Below is a blog response to the BJSM blog titled “Is it scientifically valid, sensible, or safe to use biomarkers to diagnose concussion?” published on November 27th (click here to view the original blog post). A reply from the original blog authors is also included.
Response:
Dear Editor,
We read with interest the BJSM blog post by McKeever and Hamilton on November 27th regarding the use of salivary biomarkers in the diagnosis of concussion.
We would like to add some context to aspects of the article which, we feel, may be misinterpreted.
Regarding the current state of play, we would echo the authors sentiments that the Department of Culture Media and Sport guidelines on the diagnosis and management of concussion for grassroots sport is a hugely significant step forward in concussion care, enabling the sporting community to unite around a common framework rather than relying on guideline variations in different sports.
We would like to correct the authors that the Sport Concussion Assessment Tool 6 is advocated for use by the Concussion in Sport Consensus Group by healthcare professionals and not by coaches who instead would be better advised to use the Concussion Recognition Tool 6. The SCAT6 is a valuable tool supporting the diagnosis and management of concussion, however, in settings without access to healthcare professionals an approach which tries to recognize potential concussion and remove from play is more appropriate [1–3].
Like previous iterations, the SCAT6 is a multi-faceted evaluation which includes assessments of balance, concentration, memory and symptomatology among others. It is not a standalone device, rather, it should act as an aide to a multi-modal, and ideally, multi-time point assessment of an individual by a healthcare professional with experience in it’s use.
McKeever and Hamilton suggest there is an appetite for “quicker and less resource-consuming” alternatives to the SCAT6 for concussion diagnosis. However, we feel this does not really capture the nature of the issue. Certainly we would not dispute that faster and simpler tools are desirable. However, the major challenges of using the SCAT6, outside of the need for a healthcare professional to administer it, are two-fold.
Firstly, even for experienced clinicians who manage concussion regularly the diagnosis is difficult to make. The proper use of the SCAT6 requires the triangulation of multiple different sources of information and the skilled combination of that with clinical suspicion. Indeed, in the ongoing evaluation of their Head Injury Assessment process, World Rugby have demonstrated the valuable role clinical suspicion plays in terms of maximising the accuracy of that decision. The development of the skills and experience required to make these judgements reliably is challenging[4,5].
Secondly, the SCAT6 assesses neurocognitive function in a number of different ways. However, none are unique to the pathology of sport related concussion. Conditions such as migraine may result in compatible symptomatology, dehydration and intercurrent illness may result in compatible deficits in concentration etc. The SCAT6 measures constructs which are very relevant to sport related concussion but cannot measure the pathophysiology of the injury itself, hence the need for judicious use [6,7].
These issues with the nature of concussion diagnosis (and it should be recognized the same concerns apply with regards to clearance to return to play) are at the heart of the search for reliable biomarkers and offer opportunities well beyond simply being faster and less “resource-consuming”. Tools which measure the pathophysiology of the injury itself offer those engaged with neurotrauma research the possibility of a new understanding of the injury and it’s management [8]. Likewise for athletes at all levels they create the opportunity for a huge shift in athlete reporting behaviour. This is particularly true at the grassroots level where the “if in doubt, sit them out” mantra may encourage only those with clear and obvious concussion presentations to be withdrawn [9,10].
Regarding the discussion of collaboration with World Rugby, we feel it is important to point out that the focus of this collaboration is to evaluate the degree to which the salivary biomarker test developed by the University of Birmingham, Marker Diagnostics and the RFU, can aid the diagnosis of concussion in elite male and female rugby union. The test is the first to achieve a CE Mark for use in the diagnosis of concussion and this is something of which Marker Diagnostics are rightly proud.
However, rightly, the implementation of new technologies like this should only occur in the context of a robust evidence base supported by research of real world clinical application. Though it is beyond the scope of this discussion to review the nuances of medical regulation, it is important to recognize that there is a difference between the granting of medical regulatory approval and the recommendation for clinical use.
There are, for instance, examples of blood biomarker tests which have received FDA approval but still have not yet been recommended for clinical use after recent review by either the Concussion in Sport Group consensus statement or the UK National Institute for Health and Clinical Excellence guideline update on head injury management [1,11].
This World Rugby announcement discusses the continuation of this evaluation, not the implementation of a change in clinical practice. This is in contrast, for example, to World Rugby’s recent announcement regarding the implementation of instrumented mouthguard technology in order to support the identification of players who should be evaluated for concussion where such clinical evidence has led to a change in practice [12]. However, both announcements highlight World Rugby’s status as being at the forefront of developments to protect athlete welfare in this challenging area by evaluating their existing procedures and remaining vigilant for promising new developments in the field.
The authors critique the involvement of “private firms” in what they describe as the “concussion problem”. This is a problem which includes challenges around defining, recognizing, diagnosing, treating and prognosing a common injury. Such is the scale of the problem, and the realities of research funding (directed towards an injury still, incorrectly, believed to affect predominantly elite athletes and be relatively harmless), that collaboration with multiple stakeholders from sport, academia and industry is necessary and welcome in order to do the work required to make a meaningful and impactful contribution to clinical practice in this area.
