At the heart of the clinical trial issue is the belief that all clinical trials are necessary and they somehow add to the GDP and pharma research capabilities of India. We will assume that to be true for the time being although the evidence in this regard is not clear.

We need tighter regulations on clinical trials simply because most trial participants are vulnerable — their rights are not clear especially in the matter of compensation, even as the clauses already passed are being diluted. The laws regulating clinical trials seem to allow the trial sponsors to literally get away with the death of patients. According to the Ministry of Health and Family Welfare, in clinical trials in India during 2005-2012, there were 2,868 deaths of participants, out of which only 89 were accepted as trial-related, and 82 were compensated.

The trial-related deaths seem to be underestimates, given the methodology adopted by the Ministry.

Sponsor’s responsibilities

There is no simple way (even with the recent modifications of compensation rules) by which a trial participant or his/her family can question the compensation award. The trial participant has no agency. Till recently it was not even clear, until mandated by law, that the sponsor of the trial had an obligation to provide and manage the health problems of the participants — whether related or not to the drug under investigation. Even at present, there is no punishment to the trial investigators if informed consent was not taken according to the rule book.

Trials are not easily subject to RTI, even in areas like disclosing clinical trial protocols where no patient confidentiality is involved.

In addition, the government is in no position to stop needless bioavailability/bioequivalence (BA/BE) studies demanded by importers on drugs already tested and approved in India.

Does not an industry that is so fatality-prone need tighter regulation? The phrase, “India is an attractive destination for clinical trials”, cannot be understood to mean ‘anything goes’. Or that human life is cheap in India and that evidence can be suppressed by saying it is not trial-related, leaving trial participants or their survivors high and dry.

India is an attractive destination for trial sponsors but a nightmare for poor and vulnerable trial participants. The government is unable to decide between valuing for human life and kowtowing to the demands of the clinical trial industry and their lobbyists.

Concurrent Trial dangers

There are broadly three categories of drug-related clinical trials carried out in India. In media discussions they are conflated with each other.

Category A: The first of these, concerning the Supreme Court, is the need for regulation on concurrent or simultaneous phase 2 and phase 3 trials — on substances called new chemical entities/new molecular entities (NCEs/NMEs) discovered abroad . (Phase 1 trials are generally not permitted for entities discovered abroad.) Clinical trial laws were amended in 2005 to “open up” India to international clinical trial research and allow concurrent phase 2 and 3 trials. Before 2005, phase 2 and 3 trials were allowed with a phase lag — that is after their gross safety aspects were somewhat known abroad.

NCEs ought not to be allowed to be tested at the same time as in the West because their serious adverse effects are not even known in the originating countries. Especially for trials within India on NCEs originating abroad, we need sufficient emergency and routine healthcare services, in case the trial participant is seriously affected. Such a back-up is non-existent in most rural areas where many of these trials take place.

The alleged deaths in India following trials on a drug called Rivoraxaban (a blood thinner) in India would not have occurred if the trials had been planned after a mandated lag.

In fact, with data about the deaths abroad (mostly in the US) coming in, the trial would not have been approved in India, had there been a mandated phase lag in conducting phase 2/phase 3 trials.

India has nothing to gain from these concurrent trials — it mostly helps some procedural requirements of Western pharma companies. We will not get the drugs at a concessional price when marketed much later in India.

These trials have been mostly carried out, among others, by middlemen and contract research organisations (CROs) on behalf of Western pharma companies. The beneficiaries in India are the few researchers in academia and CROs.

It does not add to the research capabilities of India.If you don’t let the research on these NCEs be done here, it does not mean they will not be marketed in India or approved abroad. Much of the data collection as part of the drug trial has in any case, to be done in the West.

All the 89 trial-related deaths mentioned above were due to NCEs/NMEs. Notwithstanding these disturbing figures, the Drugs Controller General of India has approved 162 out of a total of 259 applications for trials relating to NCEs between July 3 and August 31 this year.

There is a good case for going back to at least a lag in the conduct of phase 2 and 3 trials on NCEs discovered abroad — if not a complete ban on NCE-related trials with exceptions for emergency conditions like swine flu epidemic and so on.

Accounting for diversity

Category B: All drugs approved in well-regulated countries (that is, successful NCEs originating abroad that have gone on to be approved as drugs with acceptable safety and efficacy) need phase 3 trials in India, and ideally bridging studies for ethnic diversity in India, before being approved for manufacture and/or marketing in India.

The 59th Parliamentary Standing Committee Report is only about these kinds of phase 3 trials — drugs discovered abroad that were approved in India without properly conducted phase 3 trials/pre-approval studies and bridging studies.

Category C: If an NCE/NME is discovered within India, the law does not stop anybody from doing phase 1, 2 and 3 trials in India. Neither do our laws stop any other kind of medical research on various aspects of already approved drugs.

To seek restrictions on Category A trials does not mean we are seeking a ban on Category B and C clinical trials and/or medical research in general. This is disinformation. It looks like the commerce-oriented clinical trial lobby would like us to return to a time of no regulation of clinical trials and no questions asked about human right violations. That is unacceptable.

( The author is with LOCOST, Vadodara and All-India Drug Action Network.)

Related Topics
comment COMMENT NOW