Clinical trials conjure up different realities to different stakeholders. To a patient, it could mean life, death or disability. His doctor/investigator sees a trial as his attempt to give his patient the best treatment as well as contribute to medical research. The company whose drug is on trial also has its corporate reputation on line, not to mention its revenues. The media and the lay public have their own take and it is these conflicting perspectives that deepen the divide between the various players.
But the regulator probably bears the heaviest burden, because he has to protect as well as punish all of these stakeholders. Protecting the rights of patients by punishing errant doctors and pharmaceutical companies has to be balanced with the long-term objective of making the best medicines available to Indian patients, at affordable prices. This cannot be met without creating a viable ecosystem for corporates to be profitable.
This balancing act was very much in evidence at this year’s India Pharma Summit. (See report on page 18). In a session moderated by RK Jain, Additional Secretary & Director General (CGHS), Ministry of Health and Family Welfare, he stressed that all the measures taken so far were to bring transparency, predictability and reasonability into the clinical trial process; while ensuring patient safety. “We are not against clinical trials but want it to happen in a regulated regime,” he said.
For his part, Dr G N Singh, Drug Controller General (India) (DCGI) too stressed that their prime commitment is to patient safety and indicated a willingness to discuss the concerns of industry.
What industry wants …
The day’s proceedings were a free and frank exchange of views industry representatives highlighted their concern areas and regulators replied with clarifications of the rationale behind each notification.
For instance, Dr Urmila Thatte, Head, Department of Pharmacology, KEM Hospital, Mumbai expressed her concerns over the mandatory registration of ethics committees (ECs).
Firstly, there was a huge skew in the numbers of registered ECs across states, she pointed out, with Maharashtra at the highest (167), followed by Pune (46) but with large states like Bihar having just three registered ECs. Madhya Pradesh has 16 medical colleges but only six of them have registered ECs. Many independent ethics committees (IECs) ‘vanished’ after the ruling and she wondered about the fate of patients on trials under these IECs. “We must not ‘orphan’ these patients,” she said.
Her point was that registration of ECs was a first step but it still didn’t reveal the level of standards, etc. Accreditation of ECs is the next logical step and is needed, but Dr Thatte cautioned that we needed to think this through carefully and ask if we have the capability and manpower required for this step. She also related the mixed reactions to the need for AV recording of the informed consent process, highlighting how it would be difficult to get the assent of children or terminally ill patients to this step.
Industry sees a clear dip in the number of trials approved in India vis a vis in other Asian countries (see figure: Impact On India’s Share Of Clinical Research in Asia).
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Impact On India’s Share Of Clinical Research in Asia
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| Source : US National Institutes of Health, ClinicalTrials.gov Database accessed 11 Feb 2014 Source: Assansa |
The main grouse of the industry seems to be approval timelines. Dr Surinder Kher, Chair of the FICCI taskforce on clinical research and also CEO, Manipal Acunova, lamented the lack of predictability of the process as well as of the outcome. He pointed out that there is no scientific basis to some of the regulations (like for example there is no need for a post marketing surveillance study to go for approval to the experts committees set up, particularly when it was an observational study of a cough medication in use for many years in the country).
Industry observers opint out that the delays also impact doctors who might have put in place infrastructure for conducting trials but then have to cool their heels waiting for the trials to be approved.
… and the regulator’s rationale
The regulators for their part justified each notification released. Jain said that mandatory registration of ethics committees (ECs) was required to bring in some discipline so that only registered ECs could function. So also the restraint on the number of trials each principal investigator (PIs) could take on was aimed at ensuring that there is no burden on individual PIs and patients are not short-changed. The regulators also hoped that this move would encourage more clinicians to turn investigators.
In fact the regulators have addressed some concerns, with Jain clarifying the notification on EC registration applied to future trials and were not retrospective in nature. He also indicated that issues pertaining to placebo arm related injuries would shortly be addressed.
Regulators have tried to meet industry half way but this is a work in progress. For instance, Jain pointed out that the gaps in the medical/scientific expertise within the administration has been met by the therapy-wise expert committees set up but on this count too, industry was not happy with their functioning.
The stipulation that trial sites have to be spread across the country and also include government institutions was irrational because it neglected to weigh the actual quality of such sites.
Resurrecting clinical research in India
Industry’s angst was perhaps best captured by Dr Aamir Sheikh, Founder and Healthcare Consultant, Assansa when he said that clinical research in the country was in dire need of nothing short of an ‘Operation Phoenix’, to be resurrected from the ashes.
He proposed a streamlining of the regulatory landscape and a three-step approach. Firstly, crafting a national vision for clinical research, to be followed by creating capacity at both and individual and institution level, and lastly, cultivating a sound regulatory mindset.
When a regulator objected to the term “promotion of clinical research/trials” saying that thinking of it as an industry led to exploitation of patients, a voice from the audience suggested that the terms were not a contradiction to patient safety, because only if we have patient safety can we have a thriving clinical trials industry. This opposing stance best illustrates the long journey ahead.
The March 20 Summit was just one of many formal and informal meetings between regulators and industry; both individual and at an association level that are part of the consultation process. With the general elections around the corner, regulators were mindful of the model code of conduct and refrained from giving details of policies being crafted.
But there is a sense of cautious optimism, that regulators are listening and willing to act and even backtrack on key issues. Or is this merely an illusion? Only time will tell.