Pharmacovigilance of medicines for rare and ultrarare diseases

Abstract

Abstract:The assessment of the safety of medicines for rare diseases during the development phase is often limited by the few data available from small numbers of patients. This also applies to a lesser extent during the postmarketing phase of the lifecycle of a medicine. By using all available sources of data for rare diseases drugs, and by carefully assessing these data, the most informed safety profile can be obtained. This should also allow a clear view of data that are not available at any given time point and facilitates planning of strategies to obtain data through appropriate postmarketing risk management. Although it is not always easy, there are possibilities to increase the speed by which data in the postmarketing period can be generated by better use of data from ongoing formal clinical trials, by early planning of drug or disease registries and leveraging the power of both disease patient support groups, which are often well established, and networks to facilitate international research, specifically in rare diseases. The future may offer approaches using personal medical monitoring data tools and 'big data' to further facilitate the availability of information and to determine the effectiveness and safety profiles of drugs used for rare diseases and thus allow the benefit/risk of these drugs to be optimized. These issues will be discussed here.

Summarising salient information on historical controls: A structured assessment of validity and comparability across studies

“…Under these criteria, meta-analytic approaches for combining the historical and current controls may be applied. The use of historical data has proven to be a useful tool for studies on orphan diseases, 12 , 13 whereas it remains controversial in the primary analysis of a phase III RCT.…”

Administration of gamma‐hydroxybutyrate instead of beta‐hydroxybutyrate to a liver transplant recipient suffering from propionic acidemia and cardiomyopathy: A case report on a medication prescribing error

“…The European Medicines Agency and the United States Food and Drug Administration both encourage academics and pharmaceutical companies to research and develop medicines for rare diseases orphan F I G U R E 1 Chemical structures of sodium gammahydroxybutyrate (GHB) and sodium beta-hydroxybutyrate (BHB) drug development via fast-track authorization programmes, orphan drug designations, and the Priority Medicines scheme, for example. [10][11][12][13][14][15] In addition to the abovementioned clinical trials of advanced therapy medicinal products, pediatric patients with rare diseases can also receive off-label treatments or extemporaneous preparations in which the drug's regimen and pharmaceutical formulation are adapted for pediatric use. Although the recent medical literature emphasizes the fact that the use of computerized prescription systems can decrease the frequency of prescription errors and iatrogenic adverse events and increase the safety of drug prescriptions, we consider that the system correction algorithm can sometimes generate errors -especially in the setting of rare diseases.…”

“…BHB is a synthetic ketone body that is formulated as a capsule in hospital immediately prior to use (at a dose of between 400 and 800 mg/kg per day) as an adjuvant energy substrate in cases of metabolic cardiomyopathy. In contrast, GHB (a precursor of the neurotransmitter GABA) induces central nervous system inhibition, narcolepsy and respiratory drive inhibition . However, GHB is abused recreationally as a “party drug” or “club drug,” with a wide array of formulations, patterns of use, and health risks .…”

“…In contrast, GHB (a precursor of the neurotransmitter GABA) induces central nervous system inhibition, narcolepsy and respiratory drive inhibition. 10 However, GHB is abused recreationally as a "party drug" or "club drug," with a wide array of formulations, patterns of use, and health risks. 11,12 In a clinical context, commercially available solutions for injection of GHB are used as a general anesthetic, thanks to the rapid induction sedation and amnesia.…”

Precision Child Health: an Emerging Paradigm for Paediatric Quality and Safety

“…Moreover, research studies do not always address the question of how to scale without sacrificing quality and safety. Ongoing surveillance is needed after a test first becomes available in clinical practice to ensure that standards are maintained and that implementation issues are addressed; ongoing pharmacovigilance is similarly a requirement for orphan drugs [ 33 ]. While WES and WGS can facilitate timely and accurate diagnosis, these tests also do not address system-related issues derived from ongoing patient care needs [ 34 ].…”