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

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.

Cited by papers we hold 6

• Targeting Aquaporin-4 Subcellular Localization to Treat Central Nervous System Edema · 2020
  No notice
• Revisiting Traumatic Brain Injury: From Molecular Mechanisms to Therapeutic Interventions · 2020
  No notice
• Progesterone in the Brain: Hormone, Neurosteroid and Neuroprotectant · 2020
  No notice
• How to Translate Time? The Temporal Aspect of Human and Rodent Biology · 2017
  No notice
• The Controlled Cortical Impact Model: Applications, Considerations for Researchers, and Future Directions · 2016
  No notice
• Progesterone treatment reduces neuroinflammation, oxidative stress and brain damage and improves long-term outcomes in a rat model of repeated mild traumatic brain injury · 2015
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.