In recent months, the quest for a safer, more transparent clinical trials regime has found new momentum. Fourteen notifications in July 2014, governing various aspects pertaining to a clinical trial — ranging from placebo-controlled trials to compensation awards — have been notified. Further, the Central Drugs Standard Control Organization (CDSCO) has proposed a forward-looking IT-enabled information system that will ensure transparency and protect the interests of trial subjects.
These developments are important steps for the clinical trials regime in India to satisfy the three principles laid down by the Supreme Court for approving trials — assessment of risk versus benefit to patients, need for innovation vis-à-vis existing therapeutic option and the unmet medical needs in the country. But for satisfying these standards, much more remains to be done. The entire regulatory framework pertaining to clinical trials needs to be overhauled and a clear, coherent and succinct set of stand-alone rules needs to be introduced for this purpose. This will not only ensure adherence to the principles laid down by the Supreme Court but also give impetus to the clinical trials industry in India, currently languishing due to an uncertain regulatory environment.
Accreditation and ethicsThere are three key changes that are essential if the clinical trials regime in India is to be put on a firm foundation — instituting a structured accreditation process accrediting investigators, trial sites and ethics committees, making ethics committees function effectively and ensuring diligent adherence to guidelines concerning informed consent from trial subjects. Each of these three aspects has been studied closely by the committee headed by one of us, the Ranjit Roy Chaudhury Committee, with detailed recommendations provided.
Accreditation must become the centrepiece of a new clinical trials regime founded on the principle of patient safety. Accreditation ensures adherence to certain quality standards thereby instilling confidence not only in patients who will be trial subjects but equally in the industry, which is responsible for conducting the trials. Thus, principal investigators of trials should be accredited depending on their qualifications, experience and training; trial sites should be accredited on the basis of infrastructure, personnel and systems; finally, institute ethics committees must be accredited keeping in mind the experience of their members and the standard operating processes for review which are used. Guidelines in this regard have been prepared recently by an expert committee; these must be implemented post-haste. If this is done, India would be the first country anywhere in the world to institute such a structured process of accreditation.
Conflicts of interest and consentAccreditation of ethics committees is an especially central element towards making such committees effective custodians of the safety and probity of all clinical trials. Several cases of casualties in clinical trials have emerged in the past few years, where compliance with standard operating processes were shoddy or such processes themselves were absent. In an Indian Council of Medical Research (ICMR) publication, the independence of ethics committees and conflict of interest questions were highlighted. To correct this, it is not only essential that ethics committees are accredited but also develop standard operating procedures that are capable of effective implementation. To follow such procedures, members of ethics committees need to undergo high-quality mandatory training. This requires a combination of men and women of wisdom and experience and training protocols that are succinct and geared towards ensuring safe and effective trials where all norms are strictly followed.
A key positive spin-off of accredited ethics committees would be to prevent conflicts of interest. The Ranjit Roy Chaudhury Expert Committee Report pointed out gross malpractices and unscrupulous decisions in clinical trials caused owing to ethics committee members having an interest in the trial itself. To offset this, a key facet of accreditation would be a strict adherence to finding independent persons to serve on ethics committees. This can be achieved by a combination of randomised allocation of experts to particular ethics committees together with a supplementary check by the accrediting body. A hybrid process, part-automatic with a supplementary human element, would not only ensure independence of the ethics committee in fact, but also create a positive perception of such independence in the minds of trial subjects.
Such a positive perception of the independence of ethics committees, it is believed, would become a key facet of securing informed consent of trial subjects. The need for informed consent was a key norm that was recently found by the United States Office for Human Research Protections (OHRP) to be flouted in a cervical cancer study funded by the U.S. National Cancer Institute and the Bill & Melinda Gates Foundation. Till April 2014, 254 women in unscreened control groups in these trials have died. The OHRP determined that insufficient information was provided in order for these and other women to give informed consent to participate in the trial.
Towards a new orderCulpability in this matter is still an open question that might require judicial intervention. However, at this stage, it is clear that the episode demonstrates the lack of effective protocols to ensure that informed consent is truly on the basis of relevant information and the lack of clear methods to ascertain the taking of such consent. This has been partially offset by CDSCO which issued draft guidelines earlier this year on audio-visual recording of informed consent process in clinical trial. This mandates audio-visual recording and safe storage of the taking of informed consent from trial subjects. This is a welcome move. However it is imperative to keep in mind the privacy of patients who might not wish to be recorded. Thus, it is recommended that such recording should be mandatory subject only to waiver by the trial patient or the ethics committee, keeping in mind the equally significant principle of patient privacy.
Not only is the substance of the changes mentioned significant, but equally the form it takes. Best practices worldwide demonstrate that having a succinct, stand-alone set of rules governing clinical trials promotes transparency and increases certainty. Currently, the legal architecture governing clinical trials is complex with several facets governed by the Drugs and Cosmetics Rules, 1945, a slew of notifications thereunder, and some facets regulated by the proposed Drugs and Cosmetics (Amendment) Bill, 2013, pending in the Rajya Sabha.
It is essential that the recommended reforms together with any other changes proposed by CDSCO are brought under a consolidated umbrella of rules governing clinical trials. This will give the clinical trials industry the necessary certainty to undertake trials in India with confidence. The benefits for India — in terms of development of new drugs, employment generation in the clinical trials industry and ensuring a safe environment for its citizens desirous of participating in clinical trials — would be tremendous. Most crucially, it would demonstrate the seriousness that the government attaches to effective public health systems and scientific progress, two goals of a well-functioning clinical trials regime that must also become the pillars on which modern India is built.
(Ranjit Roy Chaudhury was Chairman of the Expert Committee to formulate policy, Guidelines, SOPs for approval of new drugs and clinical trials and banning of drugs. Arghya Sengupta is Research Director, Vidhi Centre for Legal Policy.)
