2017. Maier WC et al. – Post-approval studies for rare disease treatments and orphan drugs


Maier W.C., Christensen R.A., Anderson P. (2017) Post-approval studies for rare disease treatments and orphan drugs. In: Posada de la Paz M., Taruscio D., Groft S. (eds) Rare Diseases Epidemiology: Update and Overview. Advances in Experimental Medicine and Biology, vol 1031. Springer, Cham, pp 197-205.


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Drug development involves a multi-stage process of drug discovery, animal studies and human clinical trials to assess the safety and efficacy of new medications. Rare disease drug development involves a much smaller number of affected patients, a predominance of pediatric patients and more complicated disease presentation. Post-approval studies are designed to address several limitations associated with the rare disease clinical trials.National and international regulatory agencies in the US and Europe have adopted similar approaches to requirements post-approval data for rare diseases and orphan drug indications. The US FDA published guidance in 2011 and the European Medicines Agency in 2015. Post-approval studies for rare diseases include observational studies, pragmatic trials and randomized controlled studies. Observational studies include both original data collection studies and the use of secondary data (retrospective studies). Original data collection can address limitations of retrospective studies resulting from incomplete information in secondary data sources. Disease registries focus on detail about a broad range of patients with a rare disease while product-related registries focus on specific health care outcomes associated with a single product and may incorporate a comparator of an alternative therapy or therapies. Rare disease patients can be difficult to find and enroll in a registry using conventional physician based driven recruitment. The study process also needs to recognize changes in the patient’s disease and lifestyle and adapt both the study design and methods over time. Many rare diseases have strong patient advocacy groups that can in aid the design and execution of rare disease registries.