November 12, 2012

Post Approval Clinical Epidemiological Studies (PACES)

Post Ap­proval Clinical and Epidemio­logical Studies (PACES) that in­clude Phase IV and Post Mar­keting Observational Studies (PMOS) have evolved into an integral and essential phase of the drug develop­ment life cycle with implications that have comparable weight to that of the Phase II and III registrational studies. While Phase II – III controlled clini­cal trials provide evidence of efficacy under ideal conditions, PACES are the only source of information that allows the assessment of real – life effective­ness. In addition, ongoing surveillance for safety signals under routine clini­cal practice allowing the detection of rare but potentially serious adverse events could only be accomplished by the accumulation of data from several PACES capturing data from large pop­ulations and over sufficient periods of treatment exposure.

Phase IV studies emulate the real – life setting, however, the fact that the spon­sor provides medication at no cost to the patient affects the generalizability with respect to access of care and com­pliance that is artificially enhanced in the Phase IV setting. Furthermore, Phase IV studies are conducted under pre-determined protocols dictating pa­tient follow up schedules and assess­ments. Nevertheless, there is signifi­cant value in Phase IV studies, which should be considered as the real – life extension of the Phase III registration­al studies. Under the Phase IV studies, treatment effectiveness for specific patient subgroups or enriched popula­tions can be evaluated. Randomization for the assessment of differences with respect to treatment effectiveness is also possible in Phase IV studies.

Post Marketing Observational Stud­ies (PMOS) are true epidemiological studies in which treatment is provided to patients without any intervention by the sponsor or the investigator. In the PMOS payment for treatment is provided as per real life, including in­surance plans or by the patients them­selves. PMOS provide evidence on real – life effectiveness and safety in combination with assessment health care utilization, direct and indirect health care costs that are essential for a comprehensive health economic eval­uation and assessment of treatment im­pact on burden of illness.

One of the most important consider­ations of PACES is regional specific­ity. This is due to regional variations in the patient profile, cultural influ­ences, practice patterns and local re­imbursement policies affecting access to care. Consequently, PACES must be designed and conducted taking into consideration regional needs and treatment gaps while global wide stud­ies are less relevant. It follows, that at the minimum country specific PACES will be required to conduct regional evaluations of marketed treatments. However, the aggregation of evidence from several regions or countries could be employed to provide global assessments.

Given the importance of the PACES and the potential implications of the results to health care stakeholders it is essential that these studies are con­ducted with the same scientific rigor as Phase II and Phase III studies. Clini­cal epidemiology provides the only methodological platform upon which PACES can be developed and execut­ed. Essential elements of properly con­ducted PACES include well defined hypotheses addressing knowledge gaps that define clear objectives and research questions. Statistical consid­erations must include precise sample size requirements that ensure suffi­cient power to address the research objectives and statistical analyses that incorporate advanced methods to com­pensate for the lack of randomization, non – standardized follow up and the observational nature of the design. As such, PACES must be conducted under the aegis of clinical or health outcomes departments of pharmaceutical spon­sors in collaboration with third parties that have experience in the design, the conduct and analyses of epidemiologi­cal studies with appropriate training in the field.

• VPs/Directors of Medical Affairs
• Medical Advisors
• Medical Science Liaisons
• VPs/Directors/Managers of Health Economics & Drug Reimbursements
• VPs/Directors/Managers of sales in Pharma

From pharmaceutical and biotechnology companies                                                           

Dr. Sampalis is a clinical epidemiologist with undergraduate training in Microbiology, Immunology and Neuroscience and graduate training in Clinical Epidemiology and Biostatistics (M.Sc. and Ph.D.) from McGill University. Currently a tenured Professor of Surgery and, Medicine with the Faculty of Medicine of McGill University, University of Montreal and University of Laval, Director of Surgical Research Jewish General Hospital, Head Surgical Epidemiology Division of Surgical Research McGill University. He has extensive expertise in health services research, clinical trials and the evaluation of medical technology.

Founded in 1985, JSS Medical Research Inc. is a Contract Research Organization that manages Phase I to Phase IV trials and specializes in Outcomes Research on behalf of pharmaceutical, biotech and nutraceutical companies. The organization responds to the evolving needs of the stakeholders in the healthcare field for high quality, scientifically rigorous and sound clinical research services.