Health-related quality of life (HRQoL) in German early benefit assessment: The importance of disease-specific instruments.

INTRODUCTION: Health-Related Quality of Life (HRQoL) data is frequently requested in early benefit assessment in Germany. To test the hypothesis that the importance of HRQoL in general and the significance of disease-specific instruments in particular has increased since the introduction of AMNOG in Germany, we analysed all early benefit assessments between 2011 and 2022. METHODS: All 793 early benefit assessments completed between 01/01/2011 and 03/11/2022 were systematically analysed. The HRQoL instruments featured in the dossier submissions were extracted for all assessments and categorized into generic and specific instruments. All G-BA resolutions were likewise assessed for consideration and acceptance of generic and specific HRQoL instruments. In addition, it was examined whether there was an association between HRQoL data and the extent of additional benefit. RESULTS: Since 2014 HRQoL data have continuously been submitted in 70% to 80% of assessments per year with the exception of 2022 (63%). Generally, disease-specific instruments are favoured, regarding submissions by industry but especially with higher acceptance by the G-BA in the resolution. Subgroup analyses revealed oncology as a major contributor to the submission and acceptance rates of disease-specific instruments. Disease-specific instruments were submitted in 81% of all oncology assessments and accepted in 53% of assessments. Overall, assessments with accepted HRQoL data tend to reach a higher overall benefit. Procedures with accepted HRQoL were most likely to receive a considerable benefit (31%), while for procedures in which HRQoL data were not accepted, a benefit was most often (65%) not proven. DISCUSSION: Industry has followed the request for submission of specific HRQoL instruments early on. Higher submission rates of specific instruments over time which at the same time meet the methodological requirements indicate that industry has learned from early assessments. A potential reason for the high submission- and acceptance rates of specific HRQoL instruments in oncology might be the particularly high relevance of HRQoL in this indication. Possible effects of changes in legislature on the future development of submission and acceptance of HRQoL data need to be monitored. CONCLUSION: In Germany, HRQoL has gained a relevant position in early benefit assessment over time. Overall specific instruments are favoured, regarding submissions by industry but especially through consideration by the G-BA in the resolution. Furthermore, HRQoL data can be supportive for benefit assessments, in particular to show that advantages in morbidity and/or mortality are reflected in HRQoL and not at the expense of HRQoL.

[Involvement of scientific societies in early benefit assessment: Simulated participation or valuable additional input?] / Einbindung wissenschaftlicher Fachgesellschaften in die frühe Nutzenbewertung von Arzneimitteln: simulierte Teilhabe oder wertvolle zusätzliche Information?

BACKGROUND: The German framework of early benefit assessment (EBA) of drugs also provides for the participation of scientific medical societies. The aim of their inclusion is to assure that care providers can critically assess all aspects of the EBA and provide insights into relevant aspects regarding the provision of care. This study systematically reviews the frequency of participation of the scientific medical societies (FGs) and the Drug Commission of the German Medical Association (AkdÄ) within the scope of the EBA. In addition, the positioning of AkdÄ/FG is compared to the Institute for Quality and Efficiency in Health Care (IQWiG) and the Federal Joint Committee (G-BA) with a focus on antidiabetic drugs and cancer drugs. METHODS: A literature analysis was performed based on the comprehensive documentation of benefit assessments published by G-BA. All proceedings of antidiabetic drugs and cancer drugs were included, for which a decision was published by August 6, 2015. In addition, statements of FGs or AkdÄ were identified by an exploratory literature review and included in the analysis. The statements considered were assessed with regard to three categories: (1) additional benefit, (2) appropriate comparator (ZVT) and (3) suitability of the endpoints. For each procedure and category, it was assessed whether there was agreement or disagreement between IGWiG/G-BA and AkdÄ/FGs statements. Regarding the additional benefit, a deviating position was further differentiated according to the level of additional benefit (higher/lower). Afterwards, the proportion of favorable and unfavorable positions was calculated, stratified by FGs and AkdÄ and, separately, for proceedings of antidiabetics and cancer drugs. RESULTS: The literature review revealed 41 proceedings of cancer drugs and 21 proceedings of antidiabetic drugs which were included in the analyses. Statements by AkdÄ/FGs were identified in 90 % of the proceedings for antidiabetic drugs and in 98 % of the proceedings for cancer drugs. In general, the AkdÄ was more often in agreement with the IQWiG than with the FGs' positions. In addition, a different position was more frequent in the proceedings concerning antidiabetic drugs than in the proceedings concerning cancer drugs. Furthermore, the G-BA decision was more frequently in line with the AkdÄ position than with the FGs' position, and this applies to both indications. CONCLUSION: There was a high willingness to participate in the commenting procedure of the EBA. At the same time, the analyses revealed partially heterogeneous positions, both between FGs/AkdÄ and IQWiG/G-BA, as well as between FGs and AkdÄ. The results thus emphasize the need for such discussions within the framework of the EBA.

[Patient-relevant outcomes and surrogates in the early benefit assessment of drugs: first experiences]. / Patientenrelevante Endpunkte und Surrogate in der frühen Nutzenbewertung von Arzneimitteln: erste Erfahrungen.

The Act on the Reform of the Market for Medicinal Products (AMNOG) became effective in Germany on January 1, 2011. Since then, the assessment of the added benefit of new drugs versus a therapeutic standard on the basis of dossiers submitted by pharmaceutical companies has been required by law. The Federal Joint Committee (G-BA) generally commissions the Institute for Quality and Efficiency in Health Care (IQWiG) with this task. The added benefit is primarily to be demonstrated on the basis of patient-relevant outcomes. The aim of this paper is to describe the feasibility of the early benefit assessment on the basis of patient-relevant outcomes by systematically characterising the outcomes available in company dossiers and comparing the companies' and IQWiG's evaluations regarding patient relevance and surrogate validity. Dossier assessments published between October 2011 and June 2012 were used for this purpose. The outcomes available and the respective evaluations were extracted and compared. 12 out of 22 submitted dossiers contained sufficient data to assess outcomes; all 12 assessable dossiers provided data on patient-relevant outcomes. Data on mortality and adverse events were available in all dossiers, except that one dossier did not contain adverse event data on the relevant subpopulation. In contrast, data on morbidity and health-related quality of life were available in 8 and 7 dossiers, respectively. Of a total of 214 outcomes extracted by IQWiG, 124 patient-relevant and 3 surrogate outcomes were included in IQWiG's assessment (companies: a total of 183 outcomes included, of which 172 were patient-relevant and 11 were surrogates). The first experiences with AMNOG have shown that in principle an early benefit assessment of drugs based on patient-relevant outcomes is feasible. The companies' and IQWiG's evaluations regarding patient relevance and surrogate validity of outcomes partly deviated from each other. By increasingly considering patient-relevant outcomes in approval studies, pharmaceutical companies can create the necessary data basis for the early benefit assessment.

[Methodology for analysing quality-of-life data in the benefit assessment of pharmaceuticals]. / Methodik für die Auswertung von Lebensqualitätsdaten im Rahmen der Nutzenbewertung von Arzneimitteln.

Early benefit assessment aims to prove a benefit of a new pharmaceutical over the appropriate comparator based on patient-relevant endpoints. In addition to mortality and morbidity, quality of life is a patient-relevant endpoint. Thus, phase III clinical trials are the basis of evidence. But HTA and health authorities attach different importance to quality of life. Using the example of oncology, the challenges with study design and analysis will be discussed. A particular challenge to the analysis of quality-of-life data is varying observation times in treatment arms with different effectiveness. Based on the example of Crizotinib possible solutions will be presented.