An evidence-based methodology for systematic evaluation of clinical outcome assessment measures for traumatic brain injury

PLoS One. 2020 Dec 14;15(12):e0242811. doi: 10.1371/journal.pone.0242811. eCollection 2020.

Abstract

Introduction: The high failure rate of clinical trials in traumatic brain injury (TBI) may be attributable, in part, to the use of untested or insensitive measurement instruments. Of more than 1,000 clinical outcome assessment measures (COAs) for TBI, few have been systematically vetted to determine their performance within specific "contexts of use (COU)." As described in guidance issued by the U.S. Food and Drug Administration (FDA), the COU specifies the population of interest and the purpose for which the COA will be employed. COAs are commonly used for screening, diagnostic categorization, outcome prediction, and establishing treatment effectiveness. COA selection typically relies on expert consensus; there is no established methodology to match the appropriateness of a particular COA to a specific COU. We developed and pilot-tested the Evidence-Based Clinical Outcome assessment Platform (EB-COP) to systematically and transparently evaluate the suitability of TBI COAs for specific purposes.

Methods and findings: Following a review of existing literature and published guidelines on psychometric standards for COAs, we developed a 6-step, semi-automated, evidence-based assessment platform to grade COA performance for six specific purposes: diagnosis, symptom detection, prognosis, natural history, subgroup stratification and treatment effectiveness. Mandatory quality indicators (QIs) were identified for each purpose using a modified Delphi consensus-building process. The EB-COP framework was incorporated into a Qualtrics software platform and pilot-tested on the Glasgow Outcome Scale-Extended (GOSE), the most widely-used COA in TBI clinical studies.

Conclusion: The EB-COP provides a systematic methodology for conducting more precise, evidence-based assessment of COAs by evaluating performance within specific COUs. The EB-COP platform was shown to be feasible when applied to a TBI COA frequently used to detect treatment effects and can be modified to address other populations and COUs. Additional testing and validation of the EB-COP are warranted.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Brain Injuries, Traumatic / diagnosis*
  • Brain Injuries, Traumatic / therapy*
  • Clinical Trials as Topic*
  • Evidence-Based Medicine*
  • Humans
  • Outcome Assessment, Health Care*
  • Prognosis
  • Psychometrics
  • Software

Grants and funding

This study was supported by a seed grant awarded to JTG by the University of California at San Francisco (UCSF) as part of a prime award (TBI Endpoint Development Initiative; URL: https://tbiendpoints.ucsf.edu/) issued to UCSF by the U.S. Department of Defense (DoD) Army Medical Research and Materiel Command (W81XWH-14-2-0176; URL: https://mrdc.amedd.army.mil/). GM served as the PI on the primary DoD grant. The funder provided support in the form of salaries [JTG, AC, MJB, GM, AM] and consulting fees [MJA, AR, SM, PE, TSG, MM] for authors. The specific roles of these authors are articulated in the ‘author contributions’ section. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. One author [AR] has a commercial interest as the President of Ann Robbins, LLC, a regulatory affairs consulting company that provides regulatory consulting services to drug development and non-profit research organizations. Dr. Robbins’ commercial affiliation did not play any role in this study and she was not compensated for her participation.