Procedure for pooling clinical outcome data from DRUP-like clinical trials using the OMOP model.

Background: PRIME-ROSE is a European Cancer Mission project focused on advancing precision cancer medicine (PCM) trials and innovative processes for implementing PCM. The initiative encompasses 11 ongoing or upcoming DRUP-like clinical trials across various European countries (www.prime-rose.eu), investigating more than 60 drugs from over 20 different companies. These trials aim to evaluate biomarker-driven treatments beyond their approved indications in a wide range of tumor types. Within PRIME-ROSE, data from individual trials are shared and aggregated for patients with the same tumor type, biomarker, and drug combination. This collaborative approach enhances recruitment rates, accelerates evidence generation, and ultimately improves patient care. Currently, the trial network covers a population of 71 million inhabitants. Methods: To merge outcome data from patients enrolled in the DRUP-like clinical trials, a protocol for harmonizing and standardizing approximately 40 clinical variables was developed using the OMOP (Observational Medical Outcomes Partnership) model. A unified statistical analysis plan evaluates shared endpoints, while the sampling plan follows a Simon two-stage design to guide cohort progression. Specifically, cohorts of 8 patients (stage I) are assessed for clinical benefit (CB)—defined as confirmed objective response or stable disease lasting ≥16 weeks. Cohorts demonstrating ≥1 CB at 16 weeks advance to stage II, expanding to 24 patients for further evaluation. Expansions beyond 24 patients at stage III can trigger reimbursement negotiations depending on treatment efficacy. To date, data have been pooled from six trials: FINPROVE (Finland), ProTarget (Denmark), IMPRESS-Norway (Norway), DETERMINE (UK), MegaMost (France) and DRUP (Netherlands). Results: Clinical variables from each trial have successfully been harmonized and standardized using the OMOP model, enabling effective cohort merging. A total of 198 cohorts with a total of 765 patients have currently been aligned and are monitored for expansion. So far, 19 cohorts have been expanded from stage I (8 patients) to stage II (24 patients) based on pooled data from the PRIME-ROSE trials out of which 3 cohorts have completed enrollment in stage II (≥24 patients). These aggregated cohorts are now undergoing outcome analysis. Conclusions: The harmonization and standardization of clinical outcome data across DRUP-like trials are feasible and significantly enhance cohort inclusion rates. In addition, the use of the OMOP model can facilitate federated analysis with other PCM trials around the world. This collaborative approach accelerates data generation, enabling more rapid evidence-building for biomarker-driven treatments and improving outcomes for patients with hard-to-treat advanced cancers. Affiliation: On behalf of the PRIME-ROSE Consortium.