Intended for healthcare professionals


India’s new policy to protect research participants

BMJ 2013; 347 doi: (Published 31 July 2013) Cite this as: BMJ 2013;347:f4841
  1. Jeremy Sugarman, Harvey M Meyerhoff professor of bioethics and medicine1,
  2. Anant Bhan, senior research consultant 2,
  3. Robert Bollinger, professor of medicine3,
  4. Amita Gupta, associate professor of medicine3
  1. 1Johns Hopkins Berman Institute of Bioethics, Baltimore, MD 21205, USA
  2. 2Ethical, Social, and Cultural Programs for Global Health, Sandra Rotman Centre, University Health Network, Toronto, ON, Canada
  3. 3Center for Clinical Global Health Education, Johns Hopkins University, Baltimore, MD, USA
  1. jsugarman{at}

Urgent need to deal with its unintended consequences

India, the country with the largest disease burden in the world,1 is now a major international hub for clinical research. However, a recent policy that was meant to mitigate important ethical concerns may have profound and unintended consequences for public health and may threaten the viability of clinical research in India.

India has an impressive profile of research. Its clinical research market alone has been estimated to be worth nearly $500m (Rs30 240m; £326m; €376m) in revenues.2 India has also been an active partner in international collaborative global health research, including the recent development of a low cost rotavirus vaccine Rotavac.3

In 2011, the Clinical Trials Registry of India registered more than 1800 trials.4 These included studies of treatments for cancer, diabetes, and cardiovascular disease, as well as public health trials of optimal childhood vaccination and HIV treatment. In addition, India is the world’s largest producer of generic drugs—$10bn worth—and the main supplier of antiretrovirals to donor supported HIV treatment programmes in developing countries.5 6 Furthermore, the country supplies nearly 80% of the global supply of DPT (diphtheria, pertussis, and tetanus) and BCG vaccines and 90% of the measles vaccine.7

Several factors have contributed to India’s global leadership in research and the production of generic drugs. Most important is the presence of a cadre of well trained multilingual professionals with relevant expertise in research. Research in India is also less expensive than in many other countries; and India has a large patient population with a variety of communicable and non-communicable diseases.8 9

Despite these strengths, important ethical concerns have been raised about some of this research. Such concerns relate to allegations of exploitative enrolment of vulnerable (for example, impoverished or illiterate) participants, weak oversight structures, and lack of consistent guarantees for medical care and compensation of participants who experience research related injury. According to one report that cites an affidavit prepared for the Supreme Court, 2644 deaths occurred in research between 2005 and 2012, with 80 causally linked to the research itself.10

Responding to these concerns, earlier this year India passed a new policy, known as the “Drugs and Cosmetics (First Amendment) Rules 2013,” aimed at protecting research participants.11 The policy’s central features include the provision of compensation for research injuries and the required registration of ethics review committees. The new policy has many laudable aspects.12 For example, providing compensation for research injury is consistent with prominent international guidelines,13 and registration of ethics committees promises to enhance research integrity through promoting responsible review. As of 26 July 2013, about 500 ethics committees have been approved for registration.14 In addition, there will be more transparency regarding clinical trials, and requirements for at least annual trial inspections have been announced.15

Unfortunately, despite these important goals and promising provisions, the policy has some worrisome aspects that have profound implications for multiple stakeholders and will make implementation difficult. Firstly, it is unclear how injuries that require compensation will be deemed directly attributable to participation in a clinical trial.

Secondly, attributing specific conditions such as “failure of investigational product to provide intended therapeutic benefit,” “use of placebo in a placebo controlled trial,” and “adverse effects due to concomitant medication, excluding standard care” to research injury is problematic (box).16 Clinical trials are mainly conducted to see whether the investigational product reaches its intended therapeutic benefit. Failure to do so should not be deemed a clinical trial injury and grounds for compensation. Furthermore, if a trial includes placebo controls, causality of harm is assumed in the new policy, but placebos are not necessarily harmful. Indeed the use of a placebo is often the only way of truly assessing whether the agent under study is associated with undue risk or significant benefit.

Conditions attributable to clinical trial injury or death in the Drugs and Cosmetics Act (First Amendment) Rules, 2013

  • Adverse effect of investigational product

  • Violation of the approved protocol; scientific misconduct or negligence by the sponsor or the sponsor’s representative or the investigator

  • Failure of investigational product to provide intended therapeutic effect

  • Use of placebo in a placebo controlled trial

  • Adverse effects due to concomitant drug, excluding standard care, used as part of approved protocol

  • Injury to a child in utero because of the parent’s participation in a clinical trial

  • Any clinical trial procedures involved in the study

Thirdly, the policy requires that ethics review committees and the licensing authorities help determine compensation for research injuries, but it is unclear whether they have relevant skills and resources to make such determinations.

The recent policy changes have led to a reported drastic fall in the number of clinical trial applications and approvals in India17—some estimate a $150-200m loss this year.18 This is especially worrying because this could ultimately reduce the availability of registered drugs and other health related products. The Indian regulatory authority usually insists on local efficacy data in India before providing marketing clearance to new products, and such data are also often a prerequisite for decisions about adopting such products (such as new vaccines).

To make matters worse, the policy also has some unintended consequences for public health and health related research. Although comprehensive information from multiple potential research sponsors is unavailable, as a result of the policy at least 35 collaborative research projects funded by the US National Institutes of Health have been suspended since March 2013.19 In general, these projects were not aimed at new product development, but rather at investigating large scale public health problems relevant to India. Halting these trials could ultimately have profound effects on public health. Also, funders might exclude India from international collaborative global health research because global clinical trials are competitive.

A drop in research activity might also reduce India’s research capacity. Moreover, global research efforts will suffer as a result of limited participation of Indian clinical research experts. The relevance, impact, and quality of global health research have been greatly strengthened by engagement of Indian scientists and participation of Indian research volunteers. Advances in health research need India’s leadership and participation.

Although efforts to provide robust protections to research participants and to enhance the quality and integrity of research should be applauded, some aspects of this policy are worrying. Promulgating overarching regulations that are not sensitive to science can ultimately undermine public health and harm those whom the regulations were intended to protect.

Fortunately, as part of the repercussions of an ongoing case in the Supreme Court, and based on recommendations from an advisory committee,20 the Indian Parliament and regulatory authorities have an opportunity to deal with these concerns as they continue to overhaul India’s clinical trials mechanisms.21 In doing so, it is essential that the unintended consequences of the new policy are dealt with effectively but rapidly to help ensure that India remains an active partner and leader in global health efforts.


Cite this as: BMJ 2013;347:f4841


  • Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: All of the authors receive funding from the US National Institutes of Health. RB and AG conduct collaborative research in India that has been affected by the policy described in this article. JS serves on Merck KGgA’s bioethics advisory panel and Quintile’s comprehension of informed consent advisory board. AB works as a research consultant with a programme that receives funding from the Gates Foundation. These entities had no role in the conception, design, or review of the article.

  • Provenance and peer review: Not commissioned; not externally peer reviewed.


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