Periodic Reporting for period 1 - PRIME-ROSE (PRecisIon Cancer MEdicine RepurpOsing SystEm Using Pragmatic Clinical Trials)
Reporting period: 2023-07-01 to 2024-12-31
The PRIME-ROSE project (Precision Cancer Medicine Repurposing System Using Pragmatic Clinical Trials) aims to advance the implementation of precision cancer medicine (PCM) across Europe. Leveraging the successes of ongoing national initiatives, PRIME-ROSE brings together 28 partners from 19 European countries to facilitate the implementation of PCM in Europe.
Despite the introduction of novel anti-cancer drugs targeting specific molecular alterations, access to these therapies remains uneven across Europe due to:
a) unequal availability of molecular diagnostics,
b) variations in knowledge and expertise,
c) uncertainties around real-world effectiveness,
d) challenges in co-payment and reimbursement,
e) lack of harmonized regulations for off-label use, and
f) limited access to clinical trials and early access programs.
These challenges disproportionately affect patients with poor prognoses or rare tumor mutations who have exhausted standard-of-care options.
PRIME-ROSE builds on national initiatives centered around Drug Rediscovery Protocol (DRUP)-like clinical trials (DLCTs). DLCTs are phase II umbrella-basket trials in which patients with advanced cancers receive targeted therapies based on their tumor's genomic alterations. By aligning with the original DRUP protocol from the Netherlands, these trials facilitate data sharing across borders.
The project aims to establish an automatic data-sharing platform to accelerate evidence generation. This platform will merge data from all DLCTs to monitor recruitment, conduct cross-trial cohort evaluations, and enable federated analyses with non-European trials. Collaboration with pharmaceutical companies will be streamlined, offering a single point of entry for drugs to access multiple trials.
One critical limitation of PCM trials is the absence of control arms. PRIME-ROSE addresses this by developing new and advanced methods for establishing synthetic control groups that leverage access to large European registries.
PRIME-ROSE also focuses on reimbursement systems. The project will assess requirements for on and off-label reimbursement across participating countries and develop economic evaluation models that include budget impact and cost-effectiveness analyses. These models will integrate the entire PCM pathway, from molecular diagnostics to treatment. PRIME-ROSE will provide actionable insights into how reimbursement systems influence access, timing, and affordability to both on- and off-label drugs.
Strategies for pragmatic, outcome-based risk-sharing agreements will be explored by analyzing successful examples from the Netherlands and Norway. The project will assist policymakers, healthcare providers, and other stakeholders in adopting these models, ultimately contributing to a European framework for efficient PCM evaluation—particularly for rare cancers and unmet needs.
PRIME-ROSE will map the PCM ecosystem to support system-wide change, developing a theory of change for healthcare as a complex adaptive system. This work will inform governance, policy, and innovation strategies.
Despite the introduction of novel anti-cancer drugs targeting specific molecular alterations, access to these therapies remains uneven across Europe due to:
a) unequal availability of molecular diagnostics,
b) variations in knowledge and expertise,
c) uncertainties around real-world effectiveness,
d) challenges in co-payment and reimbursement,
e) lack of harmonized regulations for off-label use, and
f) limited access to clinical trials and early access programs.
These challenges disproportionately affect patients with poor prognoses or rare tumor mutations who have exhausted standard-of-care options.
PRIME-ROSE builds on national initiatives centered around Drug Rediscovery Protocol (DRUP)-like clinical trials (DLCTs). DLCTs are phase II umbrella-basket trials in which patients with advanced cancers receive targeted therapies based on their tumor's genomic alterations. By aligning with the original DRUP protocol from the Netherlands, these trials facilitate data sharing across borders.
The project aims to establish an automatic data-sharing platform to accelerate evidence generation. This platform will merge data from all DLCTs to monitor recruitment, conduct cross-trial cohort evaluations, and enable federated analyses with non-European trials. Collaboration with pharmaceutical companies will be streamlined, offering a single point of entry for drugs to access multiple trials.
One critical limitation of PCM trials is the absence of control arms. PRIME-ROSE addresses this by developing new and advanced methods for establishing synthetic control groups that leverage access to large European registries.
PRIME-ROSE also focuses on reimbursement systems. The project will assess requirements for on and off-label reimbursement across participating countries and develop economic evaluation models that include budget impact and cost-effectiveness analyses. These models will integrate the entire PCM pathway, from molecular diagnostics to treatment. PRIME-ROSE will provide actionable insights into how reimbursement systems influence access, timing, and affordability to both on- and off-label drugs.
Strategies for pragmatic, outcome-based risk-sharing agreements will be explored by analyzing successful examples from the Netherlands and Norway. The project will assist policymakers, healthcare providers, and other stakeholders in adopting these models, ultimately contributing to a European framework for efficient PCM evaluation—particularly for rare cancers and unmet needs.
PRIME-ROSE will map the PCM ecosystem to support system-wide change, developing a theory of change for healthcare as a complex adaptive system. This work will inform governance, policy, and innovation strategies.
Key activities during the first project period include:
Data Sharing Platform:
Approval and signing of data-sharing agreements by all partners sharing data.
Established collaboration within the Horizon Europe Cancer Mission ‘Diagnostics and Treatment’ cluster
Initiated the work on an OMOP-model-based data-sharing platform to standardize trial variables.
Determined procedures for harmonizing shared variables.
Agreed upon method for data merging described in a detailed report on data sharing, including trial overlaps in inclusion/exclusion criteria and endpoints.
Synthetic Control Groups:
Statical models for randomized synthetic control arms developed.
Registry data from multiple sources, including Norwegian and Dutch datasets, has been applied for. The data will be used to develop synthetic control arms for the cohorts in PRIME-ROSE.
Reimbursement Analysis:
The health technology assessment (HTA) requirements across countries have been mapped
Results from the investigation of off-label use in the Netherlands presented at ESMO 2024.
Mapping of off-label procedures across different European countries initiated.
Patient-Centric Outcomes:
A set of health-related quality of life (hrQoL) tools to be used within the DLCTs has been agreed upon.
Data Sharing Platform:
Approval and signing of data-sharing agreements by all partners sharing data.
Established collaboration within the Horizon Europe Cancer Mission ‘Diagnostics and Treatment’ cluster
Initiated the work on an OMOP-model-based data-sharing platform to standardize trial variables.
Determined procedures for harmonizing shared variables.
Agreed upon method for data merging described in a detailed report on data sharing, including trial overlaps in inclusion/exclusion criteria and endpoints.
Synthetic Control Groups:
Statical models for randomized synthetic control arms developed.
Registry data from multiple sources, including Norwegian and Dutch datasets, has been applied for. The data will be used to develop synthetic control arms for the cohorts in PRIME-ROSE.
Reimbursement Analysis:
The health technology assessment (HTA) requirements across countries have been mapped
Results from the investigation of off-label use in the Netherlands presented at ESMO 2024.
Mapping of off-label procedures across different European countries initiated.
Patient-Centric Outcomes:
A set of health-related quality of life (hrQoL) tools to be used within the DLCTs has been agreed upon.
We have established a proof-of-concept platform for cross-border data sharing between trials.
The Netherlands demonstrates the extended use of off-label reimbursement in cancer care.
The Netherlands demonstrates the extended use of off-label reimbursement in cancer care.