The Role of Biomarkers in Drug Development
Kunihiko Hayashi (Senior Researcher, Pharmaceutical and Industrial Policy Research Institute)
(No.57: Published in March 2013)
Against the backdrop of societal pressure on healthcare financing and expectations for improving the quality of healthcare, the level of safety and efficacy required of pharmaceuticals is increasing. At the same time, pharmaceutical R&D is becoming increasingly difficult, and R&D productivity is declining. Therefore, the use of biomarkers is attracting attention as a means of improving R&D efficiency. >In this paper, we analyze the current status of biomarker use in clinical research, quantitatively analyze the impact of patient-specific markers on drug development efficiency, and conduct a questionnaire survey on pharmacogenomics research in Japanese pharmaceutical companies to elucidate the mechanisms by which biomarkers affect R&D efficiency and R&D competitiveness. In addition, based on an analysis of the current status of companion diagnostics development and utilization, we discussed the biomarker R&D environment in Japan.
The analysis of the current status of biomarker use in clinical trials revealed that the number of trials and the percentage of clinical trials using biomarkers increased, that the use of biomarkers was most active in the field of oncology, and that the largest number of trials were conducted by U.S. sponsors. These findings suggest that there are differences in the conduct of clinical trials by region, disease area, and other factors, and that these differences may lead to differences in R&D competitiveness. In a quantitative analysis of the impact of patient stratified markers on drug development efficiency, the phase transition probability of anticancer drug development items with and without the use of patient stratified markers revealed that items with patient stratified markers showed higher phase transition probability in each phase than items without the use of patient stratified markers. The use or non-use of patient stratified markers may affect the efficiency of drug development. A questionnaire survey on pharmacogenomics (PGx) research in pharmaceutical companies revealed that the percentage of companies conducting PGx trials varied depending on company attributes (domestic, foreign, and company size), and that internal and external factors were also considered to influence the obstacles to PGx trials, depending on company attributes. Differences in PGx clinical trials may lead to differences in R&D competitiveness in the future. In the analysis of the current status of companion diagnostics development and utilization, it was shown that there are differences in the development process between drugs and diagnostics and differences in regulations in each country regarding companion diagnostics as development issues, and that there are issues in the reimbursement price and insurance reimbursement of companion diagnostics in terms of utilization. Improving R&D production efficiency with patient stratified markers will require resolution of these issues.
The use of biomarkers acts to improve R&D efficiency and contributes to R&D competitiveness. In order to effectively use biomarkers and improve R&D competitiveness, it is necessary for pharmaceutical companies, government, and academia to address the issues identified in this paper, and we have summarized possible recommendations for each. Based on these recommendations, we hope that an environment that promotes the use of biomarkers will be established to improve the efficiency of pharmaceutical R&D and to contribute to the improvement of the quality of medical care.