‘India has highly qualified clinicians providing excellent clinical care’

Dr Ravi Anand, MD, a resident of Switzerland, an independent consultant specialises in the development and commercialisation of New Chemical Entities (NCE) for Central Nervous System (CNS) disorders. He is a consultant to pharmaceutical and biotech companies, contract research organisations (CROs), universities and financial institutions. Dr Anand was educated in New Delhi, and trained in New York, US, in psychiatry and neurology. He has worked in international drug development and registration departments of major pharmaceutical companies for over 20 years. Companies that he has worked for include F. Hoffman LaRoche, Switzerland, Sandoz/Novartis, US, and Organon, Netherlands. He served as the international head of CNS medical affairs at Novartis and as the global head of CNS clinical research at Organon. During his tenure in the pharmaceutical industry, he has worked in all phases (I-III) of drug development and also in medical commercialisation (phase IV). Overall, he has been responsible for the conduct of clinical trials in over 30 countries. He has been involved in over 25 IND submissions, and over seven international New Drug Applications (NDAs). He has published extensively (over 50 papers and over 200 abstracts, posters and presentations). Dr Anand who recently visited India, is an advisor to international pharmaceutical companies and CROs in US, Europe, Middle East and Asia. Dr Anand in an exclusive with N V Ramamurthy discusses various issues in clinical trials. Excerpts:

How different is the perspective of heading the medical affairs activities in industry from that of being a pharmaceutical development consultant? What were the reasons for you to make this change and why?

Clinical research and medical affairs activities in the pharmaceutical industry require an in-depth knowledge of pharmacology, medicine, clinical trial design and methodology, statistics, regulatory affairs, and medical marketing. All these activities are conducted on behalf of the company that one works for. As an independent consultant, I advise on the same issues, but to different clients, and I have the freedom to propose the best solution without having to consider internal pharmaceutical company biases.

What are your observations in general about India’s clinical research activities today? During the last decade, where has it made progress and what are the areas it has still to catch up with the developed world? Are there concerns in terms of Good Clinical Practice (GCP) in India still?

India has highly qualified clinicians who provide excellent clinical care. The number of investigators who are qualified to conduct clinical trials are small. Advances in technology are not available at many of the sites that one could consider for conducting trials. Over the last few years there has been a significant improvement in the creation of a research environment including establishment of ethics committees, good clinical practice training, understanding the distinction between good clinical care and good research design and the promotion of the concept of informed consent.

There needs to be a determined effort to train medical students, junior doctors, nursing staff in research methodology. Hospitals do need to improve infrastructure to allow research activities to be performed in better surroundings. More sites need to be trained in the concept of GCP.

At the international level, what are the new trends that are taking place in the conduct of clinical trials? How stringent are the regulatory requirements for both sponsors and investigators compared to a decade ago?

Globally, patients, care givers, governments and NGOs are getting involved in clinical trials of both marketed drugs as well as those in development. Virtually every stage of a drug development phase is in the public scrutiny. All protocols and the results of these studies will be in the public domain. The regulatory requirements are, perhaps, not more stringent but are more rigorously applied.

There’s been a rush of CROs working out of India of late. What are your observations and comments? How do you think they should be equipped to deal with the challenges of conducting trials in India?

More and more clinical trials are being performed in India, both by local and international companies. As the new trials will need to be performed to an international standard, and the number of trained staff to monitor in companies in India is low, it is evident that CROs will be mandatory to ensure the quality of the trials. Furthermore, CROs will be necessary to ensure that informed consent procedures are followed and the rights of patients are protected. CROs will need to find staff that are experienced and educated in biological sciences. They must be trained to detect deviations from protocol, and vigilant regarding quality of the data being collected.

Given the limitations in the present scenario, what are the opportune areas where Indian CROs can make a contribution and how should they maximise this? What kind of business opportunity do you see for the CROs in the next few years in India?

Indian CROS have the advantage of knowing the local procedures. If they can demonstrate that they are as good as international CROs with regard to quality and timeliness they will be able to make significant contributions. Over the next few years, the number of trials being performed in India will multiply; a large portion of this business could go to Indian CROs.

In the context of work being outsourced to Indian CROs, could you elaborate on the important pre-conditions International sponsors expect from the above outfits.

International sponsors will expect Indian CROs to maintain and follow international standard operating procedures, establish data audit trails, select only qualified investigators, ensure patient confidentiality and protect their interests, follow GCP guidelines as well as all applicable requirements, hire experienced and qualified staff, and ensure transparency of all financial transactions.

How do you think the international sponsors react to issues of ethics in trials in India? Do they have reservations about patient education and awareness? Don’t you think they can play a significant role in enhancing these levels before outsourcing work? How can this be done?

International sponsors are beginning to realise it is possible to conduct good quality trials in India that conform to high ethical standards. Clearly, this may not be the case at all sites that could perform trials but only at major hospitals, university institutions, etc. Patient education, awareness and informed consent are major issues that all sponsors will require to be enforced.

Do you advocate the role of NGOs and patient representatives being pro-actively involved in the conduct of clinical trials in India? If yes, your suggestions to strengthen such groups.

NGOs, and patient support groups can play a key role in ensuring that patients receive guidance regarding what to expect from clinical trials, their rights including the right to withdraw at any time-point, the benefit they or society may accrue as a result of participation, the alternative therapeutic strategies that may be available to them if they choose not to participate in a trial.

Representing the sponsors, do you feel they have reservations on methodologies used for site identification, feasibility set-up and location of site? How should this be done ideally?

Site identification should be based on the qualification of the investigator, the staff, the infrastructure at the site, the physical environment where the trial will be conducted, the presence of an ethics committee, the number of patients available at the site as well as the site’s prior experience in conducting trials. This is always difficult to ascertain for a sponsor. In general, sponsors evaluate the CROs recommendations based on third party inputs prior to deciding which sites to select.

Your comments on the Indian regulatory system, especially with the revised schedule Y guidelines. What about regulatory framework to aid the growth of Indian CROs?

Schedule Y is a well thought out guideline. The standards proposed are consistent with ICH/EMEA guidelines. If this schedule is followed rigorously, the quality of trials, and consequently the quality of care of patients enrolled in the trials will be high. The rights of patients have been protected. The oversight procedures including the government review of the protocol would meet international standards.

—nvramamurthy@expressindia.com