Abstract
Phase II is the critical development stage in which most clinical attrition
occurs. This report focuses on approaches to improving R&D productivity in the
pharmaceutical and biotechnology industries and considers:
Leading-edge strategies being pursued to improve success rates of therapeutic
candidates in clinical development The use of translational medicine studies
and early clinical trial protocols designed to reduce Phase II attrition
Survey results and expert interviews on efforts to improve R&D efficiency.
Pharmaceutical companies have been responding to a combination of major
challenges that many commentators call a "perfect storm." It is clear that the
high rate of attrition in the drug development process is severely limiting
the numbers of high-quality novel drug candidates, especially for innovative
drugs that address unmet medical needs. In order to overcome this limitation,
the industry must develop strategies that can reduce attrition during Phase
II, where most attrition occurs, especially as it continues to drive up the
cost of R&D to unsustainable levels.
Approaches to Reducing Phase II Attrition considers examples of leading-edge
strategies being pursued to improve target selection and other aspects of drug
discovery. These include development of multitargeted therapies, whole-pathway
approaches, biology-driven drug discovery, analysis of multigenic complex
diseases, and network pharmacology. Strategies for improving early-stage
clinical studies are discussed, including the use of Phase 0 and adaptive
trials, and employing early proof-of-concept trials. Ways in which some
companies have adopted new corporate structures designed to increase
innovation or make R&D more "biotech-like" are described.
Poorly predictive animal models constitute a major cause of drug attrition. We
present two case studies in CNS and cancer, two therapeutic areas in which
animal models are notorious for being poorly predictive. The CNS case study
focuses on attempts to improve animal model efficacy studies, and the cancer
case study focuses on industry' s adoption of improved animal models developed
in academia. In these discussions, we indicate how these particular case
studies may have lessons for efficacy studies in most therapeutic areas.
Well-designed translational studies may enable drugs that do not work in
humans to fail early. We examine various aspects of translational studies,
including definition of responder versus non-responder populations, and
optimal dosing regimens; and identification of early and sensitive markers of
efficacy, and of those patients who are likely to experience adverse effects.
Examples of ways in which translational medicine is changing the organization
of clinical trials in some companies are discussed. We also study the roles
that various types of biomarkers play in translational medicine, as well as
the current state of biomarker science. Case studies on stratification
biomarkers in cancer are presented.
Approaches to Reducing Phase II Attrition analyzes results from a survey of
current practices and views toward improving the efficiency and effectiveness
of drug development. Finally, the complete transcripts of interviews conducted
with experts in the field are provided.
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