Today in this country the Supreme Court found it appropriate to put a stop to all clinical trials in response to a PIL filed by an NGO, on the grounds that the regulatory mechanisms were grossly inadequate, and unsuspecting patients were being used as guinea-pigs.
The issue exploded on the Indian scene after reports emerged of a phase IV trial for a vaccine was carried out on unsuspecting tribal girls. The vaccines were provided by Merck and GSK, with collaboration from the ICMR and funding from the Bill and Melinda Gates Foundation. There were seven deaths; the trial had to be stopped, and an enquiry instituted. The organisation, PATH NGO, was let off with a warning in spite of gross irregularities; which led to an uproar ending in the SC.
More worms emerged in the process of the hearings. Cases were reported of patient left with crippling side effects of trial drugs and financially ruined because they were left to deal with medical costs of treatment sequel. No provisions had been made in any of the trials to deal with treating patients who suffered side effects. The government affidavit placed before the court revealed that there had been 2644 reported deaths in the course of trials of 475 drugs between 2005 and 2012; in addition to 11972 serious adverse events (SAE). Justice Lodha junked the governments’ explanation that of these only 80 deaths and 506 SAEs were directly attributable to the clinical trial. He remarked to Luthra appearing for the government “Look, it is not a question of one, two or three deaths. The figures say that there were 3,458 deaths. It is a very serious matter and disturbing. We want to know what is the mechanism that you have put in place to prevent it.” In view of the unsatisfactory replies, all clinical trials were put on hold till the authorities had put in place adequate regulatory and compensation mechanisms.
Clinical trials arrived on the Indian scene in 1995, when India joined the WTO, and took off when the country adopted the product patent regime in 2005, spurred on by the fact that trials were much cheaper to conduct in this country. There was big money involved with trial managers grossing incomes nearing 2 crores as reported by the MP economic offenses wing in their investigation. The market is estimated to be worth $100 million according to the Indian Society for Scientific Research (ISCR). The country even went to the extent of amending its laws in 2004 to facilitate trials; phase I trials which could not be conducted in India for drugs developed outside the country, could now be done if the international company “partnered” with an Indian firm and thus became classified as a domestic company.
So what does a clinical trial involve? It is certainly more than giving patients a few doses of a new drug to see if it works. After years of laboratory research and animal experiments, the drug is presented to the Central Drug Standards Control organization (CDSCO) for approval for human testing. Following such approval, it goes through four phases. Some drugs are on record for being withdrawn even after Phase IV has been successfully completed, because of unacceptable risk factors. However the present status of the existing procedure is full of holes as unearthed in the course of the SC hearings.
Manpower: The CDSCO which is entrusted with overseeing such research simply does not have the manpower to deal with the increasing number of trials. This was anticipated by both the Hathi (1975) and the Mashelkar (2003) committees; but as usual did not result in any action
Transparency: The Ethics committees which were supposed to monitor the trials and investigate any untoward events were set up by the sponsors of the trials themselves. In many cases, the principal investigator was part of the investigating committee. How on earth a conflict of interest was to be avoided is beyond me.
Informed Consent: Patients recruited for such trials were most often from the low income group, lured by the bait of free and “latest” medicines. In many cases particularly those involving difficult treatment options, they were also reassured that they would be compensated in the event of problems.
To resolve these and other issues, a committee was appointed headed by Prof. Ranjit Roy Choudhary which has just finalised its report. The CDSCO will now be responsible only for approval of trials. A process of accreditation is to be established with the formation of a proposed Central Accreditation Council; and only accredited bodies will be permitted to conduct the trials. Investigative committees will function independently of these. Significantly, any death occurring during a trial has to be compensated whether the patient was in the control, placebo or standard drug group; unless the death is definitely proven to be due to injury or a completely unrelated cause. A compensation formula has been suggested based on the patients existing earnings capacity. Rules for consent have been tightened up and audio-visual recordings are now required.
There have been murmurs of discontent with Prof. Roy Choudhury’s role in this committee. He is the head of the Apollo Hospitals clinical trial unit, and vulnerable to a conflict of interest.
But whatever the issues, the existing mess wherein the poorest patients stand to lose the most has to be set right.
(Dr Gladstone D’Costa is the Chairman,
Accreditation Committee and member,
Executive Committee, Goa Medical Council)
