Addressing uncertainties of clinical value and improving access for newly authorised indications through DRUG-Access Protocol (DAP)-like platforms: Joint collection and evaluation of real-world evidence

BackgroundStarting in 2025, every novel anticancer drug in the European Union will undergo a unified Health Technology Assessment (HTA). The HTA will focus on clinical outcome and is conducted in parallel with the scientific advice provided by the European Medicines Agency. The joint clinical assessment explores relative efficacy and identifies the strength and uncertainty regarding the evidence. However, it does not present any solutions to mitigate risks for healthcare systems.MethodsIn the Netherlands, the DRUG-Access Protocol (DAP) provides an infrastructure for access to promising oncology drugs while gathering real-world effectiveness data. Access is facilitated through a pragmatic outcome-based risk-sharing agreement between payers and the Market Authorization Holder (MAH). The MAH covers the costs of the initial part of the treatment until any response or stable disease is confirmed. This mitigates risk for the healthcare system to fund less effective therapies. Based on results from DAP; cemiplimab, larotrectinib and entrectinib received full reimbursement while tepotinib, selpercatinib and amivantamab are currently under evaluation. Implementing similar protocols in EU countries can provide access and accelerate real-world data generation. Such a collaboration currently exists in a consortium of 18 European countries that share the pragmatic trial design of the Drug Rediscovery Protocol (DRUP). This consortium, PRIME-ROSE (Precision Cancer Medicine Repurposing System Using Pragmatic Clinical Trials), aims to improve access to affordable treatment interventions.ResultsBy collecting real-world data using the DAP in countries that already have access to a particular medicine (e.g., through an early access program or reimbursement), we can rapidly generate valuable insights.ConclusionsClinical decision-making for patients and healthcare providers can benefit from the consolidation of data from DAP-like initiatives. Moreover, healthcare funders will be able to assess the true value of interventions and make informed decisions regarding the allocation of budgetary resources.Legal entity responsible for the studyThe authors.FundingPrecision Cancer Medicine Repurposing System Using Pragmatic Clinical Trial (PRIME-ROSE), funded under the Horizon Europe programme (grant: 101104269).DisclosureA. Helland: Financial Interests, Institutional, Advisory Board, Advisory boards: Janssen, Takeda, AstraZeneca, AbbVie, Roche, BMS, Pfizer, MSD, Bayer, Lilly, Medicover; Financial Interests, Institutional, Invited Speaker, talks at meetings: AstraZeneca, Roche, AbbVie, Pfizer; Financial Interests, Institutional, Coordinating PI, BMS provides drug to patients in an investigator initiated clinical trial: BMS; Financial Interests, Institutional, Coordinating PI, Ultimovacs provides drug and funds for investigator initiated clinical trial: Ultimovacs; Financial Interests, Institutional, Coordinating PI, AstraZeneca provides drug and funds for investigator initiated clinical trial: AstraZeneca; Financial Interests, Institutional, Coordinating PI, Roche provides drug and funds for investigator initiated clinical trial: Roche; Financial Interests, Institutional, Coordinating PI, Novartis provides drug and funds for clinical trial: Novartis; Financial Interests, Institutional, Coordinating PI, Eli Lilly provides drug and funds for clinical study: Eli Lilly; Financial Interests, Institutional, Coordinating PI, Incyte provides drug and funds for clinical study: Incyte; Financial Interests, Institutional, Coordinating PI, Illumina provides assays for patients in a clinical trial: Illumina; Financial Interests, Institutional, Coordinating PI, GSK provides drug and funds for investigator initiated clinical trial: GSK; Non-Financial Interests, Other, Board member in the patient organisation until 2022. Provides advice and gives talks.: The lung cancer patients organisation. B. Ryll: Financial Interests, Institutional, Other, Support for MPNE yearly activities for 2021, 2022 and 2023- projects are always multi-sponsored and support never gives rights to any influence wrt content, program, speakers or other; this reflects MPNE’s total budget: BMS; Financial Interests, Institutional, Other, Support for MPNE yearly activities for 2022, projects are always multi-sponsored and support never gives rights to any influence wrt content, program, speakers or other; this reflects MPNE’s total budget: MSD; Financial Interests, Institutional, Other, Support for MPNE yearly activities for 2021,22 and 23 projects are always multi-sponsored and support never gives rights to any influence wrt content, program, speakers or other; this reflects MPNE’s total budget: Novartis; Financial Interests, Institutional, Other, Support for MPNE yearly activities for 2023, projects are always multi-sponsored and support never gives rights to any influence wrt content, program, speakers or other; this reflects MPNE’s total budget: Roche; Financial Interests, Personal, Advisory Board, Ethics Board for EAP programs: Clinigen; Financial Interests, Personal, Advisory Board, Access to medicines AD board: AstraZeneca; Financial Interests, Personal, Invited Speaker, Patient Summit: Pfizer; Financial Interests, Personal, Advisory Board, Histology-agnostic ad board, contribution to internal event: Roche; Financial Interests, Personal, Advisory Board, Patient Expert Ad board: Amgen; Financial Interests, Personal, Invited Speaker, Patient Ad board, internal meeting: Novartis Sweden; Financial Interests, Personal, Invited Speaker, Baltic Oncology Summit, webinars: MSD SE; Financial