NordPerMed: PRECISE - A health economic apPRoach to Evaluate unCertain evIdence in perSonalisEd medicine

Limitations in the evidence base for personalised medicine and accelerated licensing processes for new pharmaceuticals have led to considerable uncertainty surrounding the added value of novel interventions. Without a sufficient health economic evidence base, decision makers risk making incorrect coverage decisions that may result in an inefficient use of healthcare resources and reduced patient health benefits. PRECISE will improve decision making by developing new health economic methods, generating new evidence and improving national pharmacoeconomic guidelines to account for uncertain evidence and heterogeneity when evaluating the health effects and costs of personalised medicine. PRECISE consists of two work packages (WP): WP1 is centered at the University of Oslo and the Norwegian Medicines Agency, and WP2 is centered at Linköping University. Project collaborators include researchers from the Norwegian Institute of Public Health, University of Sheffield, University of York and University of Bristol. WP1 will be focused on developing new health economic methods for deciding whether the benefits of patient access to a new healthcare intervention outweigh the consequences of uncertain evidence. Different perspectives on the usefulness of value of information analysis for healthcare decision making will be explored, and the needs and requirements of decision makers will be addressed. The value of the methods will be demonstrated in case studies that will inform healthcare decisions. In WP2, a decision-analytic model will be developed that synthesizes evidence relating to the health effects and costs of MRI-diagnostics to tailor treatments for non-alcoholic fatty liver disease. The model will enable a cost-effectiveness analysis and facilitate the development of methods to evaluate emerging diagnostic methods and tailored treatment strategies. Findings will be used to make recommendations for updating national pharmacoeconomic guidelines. Grueau and collegues in WP2 have conducted a systematic literature review investigated modeling of the natural history of NAFLD (non-alcoholic fatty liver disease) in economic evaluation studies. From the 28 articles were identified, they found that there were huge differences between the models applied in the cost-effectiveness analysis and that there is a need for more detailed information about the patient pathways. Researcher in both Sweden and Norway have been involved in additional work with precision medicine. In Sweden, Grueau and Henriksson have written a report for TLV about health economics and precision medicine and advanced therapy medicinal products (ATMP). In Norway, Aas has joined the CONNECT group, a network of industry, clinicians, stakeholders and academia to jointly address important challenges in precision medicine. The work in PRECISE has shown to be highly relevant for current practice, and contribute with valuable input for the ongoing European process at EMA and EUnetHTA with regard to handling uncertainty with regard to immature data, single-arm trials and precision medicine. The project has contributed with methods development for immature data and computing EVSI (both papers by Vervaart et al in Medical Decision Making) and a case-study with a tutorial that will be published during 2023. Furthermore, a review and mathematic simulation model for NAFLD has been published (Gruneau et al) and reveal the complexity of treatment pathways for this patient group and establish a foundation for evaluating precision medicine. PRECISE has been important for several new involvement. First of all, results from PRECISE will be important input for the newly funded HORIZON 2020 project ASCERTATAIN (access2meds.eu), PRIMEROSE and PCM4EU.

Nordic and international impact of the project a. Potential of the project to add value for society, citizens and patients. b. Potential to provide Nordic added value, i.e. that Nordic collaboration generates more value than would be the case through national activities alone. c. Potential of the project to contribute to a stronger international position for the Nordic countries within PM. PRECISE will improve decision making by developing novel health economic methods to handle uncertain evidence and heterogeneity when evaluating the benefits and costs of personalized medicine. PRECISE will generate new health economic evidence based on real case studies. A close collaboration with Nordic healthcare decision makers provides a platform for improving national pharmacoeconomic guidelines. PRECISE will contribute to better healthcare decisions that facilitate the implementation of cost-effective interventions for personalized medicine in clinical practice in all Nordic countries. During the four years of the project period, it is clear that the issues addressed in PRECISE is topics that not only the Nordic countries are faced with, but Europe in general. The added value of this project in a Nordic setting, is continuation of the work in new EU-funded projects. The recent project is ASCERTAIN, a Horizon 2020 project where Oslo is one of the partners. In addition, we are part of two other EU-funded projects on precision medicine, PRIMEROSE and PCM4EU. PRECISE have received attention both in Sweden and Norway, as researcher are invited to discussions and guidelines development.

The value of diagnostic methods and tailored treatment strategies for healthcare is unclear as the current health economic evidence base to support the more widespread use of personalised medicine in clinical practice is very limited. Randomized clinical trials will rarely be available to assess the cost-effectiveness of the complete pathway of diagnostic testing and tailored treatment strategies. Hence, decision-analytic modelling plays a crucial role as the appropriate evaluation method. The greater complexity in evaluating the added value and costs of personalised medicine requires an improvement of existing health economic methodology and national guidelines. A clear policy framework needs to be developed and incorporated in national guidelines for when and how value of information analyses should be used to inform adoption and research decisions for diagnostic methods and tailored treatment strategies. Current methods should be adapted and extended to include the perspective of decision makers that cannot commission new trials in order to obtain additional information. Furthermore, an integrated framework for accounting for patient heterogeneity and uncertain evidence, crucial for evaluating the added value and costs of personalised medicine, needs to be developed and anchored in national guidelines. The project consists of two WPs: WP 1 - Benefits and costs of early access to novel interventions – when is evidence sufficient? WP 2 - Right treatment to the right patient with the right evaluation methods and research portfolio