Does biomarker use in oncology improve clinical trial failure risk? A large‐scale analysis. (23rd February 2021)

• Record Type: Journal Article
• Authors: Parker, Jayson L.; Kuzulugil, Sebnem S.; Pereverzev, Kirill; Mac, Stephen; Lopes, Gilberto; Shah, Zain; Weerasinghe, Ashini; Rubinger, Daniel; Falconi, Adam; Bener, Ayse; Caglayan, Bora; Tangri, Rohan; Mitsakakis, Nicholas
• Is Part Of: Cancer medicine. Volume 10:Number 6(2021)
• Page Start: 1955
• Page End: 1963
• Publication Date: 2021-02-23
• Subjects: biomarkers -- breast cancer -- cancer -- clinical trial -- drug development -- lung cancer -- melanoma -- oncology -- risk; 616.994005
• DOI: 10.1002/cam4.3732
• Languages: English
• ISSNs: 2045-7634

Abstract

Abstract: Purpose: To date there has not been an extensive analysis of the outcomes of biomarker use in oncology. Methods: Data were pooled across four indications in oncology drawing upon trial outcomes from www.clinicaltrials.gov : breast cancer, non‐small cell lung cancer (NSCLC), melanoma and colorectal cancer from 1998 to 2017. We compared the likelihood drugs would progress through the stages of clinical trial testing to approval based on biomarker status. This was done with multi‐state Markov models, tools that describe the stochastic process in which subjects move among a finite number of states. Results: Over 10000 trials were screened, which yielded 745 drugs. The inclusion of biomarker status as a covariate significantly improved the fit of the Markov model in describing the drug trajectories through clinical trial testing stages. Hazard ratios based on the Markov models revealed the likelihood of drug approval with biomarkers having nearly a fivefold increase for all indications combined. A 12, 8 and 7‐fold hazard ratio was observed for breast cancer, melanoma and NSCLC, respectively. Markov models with exploratory biomarkers outperformed Markov models with no biomarkers. Conclusion: This is the first systematic statistical evidence that biomarkers clearly increase clinical trial success rates in three different indications in oncology. Also, exploratory biomarkers, long before they are properly validated, appear to improve success rates in oncology. This supports early and aggressive adoption of biomarkers in oncology clinical trials. Abstract : We reviewed clinical trial success rates in 4 cancers: breast cancer, melanoma, colorectal and lung cancer. We examined the effect of biomarker use on the risk of clinical trial failure. We found that biomarker use best accounted for clinical trial success rates and provides the first extensive statistical analysis to support its use in clinical trial design.