Compensation in clinical trials has its own roots in the 2013 version of the “Declaration of Helsinki” which states that “appropriate compensation and treatment for subjects who are harmed because of participating in research must be ensured.” This declaration is widely regarded as the foundation document on human research ethics. Over a period of years, the compensation has been provided to the clinical trial participants by sponsor organisations to encourage them to participate, or compensating them for their time (e.g., daily wages, travel fees, reimbursement for food). The following article provides more information on the updated compensation rules in India and their associated issues.
NEED FOR UPDATED COMPENSATION REGULATIONS
India has diversified patient population and one of the hottest destinations to conduct clinical trials. Since late 2013 however the number of clinical trials started sinking due to various ethical and compensation issues reported by the media. The issue of compensation was of more concern in case of vulnerable, poor and illiterate populations. The majority of participants in this group found to be unable to comprehend the trial research information provided in the informed consent document but moreover interested from the financial benefit in their lives and therefore participated in the clinical trial without knowing the risks. According to data given by the government, there were 370 deaths in clinical trial was reported from 2007-2011. Out of 370 cases only 21 were said eligible for compensation on account of deaths associated with drug. There was however no sound basis on which the eligibility and amount of the compensation was decided. The litigation filed by a Non-Governmental Organization (Swasthya Adhikar Manch) in the Supreme Court of India resulted in an avalanche of change to the regulations related to the compensation.
Indian regulatory Drug Controller General of India (DCGI) released new rule 122 DAB, “Compensation in case of injury or death during clinical trial” in the form of gazette notification DAB rules 53 (E) effective 30-Jan-2013 and further in the form of amendment, GSR 889 (E) dated 12-Dec-2014 which mandated sponsors to pay free medical management and compensation in case of clinical trial related injury or death to the clinical trial subject or nominee for the reasons.
- Adverse effect of investigational product
- Violation/scientific misconduct/negligence of the protocol by the sponsor/investigator
- Failure of the investigational product from providing therapeutic effect where the standard care though available was not provided to the subject per clinical trial protocol
- Use of placebo in placebo-controlled trials where the standard care though available was not provided to the subject per the clinical trial protocol
- Adverse effect due to concomitant medication
- Injury to child in-utero
- Injury due to any clinical trial procedures in study
DECISION MAKING IN QUANTUM OF COMPENSATION
The DCGI is the final decision maker on finalizing compensation amount. The sponsor is required to forward Serious Adverse Events (SAE) reports to the expert committee and DCGI to decide the quantum of compensation. The ethics committees are also required to opine on the amount of compensation. An independent expert committee was formed by the DCGI responsible for analyzing the SAE report and recommending the quantum of compensation to DCGI. The DCGI at the end is responsible for passing the orders to the sponsor with respect to the quantum of compensation within one hundred and fifty days of the receiving of SAE.
FORMULAE TO DETERMINE COMPENSATION IN DIFFERENT SCENARIOS
The members of Independent Expert Committee discussed the various possible factors that could be considered while deciding the quantum of compensation and came up with notification order dated 15-Dec-14 which included formulas to handle different scenarios to pay compensation.
- SAE FOR DEATHS
Compensation = (BX F x R) / 99.37
where B= Base amount (8 lakhs), F (factor depending on the age of the subject based on Workmen Compensation Act), R= Risk Factor depending seriousness and severity of disease. However, in case of patients whose expected mortality is 90% or more within 30 days, a fixed amount of Rs. 2 Lakhs should be given.
- SAE CAUSING PERMANENT DISABILITY
Compensation= (CxDx90)/ (100X100):
C= Percentage disability that subject has suffered, D=Quantum of compensation which would have been due for payment to the subject’s nominee in case of death of the subject
- SAE CAUSED LIFE THREATENING DISEASES AND REVERSIBLE SAE IN CASE IT IS DISSOLVED
W=Minimum wage per day of the unskilled worker and N= Number of days of hospitalization
These guidelines have tightened the compensation rules however there was drastic decrease in the number of clinical trials in India.
It is envisioned that these updated regulations will enhance the safety of the subjects and adequate compensation would be paid in the event of injury or death. The rules are vital to establish a trust among trial participants. There are yet some scenarios not explained in the regulation including how to handle situations of compensations for occurrence of the secondary SAE during management of the primary SAE, Occurrence of SAE when trial participant violets the protocol etc. The compensation regulations would may affect the trials running in academic and research institutes because these trials are conducted with the limited monetary support. The things are moving in an appositive way. What is your take on this?