Harmonization and Standardization of Personalized Oncology Care within the German Network for Personalized Medicine (DNPM): Methods of a Controlled Observational Study employing an adapted stepped-wedge design

Antonia Bauer^1*Sebastian Himmler²Nisar Malek³Lisa-Marie Brenner⁴Yvonne Möller^3,4Stephanie Vigier⁵Markus Buchner¹Leonie Sundmacher²Stefanie Joos¹Peter Martus⁵

• ¹Institute of General Medicine and Interprofessional Care, University Hospital Tuebingen, Tuebingen, Germany
• ²Chair of Health Economics, Technische Universitat Munchen, Munich, Germany
• ³Department of Internal Medicine I, University Hospital Tuebingen, Tuebingen, Germany
• ⁴Center for Personalized Medicine, Tübingen, Germany
• ⁵Institute for Clinical Epidemiology and Applied Biometry, University Hospital Tuebingen, Tuebingen, Germany

Background: The goal of Personalized Medicine (PM) is to provide tailored diagnostics and therapies for individual patients, primarily in oncology. However, significant regional disparities exist in its implementation. The DNPM project (German Network for Personalized Medicine), aims to harmonize and network the implementation of PM in Germany. Methods: The DNPM-Project is evaluated as a Hybrid Type 3 implementation study using a non-randomized, modified stepped-wedge design. Twenty-one university hospital sites across Germany will transition from standard, non-harmonized care to a harmonized personalized medicine intervention at different time points, based on administrative readiness indicated by certification. The primary outcome is change in patient management due to Molecular Tumor Board (MTB) decisions, assessed on three tiers using prospectively collected primary data entered by clinical staff: (1) number of patients with access to an MTB (2) proportion with revised diagnostic or therapeutic recommendations, and (3) proportion with implemented changes. Therefore, the study aims to include 4807 patients (intervention group: 3.507). A mixed-methods approach is employed to evaluate further aspects of the implementation process including patient and staff satisfaction, perceived quality of care, and the degree of harmonization and collaboration within the network. Health economic outcomes include health-related quality of life, healthcare utilization costs, and intervention-related costs. Discussion: The study's wide range of outcome parameters and mixed-methods approach yield robust results for implementation insights. A limitation of the study design is the lack of a clear cutoff for transitioning from the control to the intervention group as well as the lack of randomization. Additionally, the health economic evaluation is limited by the absence of health insurance claims data, as no insurance company is involved in the project. Trial registration: This trial is registered with the German Clinical Trials Register (DRKS) under the trial number DRKS00031622 (registration date: 23.05.2023)