Diagnostic regulatory pathways are an underrecognized bottleneck in precision oncology clinical trials: Real-world...

Using real-world data (RWD), we assessed the impact of diagnostic regulatory pathways on activation timelines and biomarker testing implementation in biomarker-driven clinical trials across Europe.

RWD from 132 Clinical Performance Study Applications (PSAs) and Ethics Committee (EC) submissions across 18 European Union Member States (EU-MS) and 2 non-EU countries that operate under the In Vitro Diagnostic Medical Devices Regulation 2017/746 (IVDR) were pooled for analysis. Statistical, outlier assessments and comparative analyses were performed to evaluate differences in timelines between submission pathways. Statistical significance was assessed using Welch's t-test and the Mann-Whitney U test.

Mean combined approval time for all submissions (EC and PSA) was 129.39 days (median, 116.5; range 32-346). Sequential submissions averaged 139.97 days versus 121.11 days for parallel submissions, corresponding to a ∼15.6% longer timeline than sequential pathways (mean difference 18.86 days; p = 0.0411). Mean country-level combined approval timelines varied substantially across countries, ranging from 75.66 to 175 days among countries (n = 17) with ≥ 3 submissions. Substantial cross-country variability in operational implementation challenges was observed.

Diagnostic approvals represent underrecognized bottlenecks in precision medicine (PM) trial activation, with approval timelines frequently exceeding those of Clinical Trial Applications (CTAs), median 108 days. Fragmented IVDR implementation has created substantial cross-country variability and uncertainty for trial activation. Biomarker strategies and diagnostic testing approaches should be thoughtfully constructed and considered pragmatically, as inefficient implementation may directly affect trial interpretability, efficacy assessment and regulatory success, substantially compromising trial delivery in Europe.