Since compensation to the victims of clinical trials is a critical area that is being neglected by the pharma companies and the Clinical Research Organizations (CROs) , it is essential that the government should stipulate adequate compensation to relatives of subjects who die during a trial or get seriously injured , say industry veterans.
Last year a probe by the Union Health Ministry into the ways in which pharmaceutical giants are conducting clinical trials in India had revealed that these companies have not given compensation to majority of the volunteers who died during the course of trials.
It is unfortunate that the pharmaceutical companies and their agents are getting away with this kind of gross unethical practices in the name clinical trials. Ever since the clinical trials started on a big scale in the country, reports were appearing in the media about the unethical practices indulged in by clinical research companies. The health ministry is fully aware of this fact but has not been taking any serious steps to bring in effective regulation in this sector.
A comprehensive legislation is the need of the hour. The Drugs Technical Advisory Board (DTAB) has approved the proposals to strengthen the regulations and draft notification for soliciting view of various stakeholders was made public. However, it is made into a law by amending the Drugs and Cosmetic Act.
The draft has detailed provisions for incorporation of financial compensation to trial subjects in case of trial related injury or death. Enhancement of responsibilities of Ethics Committee (EC), Sponsor & Investigator to ensure medical care is also provided to trial subjects who suffer trial related injury or death and such information is provided to the Drugs Control General of India (DCGI), according to the draft.
Another are amendment being proposed is in the format for obtaining informed consent of trial subjects to include the details of address, occupation, annual income of the subject so as to have information regarding socio-economic status of the trial subjects.
Of the 671 deaths recorded during trials in 2010, the ministry had evidence of just three cases of offering compensation. The ministry sought clarifications from 44 pharmaceutical companies on the compensation given by them for trial deaths. Top multinationals such as Eli Lilly, Novartis, Pfizer, Bayer, Merck, Johnson & Johnson, sanofi aventis and others who had been conducting clinical trials for some years had given the standard explanation that deaths were due progression of underlying diseases of the trial subjects. Therefore, they were not bound to pay any compensation. MNCs and CROs know very well that there are no competent consumer action groups and well informed judiciary to take them to task on such offences. Responses from them are not totally unexpected as the ministry has no records to counter their stand.
Indian Council of Medical Research's (ICMR’s) Ethical Guidelines for Biomedical Research on Human participants,2006 have specified the need for a provision for compensation to participants for research related injuries. In October 2008, ICMR had invited comments from the experts on the draft guidelines as a step before notifying them. The draft guidelines apply to all kinds of clinical research, whether sponsored by the pharmaceutical or medical devices industry, government or academia or individual investigators.
As per the guidelines, compensation should be provided to the research participants when temporary or permanent injury occurs in the clinical research and also when injury is caused by a procedure which has been undertaken to manage an adverse reaction occurring during the research.
The guideline proposes compensation to the participants irrespective of whether injury was foreseeable, predictable or not.
Even as the number of deaths of patients participating in clinical trials are steadily increasing over the years in consonance with the increase in the number of clinical trials by MNCs in the country, experts say there is gross discrimination in payment of compensation to the victims by multinational pharma companies.
According to data made available by the experts, the number of deaths of patients participating in clinical trials have increased as is the number of clinical trials by MNCs involving new drugs in the country. While 137 deaths were registered in the year 2007, the number rose to 288 in 2008, 637 in 2009 and 668 during 2010.
Meanwhile, experts are of the view that these figures are understated because many deaths are not reported to the DCGI by treating them as 'routine deaths not related to clinical trials'. Ironically, the investigators, who are on the payroll of drug companies that sponsor and fund the trials, are the ones who decide the causes of the deaths.
Regretting that the trial victims are well compensated abroad while they are humiliated at home by the MNCs, a well-known health expert said that case histories show that there are double standards employed by drug companies in different countries in paying compensation to trial victims.
He said that till the end of 2009, there was not even one case of compensation to patients who died during clinical trials even though it is mandatory in India. Lately, a total of 10 companies submitted a list of just 22 patients to whose families compensation was paid. In the case of Bayer, only five out of 138 deaths and in the case of sanofi aventis, only three out of 152 patients who died were offered compensation.
A glance at the amounts shows that an arbitrary sum of Rs.1,50,000 was paid to each of the eight victims by five different companies (Merck, Wyeth, Amgen, Sanofi and Pfizer). Bayer paid Rs.2,50,000 each in five cases while Eli Lilly paid Rs.2,00,000 to two families each and Rs.1,00,800 to one family. The average of all payments comes to a measly Rs.2,38,000 (or US$ 5,000) per dead participant.
