Bioethics Blogs

Shedding (Dim) Light on Clinical Benefit in Biomarker-Based Drug Development

Despite the appeal of personalized medicine (that is treatment selection based on the presence of a particular marker), uncertainty remains regarding the broad utility of this selection strategy in oncology. A recent meta-analysis by Jardim et al. in the Journal of the National Cancer Institute attempted to provide some clarity by comparing efficacy outcomes between personalized and non-personalized clinical trial designs leading to the new FDA approval of drugs between 1998-2013. The publication concluded that using a biomarker-based selection strategy led to improved response rate, progression free survival and overall survival across a range of cancer subtypes and selection biomarkers.

The study should be applauded for its unique approach in trying to determine the benefit of personalized drug development, the paper’s conclusions are qualified by five issues.

No information about drugs that do not receive license 

Personalized Drug Development

The study only evaluated efficacy outcomes for trials directly leading to the FDA approval of the drug (the authors acknowledge this). This may prevent generalizability of conclusions, as it does not capture drugs that failed during testing. However this search strategy also excluded studies earlier in the development of approved drugs, where they were explored unsuccessfully for various indications or biomarker subgroups. In contrast to FDA approval for non-personalized drugs, which just requires identifying the proper indication, personalized strategies in addition require finding optimal test conditions for biomarkers used in patient selection. It is therefore conceivable that greater failed exploration goes into the development of a personalized strategy and therefore that an overall comparison of efficacy outcomes between personalized and non-personalized designs may not reach the same conclusions as a comparison of the FDA approval trials.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.