Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Medicines for vulnerable populations - current regulatory status ***

Carolin Himpel (Abschlußjahr: 2022)

Summary
Language: English
Everyone has to use medicinal products, but some groups within our societies are more vulnerable and face higher risks compared to the general population, thus needing adequate safety information for the use of medicines.
Classically, randomised controlled trials (RCTs) are the gold standard in the development for demonstrating the efficacy and safety of medicinal products prior to granting marketing authorisations. However, vulnerable populations, such as older people aged 65 years or above are often underrepresented and women who are pregnant or breastfeeding are strictly excluded from clinical trials. Thereby, the elderly are among the main consumers of medicines, and Europe, like other parts of the world, is facing a growing number and proportion of older people. Likewise, pregnant and breastfeeding women get sick like the rest of the population, as exemplified by the current Coronavirus disease 2019 (COVID-19) pandemic, and therefore medication use is not an exception, but the norm. The deficit of understanding which medicinal products can be safely used and the insufficient development of new medicines for pregnant women is a major public health concern worldwide.
Besides the ICH E7 guideline, the European Medicines Agency’s (EMA’s) geriatric medicines strategy has represented the main available regulatory framework regarding medicines for geriatrics until 2011. Ten years after publication, the implementation of the intended measures for older people has been reviewed in this thesis. Furthermore, an overview of the current relevant EMA guidelines and guidance from GVP modules is given concerning the use of medicines during pregnancy and breastfeeding. The real-world evidence (RWE) approach is considered as an alternative to generate evidence by observational data based on real-world data (RWD), which have the potential to fill the gaps in evidence not addressed by RCTs.
The objective of this thesis is to assess the available safety and efficacy information provided in the Summary of Product Characteristics (SmPC) on the use of medicines in patients older than 65 years as well as pregnant and breastfeeding women. The SmPC is the main source of safety information of a particular medicine for the physician or pharmacists; thus, it must contain all the information required to guide decision-making and ensure safe treatment. In summary, 27 SmPCs of new human medicinal products authorised in 2021 by the EMA were retrieved from the EMA website, geriatric and pregnancy / breastfeeding information were extracted and a questionnaire with six information items derived from the EMA guidance was created to evaluate the SmPCs. The overall result of the questionnaire indicates that important information included in the SmPCs for a safe and effective use of medicinal products in older patients is incomplete, with a total availability of 27.1%, and likewise for the use during pregnancy and breastfeeding information is missing, with a positive presence of 30.8%. Until recently, the needs of geriatric, pregnant and breastfeeding patients still have not been adequately addressed, even after more than 60 years passed since the thalidomide tragedy, as demanded by the ICH E7 guideline including the questions and answers document as well as requested by the EMA geriatric medicines strategy from 2011.
The effective reflection papers on physical frailty and pharmaceutical development for older people and a proposed revision of the ICH E7 can be seen as suitable approaches to address and improve the needs of older people. Measures that have already been initiated by the EMA for the elderly will be continued as announced in its “Regulatory Science to 2025” strategic reflection and the CHMP workplan for 2022. The development of a pregnancy strategy paper by EMA and the introduction of a maternity investigation plan similar to the PIP would be measures to provide safe and effective medicines for pregnant women. Moreover, RWD analyses generated by DARWIN EU can be useful and help to tackle the knowledge gaps in the future. Given the importance taken by RWD and RWE, especially in the context of the COVID-19 pandemic, it can be understood as an area of research that supports regulatory decisions on medicinal products and public health in general.
Pages: 40
Annexes: 2, Pages: 35