Canada has a problem with clinical trials: We cannot see them
Canada has the opportunity to become an active and innovative regulator of clinical trial transparency, Anmol Gupta argues in this guest blog. He suggests three ways to improve trial reporting in Canada.
Just three percent of all Canadian clinical trials were properly registered and their results made publicly available in the last decade, according to a recent preprint study.
Human clinical trials are the primary method of evaluating the safety and efficacy of new therapies, and their transparency is vital for regulators, physicians and the public to make informed decisions.
Of the hundreds of trials sponsored by universities and hospitals every year, many go unreported because their findings are negative or inconclusive. These unreported results create an incomplete and distorted picture of the risks and benefits of new therapies, restrict the ability of physicians and patients to make informed decisions and risk patient harm.
It is why both the World Medical Association and World Health Organization have released guidelines that underscore the ethical imperative for complete clinical trial transparency – frameworks that Canada has voiced its support for or been a signatory to.
Even the United Nations has urged governments to act, encouraging the use of public registries to make available the results of completed and discontinued trials.
Failing patients, physicians and taxpayers
With just three percent of trials meeting these international reporting standards, Canada is failing to protect the interests of its patients and physicians.
Full transparency is also in the interest of the Canadian public. With over $1 billion of taxpayer money funneled through the Canadian Institutes of Health Research (CIHR), the public is a significant funder of biomedical research, including clinical trials.
Weak trial transparency prevents effective coordination between researchers, and the lack of easily accessible information about past studies often leads to duplicated and inefficient research that hinders medical progress.
Calculating the costs of opacity
With the cost of individual clinical trials ranging from an estimated $3 million to $21 million, needless replication is a costly proposition.
Even harder to capture are the costs to Canada’s publicly-funded health system, faced with information asymmetry upon which it must make critical decisions on the treatments it will fund.
Public financing demands public results
Some researchers and corporate sponsors have downplayed concerns about poor trial registry or reporting, arguing that peer-reviewed studies are an adequate avenue to communicate clinical trial results to necessary decision-makers.
This does not address the fact that scientific journals rarely publish results of incomplete trials, nor that information submitted to regulatory bodies is often kept hidden from providers and patients.
Even private investors have joined the call for trial transparency, recognizing that information asymmetry exposes them to risk and liabilities.
Canada's rules must be enforced
Until recently, Canada did not have meaningful legislation mandating sponsors to register studies or report their findings.
In its 2018 Tri-Council Policy Statement on the Ethical Conduct for Research Involving Humans, CIHR began to require a public registry of all trials; however, the policy lacks any clear enforcement mechanisms.
More recently, in response to concerns about existing medicines being studied for the treatment of COVID-19, CIHR released information on a new process to assess and publish compliance. Most notably, CIHR announced it will withhold future funding for sponsors who fail to remain compliant, representing an approach unique to Canada.
This new policy framework represents an acknowledgment by the federal administration of the need for enforcement.
[Note: Recent policy developments in Canada are also discussed in this TranspariMED blog.]
However, details on how CIHR will accurately determine compliance with the use of self-reporting and audits are left to be desired, and it is difficult to predict how threat of access to future funds will motivate sponsors.
Canada does not face this challenge alone. Less than half of all clinical trials in the United States (U.S.) and the European Union (EU) are estimated to go unreported.
Three ways to improve trial reporting
If Canada seeks to be a leader on this policy challenge, it needs to go further in becoming an active and innovative regulator of clinical trial transparency.
There are three ways it can [do this].
1. Name and shame
CIHR could step up its enforcement by publicly identifying and notifying noncompliant sponsors, instead of its current proposal to publish anonymous compliance data.
Enforcement gaps left by CIHR, the U.S.’s Food and Drug Administration and the European Commission, have been filled by NGOs. Two NGOs, TranspariMed and Universities Allied for Essential Medicines (UAEM), published a report identifying specific institutional sponsors that have failed to meet reporting requirements, highlighting the vast degree of noncompliance among the U.S.’s largest 40 medical research institutions.
In just the two years after the release of this report, without much significant policy change at the federal level, the percentage of unreported trials fell from 31% to 7%.
Naming and shaming can be an agile policy tool, not only to make sponsors aware of their noncompliance but to build public and media pressure against Canadian universities and health systems that care deeply about their reputations.
We should not, however, be relying on NGOs to carry the burden of this work. With the breadth and depth of resources at its disposal, this Canadian government can begin to nudge sponsors into compliance immediately.
2. Prospective registration
Failures to register and report clinical trials exist, in part, because it presents an administrative burden for sponsors. As the predominant funder of clinical trials, CIHR is best positioned to reduce this burden for researchers.
Models, like the United Kingdom’s “Make It Public” strategy, have created mechanisms for automatic trial registration that are incorporated into the process of grant approval.
Canada can do the same. Prospective registry would guarantee all clinical trials are visible to the public before their commencement and help CIHR better certify result reporting without chasing after noncompliant sponsors or relying on self-reported data.
Prospective registry would also create opportunities for CIHR to institute targeted peremptory policy tools, like monetary penalties, to encourage more steadfast compliance.
3. Clinical trials and pandemic preparedness
As Canada reflects on the past two years and begins to build strategic plans for pandemics of the future, it must recognize the need for special policy and guidelines on the transparency of clinical trials in health emergencies.
During pandemics, when expedited regulatory reviews are necessary to bring health solutions to the public as fast as possible, requirements for clinical trial results to be reported within 12 months of completion become inadequate.
The creation of clear guidelines on the powers CIHR can and cannot have to compel accelerated registration and reporting during public health emergencies is critical to a thoughtful Canadian pandemic strategy.
The opportunity ahead
Canada can become a leader on ensuring timely and public access to all clinical trial results – the good, bad, and inconclusive.
Canada’s proposed regulations are a step in the right direction, yet there remain gaps in the current framework.
It is time Canada seriously consider the untouched policy levers available to it, to fuel more immediate action on behalf of its taxpayers, patients and their physicians.
Guest blogger Anmol Gupta is a Master of Public Policy candidate at McGill’s Max Bell School. He is also a Doctor of Medicine candidate in the United States. Anmol is a student-member of Universities Allied for Essential Medicines (UAEM), an organization that is mentioned in the article; however, he did not contribute to the report cited. Anmol Gupta can be contacted on Twitter.
This article was originally published by The Bell, the student-run newsletter of the McGill Max Bell School of Public Policy, on 17 October 2022.