Clinical pharmacology training in India: Status and need.

Clinical pharmacologists undertake many tasks, and this makes defining a curriculum challenging. This is especially so under the changing circumstances in developing countries, where clinical pharmacology has an expanding role. The clinical pharmacologist may be responsible for conducting ethical clinical trials, supporting the needs of the generic drug industry, providing access to safe, effective and affordable medicines, guiding their rational use, achieving millennium development goals, and supervising medicines management standards for hospital accreditation. Clinical pharmacologists, including those in developing countries, have a great opportunity to contribute to public health and the growth of pharmaceutical industry, but at present, less clinical research is undertaken and fewer clinical trials are done than might be expected. Here we review clinical pharmacology training in India, consider the needs of different professionals contributing to clinical research and medicines utilization, and suggest ways in which current programs can be modified and new programs started. The conclusions are relevant to clinical pharmacology in both the developing and the developed world.

Introduction

Clinical pharmacology which involves all aspects of the relationship between drugs and humans, sets out to describe, explain, and predict the fate and the effects of drugs in human, developed as a discipline in the 1960s in USA, Europe, and UK.[123] At the same time, clinical pharmacology began in India due to efforts of stalwarts like Dr. U.K. Sheth, Dr. Ranjit Roychaudhary, Dr. P. L. Sharma, and many others.[4]

In the past 50 years, the discipline has grown. However, now there is an enormous need of trained clinical pharmacologists. The pharmaceutical industry has prospered. There is generic pharmaceutical industry, which is multibillion dollar in India.[5] With changes in patent laws and drug regulations, large numbers of clinical trials are being done in developing countries, on drugs developed in other countries as well as on new drugs developed by local industry and academia.[6] On the other hand, in the public health scenario, there are several government and even industry initiatives to expand the coverage of healthcare and reach medicines to rural areas.[7] The National Accreditation Board for Hospitals (NABH) has outlined standards to improve hospital services, pharmacy, and medication usage.[8] To meet industry needs, there has been a great rush to develop clinical trials sites, contract research organizations, and bioavailability centers. But, there is need to provide training in clinical pharmacology and clinical research to contribute to public health, hospital practice, and ethical drug development process. This commentary reviews the current status of training in clinical pharmacology, clinical research, and pharmaceutical medicine in India, its deficiencies and suggests a way forward. While it is based on scenario in India, it should be useful to other countries facing similar challenges.

Current Status

Clinical pharmacology and the related subjects, clinical research, and pharmaceutical medicine are taught in undergraduate and postgraduate programs of medicine, dentistry, nursing, alternative systems of medicine (such as Ayurveda), pharmacy and also as specialized courses in clinical research and pharmaceutical medicine.

Undergraduate and Postgraduate Programs in Medicine [Table 1]

A great deal of effort has gone into integrating teaching of pharmacology and clinical pharmacology with clinical subjects, but there is still a long way to go.[9]

The undergraduate program does not include training in research though it is proposed.[10] A few students avail themselves of the research fellowship for undergraduate.[11] For postgraduate courses (MD/MS), a research project and dissertation are mandatory.[12] Only recently, approval by an ethics committee has been made necessary for these research projects.[13] Postgraduate students and teachers must now undertake training in research methodology.[1013] The three years M.D. Pharmacology program, open to medical graduates, covers many aspects of Clinical Pharmacology.[14] The three years D.M. Clinical Pharmacology super specialty course open to candidates who have completed the M.D. Pharmacology course, covers all aspects of drug development, clinical research, regulatory requirements ethics, and patient care issues such as drug prescription, adverse drug reactions, and therapeutic drug monitoring.[15] It does not include market research or other management topics, which are useful in evaluating the societal needs and formulating an essential drugs list.

Undergraduate and Postgraduate Pharmacy Programs [Table 1]

Pharmacy is taught as an industry- and product-oriented profession. During the two-year postgraduate pharmacology course (M. Pharm. Pharmacology), students study the preclinical evaluation of the efficacy and toxicological effects of drug molecules, but very little about the phases of clinical trial as a part of the drug development process. The curriculum for M.Pharm degree in clinical pharmacy and pharmacy practice includes subjects related to hospital practice and requires a thesis based on a year of clinical research in a hospital. In the six-year Pharm D program, the student take courses in clinical research, Pharmacoepidemiology and pharmacoeconomics, clinical pharmacokinetics, etc. and undertakes project work in fifth year.[161718]

Clinical Research

Postgraduate degree, diploma, and full time or part time certificate courses in clinical research are conducted by over 50 mostly private institutes. Admission to these courses is open to graduates holding Bachelor degree in science, medicine, dentistry, nursing, pharmacy, veterinary science, Ayurveda, homoeopathy, etc. [Table 3].