Interests, Personal, Invited Speaker, WIN symposium: Roche; Financial Interests, Personal, Advisory Board, Melanoma Academy: Novartis; Financial Interests, Personal, Advisory Board, IQVIA Oncology Ad board: IQVIA; Financial Interests, Personal, Advisory Board, Patient AD board: BMS; Financial Interests, Personal, Advisory Board, Advisor for a research project 2021: Pierre Fabre; Financial Interests, Personal, Advisory Board, Member of clinical trial steering committee COMBI-Aplus: Novartis; Financial Interests, Institutional, Other, Support of MPNE activities in 2022: SkylineDx; Financial Interests, Personal, Other, Member of the ASC Oncology Advisory Board: ASC Oncology; Non-Financial Interests, Leadership Role, I am the founder of the Melanoma Patient Network Europe: Melanoma Patient Network Europe. K. Tasken: Financial Interests, Personal, Advisory Board, Company established based on innovation in my lab. Holds stock and Scientific advisor: Serca Pharmaceuticals; Financial Interests, Personal, Stocks/Shares, Stock and Stock options, and royalty agreement through Oslo UniversityHospital / University of Oslo Tech Transfer Office Inven2 AS.: Serca Pharmaceuticals; Financial Interests, Personal, Stocks/Shares, Stock.: Ledidi; Financial Interests, Personal, Royalties, Stock and Stock options, and royalty agreement through Oslo UniversityHospital / University of Oslo Tech Transfer Office Inven2 AS.: Serca Pharmaceuticals; Financial Interests, Institutional, Steering Committee Member, IMPRESS-Norway trial Trial Management & Steering Committee: Roche; Financial Interests, Institutional, Steering Committee Member, IMPRESS Norway trial Trial Management & Steering Committee: Novartis, Lilly, Incyte, Merck KGaA, AstraZeneca, Illumina. K. Jalkanen: Financial Interests, Personal, Advisory Board: MSD, Ipsen, Roche, BMS, Pfizer, Lilly, Novartis, Bayer; Financial Interests, Personal, Stocks/Shares: Faron Pharmaceuticals; Financial Interests, Institutional, Local PI, Conduct of sponsored clinical trial: Novartis; Financial Interests, Institutional, Local PI, Sponsored clinical trial: Exelixis; Financial Interests, Institutional, Local PI, Several clinical trials: BMS, MSD, Roche; Financial Interests, Institutional, Local PI, clinical trials: Incyte; Financial Interests, Institutional, Local PI, Conduct of clinical trials: Pfizer; Financial Interests, Institutional, Local PI, Conduct of clinical trial: Bayer. U.N. Lassen: Financial Interests, Personal, Advisory Board: Bayer, Novartis; Financial Interests, Institutional, Research Grant: Roche, BMS, Pfizer, GSK, Lilly, Incyte, Janssen. J. Blay: Financial Interests, Institutional, Invited Speaker: MSD, MSD, PharmaMar; Financial Interests, Institutional, Advisory Board: Bayer, GSK, Roche; Financial Interests, Personal, Advisory Board: Deciphera; Financial Interests, Personal, Other, member of the supervisory board. No remunerations in 2021 and 2022.: Innate pharma; Financial Interests, Personal, Member of Board of Directors: Transgene; Financial Interests, Institutional, Funding: MSD, BMS, Deciphera; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bayer, GSK, Novartis, OSE pharma. H. Gelderblom: Financial Interests, Institutional, Local PI: Deciphera, Cytovation; Financial Interests, Institutional, Coordinating PI: Boehringer Ingelheim, AmMax Bio, Debiopharm, Abbisko. A. Reyners: Financial Interests, Institutional, Other, Member of the board: Dutch Society of Medical Oncology; Financial Interests, Institutional, Coordinating PI, FIRST study; coordinator for the Netherlands: Tesaro; Financial Interests, Institutional, Local PI, Local PI GCT1015-05 study: Genmab; Financial Interests, Institutional, Local PI, Local PI for the RUBY study: Tesaro; Financial Interests, Institutional, Local PI, Local PI of the R2810 study: Regeneron; Financial Interests, Institutional, Local PI, PI of MK3475-C93 trial: Merck; Financial Interests, Institutional, Local PI, Local PI Insight study: Deciphera; Financial Interests, Institutional, Local PI, Local PI PEAK study: Cogent Biosciences; Non-Financial Interests, Leadership Role, Chairperson of the group that advises the Dutch Society of Medical Oncology whether EMA authorised medication should be common practice in the Netherlands (cieBOM).: Dutch Society of Medical Oncology. E.F. Smit: Financial Interests, Institutional, Advisory Board: AstraZeneca, Daiichi Sankyo, MSD, Boehringer Ingelheim, Roche, Eli Lilly, Takeda, Sanofi, Janssen, BMS; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Institutional, Other, DSMB member: DSI; Financial Interests, Institutional, Local PI: Pfizer, AZ, Genmab, DSI, Sanofi. E.E. Voest: Financial Interests, Personal, Advisory Board, Hourly rate: Biogeneration Ventures; Financial Interests, Personal, Member of Board of Directors, independent, non-executive director and share holder: Sanofi; Financial Interests, Personal, Other, Founder, strategic adviser and share holder: Mosaic Therapeutics; Financial Interests, Personal, Ownership Interest, Mandatory shares as part of board membership: Sanofi; Financial Interests, Personal, Ownership Interest, Start up company with shares: Mosaic Therapeutics; Financial Interests, Institutional, Coordinating PI, DRUP trial: Amgen, AstraZeneca, BMS, Eisai, Ipsen, MSD, Novartis, Pfizer, GSK, Seattle Genetics; Financial Interests, Institutional, Coordinating PI, DRUP trialDRUG Access Protocol: Bayer, Roche; Financial Interests, Institutional, Coordinating PI, DRUG Access Protocol: Sanofi; Non-Financial Interests, Other, Supervisory Board: HMF – Hartwig Medical Foundation; Non-Financial Interests, Principal Investigator, Senior group leader: Oncode Institute; Non-Financial Interests, Advisory Role, Editorial Board: JAMA Oncology. All other authors have declared no conflicts of interest.