Foreign firms deny wrongdoing as Indian ministry points to trials 'deficiencies'
This article was originally published in Scrip
In its recent affidavit in an ongoing legal case concerning clinical trials, India's health ministry refers to certain past lapses of large companies including Pfizer, Sanofi and the contract services provider Quintiles in studies conducted at the Bhopal Memorial Hospital and Research Centre (BMHRC), although the firms involved strongly deny any wrongdoing.
The references, which open up some old wounds in the Indian trials segment, came even as the ministry's affidavit also outlined a string of measures now in place, including a court-directed two-layered supervision system, to ensure the "ethical and scientific conduct" of clinical studies in the country.
India now follows a three-tier review process for clinical trials, under which applications are evaluated by new drugs advisory committees (NDACs). The recommendations of the NDACs are then reviewed by a technical committee and finally cleared by an "apex committee" in accordance with a court order earlier this year.
The ministry's affidavit makes specific references to three inspections conducted by India's Central Drugs Standard Control Organization at the BMHRC, concerning studies involving telavancin (performed by Quintiles), tigecycline (done by Quintiles on behalf of Wyeth, now part of Pfizer) and fondaparinux (permission originally given to Organon India and later transferred to Sanofi).
In all cases, inspections - in 2010 concerning the telavancin study and in 2011 for tigecycline and fondaparinux separately - identified "deficiencies" such as non-payment of compensation to the trial subjects for participation and non-reporting of serious adverse events within prescribed timelines.
In the case of the tigecycline study, the principal investigator is said to have clarified that there was no delay and lapse in patient care or dealing with serious adverse events and that there was no causative relationship of these to the study drug.
In all cases, the principal investigators and the concerned organizations submitted their clarifications to the Drugs Controller General of India (DCGI) and were warned against repeating such deficiencies in future, the affidavit noted.
The ministry's affidavit is related to an ongoing legal case concerning alleged illegal trials being conducted in the country amid lax regulatory procedures, checks and balances. The petitioners have, among other things, alleged irregularities in trials performed at BMHRC involving survivors of the Bhopal industrial disaster.
Earlier this year, the Supreme Court of India slammed the government for its tardy response in the case and directed the health secretary to monitor new chemical entity studies (scripintelligence.com, 4 January 2013).
In a recent hearing, the Supreme Court asked the government to re-evaluate 157 previously approved studies under a new regulatory system implemented earlier this year (scripintelligence.com, 22 October 2013); a hearing on the case is now reported to be scheduled for next year.
company responses
Quintiles, Pfizer and Sanofi have refuted any suggestion of wrongdoing in trials conducted at BMHRC.
Quintiles told Scrip that because such global studies generate data that is ultimately submitted to multiple regulatory agencies around the world, it conducts clinical trials to the same high standards everywhere. "Regardless of country, we strictly adhere to universally accepted ethical principles articulated by international and local guidelines and these are supplemented by our own policies and procedures," it stated.
With specific reference to the queries raised by the DCGI, Quintiles said it had responded with "appropriate" supporting documentation. "This was done to verify that all requisite procedures regarding ethical and regulatory compliance were in place, that these procedures were followed during the conduct of clinical trials at BMHRC and that we had complied with the International Conference on Harmonization (ICH) of Good Clinical Practice (GCP) and local regulations," it emphasized.
Any serious adverse event is reported and dealt with in accordance with local and international guidelines and causality is determined after a thorough investigation by the investigator, it noted.
The services firm added that typically it is not the owner of the new medicines being studied in clinical trials. But in situations where participation in the study causes unintended injury, compensation is addressed "seriously". "Different countries have different views on how this is done. Quintiles works closely with sponsors to adhere to all applicable compensation regulations and guidelines," it stressed.
Similarly, Pfizer underscored that patient safety is a "top priority" at the company and that all Pfizer-sponsored clinical studies, in every country, follow accepted ethical, scientific, and medical standards that protect the rights of participants. "These standards include policies on informed consent, independent review, and post-study care," it noted.
The US firm said that its studies comply with local laws and regulations and international standards such as ICH GCP guidelines, the International Ethical Guidelines for Biomedical Research Involving Human Subjects, the ethical principles set out in the Declaration of Helsinki (WMA 2008) and the US Belmont Report (1974).
The Tygacil (tigecycline) clinical trials at the BMHRC, it said, were conducted by doctors at the hospital, with the informed consent of the study participants and under the review of the hospital's ethics committee.
"We complied with all standards and the standards applicable to these clinical trials were no different than for trials conducted in the US, the EU, or elsewhere in the world. For all trials, necessary and appropriate measures are undertaken in order to be able to compensate the participants in case of any unpredictable response to the medicines. Any compensation provided to study participants was in accordance with applicable law, and approved by the principal investigators, the hospital’s Ethics Committee, and the DCGI," it said.
Sanofi India told Scrip that it had already responded in October 2012 to the DCGI, addressing each of their inspection findings at the concerned site. "In its note, the company reinforced the measures it always undertakes to ensure that our clinical trials are conducted in strict compliance with regulatory provisions and GCP guidelines," the company said.