Statistical considerations for a trial of Ebola virus disease therapeutics

The 2014 West African outbreak of Ebola virus ravaged Liberia, Sierra Leone, and Guinea, causing hemorrhagic fever and death. The need to identify effective therapeutics was acute. The usual drug development paradigm of phase I, followed by phase II, and then phase III trials would take too long. These and other factors led to the design of a clinical trial of Ebola virus disease therapeutics that differs from more conventional clinical trial designs. This article describes the Ebola virus disease medical countermeasures trial design and the thinking behind it.

[1]  P. O'Brien,et al.  A multiple testing procedure for clinical trials. , 1979, Biometrics.

[2]  KyungMann Kim.  Group Sequential Methods with Applications to Clinical Trials , 2001 .

[3]  M H Gail,et al.  Applicability of sample size calculations based on a comparison of proportions for use with the logrank test. , 1985, Controlled clinical trials.

[4]  P. Armitage,et al.  Repeated Significance Tests on Accumulating Data , 1969 .

[5]  P. Horby,et al.  Trial design for evaluating novel treatments during an outbreak of an infectious disease , 2016, Clinical trials.

[6]  J. Haybittle,et al.  Repeated assessment of results in clinical trials of cancer treatment. , 1971, The British journal of radiology.

[7]  S. Pocock.  Group sequential methods in the design and analysis of clinical trials , 1977 .

[8]  Kai Kupferschmidt,et al.  Infectious Diseases. Ebola vaccine trials raise ethical issues. , 2014, Science.

[9]  John Whitehead,et al.  Group sequential trials revisited: Simple implementation using SAS , 2011, Statistical methods in medical research.

[10]  J. Dushoff,et al.  Ebola virus vaccine trials: the ethical mandate for a therapeutic safety net , 2014, BMJ : British Medical Journal.

[11]  John Whitehead,et al.  Evaluating Clinical Trial Designs for Investigational Treatments of Ebola Virus Disease , 2015, PLoS medicine.

[12]  K. K. Lan,et al.  Discrete sequential boundaries for clinical trials , 1983 .

[13]  M. Fay,et al.  Combining one‐sample confidence procedures for inference in the two‐sample case , 2015, Biometrics.

[14]  T R Fleming,et al.  Designs for group sequential tests. , 1984, Controlled clinical trials.

[15]  G. Barnard,et al.  A New Test for 2 × 2 Tables , 1945, Nature.

[16]  Michael R. Chernick,et al.  Statistical Monitoring of Clinical Trials: a Unified Approach , 2007, Technometrics.