The Changing Face Of Post-Marketing Research

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By Dimitris Polygenis PharmD and Gabriela Radulescu MD

There is a growing paradigm shift in the area of post-marketing research. Post-marketing studies for drugs (also known as Phase IV studies) historically targeted new clinical uses and clinical indications. Now, many post marketing studies strive to study factors outside the inherent biologic actions of drugs. With the rapid expansion of available drugs and the complexity of its use, increasing the understanding of drug use, the economics of a drug and other factors related to the practice of medicine is paramount.

This apparent divergence in post-marketing research is leaving some clinical researchers puzzled. Some have chosen to view this as a choice between two opposing camps: the traditionalists or purists who maintain that post-marketing research, like early phase research, is about answering scientific questions; and the pragmatists who believe that the research is about ensuring what has been promised to regulators translates in real-world practice from all perspectives: clinical (safety and efficacy), humanistic (patient reported outcomes) and economic (cost-effectiveness). Dissention exists between the clinical and marketing teams of many biopharmaceutical manufacturers.

Clinical departments have long held strict ownership over all forms of clinical research with its methods and actions dictated by well accepted international guidelines and regulations. This group of researchers have had a single goal - regulatory approval. They are generally not well versed (or interested), in the challenges faced in successfully answering questions that allow health professionals and payers to adopt and effectively use high cost medical interventions. These questions are as important as those that lead to a drug being approved. For example, marketers are being asked to provide data that its products have proven both to be safe and efficacious but also cost-effective by payers. Marketers are being asked by prescribers and payers to guarantee safety beyond that shown in phase III trials. Physicians are demanding tools and guidelines and payers are demanding results they can take to the bank. Facing these demands and challenges, it is wrong to take the view that one has to choose to be a purist or a pragmatist. Different types of research necessitate different thinking to effectively apply the principles of sound scientific research to new spheres of study.

Marketers cannot be expected to design and execute studies. Nor should it be expected or assumed that clinical researchers or statisticians have the background and know-how to design and conduct studies which contain the pragmatic and behavioural outcomes that the post marketing healthcare system stakeholders need. A growing number of manufacturers are realizing that to have the best of both worlds, one must bring both clinical and marketing experts to the table.

Post-marketing research has evolved into patient registries, risk management programs, post-marketing surveillance programs, observational studies, disease management programs and care quality improvement initiatives (i.e., patient compliance programs, patient access programs, etc.).

Federal regulatory guidance on conducting post-marketing initiatives and patient registries is evolving. Historically, regulatory bodies had not made a priority or lacked effective tools to assess the impact of introducing new therapies on the markets. In recent years and with the 'help' of a few blockbusters failing to keep the risk/benefit ratio in balance, regulatory authorities such as the FDA and HC have been forced to review the mechanisms by which postmarketing surveillance has been conducted and monitored. Moreover, the introduction of more and more complex molecules on the market that intend to treat niche patient populations has brought the need of redesigning postmarketing research models.

There is a common understanding among the regulators and the industry that traditional epidemiological studies no longer serve all the needs identified by the stakeholders involved. Postmarketing research has been demonstrated as required to provide more insight in the real world use than in the past. Regulators are more and more comfortable conditionally approving complex drugs, putting the onus on marketers and researchers alike to create feasible mechanisms to provide the data required. To align with the changing regulatory environment and better serve its needs, Health Canada recently announced that it is in the process of revising its current approach to drugs' life cycle monitoring.

There is a general agreement that the current process offers limited provisions to monitor drugs after approval and that there are no effective mechanisms to monitor compliance or offer an open and transparent environment to assess postmarketing effectiveness and safety, while protecting confidentiality. As a result, Health Canada created a new vision for its mandate, one that will approach products from a life-cycle perspective.

The new regulatory environment aims to be proactive, to require the implementation of regulatory interventions proportional to risk and make use of all type of evidence, among other objectives. This new regulatory direction only demonstrates that the industry must align as well and facilitate creation of an environment where postmarketing research is conducted in more than one way, to address the current needs of patients, prescribers, marketers and researchers alike.

Post-marketing observational studies will continue to move away from answering scientific questions and move towards validating the safety and effectiveness of interventions in real-world settings. Recent drug recalls have made it clear that the rigorous scientific and epidemiological methods utilized in traditional drug trials are no guarantee of safety and effectiveness. People must begin to differentiate between traditional clinical trials and post-marketing research. Post-marketing studies, while respecting the principles of clinical research, cannot be run like traditional clinical trials. The success of these evaluations will be determined not by the science employed but rather its ability to meet the needs of patients, payers, prescribers and decision-makers.

Dimitris Polygenis, PharmD, vice president of McKesson Phase 4 Solutions (Toronto, ON) is a pharmacospecialist with graduate training in clinical research, health economics and health policy. Dr. Polygenis is currently Lecturer and Clinical Assistant Professor at the Universities of Toronto and British Columbia Doctor of Pharmacy Programs, Director of Health Policy for the Canadian Association of Healthcare Reimbursement and a member and previous vice-chair of an independent ethics review board. Gabriela Radulescu MD, director of clinical programs and services at McKesson is a physician with training in clinical research. Dr. Radulescu is a faculty member at the Clinical & Regulatory Affairs Program at the School of Health Sciences at Humber College.