gms | German Medical Science

Background and state of research: Precision medicine is increasingly important in cancer treatment. Tumor-agnostic therapies target specific biomarkers in tumors and are used regardless of tumor entity (e.g., breast cancer, liver cancer etc.). In Germany, the benefit assessment is based on the German Act on the Reform of the Market for Medicinal Products (AMNOG). Because benefit assessments of oncological pharmaceuticals have traditionally been entity specific, the assessment of tumor-agnostic therapies leaves stakeholders with various challenges.

Research question and objectives, hypothesis: Our aim was to systematically identify challenges and possible solutions for the benefit assessment of therapies in tumor-agnostic indications using a 2-step sequential qualitative approach.

Method: To identify relevant challenges, we conducted qualitative interviews with different stakeholders who were involved in previous benefit assessments of tumor-agnostic therapies in Germany. To identify possible solutions for these challenges, we systematically searched MEDLINE, Embase, and the websites of European health technology assessment bodies for relevant literature.

Results: We identified 9 categories of challenges of which the following were deemed particularly relevant: the absence of direct comparative studies, challenges regarding the use of basket studies and indirect comparisons, challenges in determining the appropriate comparative therapy in a tumor-agnostic indication, and challenges on the system side. Seven categories of solutions were identified, including an increased use of real-world evidence, making conditional decisions in the context of systematic reassessments, splitting the field of application, and finding (new) ways to design and analyze basket studies.

Discussion: A range of possible solutions have been found regarding the identified challenges in Germany, some of which are already underway. For example, the principle of coverage with evidence development (CED) has been used since 2021. However, it is currently intended for the evaluation of orphan drugs, conditionally authorized drugs, or drugs approved under exceptional circumstances. Furthermore, the use of real-world evidence is currently limited to data from indication-based registries [1]. Another solution approach already in place abroad are conditional reimbursements with systematic reassessments as applied for tumor-agnostic therapies, e.g. in France [2].

Implication for research: Future research should investigate the acceptance and feasibility of the identified solution approaches for Germany.