Considering the sheer number of clinical trials out there, it’s surprising that more of them don’t end in tragedy. One reason they don’t, is that those that do are scrutinized intensely.
One of the most famous clinical trial deaths was the death, in 1999, of Jesse Gelsinger, a participant in a gene therapy clinical trial (New York Times article here; Wikipedia summary, very short but not inaccurate, here). Gelsinger’s death was clearly caused directly by the treatment, and he shouldn’t have been in the trial in the first place. The death essentially shut down gene therapy for some time, and though the field has recovered, and has weathered other tragedies, anyone involved in gene therapy knows Gelsinger’s name and story.
The doctor in charge of the trial, James Wilson, recently published “Lessons learned” from this case. 1 (The article is part of a settlement with the DoJ; the university involved was fined, but didn’t have to admit wrongdoing.) No matter how you read the article — different people read it as a long excuse, as a confession, as a poignant reminiscence, as a warning — it’s worth thinking about; I’ve no doubt that the lessons Wilson talks about are still relevant to many clinical trials today.
- Lesson #1: The clinical protocol is a contract with the research subjects and regulatory agencies that must be strictly and literally adhered to. (He points out the the complexities of a clinical trial, especially involving so many new components, made the protocols “a living document”. Even though the many changes were approved, it must have been difficult to follow the changes. What’s more, changing the rules must make it seem that the rules are flexible. They’re not.)
- Lesson #2: If you think about reporting – then do so! (He notes that the trial was run by a committee of experts, which seemed like a good thing at the time. But that diluted some of the sense of personal responsibility. The person in charge has to be responsible.)
- Lesson #3: It is very difficult to manage real or perceived financial conflicts of interest in clinical trials. (Is it possible to avoid financial conflicts? Is is possible to avoid the appearance of conflict? “I conclude that it is impossible to manage perceptions of conflicts of interest in the context of highly scrutinized clinical trials, particularly where there is a tragic outcome. It must be realized, however, that a zero tolerance for real or perceived financial conflicts of interest in clinical trials … can limit the contribution of the physician-scientist to the process of bench-to-bed-side or what we now call translational research.“)
- Lesson #4: Informed consent may require objective third party participation. (The people who design the trial are invested in it — not financially, but personally; it’s their work. They are not the best people to explain the risks to potential participants. “The challenge is that the most qualified individuals to participate directly in the clinical trial are those who developed the technology and those with knowledge of the disease which unfortunately are also those with potential non-financial conflicts of interest. The crux of the problem is to assure that the subject receives a balanced and unbiased view of the risks and benefits of his/her participation in the trial.”)