Clinical trials, that hot-button subject hogging headlines up until a year ago, appears to have quietly slipped into the realm of business-as-usual. However, there are still some knotty issues to be resolved. Chief among them is the oversight of Ethics Committees (ECs) as was evident at a recent event I attended.
ECs – which are a mix of experts and lay persons – are the gatekeepers of ethics within their institutions. Just as a strong EC can blow the whistle on unethical behaviour, a weak or careless one might inadvertently abet it.
In 2013, for the first time, the Indian government ordered that all ECs be registered with it. A year later, it also called for their compulsory accreditation with an independent body. Until then, hundreds of clinical trials had been conducted under the supervision of ECs even as there was no real surveillance of the ECs themselves.
Since then, while a raft of them have registered with CDSCO, the office of the central drugs regulator (and are now seeking renewals), few have been inspected by it, let alone accredited. I spoke to K Bangarurajan, Deputy Drugs Controller General of India (West Zone) at a recent event on clinical trials in Mumbai that was co-hosted by the Indian Society for Clinical Research and K.E.M Hospital to mark International Clinical Trials Day. He confessed to an inability to take up inspections on the scale that he would’ve liked because of a manpower crunch. “The regulator also has to see to other areas like WHO GMP (manufacturing), blood bank inspections, compliance..” he told me. Maharashtra has a substantial number of ECs but hardly any had been inspected, he said. “We have requested for more staff.”
In parallel, EC accreditation has yet to start. In 2014, the government had mandated National Accreditation Board for Hospitals and Healthcare Providers (NABH) under the Quality Council of India (QCI) to draft standards. It had said that accreditation would be made mandatory. But participants in the event wondered about the status of this effort and whether it would see the light of day. “Is QCI’s involvement in limbo?” was one of the questions raised.
For clarity, I later contacted Bhupendra Kumar Rana, joint director, NABH in New Delhi. NABH had already submitted the final standards for accreditation to the Union Ministry of Health and Family Welfare a couple of months ago, he said. It had hired staff and trained outside experts and was ready and equipped to start the accreditation programme if the Ministry wanted it to, he added.
So the right question to ask is probably this : what’s holding up the Ministry’s green signal to NABH?
Even if accreditation does begin, it appears that it will be voluntary just like for hospitals, in spite of what the government had initially said. And if the experience of hospitals is anything to go by, it is going to be a slow process. India has around 1000 registered ECs a majority of which are inside institutions. The rest are independent.
Some experts say that accreditation should stay voluntary. “In general, accreditation the world over is believed to be a voluntary process,” said Urmila Thatte, head of the Department of Clinical Pharmacology at K.E.M. Hospital, at the same event. “It will be a humongous task for India (if made mandatory),” she said. Thatte advocated more aggressive inspections. “Even if you inspect 10 per cent of the ECs and put up the warning letters issued to them, others will be more careful,” she said.
The issues raised should not be dismissed. Not all ECs are made equal. While there are some who have set high standards for ethical review, there are also those that are known to be swayed by the heft of investigators who approach them for clinical research approvals. In some cases, ECs defer to a few influential or knowledgeable members among them, begging the question : are such decisions truly representative of the group? Not all have the necessary training to make judicious decisions in complex cases.
In parallel, they are being given more responsibilities, not less.
Earlier this year, the government freed academic clinical research from seeking its permission, choosing instead to vest this power with ECs. This means that clinical research that is purely academic in nature and has no commercial purpose does not need the regulator’s permission as long as the EC of the institution has approved it. The regulator, however, has to be kept informed of such research. By doing this, the government freed research that mostly involves comparing known drugs and therapies.
But some such as C S Pramesh, co-ordinator of the National Cancer Grid and key investigator in many oncology trials, object to this. “While 90 per cent of trials are to judge comparative effectiveness, there are some high-risk trials such as those for gene therapy,” he said. “These should be subject to the same treatment as ‘commercial’ trials,” he said. Thatte too asked if, in the absence of adequate training, institutional ECs were equipped to handle this additional responsibility. “The notification on academic research has opened Pandora’s Box,” she said.
For their part, at least some ECs are unhappy with the additional documentation that registration renewals have called for, such as a brief summary of every trial that an EC oversees. One EC member pointed out that the committee had 1400 trials under its supervision at any point of time and that this was proving to be an onerous task.
One has to ask : is the regulator making up for insufficient feet-on-the-ground with greater amounts of paperwork? If so, not the most encouraging sign. To be fair, the Indian government has made a strong push for reform of clinical research in the last few years with a raft of edicts aimed at improving subject safety and fair treatment.
But well begun is still only half done.
Pic sourced from Google Images