Clinical Trials in India - Need for Regulations

 What are clinical trials?

• Clinical trials are experimental studies on human participants that helps to determine whether a particular treatment (drugs, vaccines, dietary supplements, dietary choices, medical devices, etc) is safe and effective for humans.
• Clinical trials are repositories of observations and data which is valuable for the healthcare industry in aiding them in decision-making.
• These studies may help in designing best medical treatment and strategy for certain illnesses or particular groups of people. It also provides doctors and patients with reliable information for deciding between different alternative treatments.

Why clinical trials are important?
Clinical trials are important steps in developing new treatments for humans. It helps in answering the following questions about a new treatment:

• Does the treatment work well?
• Does the treatment improves patient outcomes?
• Is the treatment better than other treatments?
• Or the treatment offers no benefits?
• What is the optimum dosage of drugs required?
• Is the treatment safe?
• Does it have side-effects?

All of these results are important because they advance medical research and help improve health of patients and future generations.

How Clinical trials are conducted?
Clinical trial is a long and careful research process which is conducted in a step-by-step exercise usually comprising of the following phases:

• Phase-0/Pre-clinical testing: The clinical trial often starts in a laboratory with the scientists finalising their ideas. If they are convinced, they start with animal testing. After all the things seems to be working well, the research on humans is needed.
• Phase-1: It is the first study conducted on people in the clinical trial process. Here, the healthy participants (a small number) are given a fixed dosage and are watched closely. The aim of the study is to find the safest dose and the best treatment that can be given. It identifies side effects and studies how the dose works with other medicines or food.
• Phase-2: In this phase, the study builds upon the results of Phase-1. It further tests the safety of drug along with its effectiveness. Here, more participants are involved. Now either all the participants are given the same experimental dose or sometimes the participants are divided into groups and given different treatment doses to compare. This phase can last for several years.
• Phase-3: In this phase, the participant size is in hundreds to thousands. Here, tests are conducted to find if the treatment is better than the standard treatment available. It then compares side effects, survival rate and quality of life between the two. This phase runs over a long period of time.
• Phase-4/ Post-marketing trials: In this phase, the participant size is in thousands. The studies are conducted only after the treatment has been registered with the drug regulator. This is usually done by pharmaceutical companies that manufacture the product. The study helps to identify how well the treatment is working when used widely. The long-term benefits and risks are also monitored. It further looks for the other uses of the drug or treatment other than intended ones.

India- a preferred destination for Clinical trials

• India has a huge population with a large genetic pool and millions suffering from variety of diseases including some rare disorders.
• Secondly, in the drug development process, majority of the budget is incurred in clinical testing which is highly dependent upon human resources. And India is advantaged with availability of a large pool of English-speaking healthcare professionals and offers competitive operational costs.

Who regulates Clinical Trials in India?
Clinical Trials in India are governed by the following laws and regulations:

• The Drugs and Cosmetics Act, 1940 and the accompanying Drugs and Cosmetic Rules, 1945 which are revised from time to time. These rules mandates that clinical trial is conducted as per the Good Clinical Practices (GCP) guidelines issued by the Central Drugs Standard Control Organisation (CDSCO).
• The Medical Council of Indian Act, 1956.
• Indian Council of Medical Research as the apex regulatory body for clinical trials.
• The Supreme Court order in 2013 which has set up a three-tier review process. Firstly, the clinical trial applications (CTAs) are reviewed by the Subject Expert Committees. Then, these are monitored by the Technical Committee and finally by the Apex Committee. The principles for reviewing applications are assessment of risk versus benefit to the patients, innovation as compared to the existing therapeutic choice and unmet medical needs in the country.. Once these committees gives a green signal, then the application is moved for final approval by the Drugs Controller General of India (DCGI).
• Central Council for Indian Medicine Act, 1970.
• Also, India is a signatory to the World Trade Organisation (WTO), and complies with the Trade Related Intellectual Property Rights (TRIPS) agreement which has specific provisions related to drugs and clinical trials.

What are the key Issues regarding Clinical Trials

• Deaths and tragedy- According to a submission in Supreme Court, about 2,800 patients have died in India during 2005 and 2012, while participating in clinical trials conducted by pharmaceutical companies.
• Exploitation- It has been found that people from low-income groups are over-represented in clinical trials. Companies exploit people who are in need of money and the people who are ignorant of medical consequences of the trial.
• Problem in regulation- The regulatory system to oversee clinical trials have serious backdrops. The members in the committees formed for the approval process lacks adequate experience and qualification and have conflict of interest. Also, there is no check on the functioning of ethics committees. Further, the regulatory process is considered to be slow, hence delaying the process of drug development.
• Unethical practices during clinical trials - A very unethical practice being followed is that- usually the consent of the participants in the clinical trials is not taken. Informed consent is the process of telling the participants all the facts regarding a trial-including benefits and risks. Since a large proportion of participants are not well educated, they are trapped. It has been observed at many instances that the people who were admitted in hospitals for treatment were tested for clinical trials without their knowledge.
• Non registration-TheClinical Trials Registry formed under the Indian Council of Medical Research calls for registration of all clinical trials conducted in India. However, there is a very poor registration rate. Resultantly, the data about various trials is unaccessible or even not published at all due to "negative" results.

What are the steps taken by the government in this regard?

• Ranjit Roy Chaudhury Expert Committee constituted in 2013 by the Union Health Ministry has recommended following guidelines for clinical trials-
• Clinical trials must be carried at the centres which are accredited.
• Clinical trial sites shall have proper infrastructure, facilities, documented procedures and oversight mechanism to support clinical trial process as per the rules and regulations.
• The principal investigator of the trial must be an accredited clinical investigator.
• Ethics committee of the Institute shall also be accredited.
• It has been made mandatory to register at the Clinical Trials Registry-India. This will improve transparency, accountability and accessibility of data related to clinical trials.
• The Drugs Controller General of India has mandated audio-visual recording and safe storage of the consent taking process from participating individuals.
• A recent amendment to the Drugs and Cosmetics Act requires compensation to be paid in respect of Serious Adverse Events (SAEs) of death attributable to clinical trials.

The way forward
Following measures can be taken to improve the scenario-

• The government should specify transparent and rational procedures for conducting clinical trials.
• The functioning of ethics and review committees should be strengthened.
• It should be ensured that The Global Good Clinical Practice Guidelines, which specifies standards, roles and responsibilities of sponsors, investigators and participants are followed.
• Compulsory registration of all clinical trials should be done. This will help in stopping illegal trials and will create a database of all the clinical trials.
• Clinical trials should be done only after there is full disclosure to the participants. They should be given the right to withdraw at any stage without any consequence, and should be provided with comprehensive medical insurance. Further, the participants should be carefully monitored after drug administration for serious adverse effects, and should be provided with these drugs free of cost after it is cleared for commercial use.
• Clinical trials should be brought under the purview of Right to Information Act, 2005. Many organisations which conduct clinical trials are usually financed by donor agencies which are financially supported by the government. The Act can be used to demand information regarding conduct of clinical trials bringing transparency and accountability in the system.

By: Ziyaur Rahman