linical research in India has evolved significantly in the last two decades. In the early 1990s, clinical trials in India started with very few sites. The country not only had a treatment-naïve population, but its cohort of clinical investigators and clinical research coordinators was also naïve to global GCP and regulatory requirements.

In 2005, regulatory authorities in India allowed parallel phase clinical studies, that accelerated patient access to new chemical entities. Exponential growth in research followed; nearly 500 clinical trials were registered in the Clinical Trials Registry – India between 2005 and 2010. But that pace proved too hot for the clinical trial industry to handle, and from 2012-2013 a number of issues (ranging from ethical to regulatory oversight) brought the industry in India to a grinding halt.

But as the saying goes: Every crisis is an opportunity for improvement.

Since then, clinical research in India has gone through a flurry of debates and changes, such as mandatory audio-visual (AV) recording of consent for all trial subjects, registration of Ethics Committees, serious adverse event (SAE) notification changes, and compensation for patients in trials. As the heart and soul of clinical research, Informed Consent received the primary attention of regulatory authorities. The first introduction of AV recording of the consent process brought the ubiquitous camera into the limelight of research, and these recordings went a long way in reassuring stakeholders about the transparency of clinical trials in India. (And clinical trial teams became as adept in camera positioning, lighting, and angles as any professional cinematographer!)

The last five years have continued this transformative phase for clinical research in India. Important regulatory changes have led to a more conducive environment for research. In March 2019, the health ministry released the new guidelines for clinical research which were balanced and aligned with global standards while also addressing local issues.

With the Above as Background, What Does It Take to Transform a Physician into a Clinical Investigator in India?

The primary responsibility of a physician is to improve patient outcomes. But conducting research, in addition to providing clinical care, is one of the important steps a physician could take to improve patient outcomes. Millions of patients in India suffer from diseases for which there is no cure, or have stopped responding to medical treatment and need improved therapies.

17 percent of the global population, and 20 percent of the global disease burden, resides in India, yet less than 1.4 percent of global clinical trials are conducted there. A 2016 pilot study published in International Journal of Health Policy and Management found that mentorship in the clinical research process (52 percent), time allocated to research (43 percent), and financial reward (29 percent) were important contributors to this gap.

Although physicians based at teaching hospitals traditionally participate in research in addition to caring for their patients, the fact remains that private practitioners see a large number of patients and are also ideally positioned to be clinical investigators.

It is this author’s strong belief that being a good clinician is a prerequisite to being a good clinical investigator.

First Steps in Physician to Investigator Shift

Shifting from the role of Physician to the role of Investigator is complex, especially in the dynamic clinical research environment of India. The physician must shift their primary objective of curing the patient to finding out which therapy works better in their patient. The first steps in this transition involves understanding the nuances of research—especially the need for elaborate documentation and the familiar statement, “What is not documented has not been not done.” Extending this documentation practice into routine clinical work significantly improves the quality of patient records. Investigator experience from the informed consent process goes a long way in improving communication and rapport with patients.

The naïve physician-investigator is bombarded with hitherto uncommonly used terms such “bias” and “placebo;” learning new terms in new experiences provides a new, more open perspective on the research protocol. The concept of “equipoise,” a balance of forces or interests, becomes vital to enrolling patients into the trial. If study patients suffer from therapeutic misconception, the physician learns to transcend from the anecdotal physician (“I say so”) to the evidence-based investigator (“The protocol says so”).

The physician who has been the head of patient management now finds himself questioned by non-doctor monitors about trial conduct. One of the biggest advantages in this transition is the investigator working as part of a team; the investigator’s interaction with the Ethics Committee (EC) is one of its most vital aspects. During the initial interactions, the investigator may feel intimidated by probing questions posed by various EC members and their diverse backgrounds. The fact that all stakeholders in clinical research focus on patient safety dawns on the investigator.

Regulations and Other Next Steps

In this interesting journey, the investigator soon realizes the need to be cognizant and up to date on the regulations and laws of India. Regular sponsor interaction opens new insights into even more aspects of, and technologies for, drug development. Another new experience the investigator gains in this process is the site quality audit. The investigator and team go through intense and rigorous audit preparation, which often tests the patience and perseverance of the entire team; nevertheless, every audit and inspection presents another excellent learning opportunity and enhances the commitment of the clinical trial team.

The relationship between the investigator and the patient in a clinical trial is of utmost importance. Both investigator and patient must understand their respective roles and responsibilities as they shift from the more familiar physician-patient relationship. It is important for the physician to play the dual role of doctor/investigator while keeping in mind the patient’s best interests. Similarly, the patient begins to understand the importance of their own study responsibilities like completing the eDiary on time or compliant reporting of SAEs and other adverse events. In this author’s experience, many patients over a period of time recognize this aspect and the concept of altruism in research begins to dawn on them.

Research With Patients

The patient is the most important stakeholder in clinical research. Patient involvement in clinical research is vastly different from the patient role in the physician-patient relationship. Informed consent can be quite daunting for both the patient and the investigator, with elaborate informed consent documents presenting a constant challenge to patients wishing to understand important aspects of the study. It is important to further improve this process, perhaps by exploring the concept of the “Expert Patient.”

In a diverse country like India, the investigator must be sensitive not only to the scientific and ethical but also to the cultural aspects of a clinical trial. It is imperative that patients understand their roles and responsibilities as clinical trial participants and are active partners in research. Despite India’s large patient pool, only a small number of patients in India participate in clinical trials. Negative perception about clinical trials among the public is one important reason. Is it because only those patients whose physicians are also investigators have access to clinical trials in India? There is a pressing need to increase awareness of clinical research among the medical fraternity, and in this author’s view there must be a shift from the culture of “research on patients” to “research with patients.”

Many if not most research questions are posed from the scientific/regulatory perspective but may not be relevant from the patient’s perspective. For example, patients in a COPD trial are probably more interested in the variables impacting their quality of life instead of the surrogate marker FEV1. The author also looks forward to clinical trials that prioritize patient-reported outcomes (PROs), which must still be relevant and adequately validated.

Rapid global development of drug and device therapies has led to a significant increase in the number of global clinical trials. With its current regulatory scenario, diverse disease pool, qualified investigators and study coordinators, and well-structured Ethics Committees, India is poised for high-quality ethical clinical research relevant to its own local as well as the global community.

Opportunities in Research and Understanding

Clinical research offers exciting opportunities for budding physicians to enhance their knowledge and skills, and to elevate one’s stature amongst their peers. Participation in a trial helps clinicians remain at the cutting edge of their speciality and provides publication and other opportunities. The journey from clinician to investigator leads to better understanding about the disease, improved documentation practices, better attention to detail, and improved patient communication.

The good old adage that Today’s research is tomorrow’s practice has never been more true than it is today in India.