FDA, Sponsors Continue Quest for More Efficient Trials

The decline in important new medicines reaching market in 2013 has produced multiple proposals for making clinical trials more effective and efficient. A December report from Deloitte and Thomson Reuters analyzing R&D spending by 12 leading biopharma companies describes lower return-on-investment from clinical research, which has contributed to a steady rise in the cost of taking a new drug from discovery to launch (up 18% from 2010 to reach $1.3 billion in 2013). For improvement, analysts advise sponsors to curb late-stage research "leakage," reduce research cycle times, use more appropriate outsourcing, seek out and enhance R&D talent, and bolster analytic capabilities.

A January 2014 outlook report from the Tufts Center for the Study of Drug Development emphasizes the need for more realistic assessment of the chances for success of candidates as key to curbing late-stage clinical development failures. CSDD Director Ken Kaitin advised sponsors to reassess their use of meta-analyses and sub-group analysis to justify pushing compounds forward in development despite poor Phase II results. He expects to see continued FDA encouragement for breakthrough drugs, adaptive clinical trial designs in earlier studies, and greater use of patient-reported outcomes (PRO) and social media to communicate with patients.

FDA seeks to encourage sponsors, academics, and expert coalitions to research and seek qualification of such approaches, as seen in new guidance issued last month describing the "Qualification Process for Drug Development Tools" (DDT). This document, prepared by CDER's Qualification Process Working Group, describes FDA's qualification process, including agency procedures for interacting with parties developing DDTs and its review of data submitted to support acceptance of new DDTs. FDA also explains how it will increase communication on its qualification decisions in order to make DDTs widely available to the research community for use in developing other medical products.

The complexities in utilizing PRO instruments is reflected in a draft guidance published as an attachment to the DDT guidance on the use of EXACT (Exacerbations of Chronic Pulmonary Disease Tool) in measuring symptoms of exacerbation of chronic bronchitis. Although this is a qualified endpoint for Phase II studies, FDA notes uncertainty in defining the target population and in using this measure in confirmatory clinical trials. PROs have long raised controversial issues, and continue to do so.