Innovations in clinical trial design in the era of molecular profiling

Julia D. Wulfkuhle, Alexander Spira, Kirsten H. Edmiston, Emanuel F. Petricoin

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Historically, cancer has been studied, and therapeutic agents have been evaluated based on organ site, clinical staging, and histology. The science of molecular profiling has expanded our knowledge of cancer at the cellular and molecular level such that numerous subtypes are being described based on biomarker expression and genetic mutations rather than traditional classifications of the disease. Drug development has experienced a concomitant revolution in response to this knowledge with many new targeted therapeutic agents becoming available, and this has necessitated an evolution in clinical trial design. The traditional, large phase II and phase III adjuvant trial models need to be replaced with smaller, shorter, and more focused trials. These trials need to be more efficient and adaptive in order to quickly assess the efficacy of new agents and develop new companion diagnostics. We are now seeing a substantial shift from the traditional multiphase trial model to an increase in phase II adjuvant and neoadjuvant trials in earlier-stage disease incorporating surrogate endpoints for long-term survival to assess efficacy of therapeutic agents in shorter time frames. New trial designs have emerged with capabilities to assess more efficiently multiple disease types, multiple molecular subtypes, and multiple agents simultaneously, and regulatory agencies have responded by outlining new pathways for accelerated drug approval that can help bring effective targeted therapeutic agents to the clinic more quickly for patients in need.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages19-36
Number of pages18
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

Publication series

NameMethods in Molecular Biology
Volume1606
ISSN (Print)1064-3745

Fingerprint

Clinical Trials
Biomarkers
Drug Approval
Therapeutics
Neoplasms
Histology
Mutation
Survival
Pharmaceutical Preparations

Keywords

  • Biomarkers
  • Clinical trial
  • Design
  • Endpoints
  • Neoadjuvant therapy
  • Tumor

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Cite this

Wulfkuhle, J. D., Spira, A., Edmiston, K. H., & Petricoin, E. F. (2017). Innovations in clinical trial design in the era of molecular profiling. In Methods in Molecular Biology (pp. 19-36). (Methods in Molecular Biology; Vol. 1606). Humana Press Inc.. https://doi.org/10.1007/978-1-4939-6990-6_2

Innovations in clinical trial design in the era of molecular profiling. / Wulfkuhle, Julia D.; Spira, Alexander; Edmiston, Kirsten H.; Petricoin, Emanuel F.

Methods in Molecular Biology. Humana Press Inc., 2017. p. 19-36 (Methods in Molecular Biology; Vol. 1606).

Research output: Chapter in Book/Report/Conference proceedingChapter

Wulfkuhle, JD, Spira, A, Edmiston, KH & Petricoin, EF 2017, Innovations in clinical trial design in the era of molecular profiling. in Methods in Molecular Biology. Methods in Molecular Biology, vol. 1606, Humana Press Inc., pp. 19-36. https://doi.org/10.1007/978-1-4939-6990-6_2
Wulfkuhle JD, Spira A, Edmiston KH, Petricoin EF. Innovations in clinical trial design in the era of molecular profiling. In Methods in Molecular Biology. Humana Press Inc. 2017. p. 19-36. (Methods in Molecular Biology). https://doi.org/10.1007/978-1-4939-6990-6_2
Wulfkuhle, Julia D. ; Spira, Alexander ; Edmiston, Kirsten H. ; Petricoin, Emanuel F. / Innovations in clinical trial design in the era of molecular profiling. Methods in Molecular Biology. Humana Press Inc., 2017. pp. 19-36 (Methods in Molecular Biology).
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