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Author Notes:

Correspondence: Donald G. Stein, 1365 B Clifton Rd NE, Suite 5100, Atlanta, GA, 30322, USA. E-mail: dstei04@emory.edu

Declaration of Interest: Although the author no longer has any financial gains, royalties or licensing agreements from research on progesterone, he does hold active patents related to the use of progesterone in TBI and certain forms of CNS tumours.

Subjects:

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Rehabilitation
  • Neurosciences & Neurology
  • Clinical trials
  • progesterone
  • ProTECT III
  • SyNAPSe
  • traumatic brain injury
  • TRAUMATIC BRAIN-INJURY
  • VIVO NEUTROPHIL ACTIVATION
  • COMMON DATA ELEMENTS
  • ISCHEMIC-STROKE
  • DOSE-RESPONSE
  • MEDROXYPROGESTERONE ACETATE
  • EXPERIMENTAL-MODEL
  • NERVOUS-SYSTEM
  • TIME-WINDOW
  • HEAD-INJURY

Embracing failure: What the Phase III progesterone studies can teach about TBI clinical trials

Tools:

Journal Title:

Brain Injury

Volume:

Volume 29, Number 11

Publisher:

, Pages 1259-1272

Type of Work:

Article | Final Publisher PDF

Abstract:

Background: Despite positive preclinical studies and two positive Phase II clinical trials, two large Phase III clinical trials of progesterone treatment of acute traumatic brain injury (TBI) recently ended with negative results, so a 100% failure rate continues to plague the field of TBI trials. Methods: This paper reviews and analyses the trial structures and outcomes and discusses the implications of these failures for future drug and clinical trial development. Persistently negative trial outcomes have led to disinvestment in new drug research by companies and policy-makers and disappointment for patients and their families, failures which represent a major public health concern. The problem is not limited to TBI. Failure rates are high for trials in stroke, sepsis, cardiology, cancer and orthopaedics, among others. Results: This paper discusses some of the reasons why the Phase III trials have failed. These reasons may include faulty extrapolation from pre-clinical data in designing clinical trials and the use of subjective outcome measures that accurately reflect neither the nature of the deficits nor long-term quantitative recovery. Conclusions: Better definitions of injury and healing and better outcome measures are essential to change the embrace of failure that has dominated the field for over 30 years. This review offers suggestions to improve the situation.

Copyright information:

© 2015 Donald G. Stein. This is an Open Access article. Non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly attributed, cited, and is not altered, transformed, or built upon in any way, is permitted. The moral rights of the named author(s) have been asserted.

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