Hundreds of women died for the sake of research in cancer clinical trial

20170213130000, Zayani Bhatt
The loss of lives at the expense of clinical research raises many ethical questions that demand consideration.
More women die of cervical cancer in India than in any other country. Factors like poverty and illiteracy mean general screening tests like pap smears are few and far between.

To that end, the US National Institutes of Health (NIH) and the Bill and Melinda Gates Foundation, sponsored four clinical trials on women across two states in India, between 1997 and 2012.

Study ignored guidelines on clinical trials that India has signed

The trials evaluated whether trained “non-doctors” –health workers, supplementary midwives and nurses – could use visual inspection, with acetic acid (VIA), to detect cervical cancer early. Conducted on 363,553 women from low-income backgrounds, the research divided the women into two groups – one received screening and the other (a control group), were not offered this, or any other test.

Covenants to which India is a signatory, such as the Declaration of Helsinki and the Indian Council of Medical Research, have severe restrictions on the use of placebo or no-treatment groups in clinical trials. These groups can be used only if the disease is self-limiting or when no proven preventive, diagnostic or therapeutic method exists. A total of 548 women enrolled in the trial, eventually died of cervical cancer, of which 254 were from the group that had not been screened.

There are two problems with this. Firstly the advantages of screening for cervical cancer are well known and established and therefore the researchers should have included at least another kind of screening for the control group. Secondly, it was found that the consent forms the women were provided with, were misleading and omitted important information about alternative ways to get screening, a keystone requirement for medical research involving human subjects.

Ethical implications abound, despite court dismissal

After the Indian Supreme Court dismissed a public interest litigation on unethical research, Dr Eric Suba, a pathologist and medical ethics proponent, filed a complaint against the study with the US government’s Office for Human Research Protections (OHRP) in 2011. Suba’s complaint was that using death rates as a “yardstick” for the study’s success was unethical and “scientifically gratuitous”, and that the participating women were misinformed.

In 2012, the OHRP ordered that the women in the control group of the study be screened. By this time however, the 15-year study was over and many of the women had died of cervical cancer.

Dr Surendra Shastri, one of the paper’s authors claimed that, “since the standard of care for cervical cancer screening in India is no screening, we were ethically justified in having a no-screening control group”.

This is a controversial argument because many medical ethicists believe that standards of care cannot be relative to the economic situation of a country. Similar cervical-cancer studies in China and other developing countries did not rely on unscreened control groups.

Despite this, the American Society of Clinical Oncology decided not to pursue complaints against the study because they agreed with Dr Shastri. The international dimension of this issue highlights the complexity of conducting research across different borders. For example, should the United States be allowed to fund research that does not happen in the US, especially if it would not be permitted to happen there?

Suba is also not sure if the lives of low-income women in India have changed since the trials. “The political purpose behind allowing such research is to give power to research and commercial interests, like companies producing HPV vaccines,” he alleges.

In one study conducted in the city of Osmanabad in India, Suba says that researchers trialed a HPV test which was significantly more expensive than the pap smear. "Asking, 'does it work in this city or town?' — that's a marketing trial, not a genuine scientific question," said Elizabeth Woeckner, president of Citizens for Responsible Care and Research, a New York non-profit.

Relevant issues for all healthcare professionals

In response, the American National Cancer Institute’s program director for the study said it needed to continue "until we could see a statistically significant difference" in mortality rates between the control group and the screened group.

This widespread acceptance of such unethical practices perfectly explains why healthcare professionals the world over, must care about and stand up against it. Dr Rajendra Badwe, one of the doctors on the team said that the aim of the study was "mortality reduction" but deciding against screening women is not a way to prevent cervical cancer or reduce mortality.

These are not abstract thought experiments, as these ethical conundrums affect lives and will influence the future of medical practice. MIMS

Read more:
Human experimentation: Ethical guidelines are not foolproof
Mismatch in expectations and reality of cancer patients in clinical drug trials
Singaporean study finds two tests are better than one for cervical cancer