Research Needs for Prognostic Modeling and Trajectory Analysis in Patients with Disorders of Consciousness

Abstract

Background: The current state of the science regarding the care and prognosis of patients with disorders of consciousness is limited. Scientific advances are needed to improve the accuracy, relevance, and approach to prognostication, thereby providing the foundation to develop meaningful and effective interventions.Methods: To address this need, an interdisciplinary expert panel was created as part of the Coma Science Working Group of the Neurocritical Care Society Curing Coma Campaign. Results:The panel performed a gap analysis which identified seven research needs for prognostic modeling and trajectory analysis ("recovery science") in patients with disorders of consciousness: (1) to define the variables that predict outcomes; (2) to define meaningful intermediate outcomes at specific time points for different endotypes;(3) to describe recovery trajectories in the absence of limitations to care; (4) to harness big data and develop analytic methods to prognosticate more accurately; (5) to identify key elements and processes for communicating prognostic uncertainty over time; (6) to identify health care delivery models that facilitate recovery and recovery science; and (7) to advocate for changes in the health care delivery system needed to advance recovery science and implement already-known best practices. Conclusion:This report summarizes the current research available to inform the proposed research needs, articulates key elements within each area, and discusses the goals and advances in recovery science and care anticipated by successfully addressing these needs.

Ethics and the 2018 Practice Guideline on Disorders of Consciousness

“…27,28 Misdiagnosis, by contrast, can lead to medically inappropriate, insufficient, or inefficient use of resources. 29 Increasing diagnostic accuracy, therefore, is valuable to the patient and to the stewardship of available resources. Short-term costs in accurate diagnosis may be high, but the long-term payoff is worth the investment.…”

Ethical Considerations in Clinical Trials for Disorders of Consciousness

“…Clinical trials involving participants with DoC pose a distinct challenge to the doctrine of informed consent insofar as participants by definition are unable to actively engage in decision-making [ 65 ]. However, discovery of novel therapies for this population is crucial, with survivors facing severely limited treatment options and high rates of mortality, morbidity, and long-term neurological disability [ 66 , 67 , 68 , 69 , 70 ]. Recognizing this challenge, Fins and colleagues incisively state that “[p]aradoxically… those with disorders of consciousness often have been protected from the research enterprise by regulatory exclusion, which inverts the justice ethos of Belmont” [ 71 ].…”

“…Racial-, ethnic-, and language-based disparities are also prevalent across a variety of clinical trial domains [ 176 , 177 , 178 , 179 , 180 , 181 ]. Ethical considerations of justice and equity demand close attention to these potential disparities and necessitate strategies to democratize access to DoC clinical-trial enrollment [ 67 , 69 , 70 ]. Research identifying patterns of accrual of participants in DoC clinical trials, characterizing disparities, and illuminating barriers to enrollment is needed to ensure diverse and equitable clinical-trial enrollment.…”

Coma Science: The Territory and the Map

“…CSWG modules were given a set of objectives and a time line, and were instructed to implement a gap analysis approach; in its simplified form, the latter requires the description of a desired state and a current state, and the elaboration of a strategic pathway bridging current to desired. White *Correspondence: rstevens@jhmi.edu 1 Division of Neurosciences Critical Care, Johns Hopkins University School of Medicine, 600 N. Wolfe St, Phipps 455, Baltimore, MD 21287, USA Full list of author information is available at the end of the article papers summarizing the findings of each module appear in this issue of the journal [3][4][5][6].…”

“…The prognostic and trajectory analysis module [5] recognized a number of major shortcomings in the current science of brain injury recovery, with barriers in our ability to predict, prognosticate, and treat effectively. This module articulated seven unmet needs that will need to be addressed to advance prognostication and rehabilitative care.…”