Table 3

City-wise distribution of number of publications on clinical trials/ studies and clinical research training institutes in India

These courses train participants as clinical research associates for conducting, implementing, and monitoring clinical trials to meet the regulatory requirements. Only a few courses provide practical training in hospitals and industry and have a research project as a part of their curriculum.

Pharmaceutical medicine [Table 1]

Two universities, namely the Maharashtra University of Health Sciences and Jamia Hamdard conduct M.Sc. and Ph.D. programs in pharmaceutical medicine.[1319] Practical training includes visits to hospital wards, research projects in hospitals, and a workshop on research methodology conducted by students. The MUHS program is like the program by Royal College of Physician, Faculty of Pharmaceutical Medicine, UK, except that it is also open to physicians from Alternative Systems of medicine.

Government Initiatives

Indian Council of Medical Research (ICMR), Department of Health Research (DHR), Department of Biotechnology (DBT) and AYUSH (Ayurveda, Unani, Siddha, Homeopathy) Departments of the Government of India have initiated programs in specialized areas. The Indian Council of Medical Research has been conducting workshops on clinical pharmacology for nearly 40 years at Seth G. S. Medical College and King Edward Memorial (KEM) Hospital, Mumbai.[4]

Deficiencies of Present Programs

Clinical research [Table 2]

The part time and short-term certificate courses are not accredited, are classroom-based, and provide little practical training in healthcare settings, in industry or at regulatory agencies. The contents of the programs are not updated, and there is very little faculty development or updates.

Students of the courses are from different educational backgrounds, and many are unfamiliar with the basics of modern medicine and the rigors of research.[20]

Training physician investigator

Most training programs in clinical research train students in implementing clinical trial protocols. While this is important, investigator-driven studies intended to answer relevant questions are vital in the context of advancing knowledge, bridging gaps, developing guidelines and policies, as emphasized in a recent editorial in the Lancet.[21]

Of 11,884 human trials conducted in 178 countries, only 2% were carried out in India as against an expected 15%.[22] Of 21.067 million publications in PubMed, 0.769 million have the keywords ‘clinical research’ and ‘clinical studies.’ Of these publications, 32.20% are from the U.S.A. and only 1.2% (1198) from India.[23]

Postgraduate courses offered by universities, such as the Ph.D., M.D. Pharmacology, D.M. Clinical Pharmacology, Ph.D. Clinical Pharmacy, M.Sc. Pharmaceutical Medicine, and Ph.D. Pharmaceutical Medicine, train students in hypothesis generation, framing research questions, and designing appropriate studies. The M.D., M.S., D.M., and M.Ch. courses in other clinical disciplines also do train students in clinical research. However, they give importance to learning clinical skills for patient care. The number of M.D., M.S., D.M., and M.Ch. places is grossly inadequate for societal needs for patient care, and very few students are able to devote time to research.

Training for hospital practice

MD Pharmacology, DM Clinical Pharmacology, M. Pharm Clinical Pharmacy, and Pharm.D programs encompass medicine management and usage; however, most programs lack adequate practical training.[1518]

Regional disparity

There is a regional disparity in medical colleges and training programs, with relatively few educational institutions in the eastern and north eastern states. Most training programs are conducted in big cities [Table 3] (data extracted from www.gopubmed.com).

Way Forward

Clinical pharmacology, clinical research or pharmaceutical medicine training programs should provide skill and competency that meet the needs of society and contribute to public health.

Suggested modifications in current programs

The clinical research program should provide hands-on practical experience in industry and clinical trials setting with various healthcare providers. Their training should include public health perspective so as to enhance their skills as clinical researchers.

