Clinical Trials

Clinical Trials

What is Clinical Research and a Clinical Trial?

Healthcare is guided by inputs through a wide array of agencies. Research on new molecules is conducted by Pharmaceutical Companies, through a series of drug developmental processes. Clinicians become a part of these processes, in what is termed as Clinical Research (CR), through, conduct of clinical trials.

The National Institute of Health (NIH), USA defines CR as “Patient Oriented Research", conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive phenomena) for which an investigator directly interacts with human subjects. Patient-oriented research includes: (a) mechanisms of human disease, (b) therapeutic interventions, (c) clinical trials, and (d) development of new technologies.

A clinical trial is any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions, to evaluate the effects on health outcomes. Interventions include but are not restricted to drugs, cells and other biological products, surgical procedures, radiological procedures, devices, behavioural treatments, process-of-care changes, preventive care, etc.

Clinical Research is an intrinsic component of clinical practice. It enriches practice by creating knowledge, which is then applied to improve prophylactic, diagnostic and therapeutic procedures, as also to improve understanding of the etiology and pathogenesis of disease. By challenging custom and questioning convention and focusing on groups rather than individuals, it systemically creates evidence that compels changes in practice.

Trials are conducted step-by-step, i.e. in phases. In oncology, Phase I trials done on 10-15 patients, and aim to determine the safety of the drug and define an optimal dose. Phase II trials continue to refine safety evaluation as well as get an idea of the efficacy aspects in a slightly larger (a few scores) patient population. It is the Phase III studies - Randomised Controlled Trials, where a few hundreds to a couple of thousands of patients or even more participate, which define the efficacy as compared to standard practices. Novel designs are being developed to minimise the ‘at-risk’ population while obtaining meaningful (conclusive) results.



Scenario in India


Drug Trials are conducted in India after permission from the Drug Controller General of India (DCGI). A clinical set-up referred to as ‘site’ may conduct any particular study only after the Institutional Review Board / Ethics Committee (EC) approves it. In institutions, where there is no provision for such a committee, review is sought with Independent ECs. Whether institutional or independent, guidelines laid down by regulatory and advisory bodies (DCGI and Indian Council of Medical Research 'ICMR') for the constitution and functioning of such Ethics Committees are followed in the review process, to ensure that patient well being remains the focus and there is no abuse of science, by compromising ethics.

There are Good Clinical Practice (GCP) which are universally accepted as a beacon for the conduct of clinical trials. The trial is introduced, explained verbally and through an approved consent document, which the patient can read and / or understand. It is the responsibility of the Investigator / delegated person, to ensure that patients take an independent, well-informed decision to consent for participation in a clinical trial and are not coerced into it. The mandate for registering clinical trials with the Clinical Trials Registry of India implemented since June, 2008, ensures that knowledge about trials is in public domain.


Clinical Research at RGCI & RC

 Rajiv Gandhi Cancer Institute & Research Centre (RGCI & RC) embarked on an eventful journey in Clinical Research after the constitution of the Institutional Review Board (IRB) in 1997. Currently, the IRB composition follows the mandate of Schedule Y by the DCGI. Issues related to ensuring patients’ safety and well-being govern the actions of the IRB.

The RGCI & RC has earned itself the reputation of being a destination of choice, or a preferred research centre for many pharmaceutical companies and contract research organizations (CRO). It has attracted several International academic groups, like EORTC, GELA, BCIRG etc, as well as Indian Universities like Delhi University and Jawaharlal Nehru University.

The first Phase I oncology trial, that was conducted in India was at RGCI & RC about a decade ago. RGCI & RC has had an exposure to early phase studies, but advanced phase trials have predominated, as depicted in Figure A.

Figure A

 

Specialty in which trials have been conducted.

