Clinical trials: Not a case of trial & error

Globally, clinical trials are a critical and indispensable component of the drug development process.

Clinical trials, drug development, patients
Globally, clinical trials are a critical and indispensable component of the drug development process.

– Y K Gupta

Globally, clinical trials are a critical and indispensable component of the drug development process. No drug we consume today would be available without patients who participated in clinical trials. India, which has about 17% of the world’s population and about 20% of the global disease burden, will certainly benefit from the early availability of drugs for conditions that either do not have any therapy available or the new medicine offers significant therapeutic advantage in terms of higher efficacy, reduced toxicity or cost advantage.
Given the high incidence of infectious and emerging lifestyle diseases in India, we need indigenous clinical research to develop new and effective medicines and vaccines. Incidentally, a mere 1.4% of new drug trials take place in India. It is an unjustifiable presumption for some to believe that India’s clinical trial regulations are much lax and all stakeholders do not value human life.

In fact, on many counts, clinical research regulations in India are more stringent than in most other countries and ensure that patients’ rights, safety and well-being are fully protected. However, in certain places, we do need to strengthen the enforcement of these regulations and need more clarity and simplification of the regulatory process.  Since 2013, India has taken several steps to strengthen the regulatory guidelines for clinical trials while ensuring that patient safety, confidentiality and ethics are uncompromised. Under the current regulatory framework, clinical trials for a new or existing drug or medical device can only be carried out at centres that have the appropriate facilities and are staffed with competent and experienced investigators to carry out the trials.

These institutes must also have institutional ethics committees (IECs) that are registered with the Central Drugs Standards and Control Organization (CDSCO). Without the registration of IECs, the clinical trial is considered illegal and not recognised by the Drugs Controller General of India (DCGI). Furthermore, the National Accreditation Board for Hospitals & Healthcare Providers (NABH), an arm of the Quality Council of India (QCI), has set up standards that the IECs need to maintain, in order to get the accreditation to carry out trials in India. There is, on the anvil, a process whereby IECs would need accreditation by January 1, 2018. A similar process may also be set up for accreditation of clinical trial sites and principal investigators in a phased manner. However, till that time, the responsibility of ensuring the competence of the investigator and the adequacy of a trial has been entrusted to IECs.

The CDSCO and the ministry of health and family welfare oversee the conduct of clinical research in the country. The DCGI and even international regulatory bodies like the US Food and Drug Administration (US FDA) and the European Medicines Agency (EMA) periodically carry out inspections of clinical trial sites in India. Their reports confirm the high quality of clinical trials being conducted in India, though it may, at times, be argued that the Indian oversight still needs strengthening. Reasons for patient deaths during clinical trials: Trial related or unrelated? We often come across media reports of patient deaths during clinical trials that make us question the ethical and moral basis of the trial. However, most of those reports fail to establish whether the patient died because of the trial or during the trial. Patient deaths in a clinical trial can result from several causes—natural progression of the disease a patient is suffering from, a new illness he or she may develop, age-related disorders, or a totally unrelated event like a road accident.

It is of utmost importance to establish the cause-effect relationship (causality assessment) before establishing the therapeutic intervention as the definitive reason. In some studies, such as in oncology or outcome trials, investigators follow up with patients long after the completion of treatment, until their eventual death. It is mandatory to report these deaths to the regulators. For example, a patient with diabetes has an increased risk of developing and dying from cardiovascular disease. Therefore, in a diabetes drug trial, investigators may carry out prolonged follow-ups with patients because they are keen to find out whether a new drug controls blood sugar and whether it reduces the occurrence or risk of death from major adverse cardiovascular events. Some clinical trials may also include high-risk patients—some of whom receive standard care while others are treated with the new drug.

In such trials, patient deaths, if and when they occur, are reported as the death of a patient in a trial, but as one can clearly see, it does not mean that the patient died because of the trial. However, many incidents of patient death during trials are amplified in the media without an adequate presentation of all the pertinent facts, causing the public to develop misinformed opinions about clinical trials. While episodic instances of irregularities in clinical trials in India have surfaced, these are rare and unfortunate cases. No one condones these irregularities, which deserve full disciplinary and regulatory punitive action with zero-tolerance principle. But, we must also appreciate that the overall quality of clinical research being done in India is high.  We, as a country, should recognise the benefits that clinical trials have accrued to our patients, and the role that clinical trial patients play in helping progress the scientific quest for safer and more effective medicines, as a result of which many more patients have stood to gain.

The future of clinical trials in India rests on our ability to ensure the protection of patients and the integrity of the trial. I believe India has the necessary framework and stringent control mechanisms in place to ensure that the clinical evaluation of drugs and devices is efficient, transparent, equitable and of the highest quality. If we do lag behind our western counterparts, it has to do with the quantity and not the quality of clinical trials we conduct, a situation that must improve if we are to find better and more cost-effective cures for a population that is as heterogeneous and multiracial as ours.

The writer is the Professor and head, Department of Pharmacology, AIIMS

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