Finally, we echo and support the calls of the authors to see appropriately considered and balanced reporting in the field of concussion biomarkers. Indeed, we would argue such calls are warranted more broadly in respect of the acute injury in general as well as long term health implications [13].
With that in mind, we would argue that the title of this blog post is somewhat misleading without the addition of the word “yet”. The development and discovery of robust and well evidenced biomarkers related to concussion would permit a huge leap forward in all aspects of study and clinical practice in the field and the concept that biomarkers in the abstract are not valid, safe or sensible is unwarranted.
Author Reply:
Thanks for your thoughts about our short opinion piece on the use of salivary biomarkers in concussion diagnosis, and the language around this. As you correctly interpret, we feel that the current published evidence doesn’t support the suggestion that salivary biomarkers can ‘diagnose’ concussion in any sort of clinically meaningful way, and it appears that you agree. The addition of the word ‘yet’ to our blog title would not offer any additional information as to describing the current landscape, which was the purpose of our piece, but would simply add an optimistic framing as to the future development of this science. As we stated in our original blog, the creation of such a diagnostic test/tool would be of fabulous benefit and we hope that this will become possible. We fully support research efforts in this area, and encourage responsible academics like yourselves to continue to publish data that might, in the future, allow the scientific community to support a statement that biomarkers can diagnose concussion.
Original blog authors:
Tom McKeever [1] David F Hamilton [2]
[1] School of Health and Social Care, Edinburgh Napier University, Edinburgh, UK
[2] Research Centre for Health, Glasgow Caledonian University, Glasgow UK
Response Authors:
Dr Patrick O’Halloran
Sport and Exercise Medicine Service, Queen Elizabeth Hospital, Birmingham, UK
Marker Diagnostics UK Ltd
Dr Valentina Di Pietro
Neurotrauma and Ophthalmology Research Group, Institute of Inflammation and Ageing, University of Birmingham, UK
Marker Diagnostics UK Ltd
Professor Tony Belli
Marker Diagnostics UK Ltd
Response References
1 Patricios JS, Schneider KJ, Dvorak J, et al. Consensus statement on concussion in sport: the 6th International Conference on Concussion in Sport–Amsterdam, October 2022. Br J Sports Med. 2023;57:695–711.
2 Echemendia RJ, Brett BL, Broglio S, et al. Sport Concussion Assessment Tool 6 (SCAT6). Br J Sports Med. 2023;57:622–31.
3 Echemendia RJ, Ahmed OH, Bailey CM, et al. The Concussion Recognition Tool 6 (CRT6). Br J Sports Med. 2023;57:692–4.
4 Falvey É, Tucker R, Fuller G, et al. Head injury assessment in rugby union: clinical judgement guidelines. BMJ Open Sport — Exercise Medicine. 2021;7:986.
5 Fuller GW, Tucker R, Starling L, et al. The performance of the World Rugby Head Injury Assessment Screening Tool: a diagnostic accuracy study. Sports Med Open. 2020;6. doi: 10.1186/s40798-019-0231-y
6 Collins SM, Lininger MR, Bowman TG. The Effect Of Mild Exercise Induced Dehydration On Sport Concussion Assessment Tool 3 (SCAT3) Scores: A within-subjects design. Int J Sports Phys Ther. 2021;16:511.
7 Weber AF, Mihalik JP, Register-Mihalik JK, et al. Dehydration and Performance on Clinical Concussion Measures in Collegiate Wrestlers. J Athl Train. 2013;48:153.
8 Toman E, Harrisson S, Belli T. Biomarkers in traumatic brain injury: A review. J R Army Med Corps. 2016;162:103–8.
9 Conway FN, Domingues M, Monaco R, et al. Concussion Symptom Underreporting among Incoming National Collegiate Athletic Association Division i College Athletes. Clinical Journal of Sport Medicine. 2020;30:203–9.
10 McCrea M, Hammeke T, Olsen G, et al. Unreported concussion in high school football players: implications for prevention. Clin J Sport Med. 2004;14:13–7.
11 National Institute for Health and Clinical Excellence. Head Injury Assessment and Early Management Guideline. 2023. https://www.nice.org.uk/guidance/ng232
12 World Rugby. World Rugby integrates smart mouthguard technology to the Head Injury Assessment as part of new phase of global player welfare measures. 2023. https://www.world.rugby/news/875212/world-rugby-integrates-smart-mouthguard-technology-to-the-head-injury-assessment-as-part-of-new-phase-of-global-player-welfare-measures
13 Kuhn AW, Yengo-Kahn AM, Kerr ZY, et al. Sports concussion research, chronic traumatic encephalopathy and the media: Repairing the disconnect. Br J Sports Med. 2017;51:1732–3.