The thrust of clinical research at RGCI & RC, in line with trends in the developed world, has been targeted therapies - Monoclonal Antibodies like Trastuzumab, Rituximab; Tyrosine Kinase Inhibitors (Imatinib); EGFR Inhibitors, namely, Gefitinib, Erlotinib, Lapatinib; VEGF Inhibitors like Bevacizumab. Besides, Novel Chemotherapy Agents like Alimta and Ixempra have also been used successfully in trials. A landmark study on the use of Gemcitabine in Gall Bladder (GB) Cancer way back in 1999, led to publication of results in British Journal of Cancer in 2004, which further inspired many similar studies. Based on the evidence gathered, the Institute's Investigator conceptualized a phase II project investigating the role of neo-adjuvant chemotherapy (Gemcitabine and Cisplatin) in poor prognosis but potentially resectable GB cancer. Today, not only is the protocol followed as a standard of care, but also used as a comparator arm in other drug studies for this indication. Further, a recent phase III trial by a group of British scientists, published at the ASCO, 2009 has established the protocol, as the standard of care. Considering that the incidence of Gall Bladder Cancer in Delhi, and in general, in the Gangetic belt, particularly in women, is among the highest in the world, this study has been truly path-breaking. Breast Cancer trials of various phases in adjuvant and metastatic settings are also being conducted regularly and about 3 - 4 trials for this indication are running at any given point of time.

Supportive care in oncology has seen major advances in the past two decades. Clinical trials in growth factors, observational studies in patients’ psychological needs and challenges, quality of life and surveys in patterns of utilisation of complementary medicines, all highlight the various complex aspects of patient care.

The Surgical and Radiation Oncology teams have had a variety of technique, device and drugs trials. Among the drug trials conducted by the team, prostate has dominated the scene (13 trials).

Diagnostic studies in imaging and pathology / microscopy / molecular diagnostics have been important in the understanding of patients’ disease profile. This includes pediatric patients also.

The various Registries (National and International) and other Epidemiological data collections are relatively suboptimal in India. RGCI & RC has been consistent in providing data through a handful of such studies.


Organisation of CR Activities at RGCI&RC

 
Clinical Research is a data-rich, labour-intensive activity. The set of skills required of researchers is not just the domain knowledge, but also a hawk’s eye for detail without losing sight of the larger picture. Research Methodology, Project Management, Data and Time Management are among the other essential skills. Above all, the single essential quality is, commitment to understanding and reflecting only the truth. At RGCI & RC, the CR team comprises doctors, nurses, managers & office assistants, A PhD (underway), post-graduates in medical / life sciences or management, graduates comprising 14 people have been on the job. The functions include patient management, data collection and transcription, pharmacovigilance activities etc. The site has faced a number of independent as well as sponsor / CRO driven audits. The team is geared for DCGI and other regulatory audits. The work done has been recognized by peer groups as evidenced by (a) Abstracts presented at International meetings - 25, co-authored - 15 (b) full papers published - 10, and author citations - 7. The team regularly updates its capacities in terms of training and education. Some of the senior members have been part of the consultative group that made a set of recommendations to the ICMR, contributive in formulating the ICMR Ethical Guidelines for Biomedical Research on Human Subjects in the year 2000.


Funding


 Clinical Research is a self-sustaining activity at RGCI & RC. It is funded by various sponsoring companies; and academic groups. The hospital pools the financial resources through which all funds are disbursed as per the individual protocol requiring tests and procedures as well as for the personnel. Support has also come from the Department of Science & Technology, Government of India.


Future Perspectives

Research has always had a prominent role in the hospital activities at RGCI & RC and leaders have been playing inspirational roles for the team. Besides, it has helped inculcate a culture of detailed documentation and has provided some new technological capabilities to the hospital Infrastructural and, at times, technology deficiencies, if managed in optimal time appropriately, will give Clinical Research a cutting edge knowledge advantage to lead future practices in clinical work.

Research has always had a prominent role in the hospital activities at RGCI & RC and leaders have been playing inspirational roles for the team. Besides, it has helped inculcate a culture of detailed documentation and has provided some new technological capabilities to the hospital Infrastructural and, at times, technology deficiencies, if managed in optimal time appropriately, will give Clinical Research a cutting edge knowledge advantage to lead future practices in clinical work.

 

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