Clinical research in India has gone through Dickensian times in the past two years. Alishan Naqvee, Partner and Abhijeet Das, Associate, LexCounsel opine that if 2015 sees the resolution of the Swasthya Adhikar Manch PIL, it could lend some stability to the clinical research scenario in the country as well as allow regulators to address other areas of oversight in the modified regulations
The past two years have been difficult for clinical research in India, akin to the grim dreams out of the pages of Dickens. With introduction of regulations with no parallels in the world, the stakeholders have been left baffled in their attempts to come to terms with this new regime. The genesis of the transformation can be traced to the sub judice (since early 2012) proceedings of ‘Swasthya Adhikar Manch, Indore & Anr. vs. Union of India & Ors.’ (Swasthya Adhikar Manch Case).
In the aforementioned proceedings the petitioners (including Swasthya Adhikar Manch, Indore) have alleged glaring and shocking irregularities in the whole process and administration of clinical research in India. While going into the details of the petition would not be relevant to the present discussion, it would not be out of place to mention here that some of the inferences and arguments put forth therein represent a highly myopic assessment of the whole clinical research process in India. The ensuing judicial scrutiny has resulted in a backlash that the life sciences and healthcare sector have been reeling under since the early 2013. It is pertinent to mention here that, the industry is not an absolute victim, as it waited, watched and did nothing, till disaster actually struck.
After drawing some criticism from the Apex Court along with adverse media coverage, the Government went into overdrive in January 2013, notifying amendments to the existing provisions in the Drugs and Cosmetics Rules, 1945 (Rules) in addition to certain orders applicable to the clinical research stakeholders. Some of the key revisions/additions to the legal framework vis-à-vis clinical research, since then are:
I) In case of injury (or death, as the case may be) to the patients in a clinical research, the sponsor of the clinical research, i.e., the pharmaceutical company or the institution or the academician (who initiates the clinical research):
( a) would be liable to bear the expenses for the medical management for the injury, for as long as required, irrespective of the cause thereof; and
(b)would be is liable to pay financial compensation (over and above the expenses incurred for medical management) for an injury (or death, as the case may be) related to the clinical research (related injury/death).
II) An injury or death of a patient is considered a related injury/death, if the same is resultant of:
(a) adverse effect of the drug/devise under research;
(b)violation of the approved protocol, scientific misconduct or negligence by the sponsor or his representative or the doctor (investigator);
(c) failure of the drug/devise under research to have the intended therapeutic effect;
(d) use of placebo in a placebo-controlled clinical research;
(e) adverse effects due to concomitant medication excluding standard care, necessitated as part of approved protocol;
(f) injury to a child in-utero because of participation of parent in clinical research; and
(g) any procedures involved in the clinical research.
III) The ‘provisionally final’ compensation formula was introduced providing for compensations for related injury/death, ranging from Rs 4,00,000 (Rs four lakh only) to Rs 73,60,000 (Rs seventy Three Lakh and Sixty Thousand only). Recently, on December 15, 2014, the CDSCO has notified the final compensation formula to determine the quantum of compensation in the cases of related Injury (other than deaths).
IV) Mandatory registration along with provisions for suspension or cancellation, of the ethics committees which accord approvals to the clinical research along with the layout for its composition.
V) Mandatory audio-video recording of the informed consent process in clinical research.
VI) The number of clinical research that a doctor (as investigator) can participate in, is limited to three.
The lacunae in some of these stipulations mandated under the new regime are apparent to everyone even remotely associated with clinical research in India. For instance, medical management for research patients is a noble idea, but the same may incentivise the patient to enrol in the study, thus making the enrolment unethical. Further, in spite of the fact that clinical research is undertaken to study the effectiveness of a particular drug, under the regulations if the same fails to have the desired effect, resulting in any injury/death to the patient; the sponsor would be liable to pay compensation. The aforesaid oversight by the regulators, were also compounded by the compensation formula, which has burdened the sponsor with liability in case of injury/death in the said circumstances, over and above medical management (which is irrespective of the injury being related or unrelated to the clinical research).
The aforesaid revisions have left clinical researchers in a frenzy to adapt and translate the regulatory requirements into the day to day conduct of clinical research in India. While the stakeholders were clearly hampered under the ambiguity and uncertainty of the new regulatory regime, the Central Drugs Standard Control Organization (CDSCO) was also quick to close its doors to the countless questions raised by the stakeholders. In terms of an office order, the CDSCO has mandated all queries of the stakeholders to come through the state licensing authority and not directly.
Separately, in August 2013, the Drugs and Cosmetics (Amendment) Bill, 2013 (Bill) was introduced in the Rajya Sabha, which envisaged an overhaul of the complete regulatory framework concerning clinical research. The Bill provided for the establishment of a Central Drugs Authority to replace the CDSCO, which would be in charge of registering all clinical research in India. Further, the Bill brought under its domain devices and cosmetics, which are to a large extent not included in the extant framework for clinical research, and amongst other things laid out the framework for the constitution and powers of ethics committees. One of the key features (and fear) of the Bill was the introduction of criminal/penal punishments (sometime going upto 10 years of imprisonment) along with minimum monetary penalties for most offences stipulated therein. It is pertinent to note that the Bill is presently ‘pending’ in the Rajya Sabha.
In April 2014, the government notified the Drugs and Cosmetics (Third Amendment) Draft Rules, 2014 (Draft Rules), which had signs of offering a respite to this shackled sphere. Amongst other things the Draft Rules provided for:
- Free medical management to be provided to the patient for as long as required or till such time it is established that the injury is not related to the clinical research, whichever is earlier.
- ) In case of related injury/death arising out of, failure of the drug/device under research to have the intended therapeutic effect or, a placebo controlled trial; the obligation of the sponsor to compensate would be limited to cases where the standard care, though available, was not to be provided to the patient.
- The Draft Rules also relaxed certain reporting time frames introduced under this new regime, which where proving difficult to comply with.
Since April, the sector has been waiting with bated breath for the aforementioned revisions to take effect. However, the same has not been forthcoming. This would not have been an absolute solution, but certainly would have been a welcome relief from the continuous battering that clinical research participants in India have been under.
In the last couple of years, things have taken a turn for the worse vis-à-vis clinical research in India. The uncertainty surrounding the Swasthya Adhikar Manch Case and the subsequent scrutiny that the regulators have come under, has resulted in an onslaught of regulations being dealt on the life sciences and healthcare sector, specifically in the field of clinical research. While, regulation is always welcome and over regulation is acceptable (amid protest), the one thing that is a death trap to any sector, is uncertainty and ambiguity in regulations. This is the case applicable to clinical research at the moment, and unless there’s some stability on this front, India would most certainly end up denying its citizens advanced healthcare, which it so obviously requires.
At the present time, we do not and cannot know what the year 2015 holds for clinical research in India. That being said, the ending of the proceedings in the Swasthya Adhikar Manch Case would most certainly be welcomed by the stakeholders. This might allow the regulators to turn their attention on some of the aforementioned oversights in the extant regulations. If addressed adequately, the modified regulations would go a long way in getting clinical research in the country back on its feet.
(Disclosure: Alishan Naqvee has represented ISCR in the Supreme Court in the Swasthya Adhikar Manch Case )