Design of a Randomized Controlled Trial for Ebola Virus Disease Medical Countermeasures

PREVAIL II, the Ebola MCM Study

Lori E. Dodd, Michael A. Proschan, Jacqueline Neuhaus, Joseph S. Koopmeiners, James Neaton, John D. Beigel, Kevin Barrett, Henry Clifford Lane, Richard T. Davey

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background. Unique challenges posed by emerging infectious diseases often expose inadequacies in the conventional phased investigational therapeutic development paradigm. The recent Ebola outbreak in West Africa presents a critical case-study highlighting barriers to faster development. During the outbreak, clinical trials were implemented with unprecedented speed. Yet, in most cases, this fast-tracked approach proved too slow for the rapidly evolving epidemic. Controversy abounded as to the most appropriate study designs to yield safety and efficacy data, potentially causing delays in pivotal studies. Preparation for research during future outbreaks may require acceptance of a paradigm that circumvents, accelerates, or reorders traditional phases, without losing sight of the traditional benchmarks by which drug candidates must be assessed for activity, safety and efficacy. Methods. We present the design of an adaptive, parent protocol, ongoing in West Africa until January 2016. The exigent circumstances of the outbreak and limited prior clinical experience with experimental treatments, led to more direct bridging from preclinical studies to human trials than the conventional paradigm would typically have sanctioned, and required considerable design flexibility. Results. Preliminary evaluation of the "barely Bayesian" design was provided through computer simulation studies. The understanding and public discussion of the study design will help its future implementation.

Original languageEnglish (US)
Pages (from-to)1906-1913
Number of pages8
JournalJournal of Infectious Diseases
Volume213
Issue number12
DOIs
StatePublished - Jun 15 2016

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Ebola Hemorrhagic Fever
Disease Outbreaks
Randomized Controlled Trials
Western Africa
Emerging Communicable Diseases
Safety
Benchmarking
Computer Simulation
Clinical Trials
Research
Pharmaceutical Preparations

Keywords

  • Adaptive design
  • Bayesian design
  • Clinical trials
  • Ebola virus disease
  • Emerging infectious diseases

Cite this

Design of a Randomized Controlled Trial for Ebola Virus Disease Medical Countermeasures : PREVAIL II, the Ebola MCM Study. / Dodd, Lori E.; Proschan, Michael A.; Neuhaus, Jacqueline; Koopmeiners, Joseph S.; Neaton, James; Beigel, John D.; Barrett, Kevin; Lane, Henry Clifford; Davey, Richard T.

In: Journal of Infectious Diseases, Vol. 213, No. 12, 15.06.2016, p. 1906-1913.

Research output: Contribution to journalArticle

Dodd, Lori E. ; Proschan, Michael A. ; Neuhaus, Jacqueline ; Koopmeiners, Joseph S. ; Neaton, James ; Beigel, John D. ; Barrett, Kevin ; Lane, Henry Clifford ; Davey, Richard T. / Design of a Randomized Controlled Trial for Ebola Virus Disease Medical Countermeasures : PREVAIL II, the Ebola MCM Study. In: Journal of Infectious Diseases. 2016 ; Vol. 213, No. 12. pp. 1906-1913.
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