Clinical trials are a set of practices performed to certify and ensure the safety of a new drug molecule. Pursuant to an amendment to the Indian Patents Act 1970 in January 2005, drugs can be made by following both the product and process patenting. This has facilitated the emergence of India as a preferred and sought after destination to conduct clinical trials. The availability of highly trained physicians, nurses and technical personnel; world class medical facilities; good IT infrastructure; and a robust Intellectual Property Rights regime in India have also helped the cause.
Rule 122 DAA of Drugs & Cosmetics Rules, 1945 (“D & C Rules”) defines clinical trials as a “systematic study of new drug(s) in human subject(s) to generate data for discovering and/or verifying the clinical, pharmacological (including pharmacodynamic and pharmacokinetic) and/or adverse effects with the objective of determining safety and / or efficacy of the new drug”.
It is no secret that a spate of new drugs and molecules are coming in the market and these new drugs have been mostly tried on individuals from outside the country, predominantly the Caucasian race. The genetic background, and the physical built of Indians is different from the Westerners. Therefore, it becomes imperative that any medicine which doctors plan to use on patients of Indian ethnicity, should be tried on patients from within the country so that they know the effective dosage level, and the side-effects which my occur as a consequence of these medications. It is vital that we conduct research and try the new preparations in a clinical setting on day-to-day basis in India before the doctors’ start recommending these medicines in the country based on Western studies.
Regulatory Framework and Approval Procedure
In recent past few clinical trials were conducted in India as a direct consequence of the regulatory restrictions faced by foreign pharmaceutical companies.
With time the Government of India realized the potential benefits of conducting clinical trials in India, and amended various provisions of the Drugs and Cosmetics Act, 1940 (“D & C Act”) in 2005. Pursuant to these amendments, the regulatory restrictions were eased and clinical trials facilitated. Some of the key amendments was to define the term ‘clinical trials’; and to prescribe the procedure of conducting clinical trials. The amendments also addressed responsibilities of sponsors, investigators and the Ethics Committees, besides stipulating guidelines and procedures for the import of drugs for clinical trials in India.
Further, the Medical Council of India Act, 1956 and the Central Council for Indian Medicine Act, 1970 also regulate the conduct of clinical trials in India. The Indian Council of Medical Research, the apex regulatory body for clinical trials, was set up to promote research culture in India and develop infrastructure for clinical trials. An approval from the Drugs Controller General of India (“DCGI”) is mandatory to conduct clinical trials in India. Before the DCGI can approve companies to conduct clinical trials in India, it is compulsory for applicant companies to comply with the requirements for registration as provided by the ‘Pharmaceuticals for Human Use’, ‘International Conference on Harmonization’, and ‘Good Clinical Practices’.
Clinical trials are categorized into two types:
- Type A trials: Trials for which study protocol has been approved by an authorized regulatory body in one or more developed countries like USA, Canada, U.K., Switzerland, Germany and Australia amongst several others. Such trials are approved by using a fast-track mechanism within 2 to 6 weeks after required documents are filed with the DCGI.
- Type B trials: All those trials which fall outside the TYPE A category. The DCGI takes 8 to12 weeks to get approval for conducting these trials.
Ethical and Legal Concerns
As per the Bulletin of WHO titled Clinical trials in India: ethical concerns “While good news for India’s economy, the booming clinical trial industry is raising concerns because of a lack of regulation of private trials and the uneven application of requirements for informed consent and proper ethics review”.
Indian Council of Medical Research (ICMR) is responsible for the formulation, coordination and promotion of biomedical research in India. In 2000 it issued a Policy Statement “’Ethical Guidelines for Biomedical Research on Human Subjects’ (“Ethical Guidelines”) in terms of which all clinical trials in India must be conducted in compliance with the Ethical Guidelines. ICMR has been trying to put in place systems to ensure safety of patients and good quality of clinical trials through the ‘Clinical Trials Registry of India’, which it launched in July 2007.
Interestingly, Dr. Chandra Gulhati, Editor of the Monthly Index of Medical Specialities, says “Fewer than 40 Ethics Committees in India are properly constituted and functioning, which means that the safety of the subjects of clinical trials is on the back burner.”
International agencies have put in place good clinical trial practices from which India can learn. There should be an Ethical Committee before any drug is put to clinical trial. There is also a need for adequate data of stage 1 and stage 2 trials as well as trial on animal model giving adequate safety margin for the dosage level at which it is being now tried on human beings.
