When errors can turn fatal

Nobody can deny that testing new drugs, treatment methods and health technologies among humans is necessary for overall progress of health science and for the resulting benefits to flow to the general population. This is the only way health science has progressed and given us new medicines, vaccines and diagnostic tools. Scientific evidence emerging from field trials in different settings is also necessary for governments to take key decisions relating to health policies such as screening for different diseases, preventive vaccination or introduction of new drugs in publicly funded programmes. However, clinical trials involving human subjects have to be conducted in an ethical manner and in a way that does not potentially harm people who volunteer to participate in such trials. This is the biggest challenge facing health research today.

The ethical dilemma has come into focus once again with the publication of an analysis of three field studies on cervical cancer screening among poor women, in the Indian Journal of Medical Ethics recently. In randomised control clinical trials, there are two set of people usually — one who receive the drug being tested and another set of people who serve as a ‘control’ who don’t receive any drug. Alternatively, if two drugs are being tested then each group receives one and results are compared. In trials involving new drugs and vaccines, people in the control are given placebos (which is not a drug). It is a different matter that even placebos have been found to have some therapeutic effect. In the present case, the objective was not to test a new drug but to test feasibility and cost-effectiveness of cervical cancer screening methods (Pap smear and Visual Inspection with Acetic acid or VIA). One set of women were screened, while another was not screened, and then the results were compared. The studies concluded that screening with VIA helped prevent nearly 30 per cent of deaths due to cervical cancer. Trained health workers were used to conduct VIA. This was a remarkable finding.

However, when the study results were shared in the US (the studies were sponsored by the National Cancer Institute and the Bill and Melinda Gates Foundation), some ethical questions were raised about 250 women who had died during the trial. Remember these trials were not to test any new drug, so deaths can’t be attributed to any adverse reaction or wrong administration of drugs. All the deaths occurred among women in the control group — women who were not screened for cancers. They died because their cancer went undetected. These women were mere statistics for researchers. Deaths among the unscreened groups, in fact, helped researchers compare the data with that from women in the screening group and conclude that screening indeed helped in preventing deaths.

As per rules, informed consent of all women was taken when the trials began and it seems those in control groups were verbally told about dangers of remaining unscreened. Still several questions are being raised by ethicists. Would the women in control group have participated if they were told about the likelihood of dying in case they were not screened?  Was it not ethical and moral responsibility of researchers to develop a mechanism whereby even unscreened women got medical help when they were developing cancers while participating in a trial? Since it was a long-term trial, was it not feasible for researchers to take a call mid-way about unscreened groups when they could see the data that screening indeed helps in early detection? Some people are arguing that these 250 women would have died in any case — even if they were not part of these trials — because India does not have any cancer screening programme at all. True, we don’t have cancer screening as yet but to allow unscreened women to develop cancer while participating in a clinical trial amounts to violation of fundamental patient rights. Researchers have claimed that these women were told about the pros and cons about screening through ‘health education’ and they were free to opt for screening elsewhere. Only a thorough ethical review of the three field studies would tell the truth.

The episode also raises larger issues about checks and balances we have for such trials in India, and about the role being played by foreign research and funding agencies in critical areas of health research in India. All trials have to be cleared from an ethical perspective by institutional ethics committees and central ethics committee. This process was not foolproof, as revealed later by an investigation carried out by the Office for Human Research Protections (in the Department of Human Health and Services) in the US. Based on papers supplied by Indian researchers, it was found that women in control group were not informed about alternatives in writing. They were only told about it verbally. “Subjects may not recall the information later, or may not fully understand what is told to them orally. Therefore the default is that such information must be provided in writing”, the investigation pointed out. Then the institutional review board did not review the trial continuously nor were proper minutes maintained. Regular review is necessary so that new information that becomes available may be considered to protect rights of study participants. Clearly, our ethical review mechanism is at fault and itself needs a review.

Cancer screening is necessary for a country like India where nearly one million new cancer cases are reported every year. A large number of them come at late stages. Many lives could be saved if we can detect these cases early. Screening programmes can help us do this. We need to develop cost-effective screening techniques and methodologies. Tamil Nadu has taken a lead in this area. National agencies like the Indian Council of Medical Research (ICMR) need to take a leadership role in this regard, instead of leaving the ground to funding agencies like the Gates Foundation which often tilt towards one technology option or the other. Academic and scientific collaboration with other countries is necessary for science to grow in today’s inter-connected world, but to collaborate with agencies which want to influence our health policies could be very dangerous.

The writer is a science journalist based in New Delhi