The New Drugs and Clinical Trial Rules, 2019 released by the government seeks to enable faster approvals and to cut down on red tape with respect to the clinical trials in India. It seeks to promote clinical research in India by providing for a predictable, transparent and effective regulation for clinical trials and by guaranteeing faster accessibility of new drugs to the Indian population. Thus it has the potential to reinvigorate the clinical research industry, which was almost on its death bed a few years ago.
What are clinical trials?
Clinical trials are research studies conducted on human participants that aids in determining whether a certain treatment (drugs, vaccines, dietary supplements, dietary choices, medical devices, etc) is safe as well as effective for humans.
Clinical trials are repositories of facts and data which is valuable for the healthcare industry as it supports them in decision-making.
These studies may aid in creating the best medical treatment and strategy for particular illnesses or certain groups of people. It also gives doctors and patients with reliable information for deciding between various alternative treatments.
What is the need for clinical trials?
Clinical trials are crucial steps in creating new treatments for humans. It aids in answering the following questions about a new treatment:
- Does the treatment work well?
- Does the treatment improve patient outcomes?
- Is the treatment effective than other treatments?
- Or the treatment provides no benefits?
- What is the optimal dosage of drugs needed?
- Is the treatment safe?
- Does it have side-effects?
All of these results are crucial as they promote medical research and help improve the health of patients as well as future generations.
How Clinical trials are conducted?
A clinical trial is a long and careful research process which is conducted in a step-by-step manner often consisting of the following phases:
- Phase-0/Pre-clinical testing: The clinical trial generally starts in a laboratory with the researchers finalising their ideas. If they are very sure then they begin with animal testing. After all the things seem to be working good, the trials on humans will be conducted.
- Phase-1: It is the 1st study conducted on people in the clinical trial process. Here, the healthy participants (a few numbers) are administrated a fixed dosage and are watched carefully. The objective of the study is to identify the safest dose and effective treatment that can be given. It identifies side effects and analyses how the dose works with other medicines or food.
- Phase-2: The study in this phase is based on the results of Phase-1. It further tests the safety of the drug in addition to its effectiveness. Here, more participants are involved. Now either all the participants are provided the same experimental dose or sometimes the participants are divided into groups and provided different treatment doses to compare. This phase can last for many years.
- Phase-3: In this phase, the participant size is in hundreds to thousands. Here, tests are conducted to identify if the treatment is effective than the standard treatment available. It then compares side effects, survival rate and quality of life between the two. This phase lasts for 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 often done by pharmaceutical companies that produce the product. The study aids in identifying how well the treatment is working on wide usage. The long-term benefits and risks are also supervised. It further identifies the other uses of the drug or treatment other than proposed ones.
Why is India a popular destination for Clinical trials?
- India has a huge population with a large genetic pool and millions suffering from a variety of diseases including some rare disorders.
- Secondly, in the drug development process, the majority of the budget is spent on clinical testing which is highly based on human resources. And India has the availability of a large pool of English-speaking healthcare professionals and provides competitive operational costs.
Who regulates Clinical Trials in India?
Clinical Trials in India are regulated 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 based on Good Clinical Practices (GCP) guidelines provided by the Central Drugs Standard Control Organisation (CDSCO).
- The Medical Council of India Act, 1956.
- Indian Council of Medical Research as the apex regulatory body for clinical trials.
- The Supreme Court order in 2013 which has established 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 objectives for reviewing applications are the analysis of risk versus benefit to the patients, innovation as compared to the present therapeutic choice and unmet medical requirements in the country. After the committees have given a green signal, the application then is taken for final approval by the Drugs Controller General of India (DCGI).
- Central Council for Indian Medicine Act, 1970.
- Further, India is a signatory to the World Trade Organisation (WTO) and abides by the Trade Related Intellectual Property Rights (TRIPS) agreement which has certain provisions with regards to drugs and clinical trials.
What are the key Issues regarding Clinical Trials in India?
