Unregulated Clinical Trials

[CLINICAL TRIALS in India have for long been inviting controversy due to lack of transparency and regulatory mechanism. While replying to a question in Rajya Sabha in March 2013, the then Union Health Minister Ghulam Nabi Azad said 438 deaths took place during clinical trials in 2011 while 668 people died during 2010. While hearing the public interest litigation (PIL) filed by Swasthya Adhikar Manch in 2012, the Supreme Court asked the Central government to come up with more stringent regulatory and monitoring set up to stop exploitation of gullible patients.
Amulya Nidhi, the co-convener of Swasthya Adhikar Manch, talks to Gol Monitor about the controversy, court directive and the gaps still prevailing. Excertps: ]

Q.  What were the major loopholes in clinical trials that Swasthya Adhikar Manch highlighted through its campaign?
A.  The law (Drugs and Cosmetic Act 1940) on clinical trials underwent a change in January 2005. If you examine the previous law, there were strict rules and hence less risk. But in 2005 amendments were made in Schedule Y to ease the rules. The important change was in provision of phase lag. Earlier phase 3 trial of a drug was allowed in India if the drug was already being marketed abroad. Removal of phase lag opened the country for testing of chemical entities which were not approved as drugs anywhere in the world and their potential benefits and side effects were not well established. So, the risks increased from such new chemical entities without any benefit to Indian people. Most of these products are so harmful that they never get market approval as drugs in the country of their origin.

Another major loophole was that it was not mandatory to register the ethics committee. Many a time the panel was based outstation thus weakening the monitoring mechanism. Many a time, members of the ethics committee had conflict of interests. Also, neither were they trained nor they had the resources or independence to do the monitoring job well. We also raised the issue of lack of proper guidelines for compensation and no law for punishment to investigators in case of violations.

Another major loophole was that it was not mandatory to register the ethics committee.

Q.  What are the changes made after the Supreme Court intervention?
A.  Supreme Court asked the Union government to take the matter seriously as several deaths had been reported due to absence of safeguards. After that some breakthroughs have been made. Now registration of ethics committee has been made mandatory. A new notification has been issued to ensure compensation for serious adverse event within a limited time frame.

However, no credible, transparent and independent system to determine morbidity and mortality exists except total reliance on investigators, ethics committee and sponsors. Another important outcome is related to video documentation during counselling and consent process of those enrolled in clinical trials. The pharmaceutical companies or the contract research organisation has to submit this data to the government. This will act as evidence of participation of the person as well as a check on illegal process of enrolment.
A new notification has been issued to ensure compensation for serious adverse event within a limited time frame. However, no credible, transparent and independent system to determine morbidity and mortality exists except total reliance on investigators, ethics committee and sponsors.

Q.  What are the issues still left unresolved?
A.  The case is going on in the court. The petitioners are seeking re-implementation of pre-2005 conditions as detailed earlier. Another issue is related to compensation for 17,778 deaths and serious adverse events which happened between January 2005 and December 2013. According to recent government affidavit the issue of compensation remains unresolved as there was no rule regarding that before January 30, 2013.

Q.  Besides ethical and regulatory conditions, what are the various parameters that justify a clinical trial?
A.  In 2013, the court listed three mandates for approval of a clinical trial, which have also been included in the new notifications issued by the Health ministry. These are:
*     Risk vs benefits to the subjects : If risks outweigh the benefits, the trial would definitely / not be allowed.
*    Innovation vis-a-vis existing therapy : How is the new therapy different than the treatments or drugs already available.
*     Unmet need to the Indian population : Only those trials will be allowed which are related to diseases prevalent in India.

Q.  Is it really possible to quantify clinical trials in India? How well do you think the clinical trials registry is working?
A.  In the past, there have been instances where the trials were conducted in clinics which are not even registered. The clinical trial registry was established in 2007 but it was a voluntary initiative. Registration was made compulsory in 2009. It can be further improved by including the data related to deaths, serious adverse events and compensations awarded.

Q.  How are the clinical trials done in US and Europe?
A.  There are very stringent laws and guidelines for undertaking clinical trials in US and Europe. Trials in these countries are regulated and people are sufficiently aware of the risks of participation and their right to health care. The process involves insurance of the persons involved in trial besides a proper counseling and consent process.

Q.  Pharmaceutical companies claim that the new guidelines are unjust and not conducting clinical trials in India will put new treatments out of reach of the patients here. What do you have to say on that?
A.  That is not true. The pharma companies don't want to be subjected to any regulations. The Indian pharma companies are the richest in the world, yet they don't carry out any research. Between 1985 and 2013 only seyen drugs have been discovered in India. The court has not stopped any foreign drug to be tested in India which has obtained marketing approval abroad. It has restricted only those new chemical entities which don't have approval anywhere in the world. More and more people are being killed by trials but not a single person is getting treated with a new chemical entity Our effort is to ensure safety of clinical trial participants.

Q.  Please tell us about Swasthya Adhikar Manch. How the group came together?
A.  Swasthya Adhikar Manch is an umbrella organisation of various groups working in the field of health in Madhya Pradesh. Activists come from diverse backgrounds. Some are health professionals, others are social activists, journalists, lawyers, RTI users etc. Many work in tribal areas of the state and are also members of the nationwide Jan Swasthya Abhiyan (People's Health Movement).

As many as 32 people died in Indore's Maharaja Yashwantrao Hospital in clinical trials between 2005 and 2010.

Frontier
Vol. 47, No. 30, Feb 1 - 7, 2015