In light of the controversy surrounding the conduct of clinical trials in India, the government appointed an expert committee chaired by Prof. Ranjit Roy Chaudhury (hereafter the RRC Report) to formulate policy and guidelines for approval of new drugs, clinical trials and banning of drugs. The report of the committee has been in the public domain for some three months now.

Earlier this month, the Government, in an act of unusual efficiency, came out with a note on actions taken on the recommendations – without formally taking feedback from the stakeholders.

Be that as it may, the report has made some 25 major recommendations. (The authors are realistic on their own recommendations when they remark that not all will be implemented.)

One major recommendation with which this writer agrees unreservedly, however, is the removal of potentially hazardous drugs, or drugs of doubtful efficacy.

However the committee, which had a legal expert, has not suggested how to deal with the right of the manufacturers to get a stay in court and thereby filibuster the process. Is our legal process an obstacle to the weeding out of irrational, harmful and useless drugs, even if in the public interest? For a critique on the regulatory issues in clinical trials, refer to an earlier article (“When clinical trials become dangerous”, Business Line , October 15, 2013).

The committee probably wanted to make things less bureaucratic for those intending to do clinical trials and MNCs wanting to introduce the latest drugs in the Indian market.

Thus in total negation of the spirit of the comments in the 59th Standing Committee Parliamentary Report, the RRC Report recommends that Phase 3 trials should be waived for drugs/biologicals already in the market in well-regulated countries for four years and with good safety record “subject to strict PMS (post-marketing surveillance) for four to six years or after bridging studies, on a case-by-case basis”.

Not clear

The problem is that adverse effects manifest themselves only after 9-10 years even in countries with good vigilance systems. Hence, this recommendation needs to be rejected on precautionary considerations.

It also does not say who is to do the PMS. If done by the manufacturers, they will give themselves a clean chit. It is also not clear what the phrase “or after bridging studies” means. Does it mean if bridging studies — checking the suitability of the drug on ethnically diverse populations — are done, PMS is not necessary?

India’s drug regulation has a poor record of insisting on strict PMS. Besides, PMS and bridging studies are not interchangeable.

Moreover, getting drug manufacturers to do PMS is beset with conflict of interest. The report’s summary recommendations have omitted the phrase “subject to strict PMS for four to six years or after bridging studies, on a case-by-case basis”.

The default position of the committee seems to be that more clinical trials are good for India. So, it has apparently not bothered to disaggregate the varying impact of different kinds of clinical trials — specifically the number of deaths related to new chemical entities (NCEs) that have occurred post-2005 when the clinical trial laws were amended.

Quite dangerous

We certainly know the 89 deaths that have been officially accepted as clinical trial-related out of the over 2,600 NCE-relateddeaths (Ministry of Health and Family Welfare statistics).

Nevertheless, there is no sign of worry in the report about trials of NCEs originating abroad. Concomitant Phase 2 and 3 trials of NCEs have been endorsed, instead of requiring them to be conducted with at least a mandatory phase lag so that the effects in one region are known in advance.

The report asks whether there should be a limit on the number of trials a principal investigator (PI) should be allowed to coordinate and then leaves it to the PI and institutional ethics committee (IEC). It says, “leaders in the field may be able to manage several trials simultaneously whereas the same may not be true of PIs who are not so proficient”.

This is a bit hands-off, if not dangerous — a limit of five clinical trials should be put on any PI — because many so-called proficient leaders may be actually trying to balance too many things at one time, as well as teaching and looking after patients. The question also needs to be asked as to how many ethics committees a person can serve on concurrently.

Other anomalies

At another place the report says: “Independent ethics committees should not be allowed to function, as these have not been recognised or accredited by any national agency and their past functioning has been found to be erratic and controversial.” But this statement, like many others in the report, does not turn into a recommendation. It does not go into the nitty-gritty of the issue.

Independent ethics committees, those who offer their services for clinical trials on a commercial basis, have been recognised by the Drugs Controller General of India. Also, it is not clear whether a person should be allowed to serve on several independent ethics committees in the classical Indian spirit of mutual accommodation. With good models of ethics committee audit available, the report could have applied itself more thoroughly on the subject.

The report has tried to minimise the need for bioavailability and bioequivalence (BA/BE) studies. These are studies to measure the level and acceptance of the drug in the blood. It has rightly recommended that such studies are not necessary for drugs which pass through membranes and dissolve easily.

But the committee has nothing to say on whether BA/BE studies should be treated on par with clinical trials, as some of the BA/BE studies would entail interaction with the human body. Why should the same standards, as for clinical trials, not be applied for causality and compensation and registration of centres doing BA/BE studies?.

It says in the summary recommendations that BA/BE studies, once conducted for a generic drug in India, should not be repeated for export purposes only. But in the main text it says if the importer does not agree, “they should be convinced, based on scientific data, of the futility of such a study for every trade name”. This kind of inconsistency hardly helps to enlighten the reader.

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

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