- Deaths and tragedy– According to submission in Supreme Court, around 2,800 patients have died in India between 2005 and 2012, while participating in clinical trials carried by pharmaceutical firms.
- Exploitation– It has been observed that people from low-income groups are over-represented in clinical trials. Firms exploit people who are in need of money and the people who are ignorant of the medical effects of the trial.
- Issues in regulation– The regulatory system to monitor clinical trials have serious backdrops. The members in the committees formed for the approval process lacks enough experience and qualification and have a conflict of interest. Moreover, there is no supervision on the functioning of ethics committees. Also, the regulatory process is considered to be slow, thus delaying the process of drug development.
- Unethical practices during clinical trials– A very unethical practice being followed is that- often the consent of the participants in the clinical trials is not taken. Informed consent is the process of informing the participants all the facts regarding the trial including its benefits and risks. As a large proportion of participants are not well educated, they are trapped. It has been found at several instances that the people who were admitted in hospitals for treatment were tested for clinical trials without their knowledge.
- Non-registration- The Clinical Trials Registry created under the Indian Council of Medical Research provides for registration of all clinical trials conducted in India. But there is a very poor registration rate. Consequently, the data about different trials is inaccessible or even not published at all because of “negative” results.
What are the measures taken by the government in this regard?
- Ranjit Roy Chaudhury Expert Committee formed in 2013 by the Union Health Ministry has suggested following guidelines for clinical trials-
- Clinical trials should be carried at the centres which are accredited.
- Clinical trial sites shall have proper infrastructure, facilities, documented procedures as well as a supervisory mechanism to aid clinical trial process as per the rules and regulations.
- The chief investigator of the trial should be an accredited clinical investigator.
- The ethics committee of the Institute shall also be accredited.
- It has been made compulsory to register at the Clinical Trials Registry-India. This will improve transparency, accountability, and accessibility of data regarding clinical trials.
- The Drugs Controller General of India (DGCI) has mandated audio-visual recording and safe storage of the consent taking the process from participating persons.
- A recent amendment to the Drugs and Cosmetics Act requires compensation to be paid for Serious Adverse Events (SAEs) of death due to clinical trials.
- The Union Ministry of Health and Family Welfare has notified the Drugs and Clinical Trial Rules, 2019 with an aim to promote clinical research in the country.
What are the features/significances of the new Rules?
The Union Ministry for Health and Family Welfare has notified the Drugs and Clinical Trials Rules, 2019 with an aim to promote clinical research in the country.
- The new rules reduce the time for approving applications to 30 days for drugs manufactured in India and 90 days for those developed outside the country.
- The new rules state that in case of no communication from Drug Controller General of India (DCGI), the application will be deemed to have been approved.
- The new rules will ensure patient safety, as they would be enlisted for trials with informed consent and the ethics committee will monitor the trials and decide on the amount of compensation in cases of adverse events.
- The new rules mandates that in case of injury to the clinical trial subject, medical management will be provided as long as required as per the opinion of the investigator or till such time it is established that the injury is not related to the clinical trial.
- Compensation in cases of death and permanent disability or other injuries to a trial subject will be decided by the Drug Controller General.
- The rules also waive off the requirement of a local clinical trial if the drug is approved and marketed in countries specified by the DCGI with the approval of government from time to time and certain other conditions.
- The DCGI has waived off the clinical trial for the drugs approved and marketed in the European Union, the UK, Australia, Canada, Japan, and the US.
Thus the new rules aim to promote clinical research in India by providing for a predictable, transparent and effective regulation for clinical trials and by ensuring faster accessibility of new drugs to the Indian population.
The way forward
In addition to the effective implementation of the new rules, the following measures can be taken to further improve the scenario-
- 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.
- Participants should be given the right to withdraw at any stage without any consequence and should be provided with comprehensive medical insurance.
- Clinical trials should be brought under the purview of Right to Information Act, 2005. Many organisations which conduct clinical trials are mostly financed by donor agencies which are financially supported by the government. The Act can be used to demand information with respect to the conduct of clinical trials bringing transparency and accountability in the system.