The Assessment of Patient-Reported Outcomes for the Authorisation of Medicines in Europe: A Review of European Public Assessment Reports from 2017 to 2022

Abstract

Objectives Health regulators have progressively increased their attention and focus on patient-reported outcomes (PROs), driven by the diffusion of a patient-centred approach to the drug development process. This study investigates the consideration of PROs and their measures (PROMs) in the authorisation of medicines in Europe. Methods All medicines for human use authorised or refused by the European Medicines Agency (EMA) in the period 2017–2022 were identified, and corresponding European Public Assessment Reports (EPARs) were downloaded for review. Medicine and PROs/PROM characteristics were systematically recorded. A multivariate logistic regression was performed to identify variables associated with the use of patient-reported evidence in EPARs. Results Overall, 497 EPARs of authorised medicines and 19 EPARs of refused medicines were analysed; of these, 240 (48.3%) and 10 (52.6%), respectively, reported any use of PROs/PROMs ( p = 0.710). For authorised medicines, the likelihood of using PROs/PROMs was negatively affected by generic (OR = 0.01, p < 0.001) and biosimilar status (OR = 0.46, p = 0.013) and positively affected by orphan status (OR = 1.41, p = 0.177). The use of PROMs (50.6% in 2017 vs 47.9% in 2022) did not show a clear pattern over the 6-year period considered ( p = 0.758) and was particularly uncommon in some therapeutic areas (e.g., 15.2% in infectious diseases). A total of 816 dyads of PROs/PROMs were identified. On average each EPAR considered 1.6 (range: 0–14) instruments. Patient-reported outcomes were typically secondary (53.3%) and exploratory endpoints (18.8%); in one-third of cases (32.5%), they assessed generic quality of life. Among the PROMs, 227 (27.8%) targeted general population; EQ-5D (11.0%), SF-36/SF-12 (5.9%) and EORTC QLQ-C30 (5.6%) were the instruments most frequently used. Conclusions This study suggests PROs/PROMs are considered in less than half of total medicine assessments and even more rarely in some disease areas. The adoption of PROs is key in EMA strategy to 2025 and would be facilitated by consensus development on their measures and optimisation of data collection.

Comment on: “The Assessment of Patient-Reported Outcomes for the Authorisation of Medicines in Europe: A Review of European Public Assessment Reports from 2017 to 2022”

“…For 99 of the 152 included products (65%), we found that PROs/PROMs were used as an endpoint. This is higher than the 48% observed by Meregaglia et al [1], which might be due to differences in the search terms used and included medicinal products. Particularly, the inclusion or exclusion of generics and biosimilars is a likely explanation as Meregaglia et al [1] showed that PRO/PROM use was negatively affected by generic and biosimilar status.…”

“…With interest, we have read the review of European Public Assessment Reports (EPARs) conducted by Meregaglia et al [1] titled "The Assessment of Patient-Reported Outcomes for the Authorisation of Medicines in Europe: A Review of European Public Assessment Reports from 2017 to 2022". The authors found that patient-reported outcomes (PROs) or patient-reported outcome measures (PROMs) were used in less than half of the evaluated medicinal products.…”

“…Our first study aim was similar to Meregaglia et al [1] by evaluating to what extent PROs were used as an endpoint. For this, the search terms were applied to the main study(ies) or clinical efficacy section in the EPARs.…”

Factors associated with hematological adverse reactions of drugs authorized via the centralized procedure

“…More drugs are approved through NPs, DPs, and MRPs than through the CP, but drugs authorized by the EMA are available for fewer years on the market (our study showed that half of them have been available for less than 7 years since authorization, which does not mean that they were on the market from the first day), leading to insufficient awareness of the HADR of these drugs. Additionally, we did not consider possible differences in the SmPC between the EMA and other medical agencies, e.g., the Food and Drug Administration (FDA), even though it is known that there may be discrepancies in product information and differences in the decision-making regulatory framework between these two regulators 29 – 31 and different safety conclusions between the EU and Canada and the United Kingdom (UK) 32 .…”

“…The main strength of our study was that we included all drugs authorized through the CP without therapeutic limitations or authorization date limitations, which was not the case in other studies using the EMA database as the main source of data. Mol et al excluded biosimilars when conducting a study related to postapproval safety issues with innovative drugs 23 ; Francisca RDC et al analyzed drugs authorized between 2006 and 2017, excluding generics, when analyzing the introduction or discontinuation of additional risk minimization measures (RMMs) 32 ; Zeitoun et al explored the association between regulatory review time and postmarket safety events excluding reformulations, combination therapies, nontherapeutic agents, generics and biosimilars with limitations on authorization dates (2001–2010) 34 ; and Meregaglia et al excluded drugs receiving MA before 2017 when assessing patient-reported outcomes in the authorization by the EMA 31 . We analyzed SmPC data from each of the 1349 authorized MAs for drugs for human use since SmPC is considered a routine RMM, and one study showed that 36% of additional RMMs targeted “blood and blood-forming organs” 31 .…”