Results on patient-reported outcomes are underreported in summaries of product characteristics for new drugs

Background Summaries of product characteristics (SmPCs) are regulatory documents published upon drug approval. They should report all relevant study data and advise how to use drugs safely and effectively. Patient-reported outcomes (PROs) are increasingly used in clinical trials to incorporate the patient perspective—SmPCs should thus adequately report PROs. In Germany, new drugs undergo mandatory early benefit assessment. Pharmaceutical companies submit dossiers containing all evidence; the subsequent dossier assessments focus on patient-relevant outcomes and comprehensively report PROs. Objective The primary aim was to investigate to what extent PROs recorded as outcomes in clinical trials of new drugs are reported in SmPCs. Methods We analysed dossier assessments with randomized controlled trials (RCTs) of new drugs entering the market between 01/2014 and 07/2018 and the corresponding SmPCs, and compared PRO reporting in both document types. For this purpose, we evaluated dossier assessment characteristics (e.g. drug name, indication, disease category) and study characteristics (e.g. evaluable PROs available?). PROs were divided into symptoms and health-related quality of life (HRQoL). SmPCs were screened to identify RCTs. We conducted 3 main evaluation steps: (1) Did the RCT included in the dossier assessment contain evaluable PROs? (2) If yes, was the RCT included in the SmPC? (3) If yes, were the PROs reported in the SmPC? Results are presented descriptively. Results 88 dossier assessments including 143 RCTs on 72 drugs were considered: 109 (76.2%) RCTs included evaluable PROs, of which 89 were included in SmPCs. 38 RCTs (42.7%) investigated oncologics, 18 (20.2%) anti-infectives, and 33 (37.1%) other drugs. The RCTs considered symptoms more often than HRQoL (82 vs. 66 RCTs). In SmPCs, PROs were reported for 41 RCTs (46.1%), with a slightly higher reporting rate for RCTs considering HRQoL (43.9%) than for RCTs considering symptoms (41.5%). In oncologic indications, PROs were reported for 36.7% of RCTs considering HRQoL and 33.3% of RCTs considering symptoms. In infectious diseases, the rates were 21.4% (symptoms) and 0% (HRQoL), and for other diseases about 60% (symptoms) to 70% (HRQoL). Conclusion Even though a large amount of PRO data on new drugs is available from clinical trials included in SmPCs, the corresponding results are underreported.

Patient-reported data informing early benefit assessment of rare diseases in Germany: A systematic review

Background Since the implementation of the Regulation on Patient Integration (2003), the Act on the Reorganization of the Pharmaceutical Market (2011), and the Patient Rights Law (2013), the inclusion of patient perspectives has been further anchored in the German early benefit assessment process. During the assessment of rare disease interventions, patient perspectives are particularly important, as clinical studies are often designed acknowledging small samples and patients suffering from severe symptoms and the chronic course of the disease. Therefore, our research question is whether patient perspectives are considered as part of early benefit assessments for rare diseases. We also strive to examine how patient perspectives are methodologically elicited and presented. Methods Our empirical evidence comes from a systematic review of orphan drug value dossiers submitted to the German Federal Joint Committee as well as the corresponding evaluations conducted between January 1, 2011 and March 1, 2019 (n = 81). Data on patient perspective integration were extracted using the following patient-reported outcome subcategories: clinical patient-reported outcomes, health-related quality of life, patient preferences, and patient satisfaction. Results The analysis demonstrates the specific relevance of patient-reported outcomes raised as part of the medical data set and presented during the early benefit assessment process. They are predominantly presented in the form of health-related quality of life data (n = 75%) and clinical outcomes (n = 49%). Preferences (n = 2%) and satisfaction (n = 1%) are still rarely presented, although the heated methodological discussion in Germany would suggest otherwise. While various methodologies for the integration of clinical outcomes and quality of life data were found, presenting data on satisfaction and preferences still lacks methodological rigor. The German Federal Joint Committee has not yet integrated these data in their decision text. Clinical outcomes and quality of life have been included in 46% and 73% of the cases, respectively. Conclusions The underlying analysis demonstrates that there is still a relative high potential for the regular and systematic inclusion of patient perspectives within the early benefit assessment process for rare diseases. In particular, patient preferences and patient satisfaction are still rarely included suggesting the need for a clear-cut methodological foundation and incentives.

PP84 Different Interpretation Of Evidence By A Health Technology Assessment Body And A Decision Maker

IntroductionWithin early benefit assessment of pharmaceuticals in Germany, addenda can be commissioned by the Federal Joint Committee (FJC) to the health technology assessment (HTA) agency, mainly as a result of a hearing. Our aim was to analyze the issues for and impact of commissioned addenda, as well as the agreement between HTA agency recommendations and FJC decisions.MethodsAll available relevant documents on addenda commissioned up to the end of 2017 were screened and their essential content extracted. Differences between the HTA agency and FJC recommendations were tested, and concordance was analyzed using agreement statistics (Cohen's kappa and Fleiss’ kappa).ResultsMost of the 90 addenda commissioned up to the end of 2017 concerned oncological products. In all contingent comparisons, positive changes in added benefit or evidence level on a subpopulation basis (n = 124) were more common than negative changes. Agreement of assessments, addenda, and appraisals reached a moderate strength for added benefit (Fleiss’ kappa 0.47, range 0.41 - 0.54). Overall agreement between addenda and appraisals on a binary nominal basis was poor for added benefit (Cohen's kappa 0.18, range 0.01 - 0.36) and fair for evidence quality (Cohen's kappa 0.35, 0.19–0.52). Cohen's kappa ranged from “less than by chance” (respiratory diseases) to “perfect” (neurological diseases), but was only statistically significant for neurological and other diseases. Three addenda are presented in detail as examples.ConclusionsAddenda have a high impact on decision-makers’ appraisals, offering additional analyses of supplementary evidence submitted by the manufacturers. Nevertheless, the agreement between addenda and appraisals varies, highlighting different methodological approaches and decision-making factors between the HTA agency and the FJC.