Ensuring the integrity of clinical research

Ramseyer Apau Bediako and Chris Kaposy urge research ethics boards to be more proactive in their research oversight responsibility.

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Scientist He Jiankui made headlines recently because of his imprisonment in China for research misconduct in the use of gene-editing technology. Though this case is particularly dramatic, research misconduct is a problem all over the world. Recent cases of Dr. Mani Pavuluri, and Dr. Charles M. Lieber in the US, and the case of Dr. Ranjit Chandra in Newfoundland show that there are problems with research integrity in Western countries. Here in Canada, a 2009 report prepared for the Canadian Research Integrity Committee showed that 29 research institutions collectively deal with an average of 39 cases of misconduct every year.

Research Ethics Boards (REBs) evaluate proposed research for ethical acceptability and compliance with institutional and national research ethics guidelines. In addition to reviewing proposed research, REBs have a responsibility to monitor ongoing research. There are three ways in which this monitoring is typically done. First, there are mechanisms for ad hoc notification of adverse events and risks by researchers. Something goes wrong, a new risk emerges, and researchers are required and expected to notify the REB. Second, REBs rely on reports and amendments from researchers, including reports used to conduct annual reviews. The researchers want to change their protocol, or they want to get the green light to continue their research for another year, so they file an amendment or an annual review application. Third, REBs typically have a complaint procedure in which research subjects are able to directly report to REBs about unnecessary exposure risks and other harms.

Given the prevalence of research misconduct, are these methods sufficient to monitor clinical research? These three methods of monitoring research depend heavily on researcher self-reporting, and they are entirely passive in the collection of information. For research misconduct to come to light, REBs usually depend on having information given to them. And most of what is known about ongoing research is provided by researchers themselves. Despite various reforms over the years, the current oversight system appears to be inadequate. Research ethics boards do not typically conduct robust continuous monitoring of even potentially harmful research. Research ethics guidelines do not require more robust monitoring from REBs.

Photo Credit: pxfuel. Image Description: Glass test tubes on a blue tray.

It would be a mistake to blame research ethics boards for failing to adequately protect research subjects. Such blame would be dismissive of the hard work and sacrifices they make­— as their work as board members is mostly voluntary. Nor do we suggest researchers and scientists engage in unethical practices all the time.

Nonetheless, there are powerful economic forces that might motivate researchers and scientists to engage in unethical practices. Advancement and promotion of scientists is usually dependent upon research output. The involvement of industry in health research can put financial pressure on researchers to suppress risks to participants, or hide unfavourable results. As we can see, the current system of ongoing monitoring is highly dependent upon trusting the researcher. REBs trust researchers to disclose adverse events and be honest about changes to research design. But this trust mechanism has, over the years, proven to be insufficient. Even though trust in researchers and scientists is necessary, it is woefully inadequate. In an attempt to address this moral concern, there are possible solutions.  

We propose continual monitoring as a better way to protect subjects in clinical research. This monitoring would focus on informed consent, conflict of interest and standard of care, and how divergences from ethical requirements in these areas would likely affect the safety of research subjects and overall study integrity. Continual monitoring can be achieved through scheduled visits, random spot-checks or both. REB representatives could be more proactive in monitoring research by reviewing study documentation such as signed consent forms, visiting study sites to observe research procedures, and in some cases, interviewing subjects and relevant research staff. The degree of monitoring could be matched to the perceived risk involved with the research.

Continual active monitoring comes would come with several substantial challenges, such as financial cost and providing adequate human resources. However, the justification for this continual monitoring responsibility comes from weighing not only the costs of doing active research monitoring, but also the costs of not doing it. Failure to protect research subject safety and research integrity incurs significant costs as well.

The strongest justification for our proposals comes from the fact that research ethics boards have a moral duty to protect research participants, not just at the beginning of research, but throughout the research process.

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Ramseyer Apau Bediako is a Master of Health Ethics student at the Memorial University Centre for Bioethics.

 

Chris Kaposy is an Associate Professor at the Memorial University Centre for Bioethics and editor of Impact Ethics. @ChrisKaposy