Pharmaceutical companies conducting clinical trials in India are increasingly taking advantage of the lacunae in the law and regulatory framework, which is resulting in a spurt in cases of “serious adverse events” (SAEs) and deaths of clinical subjects (participants on whom research/clinical trial is done). An RTI response received by NGO Swasthya Adhikar Manch, a copy of which is with The Sunday Guardian, reveals that a total of 24,117 cases of deaths and SAEs due to clinical trials occurred between January 2005 and September 2016. The RTI also revealed that out of the 4,534 deaths that have been reported, only 160 cases have received compensations from the pharmaceutical companies.
According to the RTI response, 341 cases of SAEs resulting in death were reported in 2015, out of which only four cases were compensated. In 2014 and 2013, respectively, 443 and 590 cases of SAEs resulting in death were reported, out of which 21 and 45 cases were compensated. In 2016, 252 cases of SAEs resulting in death were reported; the number of cases that has been compensated is still under examination. Other than the numbers, the Drugs Controller General of India (DCGI), in its RTI reply, has not provided any information on the compensations provided.
Researchers, lawyers and health activists that The Sunday Guardian spoke to, pointed to a lax clinical trial policy, irregularities in informed consent of the clinical subjects, and a nexus between pharmaceutical companies and doctors for financial gains as the major reasons behind the rise in unregulated trial practices.
LEGAL AND ETHICAL ISSUES
In 2009, over 24,000 tribal girls were enrolled from Gujarat and Andhra Pradesh by the Union Ministry of Health and Family Welfare, among others, in a Human Papilloma Virus (HPV) vaccination trial, for the treatment of cervical cancer. Several months into the trial, seven girls were reported to be dead. When investigated, it was found that the parents did not understand fully what they were signing up for.
Experts say that the recruitment of the potential participants is done in a questionable manner. “Most of the clinical subjects are uneducated and come from an economically poor background. Earlier, between 2005 and 2012, the drug companies would simply take the thumb prints of the patients on an information sheet, without elaborating them on the process. The Drug and Cosmetic Act makes it mandatory for these companies to get the patients a comprehensive medical insurance. But that, too, is not done,” Amulya Nidhi, chairman of Swasthya Adhikar Manch, told The Sunday Guardian.
Dr Anant Bhan, researcher in bioethics and public health, said that the practice of financial inducement leads to more voluntary enrolment of clinical subjects, who, more often than not, are not aware of what they are signing up for. This makes them oblivious to the possibility of the trial having serious biological effects. “In some cases, the due process is not followed. For example, there is no clarity on who is authorised to give consent in case a trial is to be conducted on a minor. Also, a lot of them willingly participate in these trials since they are monetarily compensated. It is the money they are interested in, rather than the science behind the subject,” said Bhan, adding that the patients do not even know that they have the right to withdraw from the trials at any time, without any consequence.
Moreover, as Supreme Court advocate Vijay Pal Dalmia told this newspaper, the Drugs and Cosmetics Act 1940 does not specifically provide for any punishment in case of fudged or uninformed clinical trials.
Experts also maintained that there was a serious lack of transparency in the availability of data shared by the Institutional Ethics Committee—a body that ensures that clinical trial is conducted, data is generated, documented and reported in compliance with the CDSCO guidelines. Amulya Nidhi claimed that the Ethics Committee had reported 22 deaths due to clinical trials in 2010, while he and his organisation, through government affidavits and RTIs, had proved that 610 deaths had happened in 2010 alone.
Bhan, on the other hand, pointed out that trials that happened outside the ambit of the CDSCO (Central Drug Authority for discharging functions assigned to the Central Government under the Drugs and Cosmetics Act), are either not reported, or are reported to the Ethics Committee at the local level. The availability of complete and comprehensive data, thereby, remains dubious.
Experts also noted that collusion is rampant between drug companies and doctors. The Indian Parliamentary Committee, in its 59th report on family and healthcare, had established “collusive nexus between drug manufacturers, some functionaries of the CDSCO and some medical experts”.
“The regulatory authority has refused to give answers when asked about the number of trials being conducted, and the details about the investigating companies are mostly confidential,” Nidhi said.
LACK OF COMPENSATION
The Drugs and Cosmetics Act provides compensation in case of injury or un-informed clinical trials. However, according to the Supreme Court advocate, Vijay Dalmia, compensation is given only when a link between the injury/death, and the medicine in question, is established. The process of establishing the link is very complex, and hence, cumbersome, which is why there are either delays, or the compensation is never given at all.
The compensation clause was added only in 2013, and according to Nidhi, the CDSCO has refused to take into account any SAEs or deaths that happened between 2005 and 2013 for compensation, because as no such law existed at the time. “We are demanding that the most important details of all the clinical trials be put on a list and be independently monitored. We are asking for transparency,” Nidhi added.
Anant Bhan, the researcher, added that while the compensation norms have been established and revised over time, the challenge remains in manoeuvring through the available data to establish the desired link. There is also no standard protocol for post-mortem mechanism to investigate the cause of death, Nidhi argued. While some companies allow a no-fault compensation—which is a certain sum of money offered irrespective of the occurrence of a serious event—the practice is not too common.
Over the past few years, however, the Drug and Cosmetics Act has seen several amendments. The Supreme Court, in 2013, ordered the government to make audio‐video recording of informed consent mandatory for companies intending to conduct clinical trials. It also mandates them to inform patients about the possible adverse health effects of the drug under trial. According to the new guidelines, a manufacturer, before requesting an individual to participate in clinical trial of a new drug, must inform the individual of any reasonably foreseeable risks or discomforts, as well as of the possible benefits.