Authors: Dr Jane Nikles and Sherin Jacob
Study summary
WORK IN PROGRESS! We are applying Bayesian modelling of prior data for a population with acute injury, to take natural recovery into account using N-of-1 trials nested in a Multiple Baseline Design.
The problem: Whiplash Associated Disorder
With costs of over $950 million annually, the economic impact of whiplash in Australia is substantial. In addition to high economic costs, whiplash also accounts for a high burden of disease: over 50% of people injured never fully recover and 30% live with moderate to severe disability. Most recovery from whiplash occurs in the first 12 weeks from injury and yet, there have been limited clinical trials on early management of whiplash injuries.
Current management strategies for whiplash are also not very effective. Although clinical guidelines recommend simple analgesia as first line treatment, there have been no trials on such drugs. Furthermore, whiplash is a heterogeneous condition, heralding the need for individualised treatments. N of 1 trials, which are both personalised and patient oriented, may have clinical utility in research for management of whiplash.
Our solution: Personalised Treatments for Acute Whiplash Injuries
At Recover Injury Research Centre, The University of Queensland, we are conducting a series of N of 1 trials, nested in a multiple baseline design, to establish clinical evidence on the effectiveness of naproxen (NSAID) and paracetamol (Panadol) in the early management of whiplash injuries. We will compare the efficacy of paracetamol, naproxen, and both paracetamol and naproxen, in both reducing dailyneck pain and chronicneck pain from acute grade II whiplash injuries.
Additionally, since N of 1 trials are usually used to study stable and chronic conditions, we will also test the utility of this design in acute conditions that are subject to natural recovery. We can do this because we have prior data collected from a similar population without an intervention, which we can model with Bayesian statistics. This has never been done before!
For this pilot study, we will be recruiting 15 participants with acute (<2 weeks) grade II WAD, experiencing at least moderate pain (NRS ≥ 5/10), and at risk of poor recovery, from local physiotherapy practices and emergency departments of hospitals in Brisbane, Australia.
In phase A, baseline Numerical Rating Scale scores, measuring daily neck pain, will be collected from participants. The length of phase A will be staggered to control for threats to internal validity (5, 8, or 11 days).
In phase B, participants will be given an evidence based advice booklet providing information, advice, exercises and more on whiplash. Phase B is five days long but participants are encouraged to use the booklet for the entirety of the study.
Following phase B, all participants will receive a randomized sequence of three cycles (Phase C, D, E) of ten day treatment triplets (paracetamol, naproxen, and paracetamol and naproxen).
Primary outcomes include daily neck pain intensity, measured with the Numeric Rating Scale, confidence to perform daily activities, and adverse events and severity. Secondary outcomes will be measured through the Neck Disability Index, Patient Global Rating of Change, Patient Catastrophising Scale, Patient Global Assessment of Treatment Satisfaction scale; Post-Traumatic Stress Disorder Checklist for DSM-5(PCL-5), Depression & Anxiety Stress Scales and EQ-5D-5L (generic measure of health status). Outcomes will be measured at baseline, at the end of each treatment cycle, post-trial, and in a 3 month follow up.
Each participant will receive a personalised report at the end of the trial detailing which treatment works best for them.
The results of our study will inform a larger study, which if successful has the potential to guide treatment recommendations for acute whiplash injuries by giving both the probability of response and side effects to each treatment. We will also be able to describe the feasibility and utility of this design in acute conditions that are subject to natural recovery.
Study team
Assoc Prof Jane Nikles, Prof Michele Sterling, Sherin Jacob, Recover Injury Research Centre, The University of Queensland, Australia
Prof Robyn Tate, Northern Clinical School, John Walsh Centre for Rehabilitation Studies, The University of Sydney, Australia
Dr Michael Perdices, Royal North Shore Hospital, Sydney, Australia
Prof Geoff Mitchell, Dr Chris Freeman, Dr Meng-Wong Tang, The University of Queensland, Australia
Assoc Prof James McGree, Queensland University of Technology, Australia
About the authors
Dr Jane Nikles is a registered medical practitioner who has conducted research at The University of Queensland, Australia, in the field of N-of-1 trials for over 20 years. Her current areas of interest mostly lie within clinical neuroscience and span pharmacological and non-pharmacological treatments, including complementary and alternative medicines. She is very interested in developing new methodology, including digital systems, for the application of N-of-1 trials and SCEDs to suit these areas of interest and the characteristics of these treatments.
Contact details: Assoc Prof Jane Nikles T: +61 408 599 033 E: uqjnikle@uq.edu.au
Ms Sherin Jacob is a medical student at The University of Queensland. Sherin has an interest in n-of-1 trials and is working with Dr Nikles on this study
Please click here if you would like to write a short blog post for the ICN