In the older system, pharmaceutical companies hosting the trial could set up their own committee and have their own investigators for inquiring into serious adverse events. But the new Rules require the setting up of independent ethics committees under medical institutes to monitor ongoing drug trials. These committees must now be registered with the DCGI before the conduct of clinical drug trials.
One of the problems in our country is that people are not educated to the level where they can understand the concept of clinical trials. It is thus important that clinical trials are conducted in the presence of social worker(s). Every person who agrees to take part in the clinical trial should be informed and made to understand what it is all about, its benefits, the likely side effects, and the methods by which we can address the problems which one might face during the course of the trial.
Another critical facet of clinical trials is that people are not ‘guinea pigs’. Reportedly as many as 2,262 people died in India in the clinical trials during the past five years. This led to a public outcry and Supreme Court intervening for stricter norms for holding these trials. The apex court had also pulled up the Health Ministry for allowing Indians to be used as “guinea pigs” in the conduct of drug trials.
If a trial takes place anywhere in the developed world, the patient is adequately compensated for putting himself through a certain amount of risk. In India, however, at times compensation is not given and even the monitoring is not done properly. This aspect becomes even more critical when the vital parameters like liver function, kidney function, heart, and certain enzyme systems, of the individual patients are affected. These health concerns need to be carefully monitored and observed during the course of the drug trial.
Role of Lawyers
The major role of lawyers before the commencement of any clinical trial comes when there is a precautionary approach taken by the pharmaceutical companies by getting legal opinions from their in-house lawyers as well as from legal practitioners. Any pharmaceutical company which plans to start a trial has to first ensure that it has all the data available and that all the legal compliances are being carried out. To address any eventuality, there needs to be a mechanism.
Another area where legal professionals have a role is the drafting of the confidentiality clause. One of the major reasons why our country does not get too many clinical trials is that we are unable to keep the confidentiality of a trial. This shortcoming can be overcome if there is meticulous drafting of the confidentiality clause. The lawyers advising the drug companies have to ensure that the confidentiality of the patient is maintained and the same is not compromised in anyway. If the clause in the consent form signed by the patient is drafted properly, it would help devise a mechanism by which the patient would be able to appreciate that he/she is participating and will be compensated for the same. Only in such a situation, will the patient treat it as a moral responsibility in the sense that he/she will feel obligated to follow the trial until and unless there is a reason for him/her to opt out.
Dr. Sharmistha Rout from KIMS Hospital, Bhubaneswar opines, “all the subjects ought to be informed about the advantage, adverse effects and the method to be followed for the trial. Their follow-up is also a must. On the failure of any of the above criteria, the company/organization conducting the trial becomes liable and that is where legal interference becomes inevitable”.
Currently, the Indian Council of Medical Research can allow the research protocols to be carried out. Most drug trials that take place in India are pre-marketing surveillance trials i.e. the affectivity of the drug has been proven in some other part of the world.
For the medical academia, one difficulty is that there is lack of proper interaction. The medical academia’s interaction with the other parties should be at a level where they are made aware of the regulatory mechanism and also of the Guidelines for Good Clinical Practice (GCP). It is always ideal to conduct interaction between regulatory authorities and the medical academia. Most clinical trials depend on the time frame which involves waiting for regulatory approval. Effective interaction can help reduce this time bracket. As a concluding note, it is pertinent to mention that there should be a transparent monitoring system by putting the trial results in the public domain under Right to Information Act. Monitoring can be bettered by forming a monitoring committee consisting of medico-legal experts, socially committed professionals and government officials.
On a positive note, the regulatory blocks faced by foreign pharmaceuticals companies conducting clinical trials in India have now been eased and the laws governing clinical trials are at par with the International standards. However, there is now an urgent need to upgrade our systems which monitor the conduct of clinical trials in the country. But perhaps what is most needed is to ensure that the Ethical Guidelines framed by ICMR are strictly adhered to by the drug companies, investigators and all the stakeholders in the field of research on human subject.
India’s clinical research market is currently pegged at a whopping USD 500 million. It is projected to cross USD 1 billion mark by 2016. What drives this market is the large and easily accessible population with lower costs when compared to the developed world. But in the words of the Supreme Court, ‘Uncontrolled clinical trials are causing havoc to human life.’
Cover image from here.
Avinash Mohapatrais an Advocate working with a law firm in Delhi. Avinash holds an LLM from King’s College, London and has also worked with a law firm in London. Mohapatra deals in commercial and criminal litigation and is an alumnus of Symbiosis Law School, Pune.
Richa Kachhwaha is the Managing Editor of Live Law. Richa holds an LLM from the London School of Economics and is a qualified Solicitor in England & Wales.