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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)

Lookup NU author(s): Professor John Isaacs

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2018 The Author(s). 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 (80mg then 40mg 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 10months 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. Trial registration: Current Controlled Trials, ISRCTN14569274. Registered on 15 December 2014.


Publication metadata

Author(s): Williams NH, Jenkins A, Goulden N, Hoare Z, Hughes DA, Wood E, Foster NE, Walsh D, Carnes D, Sparkes V, Hay EM, Isaacs J, Konstantinou K, Morrissey D, Karppinen J, Genevay S, Wilkinson C

Publication type: Article

Publication status: Published

Journal: Trials

Year: 2018

Volume: 19

Issue: 1

Online publication date: 31/07/2018

Acceptance date: 09/07/2018

Date deposited: 16/08/2018

ISSN (electronic): 1745-6215

Publisher: BioMed Central Ltd.

URL: https://doi.org/10.1186/s13063-018-2801-6

DOI: 10.1186/s13063-018-2801-6


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