This year, Veritas IRB will celebrate the 10th anniversary of its accreditation. At that time, our president, Janice Parente, saw in accreditation an opportunity for the entire research industry to move towards a participant-centric approach to research:
“It is imperative to minimize the risks to clinical trial participants and maximize the benefits… Our industry has an excellent opportunity to lead the world in instituting clinical trial regulations and guidelines not borne of tragedy but simply out of a desire to protect the rights and wellbeing of our clinical trial participants.”
Janice Parente, January 2007
Sadly, in the last decade, we continued to witness regulations and guidelines being developed in reaction to tragedies. Many will remember the TeGenero trial in the UK where six participants were hospitalized and four suffered from multiple organ dysfunction. Montreal was the scene of a TB outbreak at a Phase I unit which infected 20 people (participants and research staff). In 2015, the errors that lead to the death of Dan Markingson at University of Minnesota were revealed to the public. And we began 2016 with another clinical trial tragedy in France which took the life of a man and seriously injured five others. The extent of the harm caused to these individuals is still unknown.
Based on the public records, these tragedies share the following flaws:
Poor scientific methodologies (e.g. improper preclinical models, scientific shortcomings)
Presence of external pressures influencing decision-making (e.g. hype, budget constraints, conflicts of interests)
Communication failures (e.g. protocol ambiguities, inappropriate delegation, inadequate supervision)
The level of harm that the research participants experienced was unnecessary and could have been mitigated had the researchers adopted a systemic approach to identify and minimize risks.
How to identify and minimize risks in clinical trials?
One systemic approach to identifying and minimizing risks of harm in research consists of conducting a benefit-harm analysis through the distinction of therapeutic procedures from nontherapeutic procedures. This approach was developed by Dr. Charles Weijer of the Rotman Institute of Philosophy and others and has been applied by Veritas IRB since 2004.
This distinction is fairly simple:
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Therapeutic procedure: If the procedure is conducted with the hope of improving the health of the participant;
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Nontherapeutic procedure: If the procedure is done purely for scientific purposes.
Once this distinction has been established, it is important to evaluate if the proposed therapeutic procedure is supported by scientific data and if experts would agree that there is no clearly preferable treatment.
Regarding nontherapeutic procedures, it must be established whether risks to participants can be minimized and if the remaining risks of harm are reasonable in relation to the knowledge to be obtained from the research. Minimizing risks, like any procedure in the study, must be consistent with sound scientific design.
What are the risks that must be identified and minimized?
It is the duty of sponsors, researchers and IRBs to identify all potential risks faced by research participants including physical, psychological, social, legal and economic.
In research where there is a high prevalence of uncertainty, no risk can be overseen based on its low probability. The above-mentioned tragedies are a testimonial that, in research, you need to expect the unexpected. Indeed, the duty to identify, minimize and disclose risks is significantly greater in research than in clinical settings. This will definitely be the topic of a future blog posting.
Bottom line: Develop a systemic approach to clinical trial risk management
The complexity of clinical trials has significantly increased over the recent years and often presents a greater challenge in terms of safety. A comprehensive risk assessment through the adoption of a systemic approach provides an in-depth analysis and allows for the development of safety measures that are consistent with sound scientific design.
A systemic approach makes risk management immune to the noise caused by preconceived ideas, constraints of time or money as well as other potential competing interests that have no correlation with the scientific merit of the trial. It is when these elements interfere with a trial’s risk assessment that tragedies occur.
While the above solution may sound obvious or simplistic, we invite you to ask your colleagues, your researchers, and your IRB what their approach is to identifying and minimizing the risks of research. You may be surprised by the answer you will receive.
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About the Authors
Martin Letendre
Martin Letendre is responsible for managing Veritas IRB's business operations and administering the activities of the Veritas IRB Boards. Martin is a member of the Quebec Bar and brings more than a decade of experience in health law and research ethics. His expert knowledge of, and ongoing activity and interest in research ethics have led to the publication of several reports and articles in peer-reviewed journals, and invitations as guest speaker at numerous conferences and scientific meetings. Martin was actively involved in the creation of an on-line tutorial for institutional research ethics boards in Quebec and was a member of Canada's three federal research agencies' Panel on Responsible Conduct of Research.
I believe it to be of utmost importance for reporting agencies to differentiate this risk classification in the existing study phases.
This risk classification is also an important frame of reference to evaluate the most appropriate type of insurance for a clinical study and determine its level of severity.
As a tool, it would already provide insurance companies with a direction for the analysis of its subscribers.