In comparison, he said, on August 11, 2011, Pfizer handed over US$ 1,75,000 (Rs.84 lakh) to each victim of its Trovan (trovafloxacin) trial on children in Kano, Nigeria. In addition it agreed to pay US$ 10 million (Rs.48 crore) to the state government of Kano towards legal expenses incurred in long drawn litigation on behalf of its citizens.
In Germany, the erstwhile Hoechst (now part of Sanofi Aventis) paid more than 60,000 Euros (Rs.40 lakh) to the family of a woman who died during trial of an antidepressant agent nomifensine (Alival) later withdrawn on safety concerns. The company's top executive in the United States was slapped a fine of US$ 300,000 (Rs.1.44 crore) for concealing the drug's adverse effects.
In the US compensation valued to the tune of US$ 3.8 million (Rs.18 crore) was paid to poor women with high risk pregnancies who did not suffer any physical harm but asserted that that they were not informed that administered drugs were ‘experimental’ and the consent form was far ‘above their reading level’ and therefore invalid.
However according to Shoibal Mukherjee, Chief Medical Officer, Quintiles India, healthy clinical trial volunteers in India are paid quite well by global standards. Volunteers generally receive Rs 6,000 to Rs 12,000 for a single dose cross-over bioequivalence study for which they have to spend 4 to 8 days at the facility. This range overlaps with developed countries where volunteers receive only slightly higher payment despite a much higher cost of living.
“As a general rule across the world, patients do not receive payment for participating in a clinical trial. However, they receive reimbursement of costs which may include travel cost as well as medical costs directly related to the trial. Since Indian patients usually do not have health insurance, sponsors tend to reimburse more of the medical costs in India than is the practice elsewhere in the world. This is particularly true for trials in life-threatening diseases. Some commentators feel that in developing countries, patients should be paid for study participation even though this could be considered an inducement elsewhere around the world,” Mukherjee added
"Worldwide, compensation for injury is generally paid only in response to a claim alleging misconduct or negligence. In India regulations require payment of hefty compensation for any adverse medical event if the doctor treating the patient feels that the trial may have had something to do with the event. On balance Indians are compensated on par with other populations for study participation, but receive much higher payments for putative study-related injury", informed the Quintile India CMO.
According to a recent government notification it is mandatory for pharmaceutical companies sponsoring clinical trials in the country to pay financial compensation to volunteers in case a trial-related death or injury is proved.
The onus of proving that clinical trials did not cause death or injury will now lie with the drug company. Failure to pay up the compensation within a specified time may not only lead to suspension or cancellation of the ongoing trials, but in more severe cases, may also result in a permanent ban on the pharma company and the CRO, barring them from conducting any further trials in India. The amount of compensation will be decided on a case-to-case basis by the ethics committee, while the quantum of minimum compensation would already be mentioned in the informed consent form that the pharma company needs to get signed by the volunteer, before enrolling the subject into a trial.
Till now, India had no clear, enforceable law mandating a drug company to provide financial compensation to the affected party or his or her dependents in case of injury or death during clinical trials. Neither the ICMR Ethical Guidelines for Biomedical Research nor the Good Clinical Practices guidelines that deal with the subject have the status of law. These guidelines spell out the obligation of the trial sponsor in case the participant incurs physical or psychological injury, but do not delve into how to deal with complications that might arise in such cases.
“In the event of an injury or death occurring during the trial, the sponsor or his representative shall prove before the ethics committee that the injury or death is not on account of the clinical trial within 30 days of receiving the report, failing which there is a liability to compensate within 60 days, according to the government notification.
After a serious adverse event is reported during the trial, the pharma firms or their CROs must pay the required compensation and report the details of such action to the drug regulator within 90 days of the reporting of the side effect. The amount of compensation would be recommended by the ethics committee in the first place. If the pharma company doesn't agree with the amount or terms of payment, it may seek a review of the matter by the ethics committee, whose decision would be final. If the pharma firm is still dissatisfied with the verdict, it can seek legal recourse.
Now with the government’s stringent regulations on seeking informed consent and providing compensation to clinical trial victims would increase the number of volunteers and patients going for a trial in India, opine experts.
According to industry cognoscenti, insisting the clause of compensation is an assurance for the patients and for CROs to participate in human study and carry out the trial respectively.
There is no doubt that both informed consent and compensation to victims are the two key factors which are giving the Indian volunteers and patients the confidence of participating in a clinical trial. While the former helps the volunteer or patient to understand the risks of the human study, the latter provides the much needed financial and medical support if the medicine turns fatal or reports an adverse drug reaction, they say.