Are Canada’s clinical trials in need of reform? Experts weigh in.

I don’t think anyone who’s in the clinical trials space is surprised by the things the investigation brought out.

Given the money involved in these initiatives and that regulatory oversight is often lacking, it’s been a quite open secret that the Phase One clinical trial industry is largely often exploitative and takes advantage of vulnerable people.

Health Canada has been the overarching body that looks at and has to approve all novel drug clinical trials in Canada. Something that wasn’t really mentioned in the article itself is that Health Canada defers primary oversight of ethical issues within a clinical trial to research ethics boards. As long as those ethics boards are doing their job, these things shouldn’t happen.

Why isn’t an ethics board looking at these protocols, seeing some of the limitations that were addressed and not doing anything about it?

The question then emerges: “Why isn’t an ethics board looking at these protocols, seeing some of the limitations that were addressed and not doing anything about it?” In the United States, for example, a lot of private ethics boards have popped up. That same infrastructure is growing in Canada, with independent, non-academic ethics boards emerging where probably a lot of these issues are living. Then there (are) clinical trials ethics boards that are affiliated with universities and academic institutions. We would hope that these ethics boards would see where there’s exploitation occurring and flag it.

The question is, “Why aren’t these trials being flagged by the relevant ethics boards?” The answer is typically that the ethics board that is looking at it doesn’t have the resources to actually enforce or review things closely.

We’re always very quick to blame the companies in these instances. They obviously have some of the blame, but they’re just working within a system that’s designed to do exactly this. Without very stringent oversight, obviously this is what is going to happen. It’s very easy just to say “pharma bad” but it’s not as simple as that if we allow them to do bad things.

This article suggests that we have similar issues in Canada that we’ve been seeing in the States, where humans have been acting as guinea pigs in clinical trials for money. This can compromise their health. We also see the same pattern of people running from one trial to another, trying to get as much money as they can, even if it means not notifying the other trials they’ve been involved with or not disclosing when they’ve developed side effects from the medication. This is not to blame the participants, because they are put in a position where they have strong incentive not to terminate the clinical trial so that they can be paid. But I think this should concern all of us from a public health standpoint.

First of all, we need to reflect on whether we’re offering too much money for these trials. In Quebec, a participant in a trial should not receive salary for it, they can only be compensated:

“A person’s participation in research that could interfere with the integrity of his person may not give rise to any financial reward other than the payment of an indemnity as compensation for the loss and inconvenience suffered.”

If participants are only participating in the trial for money, then that should raise a flag for us.

This is meant to protect from what we’ve seen in this article. But a lot of big companies try to find ways to give huge compensation to people. That becomes a legal issue from an ethics viewpoint and raises concerns about free and informed consent. If participants are only participating in the trial for money, then that should raise a flag for us because it means those people will take higher risks and potentially lie about the side effects and so on, as we have seen in that article.

On a smaller scale, we should also look at the issue that participants can only receive compensation if they complete the study. For example, if they only participate in 20 per cent of the study but need to stop because of side effects, they should still receive full compensation for the study.

We need to think of how we can develop more thoughtful incentives and ways to respond to those situations. In Canada we have the  Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS 2), but private companies are free to adhere to it or not..

From a public health standpoint, we need to look at how people with low income are less able to raise concerns within a study and are more vulnerable in these settings and develop stronger laws and standards to protect them. Health Canada needs to be more proactive in the inquiry and supervision around what’s happening in the field.

The story was very specific to industry-sponsored trials and using CROs.

As the Canadian Institutes of Health Research (CIHR), we’re the federal funder for health research. We fund maybe 150 trials a year, while industry-sponsored trials are around 750 to 1,000 a year. We fund only a small fraction of the clinical trials in Canada and our money flows through eligible institutions, like universities and their associated research institutes.

Where our work touches on patient safety is that to be eligible for agency funding, institutions have to be compliant with the CIHR policies. The biggest one here is the TCPS2, which is a joint policy of Canada’s three federal research funding agencies that provides guidance for any human research. It’s ultimately the responsibility of the institution to have a compliant and independent research ethics board that follows the TCPS2.

