For anyone involved with the ethics of clinical research, our daily routines sometimes can obscure the core reason why our roles matter. While we prepare agendas for review board meetings, check IRB submission forms for accuracy, and audit files to ensure versions and dates of all the paperwork align, we can overlook the fundamental ethical issues involved with studying health in other human beings. But sometimes a situation or a story recall the questions we must continue to pose and–even more importantly–answer.
A colleague reminded me about these questions when he forwarded a recent article from the Times of India. The article reports that ethical lapses in two long-term cancer screening studies allowed over 200 women to die unnecessarily. The article (as well as one in the Arizona Republic last year) reviews how in the mid- to late-90’s, researchers began comparing screening procedures for cervical cancer in Indian women. The goal was to find inexpensive, effective and relatively easy tests for cervical cancer. After 14 years of research that involved over 140,000 women, the results received wide attention, including a report in the New England Journal of Medicine. But questions about the ethics of the study design rose quickly.
The two studies used three groups of ‘clusters’ to compare two types of screening: one group for each of the two procedures mentioned above, and a third which received no screening whatsoever. According to the New England Journal of Medicine article, all of the participants, were told of the importance of preventive screening, but few of the control group participants sought treatment outside of the study. The NEJM article summarized that “Women in the 13 control clusters were not offered screening but were advised on how to seek screening at local hospitals. Women in the clusters who were assigned to screening were given a card indicating the date, time, and place of screening.” The Times of India reports that participants who were screened and found to have cervical cancer received treatment for it.
Critics have focused on two elements of this approach:
- Because the advantages of pre-screening for cervical cancer are well-established, the researchers should have included some kid of screening for all participants; and
- participants in the groups that received screening benefited more from the research than did those in the control arm of the study
The researchers and study designers have countered to say that no screening is the standard of practice in India, and that having a control group was essential to gauge the effectiveness of the two screening options.
According to the the Times of India article, 254 women in the control arm of the study have died from cervical cancer. The article argues that researchers knew any screening was better than none, and so for the sake of the participants they should have screened everyone involved. This raises the recurring issue that research should not be considered health care, but in practice those screens were the only preventive test the Indian women pursued. It also casts a light on an issue in international research: the funding for these studies came from sources in the United States, where standard practice would include tests and screening that India does not. Should American funds support research that most likely would not happen in the United States? At the same time, this research targeted care and processes specific to India, and so conducting the research there seemed appropriate. The international dimension of this issue, how it highlights differences in care, and in expectations of health systems, demonstrates the complexity of conducting research across borders and cultures. In a review of one of the studies, OHRP cited a number of problems with conduct and design of the research. To date, the FDA has yet to comment on the other study.
Weighing the ethical concerns of these studies against their scientific goals of the research could pose a challenge for any review board. And these are not abstract thought experiments; the ethical questions that IRB/ethical boards ask can affect lives and influence the future of medical practice. But we do not always find the answers within the regulations or standard operating procedures. We need rigorous debate, and consideration of all the issues. As if we need a reminder, it’s not always easy.
Tags: Arizona Republic, cancer screening, cancer studies, cervical cancer, Clinical Trials, ethical issues, FDA, health care, India, New England Journal of Medicine, OHRP, Quorum Review IRB, Times of India