Title: Clinical and Cost-effectiveness of Posterior Cervical Foraminotomy versus Anterior Cervical Discectomy in the Treatment of Cervical Brachialgia: A Multicentre, Phase III, Randomised Control Trial (FORVAD Trial)
Funder: Department of Health and Social Care

Abstract: Title: Clinical and Cost-effectiveness of Posterior Cervical Foraminotomy versus Anterior Cervical Disectomy and Fusion in the Treatment of Cervical Brachialgia: A Multicentre, Phase III, Randomised Controlled Trial (FORVAD Trial) DESIGN: A multicentre, Phase III, unblinded, parallel group, individually randomised controlled trial RANDOMISATION: Eligible patients randomised via a central 24-hour automated service. Minimisation with random element stratified by centre, age, gender, current smoking status and time with condition SETTING: Participant enrolment, allocation and treatment will take place in participating UK neurosurgical units (NSU) TARGET POPULATION: Inclusion criteria: Aged 18 or over; Unilateral cervical brachialgia secondary to nerve root compression for at least 6 weeks; Single or 2-level nerve entrapment; Postero-lateral disc &/or foraminal narrowing; Failed conservative management; consent Exclusion criteria: Cervical disc causing cord compression; Cervical myelopathy; Previous cervical spine surgery; Professional singers; Skin disease on surgical sites; cervical deformity; pregnancy HEALTH TECHNOLOGIES Comparison of two procedures, Posterior Cervical Foraminotomy (PCF) versus Anterior Cervical Discectomy (ACD) MEASUREMENT OF OUTCOMES: Primary outcome: Neck Disability Index (NDI) at 52 weeks post-surgery Secondary outcomes: NDI at 1 day and 6, 12, 26, 39 and 52 weeks post–surgery; VAS score for neck (VAS-NP) and arm pain (VAS-AP) at 1 day and 6, 12, 26, 39 and 52 weeks post-surgery; Quality of life using EQ-5D-3L (1 day and 6, 12, 26, 39 and 52 weeks post-op); ASIA score (1 day and 6weeks post-op); Surgical complications (1 day and 6 weeks post-op), revision surgery, adverse events (e.g. dysphagia, hoarse voice, infections and new neurological symptoms; Health resource use and costs: hospital resource use (duration of stay, operating time, implant use) and patient health resource use; cost-effectiveness (Cost/QALY) of PCF versus ACD at 52 weeks post-surgery. SAMPLE SIZE:A total of 252 patients (126 per group) are required to have 90% power for demonstrating superiority of PCF to ACD in the change in NDI at 52 weeks post–surgery at a 2-sided 5% significance level, and with 10% loss to follow-up ANALYSIS: Primary analysis on the primary endpoint NDI at 52 weeks post-surgery will be conducted on the intention-to-treat (ITT) patient population using a multivariable linear regression model with covariates entered for the minimisation factors, baseline NDI and treatment group. The effect of treatment group will be assessed using a likelihood ratio test. Generalised linear models will be used for the secondary endpoints, using either the identity or logistic link function, including the minimisation factors, treatment group, and baseline NDI as covariates. A repeated measures regression model will be fitted to EQ-5D-3L over time. In all models centre will be fitted as a random effect. Safety data will be summarised by treatment received. Health economic analysis will be a within trial and model based cost-utility analysis of PCF vs. ACD from the UK, NHS, Personal and Social Services and societal perspective CARE PATHWAYS: The care pathway for patients in both the intervention and control arms of the trial will be the same and reflect NHS management responsibilities PROJECT TIMELINES: Total 54 months: set-up 9 months; recruitment 27 months (including internal pilot phase); follow-up 12 months; analysis 6 months. Recruitment rate: overall average recruitment rate of 10-11 patients /centre /year across 10-15 centres over a 23 month randomisation phase (27 month recruitment phase). EXPERTISE IN THE TEAM: Multidisciplinary team with clinicians Neurosurgeons), methodologists (Trialists, Statisticians, Health economist) and patient representation

Lay abstract: Brachialgia is the name given to the symptom of pain that travels from the neck down to the arm and is normally due to a “trapped” nerve. A nerve in the spine becomes trapped by a slipped disc and/or joint overgrowth of the spine. The nerve can be released by either removing the disc and/or removing specific bone segments that press on the base of the nerve. Traditionally this has been done through the front of the neck (Anterior Cervical Discectomy, ACD); more recently surgeons have investigated operating through the back of the neck (Posterior Cervical Foraminotomy, PCF). Brachialgia is common in people aged 40-60 years old with 179 new cases reported for every 100,000 people per year; that is over 110,000 new cases per year in the UK. It has a major impact on quality of life and approximately 15% of people who are affected cannot work due to the pain it causes. This results in a significant burden on society in working days lost, which imposes a financial burden for both patients and the NHS. In many cases, symptoms resolve without the need for surgery; however in about one of four patients, an operation is performed to relieve the pain. Patients with brachialgia are usually seen in spinal clinics for assessment and to determine whether an operation is needed. Only patients with symptoms lasting more than 6 weeks, where pain is due to a trapped nerve, will be offered surgery. Currently patients are offered either of the above two operations depending on surgeon preference rather than based on evidence of which procedure is more effective. Although the operation from the front is more common, both operations are currently used in the UK and are safe but there are differences in side effects with each procedure. When the operation is completed from the front of the neck, patients have reported problems with swallowing and hoarse voice which, in the worst cases, can be permanent. However, when the operation is from the back, neck pain symptoms may recur more often, although the evidence for this is patchy. To date there is no good-quality research to demonstrate which operation is better or which is more cost-effective. Patients will be given information about this study at the same time as the decision to operate is made. If they agree to participate in the trial, eligible patients will be asked to attend an additional pre-operative assessment clinic to confirm that they meet the study criteria, sign a consent form and complete questionnaires. Patients will be allocated to receive either PCF or ACD using a random process on the day of surgery. All patients will then be followed up on two occasions, as per standard care, at day 1 and at 6 weeks after their operation to see how well they recover, and whether they suffered recurrence of their symptoms and require any further surgery. Patients will complete a set of questionnaires at baseline, day 1 and weeks 6, 12, 26, 39, and 52 relating to their quality of life and use of health and social care services. The assessments at weeks 12, 26, 39 and 52 will use postal questionnaires. The main outcome measures focus on activities of daily living, ability to work or complete usual activities, functioning and quality of life of patients, with a particular emphasis on pain outcomes. Finally we will also assess which operation is the best value for money over 52 weeks.

Research activity codes: 6.4 SURGERY
Health categories: MUSCULOSKELETAL