Overall, it’s important to note that clinical trials are really important.

For each situation, the benefits and risks and how you recruit patients or participants is different. I don’t believe many of our academic researchers use CROs. Even if researchers that we’ve funded used contract organizations to help them recruit patients, all that research is under the same policies that individual researchers would be. The institutions are still responsible for complying with our policies, and researchers and their research ethics boards would still have to follow the TCPS2.

Overall, it’s important to note that clinical trials are really important. There are a lot of safeguards in place to protect participants, and I wouldn’t want people to be dissuaded from seeing a clinical trial as a reasonable option for them. It provides opportunities for patients to gain access to drugs that aren’t yet available in Canada. Clinical trials are also really important for providing good data that supports health-care policy. I hope that people realize that there are good things that come from this as well and that patients are protected.

I agree with the suggestion of the Star article that a national registry for participants enrolling in clinical trials would be helpful to enhance safety of this population and to ensure scientific integrity.

We would need to instantiate an independent auditing and monitoring system, with special attention to CRO clinical trials. There needs to be accountability – an ability to know if the study is acting in accordance with the research ethics approved design of the trial.

For this there needs to be mandatory transparency regarding the conduct of the study, as CROs may be acting on part of commercial entities with proprietary interests in maintaining confidentiality of their trials. Proprietary interests should not trump participant safety and the need to ensure well-designed trials.

Canada may also want to consider establishing a national ethical compensation framework for participants in trials. Existing study protocols in hospitals for drug therapeutics provide measly reimbursement to participants and other studies don’t reimburse participants at all. Without national guidance, each individual REB sets their own thresholds which are not even consistent across studies, let alone across the country.

Generally, I believe concern about overpayment is a red herring.

Generally, I believe concern about overpayment is a red herring. Payment for research participation has historically raised concerns around the potential for excessive payment to exert undue influence on participant decision-making and informed consent. However, the ethical concern is the other way around: Not paying participants enough risks exploitation and injustice, particularly amongst those from lower socioeconomic strata who may be more inclined to participate for payment.

The solution is not to scale back payment to participants, but to strengthen the informed consent process, making certain that persons give full attention to the risks and benefits, and for ethics review boards to ensure the risks are minimized. It is crucial that all clinical trials receive independent ethics and scientific review and ongoing monitoring.

Clinical trials are an essential part of health research.

Large studies involving human volunteers allow us to determine the safety and effectiveness of vaccines, drugs, devices and other interventions. Many of the treatments we take for granted would not be possible without this crucial evidence base.

As with all research involving human participants, safety is the primary concern. Clinical trials are regulated nationally and globally by a system of rigorous processes, built up over decades, to promote safe, ethical research of the highest quality. These protections include informed consent, ethics reviews and ongoing monitoring.

Canada is well known internationally for the high quality and safety of our clinical trials. Our federal system of regulatory review and compliance is strong, and provincial initiatives led by organizations like Michael Smith Health Research BC are supporting and strengthening these protections.

We are working to ensure ethical review of clinical trials meets the highest standards for human protection.

In British Columbia, we are working to ensure ethical review of clinical trials meets the highest standards for human protection. We are bringing together the province’s health authorities and post-secondary institutions to harmonize ethics review processes to ensure consistent application of best practice.

Health Research BC has instituted a province-wide program offering clinical trials education, certification, mentorship and quality management. This initiative supports quality in trial conduct and regulatory compliance with the aim of reducing the chance of unethical practices. We also support increased engagement of patients as research team partners, which further enhances oversight and accountability of clinical trials.

Similar work is underway in other provinces. Collectively, these supports enhance a system that is already well regarded outside Canada for its safety and efficacy. We should all be proud of the continued excellence of our clinical trials ecosystem and its ability to advance vital research that is safe and beneficial to patients and the public.