Across the globe, thousands of interventional clinical trials take place every year and many healthy participants are recruited to participate in such trials. Participation in these interventional clinical trials is not without ethical concerns, and many who take part are at risk of harm and exploitation. To date, approaches to ethical consideration have been guided by legal codes such as the Nuremberg code, and the Helsinki Declaration. This is the most influential ethical framework to date and has undergone several revisions since its introduction in 1964. Within this framework, controls around vulnerability and exploitation have largely focused on the perceived vulnerabilities and protection from harm of patients who are more or less likely to benefit from participating in such research. The focus is on the need for participants in clinical trials to give informed and free consent without undue coercion. The guidelines have largely neglected mentioning healthy volunteers in interventional clinical trials. Arguably, this could be because healthy participants have been considered to be capable of being informed, giving free and rational consent, and able to understand complex clinical trial protocols, risks involved and negotiate their way through complex contracts involved in this process.
In the most recent 2024 revisions, paragraph 2 of the Declaration of Helsinki now explicitly suggests the guidelines applies to research involving both healthy volunteers and patients participants.. While it is a positive development to now have healthy volunteers mentioned in the declaration, it does not consider specific ethical concerns pertaining to healthy volunteer involvement in clinical trials. For example, the inclusion of healthy participants cannot be more different from patients. Their participation in clinical trials is mostly for safety and dosing checks, rarely do they expect or experience health benefits from their participation, and they are often paid significant sums for their participation in interventional human clinical trials. Payments are associated with participants’ tendency to participant in multiple trials risking their health and potentially compromising the integrity of the research.
An established body of research by Abadie, Devine et al, Elliot and Fisher, (in the US) and Mwale (in the UK), has identified that the focus on capability and rationality in understanding vulnerability of healthy volunteers in phase I clinical trials often functions to background concerns about the ethical processes clinical trials, which it could be argued are compromised through the payments of significant sums of money to people are mostly financially vulnerable participants. This body of work has shown how in diverse socio-economic situations the conduct of interventional clinical trials relies on mainly disenfranchised and financially straitened groups. Therefore, any regulatory code draws on conceptualisations of inequality, disadvantage and ability (to participate) must take this context into account. There is clear need for guidelines to be more nuanced, for example to include consideration of how healthy volunteering is contoured by the need to earn money from participating clinical trials. As such some healthy volunteers participate in multiple clinical trials at a time without giving time for washout periods between trials raising questions about their safety and integrity of studies they participate in. Despite this established body of evidence, guidelines around the inclusion of healthy volunteers’ still remain largely non-existent in ethical frameworks addressing human involvement in clinical trials.
In response to these concerns, as part of a multidisciplinary team of international Volunteers in Research and Ethics (VolREthics) led by the French Medical Research Agency (INSERM) ethics committee, we have developed a Charter for the Protection of Healthy Volunteers in Interventional Clinical Trials. The charter highlights 15 specific rights and tailored recommendations to encourage good practice on how best to protect both healthy volunteers and the integrity of research. The charter is not an attempt to create new protocols and guidelines but to complement existing guidelines by highlighting issues that specifically affect healthy volunteers that regulators at national and international levels should consider, in order to ensure healthy volunteers are adequately protected from harm and exploitation and research integrity is maintained. The charter calls for the need to introduce national registry systems to prevent over-volunteering. The need for appropriate, not low, financial rewards for healthy volunteers participating in clinical trials, the need for provision of appropriate acute medical care on site or near clinical trials units, the need to provide insurance to cover all harms caused by clinical trial as for the patients, and for studies to be conducted in safe and humane spaces among others.
As a team we also engaged with and responded to the amendments to the Helsinki declaration to suggest the inclusion of articles specific to healthy volunteering. It was, therefore, disappointing to note the latest, 2024, revisions to the Helsinki Declaration still continue to ignore the need for the inclusion of specific guidelines to enhance the protection of healthy volunteers in interventional clinical trials. It appears, despite clear evidence, that much more work to ensure healthy volunteers are adequately protected from harm and exploitation in interventional clinical trials still needs to be done.
