Clinical trials are significant because they serve an important role in Research and Development of new medicines and their regularization for the benefit of human population. In most of the countries, a defined criteria for clinical trials is mandatory before introduction of a medicine for public. However, there are risks involved in conducting the trials and in a country like India where a lot of people are uneducated, there is a need to maintain strict rules of compliance by the government. How far have these rules been able to help maintain a transparent system in clinical trials is studied in this article.
What are Clinical trials?
A clinical trial is a scientific investigation to evaluate the effect of new drugs or vaccines other than health interventions, by administering these to human volunteers. They are generally bio medical or health-related research studies in human beings that follow a pre-defined protocol.Clinical trials are done in different phases and each phase is designed to answer a separate research question. Normally a clinical trial has three phases before manufacture of a drug starts.
Status of Clinical trials being done in India:
According to CDSCO (Central Drug Standard Control Organisation), there are an estimated 150,000 people enrolled in clinical trials in India. According to a 2011 Associated Chambers of Commerce and Industry of India (Assocham) report, nearly 100 domestic and multinational pharmaceutical companies are conducting trials in the country and the business is worth Rs.8,000 crore. Trials in countries such as India are cheaper to run: According to a 2008 Harvard Business Review article, tracking Indian test subjects costs between $1,500 and $2,000, (Rs.79,500 and Rs.1.06 lakhs today), while in the US, it would cost $20,000.Therefore, when clinical trials are conducted ethically, India’s poor also stand to gain.
Advantages of running clinical trials in India:
India is a good country for a Clinical trials because of factors like:
- Ethical diversity in patients
- Low cost of conducting a trial
- Use of English as primary language
- Well trained medical professionals
Problems that occurred due to irregular trials:
According to a report in Livemint, In 2004, doctors at the Bhopal Memorial Hospital and Research Centre (BMHRC), established exclusively for treating the victims of the 1984 gas leak, recruited unsuspecting survivors for clinical trials without their knowledge or consent; 14 participants died during the course of the trials. This information came out when an RTI was filed regarding information as to the details of the protocol of the research.
In 2011, CDSCO suspended the licence of Hyderabad-based CRO Axis Clinicals Ltd for recruiting illiterate women for a trial without obtaining proper consent. Following the incident, DCGI ordered an investigation into the operation of all 10 CROs in Andhra Pradesh. Also it was reported that in Indore’s Maharaja Yashwantrao Hospital, 32 people died in clinical trials between 2005 and 2010.
These incidents highlighted the irregularities and ethical violations in some trials conducted by clinical research firms and pharma companies. The Supreme Court had also pointed out government’s failure to halt unethical clinical trials by multinational drug companies on Indian patients who were used as ‘guinea pigs’.
Referring to a May 2012 report of the Parliamentary Standing Committee on health and family welfare, judges R.M. Lodha and Anil R. Dave said, “it really pains us that illiterate people and children of India are being used as guinea pigs by the multinational drug companies.”
The Centre last year informed the Supreme Court that as many as 2,644 people died during the clinical trials of 475 new drugs on humans between 2005 and 2012 out of which 80 deaths were directly attributable to the clinical trials. In this time period trials of 475 new drugs took place and merely 17 of the medicines were approved for marketing in India. It was also noted that drug trial of two drugs – Bayer’s Rivaroxaban and Novartis’s Aliskiren vs. Enalapril – made up for maximum number of deaths. Further, majority of the pharmaceutical companies, whose drugs were allowed for clinical trial on human beings were of foreign origin.
Regulatory provisions and recent changes in them:
According to Schedule Y of the Drugs and Cosmetic Act,
1. The clinical trials required to be carried out in the country before a new drug is approved for marketing depend on the status of the drug in other countries. If the drug is already approved/marketed, Phase III trials as required. If the drug is not approved/marketed trials are generally allowed to be initiated at one phase earlier to the phase of trials in other countries.
2. If the trial is for phase I, then information to the authority regarding the details of the phase I trials in other countries is to be given, unless it can be sufficiently proven that the trial has not been conducted anywhere but is significant research for Indian population. For a drug discovered in India, phase I,II and III researches have to be carried in India.
3. Permission to conduct clinical trial may be sought by filling form 12 for obtaining a Test Licence (TL) along with necessary details like: a. All the information to be filled as is required under Appendix I b. Type of protocol for proposed trials, to be approved by the institution’s own, or any other ethical committee. c. Case report forms to be used. d. Name of investigators and the Institutions where the trial is to be carried out
4. The DGCI provides approval in approximately 12 weeks from the date of submission of application. The duration may be longer for drugs with special significance to the healthcare concerns of the country or those that may be considered controversial since these are liable to be referred to the Indian Council of Medical Research for comments.
5. Adverse drug reactions occurring during the course of a clinical trial need to be submitted to the DCGI within 14 days if these are unexpected or serious and causally related or result in death. All other serious adverse events need to be submitted along with periodic progress reports.
6. Sponsors are given the duty to submit an annual status report to the authority.Any unusual, unexpected or serious adverse drug reaction (ADR) detected during a trial should be promptly communicated by the sponsor to authority and investigators. An informal consent must be taken from the patient before commencement of the trial.
7. Pharmacology and toxicity studies in animals as per required according to the schedule Y regarding:
a. Acute toxicity
b. Long term toxicity
c. Reproduction studies
d. Local toxicity
e. Mutagenicity and carcinogenicity
have to be carried out and attached with the application for License. Till last year there were no provisions for compensation to the patients who take part in clinical trials and get adversely effected by them.
After the Supreme Court observed a pressing need to provide help to these victims, the government notified three changes in the Drugs and Cosmetic rules.
1. Rule 122-DAB ensures free medical management, as long as required to the clinical trial subjects in case of an injury occurring to him/her. If the injury is due to the trial, then financial compensation will be given to the subject as the licensing authority insists.
2.Rule 122 DAC gives guidelines and powers to the licensing authority.The trial has to be approved by the ethical committee and registered before it commences. In case the protocol is not up to the satisfaction of the authority, it can put up additional conditions as it deems fit.
3.Rule 122 DD says that there has to be an ethical committee which must be registered, the duty of which is to approve and review trial protocols.
Criticism of the rules:
1. There are provisions where compensation is payable even for cases that have no connection to the clinical trial but have happened to the subjects.
2. Compensation may be paid for ‘failure of an investigation product to provide intended therapeutic effect.’ The very nature of a clinical trial is to determine whether the investigation product is efficacious, so this provision is difficult to understand.
3.There is no clarity as to which authority appeals will lie and the procedure of the appeals.
It cannot be denied that drug trials are necessary evil. What has come across in numerous reports lead the Supreme Court to ask the respective government to clarify their position. During this period the new rules for the Drugs and Cosmetics Act were notified. These rules have caused a lot of confusion. It has been observed that the trials that were approved in the month of January were merely 6 while the number of trials conducted in the previous year were 262.
The steps of the Government in requiring the Ethical committees to be registered is a very important step as this will help to weed out people who used to be a part of ethics committee of a trial as well as interested monetarily or otherwise in the studies. The major problem still is ensuring informed consent from the patients. Majority of people who are a part of a clinical trial don’t know that they are part of such trial and the risks that come with them. Strong vigilance of the authority is required in this parameter.
Also the punishment to the parties convicted should be such that it is deterrent to the people who would want to use unfair means to conduct the studies in the future.