Title: Does a screening trial for spinal cord stimulation in patients with chronic pain of neuropathic origin have clinical utility and cost-effectiveness? (TRIAL-STIM Study)
Funder: Department of Health and Social Care

Abstract: Spinal cord stimulation (SCS) is recommended by NICE for severe neuropathic pain refractory to medical management conditional to a successful SCS screening trial. However, the evidence to support the use of screening trials is largely based on expert opinion with no evidence from randomised controlled trials (RCTs). Screening trials require duplication of procedures leading to higher healthcare resource consumption, expose patients to higher risk of infection, and lead to longer absence from work and higher out-of-pocket expenses. Important questions regarding the use of a SCS screening trial have to date, not been addressed: Do patients that undergo a SCS screening trial obtain improved outcomes when compared to patients who receive a permanent implant without undergoing a SCS screening trial? Is a SCS screening trial strategy predictive of long-term pain-relief? Is an implant only strategy a cost-effective alternative to a SCS screening trial prior to permanent SCS implant? Is the patient experience of SCS improved by not having to undergo a SCS screening trial? If an implant only strategy demonstrates superiority to a SCS screening trial strategy, this will lead to change of practice resulting in benefits to patients (the false negative trial group) and the NHS (reduction of healthcare resource). Study design Superiority parallel-group two-centre RCT in patients with chronic neuropathic pain with nested qualitative study and economic evaluation. Participants will be allocated in a 1:1 ratio to either a strategy of a screening trial followed by SCS implantation based on the screening trial result or an SCS implantation only strategy. Both groups will be followed-up for six-months post-randomisation. Outcomes Primary -Pain measured on a Numerical Rating Scale (NRS) compared between the screening trial and implantation strategy and the implantation only strategy at 6 months. Secondary - proportion of patients achieving at least 50% and 30% pain relief at six-months on the NRS, health-related quality-of-life (EQ-5D), function (Oswestry Disability Index), patient satisfaction (Patients' Global Impression of Change), and complication rates. A qualitative study using semi-structured interviews will explore 32 patient’s views of screening trial, implantation and overall use of the SCS device. Healthcare utilisation and non-NHS costs will be collected by self-report. Outcome measures will be collected at baseline (pre-randomisation), at three and six-month follow-up. Semi-structured interviews will be carried out before and one-month following implantation or trial exit. Sample size Our null hypothesis is that there will be no difference between an SCS screening trial and a no screening trial strategy. For our primary outcome of pain NRS (0-10), the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) propose a clinically important minimal difference of 2 points. Based on a typical pain NRS standard deviation of 2.5 seen in previous SCS RCTs, at 90% power and 5% alpha, and a worst-case attrition rate of 30%, we will require a total of 50 patients recruited per group. Statistical analysis Comparison of effectiveness will be conducted and reported in accord with CONSORT. Diagnostic performance analyses will be conducted and reported in accord with STARD. A detailed statistical analysis plan will be prepared before data analysis. Qualitative analysis Semi-structured telephone interviews will be audio recorded and transcribed. Data will be analysed using thematic analysis. Economic evaluation A within-trial cost-consequence analysis will be performed to estimate average resource utilisation, costs and health-related quality-of-life in each group. Economic evaluation will take the form of a cost-utility analysis. Recruitment rate Given current throughput of patients, previous SCS trial experience, and assuming a conservative 40% uptake (i.e. screening: recruitment ratio of 10:4) we estimate a 20-month period will be required to recruit 100 subjects.

Lay abstract: Spinal Cord Stimulation (SCS) is a National Institute for Health and Care Excellence (NICE) recommended treatment for severe nerve pain. SCS involves implanting a wire through the skin and into the spine; this then attaches to a battery placed under the skin of the stomach. Electric pulses transmitted via this wire to the nerves provide pain-relief. This therapy is only recommended for use in the NHS if patients report pain-relief from a ‘trial’ (or test) stimulation where a temporary implanted spine wire is attached to an external battery. Patients can test the system at home for up to 4-weeks. Those expressing 50 percent or more pain-relief are offered a permanent implanted battery. Although test stimulation is a widely accepted part of clinical practice the scientific evidence for its use is lacking. It is possible that a proportion of patients who fail to experience pain-relief during trial would experience pain-relief after a permanent implant. Trials expose patients to an increased risk of infection, pain and increased costs. Therefore, research is needed to answer: Is patients’ response to trial SCS stimulation predictive of long-term pain-relief success? How do the pain levels and quality-of-life of patients receiving permanent SCS implant (or not) following trial stimulation compare to those patients receiving a permanent implant without undergoing trial stimulation? Is using a SCS trial prior to permanent SCS implant a more cost-effective way to manage patients than providing a permanent implant without trial stimulation? We plan to allocate by chance, 100 consenting SCS candidates in two UK centres to either receive a permanent implant following successful test stimulation or a permanent implant without test stimulation. Patients will have their levels of pain, health-related quality-of-life, and costs assessed by questionnaire before being allocated to the two conditions and then at three and six-months.

Research activity codes: 6.3 MEDICAL DEVICES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL