There is a lot of discussion across biopharma about the increasing complexity in the design and management of clinical trials. In the following article, we outline the challenges and trends that are encouraging greater use of targeted clinical strategies and examine the application of specific biomarker roles (therapeutic effect marker, toxic effect marker, disease marker) within clinical trial design and suggest areas to focus on for future development. We show trends in how biomarkers are being applied within trial design, with implications for clinical development professionals who are designing trials and highlight the need to maintain awareness of latest scientific intelligence. Within the full analysis attached, we analyze trends in how the specific biomarker roles are being applied across a number of therapy areas.
The increase in complexity has triggered a considerable extension in the average duration of clinical trials and a reduction in the differential duration of trial phases.1 (See Figure 1.)
Any increase in trial duration leads to increasing costs, delays to launch and the potential for a drug to miss the vital slot as first-in-market, holding back potentially life-saving treatments for patients. Development strategies need to ensure that the launched compound can demonstrate sufficient efficacy while avoiding excessive recruitment demands, undesired toxicity and costly trial amendments.
Source: Journal of Health Economics, DiMasi, Joseph A, Grabowski, Henry G & Hansen, Ronald W. “Innovation in the Pharmaceutical Industry: New Estimates of R&D cost.” 47 (2016) 20-33.
While timelines are extending sharply, notably in oncology, we also note a significant rise in the volume of trials. Analyzing the number of trials within Cortellis Clinical Trials Intelligence with a “Start Date” each year between 2007 and 2016 we see an ongoing rise in the number of trials. During our two comparison periods, January 1, 2007 – December 31, 2011 (2007-2011) against January 1, 2012 – December 31, 2016 (2012-2016), we see a 33% increase in the number of trials.2 (See Figure 2.)
Source: Cortellis Clinical Trials Intelligence, Clarivate Analytics.
We believe the increasing volume of trials has implications for patient recruitment and competition, but also specifically relevant to this analysis, a heightened need to ensure that the clinical strategy is based on the best available intelligence relating to disease mechanisms, target actions and patient segmentation.
To understand whether the fundamentals of the underlying biological models are keeping pace with the complexity of trials, we consulted a recent published analysis. This demonstrated that the overwhelming majority of reasons given for failure are not due to strategic reasons, but are due to unproven efficacy and safety issues highlighting the importance of a solid biological rationale, suggesting scientific inadequacies in the understanding of the underlying disease mechanism, understanding of the drug action and the selection of patient cohorts.3 (See Figure 3.)
1 Journal of Health Economics, “Innovation in the Pharmaceutical Industry: New estimates of R&D cost.” DiMasi, Joseph A, Grabowski, Henry G & Hansen, Ronald W. 47 (2016) 20-33.
2 Cortellis Clinical Trials Intelligence, Clarivate Analytics, March 15, 2017.
3 Nature Reviews Drug Discovery, Harrison, RK. “Phase II and Phase III Failures 2013-2015.” 15, 817–818 (2016).
Source: Nature Reviews Drug Discovery, Harrison, RK. “Phase II and Phase III Failures 2013-2015.” 15, 817–818 (2016).
Read the full analysis highlighting trends in the utilization of specific biomarker roles with selected therapy areas, from Gavin Coney: “Biomarker Roles within Clinical Trials: An Analysis of Clinical Trials from 2007-2011 and 2012-2016.”