  Since the 2011 Act on the Reform of the Market for Medicinal Products,
benefit dossiers are submitted by pharmaceutical companies to facilitate the
Health Technology Assessment (HTA) appraisals in Germany. The Institute for
Quality and Efficiency in Health Care conducts the added benefit assessment
following their General Methods Paper, which was updated November 5, 2020. This
White Paper is dedicated to patient-reported outcomes (PRO) to highlight their
importance for the added benefit assessment. We focus on methodological aspects
but consider also other relevant requirements and challenges, which are
demanded by G-BA and IQWiG. The following topics will be presented and
discussed: 1. Role of PRO in HTA decision making exemplary to benefit
assessment in Germany 2. Guidances of PRO evaluations 3. PRO Estimand framework
4. Perception and requirements for PRO within the German benefit assessment 5.
Validity of instrument 6. Response thresholds for assessing clinical relevance
of PRO 7. PRO endpoints / outcome measures / operationalization 8. Missing PRO
data 9. PRO after treatment discontinuation This White Paper aims to provide
deeper insights about new requirements concerning PRO evaluations for HTA
decision making in Germany, highlight points to consider that should inform
global development in terms of study planning and frame the requirements also
in the context of global recommendations and guidelines. We also aim to enhance
the understanding of the complexity when preparing the benefit dossier and
promote further scientific discussions where appropriate.
