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The future of drug development: advancing clinical trial design

Abstract

Declining pharmaceutical industry productivity is well recognized by drug developers, regulatory authorities and patient groups. A key part of the problem is that clinical studies are increasingly expensive, driven by the rising costs of conducting Phase II and III trials. It is therefore crucial to ensure that these phases of drug development are conducted more efficiently and cost-effectively, and that attrition rates are reduced. In this article, we argue that moving from the traditional clinical development approach based on sequential, distinct phases towards a more integrated view that uses adaptive design tools to increase flexibility and maximize the use of accumulated knowledge could have an important role in achieving these goals. Applications and examples of the use of these tools — such as Bayesian methodologies — in early- and late-stage drug development are discussed, as well as the advantages, challenges and barriers to their more widespread implementation.

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Figure 1: A novel model for clinical development.
Figure 2: Dose selection in the development of a therapeutic for Muckle–Wells syndrome.
Figure 3: Re-estimating sample size while maintaining statistical power.

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Acknowledgements

A special acknowledgment to W. Dere (Amgen), S. Cummings (UCSF), A. Lee (Pfizer) and E. Berndt (MIT-CBI) for significant contributions to discussions leading to this manuscript. Also, many thanks to the McKinsey Trial Design Team for their support (M. E., E. F., N. S. and T. T.).

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Correspondence to John Orloff.

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Some authors are employed by, or have consulting relationships with, pharmaceutical companies, biotech companies, contract research organizations, academic institutions, consulting firms and/or research foundations, that might be perceived as a competing interest.

Supplementary information

Supplementary information S1 (box)

Case study: dose selection in type 2 diabetes mellitus (PDF 920 kb)

Supplementary information S2 (box)

Case study: dyslipidaemia proof-of-concept study (PDF 434 kb)

Supplementary information S3 (figure)

Advantages of a seamless/adaptive trial design compared with classical Phase IIb and III studies (PDF 259 kb)

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DATABASES

OMIM

Muckle–Wells syndrome

type 2 diabetes

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Orloff, J., Douglas, F., Pinheiro, J. et al. The future of drug development: advancing clinical trial design. Nat Rev Drug Discov 8, 949–957 (2009). https://doi.org/10.1038/nrd3025

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