IMPACT Recommendations for Improving the Design and Analysis of Clinical Trials in Moderate to Severe Traumatic Brain Injury

Abstract

Summary: Clinical trials in traumatic brain injury (TBI) pose complex methodological challenges, largely related to the heterogeneity of the population. The International Mission on Prognosis and Clinical Trial Design in TBI study group has explored approaches for dealing with this heterogeneity with the aim to optimize clinical trials in TBI. Extensive prognostic analyses and simulation studies were conducted on individual patient data from eight trials and three observational studies. Here, we integrate the results of these studies into the International Mission on Prognosis and Clinical Trial Design in TBI recommendations for design and analysis of trials in TBI:• Details of the major baseline prognostic characteristics should be provided in every report on a TBI study; in trials they should be differentiated per treatment group. We also advocate the reporting of the baseline prognostic risk as determined by validated prognostic models.• Inclusion criteria should be as broad as is compatible with the current understanding of the mechanisms of action of the intervention being evaluated. This will maximize recruitment rates and enhance the generalizability of the results.• The statistical analysis should incorporate prespecified covariate adjustment to mitigate the effects of the heterogeneity.• The statistical analysis should use an ordinal approach, based on either sliding dichotomy or proportional odds methodology.Broad inclusion criteria, prespecified covariate adjustment, and an ordinal analysis will promote an efficient trial, yielding gains in statistical efficiency of more than 40%. This corresponds to being able to detect a 7% treatment effect with the same number of patients needed to demonstrate a 10% difference with an unadjusted analysis based on the dichotomized Glasgow outcome scale.

Technology and its role in rehabilitation for people with cognitive-communication disability following a traumatic brain injury (TBI)

“…Quantitative studies MANUSCRIPT ACCEPTED -BRAIN INJURY: 02 FEBRUARY 2017 23 including participants with TBI using AT and ICT for cognitive-communication rehabilitation will need (a) a larger numbers of participants [36,41,89], (b) comparison conditions [36,41,88,97], and (c) rigorous outcome measures [36,41]. As people with TBI are a heterogeneous group [148][149][150] [36,37,55,56,136]. …”

“…Quantitative studies including participants with TBI using AT and ICT for cognitive-communication rehabilitation will need (a) a larger numbers of participants [36,41,89], (b) comparison conditions [36,41,88,97], and (c) rigorous outcome measures [36,41]. As people with TBI are a heterogeneous group [148][149][150] and recruitment to research is challenging [151], single case multiple-baseline experimental designs where participants serve as their own controls [152] are needed. Qualitative and mixed methods designs, including human computer interface studies, narrative inquiry, and network or content analysis of social media data, will help to understand the nature of social media use by people with TBI.…”

Clinical Trials in Traumatic Brain Injury: Past Experience and Current Developments

“…Recommendations and results originating from the IMPACT work are summarized in a dedicated article in this issue. 24 The IMPACT studies were conducted on individual patient data from eight RCTs and three observational studies. 25 Relevant parameters from the individual studies were merged into a large dataset, forming a "culture medium" for exploring concepts for improving the design of clinical trials in TBI.…”

Traumatic brain injury in pediatric patients: evidence for the effectiveness of decompressive surgery

“…Guidelines recommend prespecified baseline prognostic criteria, broad inclusion criteria, and ordinal statistical analysis to maximize efficiency and generalizability of the results. 33 Additionally, because functional outcome following TBI can change greatly from 1 to 5 years postincident, long follow-up periods greater than 1 year are needed. 12 The 5 trials summarized in Table 3 are the most significant and recent in the field of craniectomy following pediatric and adult TBI.…”