Although most individuals who sustain concussions recover within 2 to 4 weeks, a sizable minority remain symptomatic for months or even years.1 Persistent postconcussion symptoms (PPCS) are associated with declines in quality of life and other negative sequelae.2 To help guide clinical management of this condition, the Danish Health Authority convened a multidisciplinary panel to summarize the evidence regarding the effectiveness of selected nonpharmacological interventions in adults with PPCS and to generate a national guideline with recommendations for clinical practice. In this issue of JAMA Network Open, Rytter and colleagues3 present the results of the systematic reviews and meta-analyses that provided the basis for their attendant clinical recommendations. They conclude that the evidence base, albeit limited, supports weak or conditional recommendations for the systematic provision of early information and advice, the use of graded physical exercise, vestibular rehabilitation, manual therapy for the cervical and thoracic spine, psychological treatment, and interdisciplinary rehabilitation. No empirical evidence was available regarding oculomotor vision therapy, but it was endorsed as a good clinical practice based on expert consensus.
Rytter and colleagues are to be commended for their systematic approach, which followed a prespecified protocol that included use of the Population, Intervention, Comparison, and Outcome (PICO) framework to develop specific review questions, formal tools for assessing study quality, and reliance on Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) for formulating recommendations. They took the rather unique approach of reviewing both previous systematic reviews and individual clinical trials. Their meta-analyses and clinical recommendations reaffirm the conclusions of many existing guidelines4 but extend those guidelines by incorporating the most recent evidence and including treatment domains that have received relatively little attention in previous systematic reviews or guidelines, including manual therapy and oculomotor vision therapy.
The challenge of condensing such a herculean effort into a summary article is likely to blame for several apparent omissions or simplifications. For instance, the comparison treatment in some studies is unclear, and “treatment as usual” is not always clearly characterized but appears to vary considerably across studies, even within specific treatment domains. The omission of cognitive rehabilitation as a nonpharmacological treatment was notable, as was the relative lack of attention to questions of the timing, duration, or intensity of treatment. In some cases, components of treatment were described as if they occurred in isolation when they were administered in combination (eg, manual therapy). Additionally, the alignment of recommendations with existing guidelines was characterized somewhat inconsistently, and plans for knowledge translation and transfer were not described. More information also could have been provided regarding how patient and public perspectives were represented in the guideline process.
Several methodological limitations of the systematic reviews should also be noted. The primary outcomes for source studies were not always the same as those chosen by Rytter and colleagues for their meta-analyses, which focused largely on the broad spectrum of PPCS.3 The assignment of complex, multimodal interventions to specific treatment domains could be questioned (eg, interventions in the exercise category involved more than prescribed exercise). Most meta-analyses involved only 1 or 2 studies, with many studies included in multiple analyses; and studies included in the same meta-analysis often involved interventions that differed in content, dose, mode of delivery, and other important factors that may affect treatment outcome.
The clinical recommendations offered by Rytter and colleagues raise some important questions. Some recommendations apply to the broad population of individuals with PPCS, but others apply more selectively, without clear justification (eg, manual therapy is recommended generally when the evidence pertains to patients with indications for manual therapy, whereas vestibular rehabilitation is recommended only for patients with persistent vestibular dysfunction). Similarly, some recommendations are presented in terms of time since injury, whereas timing is not mentioned for others. The basis for recommending minimum doses (eg, 4 sessions of psychological therapy) is not described. As a result, clinicians lack clear guidance about which treatment and how much to offer, when, and to whom. The recommendation for vision therapy was based solely on expert consensus, which lacked a convincing rationale. Finally, evidence-based care depends heavily on the context of care, the availability of relevant resources (eg, clinical expertise), and patient preferences, all of which bear consideration in guideline implementation. The authors do not attend to all these factors, although they do speak to the need for engaging patients in treatment decisions, especially given the weak evidence in support of any given intervention.
Rytter and colleagues rightly highlight the relative paucity of evidence, as well as the significant risk of bias in the existing studies, which resulted in all their recommendations being offered with very low or low confidence. However, they only briefly consider the implications for future research. The methodological quality of nonpharmacological intervention studies must improve. Bias associated with the inherent inability to blind therapists in many such studies can be mitigated by other methodological strategies (eg, blinding outcome assessors). Providing credible but inert comparison interventions is challenging but possible. Theory-driven mapping of intervention components onto treatment targets5 and a staged framework for the evaluation of nonpharmacological interventions analogous to the drug development process6 may most efficiently lead to evidence-based treatments for PPCS.
In addition, studies should incorporate common data elements (CDEs), not only for measuring outcomes but also for coding treatments and their components.7 The use of CDEs for both treatments and outcomes would not only facilitate future meta-analyses and guideline development efforts but also help disentangle the effects of multimodal treatments and isolate their active ingredients, thereby improving the efficiency of resource allocation. Consistent, detailed coding of treatment elements (eg, timing, intensity, duration, and mode of delivery) would greatly assist in this goal; however, CDEs for nonpharmacological treatments are currently very coarse, and the development of more refined CDEs should be a focus of future initiatives. More attention to patient and environmental characteristics that may moderate treatment effectiveness is also warranted and should be captured by relevant CDEs. The drive for precision rehabilitation of concussion implies the need to study not only the treatments themselves but for whom and under what circumstances they work.
In the end, Rytter and colleagues have done the field a service by reemphasizing the paucity of studies and the need for much more and better evidence to guide the treatment of PPCS. Indeed, more narrative and systematic reviews and guidelines have likely been published than have clinical trials. It may be time to place a moratorium on further systematic reviews and guidelines and instead redouble our efforts to conduct research on the effectiveness of treatments of PPCS. However, waiting for individual randomized clinical trials to accumulate is likely to be impractical. We may need to reconsider the accepted wisdom regarding the hierarchy of evidence and decrease our reliance on traditional randomized clinical trials as the standard for informing treatment effectiveness.8 The adoption of alternative designs, including observational comparative effectiveness studies, pragmatic and adaptive trials, personalized N-of-1 trials, and individual participant data meta-analyses, is likely to be required if we are to move the field forward with the alacrity that our patients and the public deserve.
Published: November 9, 2021. doi:10.1001/jamanetworkopen.2021.32424
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Yeates KO et al. JAMA Network Open.
Corresponding Author: Keith Owen Yeates, PhD, Department of Psychology, University of Calgary, 2500 University Dr NW, AD254, Calgary, AB T2N 1N4, Canada (firstname.lastname@example.org).
Conflict of Interest Disclosures: Dr Yeates reported receiving grants from the Canadian Institutes of Health Research and the Brain Canada Foundation, royalties from Guilford Press and Cambridge University Press, and personal fees from the American Psychological Association outside the submitted work. Dr Schneider reported receiving physiotherapy consultant fees from Spring Into Action Physical Therapy Ltd outside the submitted work. Dr Silverberg reported receiving grants from the Canadian Institutes of Health Research, grants from the Michael Smith Foundation for Health Research, personal fees from the National Hockey League, and personal fees from WorkSafeBC outside the submitted work. No other disclosures were reported.
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