditionally approve Prochymal for the treatment of acute graft-versus-host disease in children. Approval was based on very encouraging data showing clinically meaningful responses provided by the sponsor. The U.S. FDA wasn't convinced though and denied approval of that drug. The manufacturer, Osiris, planned to use Prochymal for the treatment of many other diseases, opening the door to multiple off-licence indications.
The fact that the panel recommended a warning for the product monograph to say, “The long term effects of Prochymal® in growing children are unknown“ would, I hope, have alerted the marketed health products directorate to a ticking time bomb.
Based on limited and unpublished clinical trial data, Canada's decision to approve Prochymal was lauded as a huge achievement by the financial and drug development communities. Canada was seen to be signaling a shift, that they were open to industry for faster access, more than for the safe drugs that Canadians need as promised in the 2003 throne speech.
Health Canada's summary basis of decision-making for Prochymal presented a confused picture of the criteria and proceedings that allowed its approval. Data from two unpublished studies were used to arrive at the decision, and one didn't even meet statistical significance for the critical end point. I quote from the summary basis of decision-making:
To date, only preliminary evidence exists to indicate a potential therapeutic value for Prochymal; however, so far, Prochymal has not exhibited worrisome toxicity and has shown a relatively benign safety profile.
I submit to you that so does a placebo and the evidence was that this trial was based on only 28 days of clinical research.
HPFB's own consultations say that the summary basis of decision documents do “not contain enough detailed information about clinical trials including study participants, results and harms to truly allow consumers and health care providers to make informed choices.”
In a business article titled “How to Tell When a Drug Company Fibs About Clinical Trial Results”, Adam Feuerstein wrote:
Osiris Therapeutics “disappeared” important data when the company announced results...from a mid-stage study of its stem cell therapy Prochymal in heart attack patients.
Regulation works well when it takes nothing for granted and has multiple, iterative mechanisms to control for potential gaps. The good regulator wears both a belt and suspenders. I don't think any of us wants Canadian regulators caught with their pants down. I cannot afford a ticking time bomb—none of us can. Bill C-17 does not go far enough in ensuring independent, systematic review of all clinical trial data. Steps to ensure access to clarifications and consultations between industry sponsors and regulators, and the details in rationale for drug approval, approval with conditions, refusal, and suspended or recalled drugs, are not included in the present draft of Bill C-17. Neither is budgetary commitment to provide the resources for the enhanced regulatory activities that modernization will need to meet obligations to Canadians for the safety and efficacy of therapeutic health products. Without budgetary commitment to carry out these extra activities, provisions in the act will be futile.
Regulatory modernization has swept across nations. It's intended to keep pace with our political neighbours in terms of policy, economy, and science and technology, but it can also be an opportunity for clinical trialists and regulators to adopt new, more robust methodologies. While Bill C-17 will enhance the recall powers of the health minister, it puts no emphasis on enhancing the capacity and capability of Health Canada with the precautionary buffer of independent review and access to decision-making.
Instead, regulatory modernization has pushed for post-market surveillance and follow-up for conditionally approved drugs, many of which should be stopped at the gate. With quicker access to these drugs, Canadians risk becoming phase four clinical trial guinea pigs who are not protected by the careful controls in traditional phase one, two, and three clinical trials.
Without the benefits of independent, open and transparent access to clinical trial results, the authorization and approval of the use of medications remain an ethically unjustifiable black box. Bill C-17 will serve all Canadians better if it can address this gap. As the journal Nature points out:
Greater openness about clinical-trial data should help to speed up drug development, provide independent assessments of drug safety and efficacy and increase trust in industry science.
It's a win-win for us all.
Thank you.