Williams, N., Jenkins, A., Goulden, N., Hoare, Z., Hughes, D., Wood, E., Foster, N., Walsh, D., Carnes, D., Sparkes, V., Hay, E., Isaacs, J., Konstantinou, K., Morrissey, D., Karppinen, J., Genevay, S., Wilkinson, C. (2018) Lessons learnt from a discontinued randomised controlled trial: adalimumab injection compared with placebo for patients receiving physiotherapy treatment for sciatica (Subcutaneous Injection of Adalimumab Trial compared with Control: SCIATiC). Trials, 19:408. doi:10.1186/s13063-018-2801-6
Lessons learnt from a discontinued randomised controlled trial : adalimumab injection compared with placebo for patients receiving physiotherapy treatment for sciatica (Subcutaneous Injection of Adalimumab Trial compared with Control: SCIATiC)
|Author:||Williams, Nefyn H.1; Jenkins, Alison2; Goulden, Nia2;|
1Department of Health Services Research, University of Liverpool, Waterhouse Block B, 1-5 Brownlow Street, Liverpool, L69 3GL, UK
2School of Healthcare Sciences, Bangor University, Bangor, UK
3Arthritis Research UK Primary Care Centre, Research Institute for Primary Care and Health Sciences, Keele University, Keele, UK
4Arthritis Research UK Pain Centre and National Institute for Health Research Nottingham Biomedical Research Centre, School of Medicine, University of Nottingham, Nottingham, UK
5Centre for Primary Care and Public Health, Barts and the London School of Medicine and Dentistry, London, UK
6School of Healthcare Science, Cardiff University, Cardiff, UK
7National Institute for Health Research Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle upon Tyne, UK
8Centre for Sports and Exercise Medicine, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
9Medical Research Centre Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland
|Online Access:||PDF Full Text (PDF, 1.2 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2018100537583
|Publish Date:|| 2018-10-05
Background: Adalimumab, a biological treatment targeting tumour necrosis factor α, might be useful in sciatica. This paper describes the challenges faced when developing a new treatment pathway for a randomised controlled trial of adalimumab for people with sciatica, as well as the reasons why the trial discussed was stopped early.
Methods: A pragmatic, parallel group, randomised controlled trial with blinded (masked) participants, clinicians, outcome assessment and statistical analysis was conducted in six UK sites. Participants were identified and recruited from general practices, musculoskeletal services and outpatient physiotherapy clinics. They were adults with persistent symptoms of sciatica of 1 to 6 months’ duration with moderate to high level of disability. Eligibility was assessed by research physiotherapists according to clinical criteria, and participants were randomised to receive two doses of adalimumab (80 mg then 40 mg 2 weeks later) or saline placebo subcutaneous injections in the posterior lateral thigh. Both groups were referred for a course of physiotherapy. Outcomes were measured at baseline, 6-week, 6-month and 12-month follow-up. The main outcome measure was disability measured using the Oswestry Disability Index. The planned sample size was 332, with the first 50 in an internal pilot phase.
Results: The internal pilot phase was discontinued after 10 months from opening owing to low recruitment (two of the six sites active, eight participants recruited). There were several challenges: contractual delays; one site did not complete contract negotiations, and two sites signed contracts shortly before trial closure; site withdrawal owing to patient safety concerns; difficulties obtaining excess treatment costs; and in the two sites that did recruit, recruitment was slower than planned because of operational issues and low uptake by potential participants.
Conclusions: Improved patient care requires robust clinical research within contexts in which treatments can realistically be provided. Step changes in treatment, such as the introduction of biologic treatments for severe sciatica, raise complex issues that can delay trial initiation and retard recruitment. Additional preparatory work might be required before testing novel treatments. A randomised controlled trial of tumour necrosis factor-α blockade is still needed to determine its cost-effectiveness in severe sciatica.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
3141 Health care science
This work was supported by the National Institute for Health Research’s Health Technology Assessment Programme (grant number 12/201/02).
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