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When are healthy volunteers considered to be at risk? Reflections on the 2024 Revisions to the Helsinki Declaration
by Shadreck Mwale Nov 6, 2024Across the globe, thousands of interventional clinical trials take place every year and many healthy participants are recruited to participate in such trials. Participation in these interventional clinical trials is not without ethical concerns, and many who take part are at risk of harm and exploitation. To date, approaches to ethical consideration have been guided by legal codes such as the Nuremberg code, and the Helsinki Declaration. This is the most influential ethical framework to date and has undergone several revisions since its introduction in 1964. Within this framework, controls around vulnerability and exploitation have largely focused on the perceived vulnerabilities and protection from harm of patients who are more or less likely to benefit from participating in such research. The focus is on the need for participants in clinical trials to give informed and free consent without undue coercion. The guidelines have largely neglected mentioning healthy volunteers in interventional clinical trials. Arguably, this could be because healthy participants have been considered to be capable of being informed, giving free and rational consent, and able to understand complex clinical trial protocols, risks involved and negotiate their way through complex contracts involved in this process.
In the most recent 2024 revisions, paragraph 2 of the Declaration of Helsinki now explicitly suggests the guidelines applies to research involving both healthy volunteers and patients participants.. While it is a positive development to now have healthy volunteers mentioned in the declaration, it does not consider specific ethical concerns pertaining to healthy volunteer involvement in clinical trials. For example, the inclusion of healthy participants cannot be more different from patients. Their participation in clinical trials is mostly for safety and dosing checks, rarely do they expect or experience health benefits from their participation, and they are often paid significant sums for their participation in interventional human clinical trials. Payments are associated with participants’ tendency to participant in multiple trials risking their health and potentially compromising the integrity of the research.
An established body of research by Abadie, Devine et al, Elliot and Fisher, (in the US) and Mwale (in the UK), has identified that the focus on capability and rationality in understanding vulnerability of healthy volunteers in phase I clinical trials often functions to background concerns about the ethical processes clinical trials, which it could be argued are compromised through the payments of significant sums of money to people are mostly financially vulnerable participants. This body of work has shown how in diverse socio-economic situations the conduct of interventional clinical trials relies on mainly disenfranchised and financially straitened groups. Therefore, any regulatory code draws on conceptualisations of inequality, disadvantage and ability (to participate) must take this context into account. There is clear need for guidelines to be more nuanced, for example to include consideration of how healthy volunteering is contoured by the need to earn money from participating clinical trials. As such some healthy volunteers participate in multiple clinical trials at a time without giving time for washout periods between trials raising questions about their safety and integrity of studies they participate in. Despite this established body of evidence, guidelines around the inclusion of healthy volunteers’ still remain largely non-existent in ethical frameworks addressing human involvement in clinical trials.
In response to these concerns, as part of a multidisciplinary team of international Volunteers in Research and Ethics (VolREthics) led by the French Medical Research Agency (INSERM) ethics committee, we have developed a Charter for the Protection of Healthy Volunteers in Interventional Clinical Trials. The charter highlights 15 specific rights and tailored recommendations to encourage good practice on how best to protect both healthy volunteers and the integrity of research. The charter is not an attempt to create new protocols and guidelines but to complement existing guidelines by highlighting issues that specifically affect healthy volunteers that regulators at national and international levels should consider, in order to ensure healthy volunteers are adequately protected from harm and exploitation and research integrity is maintained. The charter calls for the need to introduce national registry systems to prevent over-volunteering. The need for appropriate, not low, financial rewards for healthy volunteers participating in clinical trials, the need for provision of appropriate acute medical care on site or near clinical trials units, the need to provide insurance to cover all harms caused by clinical trial as for the patients, and for studies to be conducted in safe and humane spaces among others.
As a team we also engaged with and responded to the amendments to the Helsinki declaration to suggest the inclusion of articles specific to healthy volunteering. It was, therefore, disappointing to note the latest, 2024, revisions to the Helsinki Declaration still continue to ignore the need for the inclusion of specific guidelines to enhance the protection of healthy volunteers in interventional clinical trials. It appears, despite clear evidence, that much more work to ensure healthy volunteers are adequately protected from harm and exploitation in interventional clinical trials still needs to be done.