Personalised treatments for acute whiplash injuries: A pilot study of nested N-of-1 trials in a multiple baseline single-case experimental design

J Nikles; R L Tate; G Mitchell; M Perdices; J M McGree; C Freeman; S Jacob; M W Taing; M Sterling

doi:10.1016/j.conctc.2019.100480

Personalised treatments for acute whiplash injuries: A pilot study of nested N-of-1 trials in a multiple baseline single-case experimental design

Contemp Clin Trials Commun. 2019 Oct 28:16:100480. doi: 10.1016/j.conctc.2019.100480. eCollection 2019 Dec.

Authors

J Nikles^{1

2}, R L Tate³, G Mitchell^{4

5}, M Perdices⁶, J M McGree⁷, C Freeman⁸, S Jacob¹, M W Taing⁹, M Sterling^{1

2}

Affiliations

¹ Recover Injury Research Centre, The University of Queensland, Herston, QLD, Australia.
² NHMRC Centre of Research Excellence in Road Traffic Injury Recovery, Australia.
³ John Walsh Centre for Rehabilitation Studies, Northern Clinical School, The University of Sydney, Sydney, Australia.
⁴ Faculty of Medicine, The University of Queensland, Herston, QLD, Australia.
⁵ Limestone Medical Centre, Ipswich, QLD, Australia.
⁶ Royal North Shore Hospital, Sydney, Australia.
⁷ School of Mathematical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
⁸ School of Pharmacy, Faculty of Health and Behavioural Sciences, The University of Queensland, QLD, Australia.
⁹ School of Pharmacy, The University of Queensland, QLD, Australia.

Abstract

Background: Whiplash associated disorder (WAD), a common and disabling condition, incurs huge burden and costs to Australia. Yet, current treatments for whiplash are not very effective; improved outcomes are urgently needed. Clinical guidelines recommend simple analgesia (paracetamol and non-steroidal anti-inflammatory drugs) but there have been no trials of guideline-recommended drugs. This study will investigate the effectiveness of evidence-based advice (EBA), paracetamol, naproxen, and both paracetamol and naproxen, in reducing daily neck pain and preventing chronic neck pain after whiplash injury.

Methods: This study is a pilot series of multi-cycle, double-blinded, randomised N-of-1 trials, nested in a multiple baseline design. The design will comprise three baselines of 5, 8 or 11 days duration. Post enrolment, participants will be randomly assigned to one of the baselines. Fifteen participants with acute (<2 weeks) Grade II WAD, experiencing at least moderate pain (NRS: ≥ 5/10), and at risk of poor recovery will be recruited from hospitals in Queensland, Australia, and through local physiotherapists. Patients will receive EBA plus a randomised sequence of three cycles of ten day treatment triplets (paracetamol designated as a C phase, naproxen, designated as a D phase, and both paracetamol and naproxen, designated as an E phase).

Discussion: We will test the effects of different treatments on the primary outcome of average neck pain intensity collected daily and at 4 and 7 months post-injury. Secondary outcomes, including disability, depression, post-traumatic stress symptoms, pain catastrophizing, and feasibility of study procedures, will also be evaluated. The results of this study will inform a larger trial aiming to strengthen the evidence on EBA and simple analgesics for WAD.

Trial registration: Clinical Trials Primary Registry: Australian and New Zealand Clinical Trials Registry.

Clinical trial registration number: ACTRN12618001291279.

Date of registration: 31/07/2018.

Primary trial sponsor: The University of Queensland, Brisbane QLD 4072 Australia.

Funding: The University of Queensland.

Keywords: Acute whiplash associated disorders; N-Of-1 trial; Non-steroidal anti-inflammatory drug; Paracetamol; Single case experimental design; Traumatic neck pain.