The programs should have common syllabus and accreditation. All programs should have sessions on ethics and talks by respected role models and experts to guide young minds into developing appropriate attitude toward patients and research. Ethics, informed consent, and truthfulness are vital for conducting clinical research, for gaining acceptance and support from society, and generating valid, relevant information and knowledge. Clinical research will survive and flourish if it is beneficial to patients and society.

At present, only 15-16 students get trained in the D.M. Clinical Pharmacology course and approximately 550 students get trained in M.D. Pharmacology every year.[24] These trainees are absorbed into the pharmaceutical industry, and only a few enter academic institutions. There could be dual appointments of teachers from clinical subjects, public health or industry in clinical pharmacology in academic institutions, increase in number of students enrolled per teacher, and in the number of departments of Clinical Pharmacology. The eligibility for enrolling for Ph.D in clinical pharmacology and pharmaceutical medicine in the different universities varies, permitting holders of undergraduate/postgraduate degrees in medicine or pharmacy.[25] Researchers working in industry have few options for midcareer breaks. Collaborations in academics, and universities would be useful to provide greater opportunities.

There is considerable emphasis on alternative systems of medicine in India. Approximately 27,000 graduates and 2300 postgraduates are trained every year.[26] Graduates are eligible to enroll in courses in clinical research and pharmaceutical medicine. Their training should include training in modern medicine, research methodology, basic laboratory work, and good clinical practices.

Initiating new programs

New programs should be initiated for various professionals involved in the drug development process and in rational use, particularly for geographical areas with inadequate training opportunities.

Clinical investigators need training in areas of need e.g. clinical trial design, statistics. ICMR has initiated programs in pharmacovigilance, pharmacokinetics/pharmacodynamics (PK/PD), outcome research, antibiotic stewardship and infection control (ASPIC) with emphasis on practical training.

NIH program for clinical investigators is being conducted at Bangalore, training 20 participants every year. Such programs need to be promoted.[27] Practical courses in newer laboratory techniques, good laboratory practices, animal experimentation, and electives in industry, regulatory agencies, different healthcare settings should be provided to medical students. Pharmacy students should have opportunity to do electives in clinical trials and regulatory requirement.

In the pharmaceutical industry, clinical research is carried out to meet regulatory requirements, contract research organizations are perceived as investment opportunities and are often controlled by management and project review teams. There should be training programs for managers so that they do not compromise ethics while achieving business targets. The Garware Institute of Career Education and Management of the University of Mumbai started a course in Pharma management, with guidance from Brian Gennery, former president of Royal College of Pharmaceutical Medicine, which at least partly met this need.[28]

The office of the regulatory agency while dealing with applications for investigational new drugs, marketing permissions, and post-marketing surveillance has to follow the provisions of the law on the one hand and the aspirations of the pharmaceutical industry on the other hand, balancing the risks and benefits to society. Training programs and workshops, especially with regulators from other countries, would be greatly useful (some such program have already been initiated).

Rational use of drugs and medicines management requires concerted efforts by hospital pharmacy. Training in clinical pharmacology and principles of clinical pharmacology should be a mandatory part of continuing professional development programs for pharmacists.

Online courses for knowledge and problem-solving skills and programs with mentors for developing clinical research skills and ethical attitude could be a way forward. Capacity building and training in important areas of clinical pharmacology and clinical research will in the long run add quality to the clinical studies for industry as well as better healthcare delivery.

Conclusions

Clinical pharmacologists have a great opportunity of contributing to public health, hospital accreditation, issues of societal importance, and to drug development and ethical clinical trials for pharmaceutical industry. Currently, the training programs are deficient in quality (lack of practical training), quantity (too few for e.g., India a country of 1.2 billion population), coverage (inadequate in some geographical areas), and in training clinician investigators and other professionals.

The existing programs need to correct these deficiencies, and new programs should be started. Tailor-made programs in ethics for managers and administrators, in statistics, design of clinical trials and rational drug use for clinicians, pharmacovigilance for public health professionals, drug development process for basic science researcher, and a midcareer opportunity of doing Ph.D for pharmaceutical industry physicians are needed. Dual appointments in clinical disciplines, public health, industry, and clinical pharmacology would help in providing the links and meeting with the current and future demands on Clinical Pharmacology training.

Table 1

Graduate and postgraduate courses in healthcare

Table 2

Deficiencies in clinical research courses