In late January, India’s Ministry of Health & Family Welfare published the rules, which allow compensation for violations of an approved trial protocol, scientific misconduct or negligence by the sponsor, CRO or investigator. But the rules that are causing confusion and concern also allow compensation if an investigational product fails “to provide intended therapeutic effect” in a trial or if a placebo is used in a placebo controlled trial.
The India Society for Clinical Research (ISCR) took issue with these final two criteria, noting they “go against the tenets of science” and “are contrary to the consensus reached in the stakeholder meetings.”
“By definition, a clinical trial is conducted to find out whether an investigational product has the intended therapeutic benefit or not so the statement questions the very essence of a clinical trial,” ISCR said. “Further, the term ‘intended therapeutic benefit’ can be open to a lot of misinterpretation particularly in end point studies like oncology.”
ACRO (Association of Contract Research Organizations) also took issue with these same criteria, noting they conflict with the reasons for running a clinical trial.
Dr. Arun Bhatt -- president of Clininvent Research, an Indian CRO -- told Outsourcing-Pharma.com that industry colleagues said government officials have agreed to make changes to the disputed rules.
“However, they may not do this [soon] as the current rules are part of the government’s actions taken” after the Supreme Court order of Jan. 13, Bhatt said. He added that the changes, if they occur, “may not happen in a hurry” because India’s health ministry may have to conduct a legal review before changes are made and could face “repercussions from NGOs/media.”
The changes also are not likely to occur before the Supreme Court hearing in May, he said. The hearing will deal with a government affidavit that will begin the adoption of new regulations aimed at reassuring the country’s top court that the approval of drugs and conduct of clinical trials are being regulated properly.
Under the new regulations, ethics committees that approve and oversee clinical trials must be registered and CDSCO (Central Drugs Standards Control Organisation) will be able to conduct unannounced inspections of trial sites and seize company records.
“These actions are welcome as they can help in streamlining the regulatory process for clinical trials,” Bhatt said, noting that the “number of clinical trials off-shored to India by pharma companies to their Indian affiliates and CROs are going down.”
New expert committees will also play a central role in looking back on cases in the past where drugs were approved unlawfully or without merit. CDSCO announced last week four experts will join an expert committee to deal with cases in which the agency was reprimanded for drug approvals without clinical trials. India’s Parliament also claims that the DCGI (Drug Controller General of India), rather than address the issues, used a “diversionary” tactic and referred the matter to clinical experts.
In one of the alleged cases, Themis Medicare’s fixed dose combination of aceclofenac and drotaverine -- which is not approved in the US, Europe or Australia – was approved based on expert letters that all seemed to be forged by the manufacturer, according to report from India’s Parliament.
In another instance, Sun Pharmaceuticals’ cancer drug letrozole was approved for use even though Phase II trials were not conducted in India prior to its approval, according to the report. Phase III trials were also approved without the requisite earlier studies, and periodic safety update reports were not submitted by Sun every six months as required by law, the report contends. Sun did not respond to a request for comment.