Title: Does Laryngeal Reinnervation or Type I Thyroplasty give better voice results for patients with Unilateral Vocal Fold Paralysis (VOCALIST): a feasibility study
Funder: Department of Health and Social Care

Abstract: Background Current treatment for patients with paralysis of one of their two vocal cords (unilateral vocal cord paralysis or UVFP) is speech therapy or injection of the vocal fold (VF) to increase its volume. When these only provide short-term relief, surgery is performed. Currently there is no robust evidence to determine if type I thyroplasty or non-selective laryngeal reinnervation is the best surgical option. Design We aim to perform a 2 year feasibility study to test the practicality of running a multi-centre, randomised clinical trial of surgery for UVFP. This feasibility study will consist of two research approaches run in parallel; a) Qualitative: A qualitative research investigation (QRI) to understand the recruitment process and how it operates in clinical centres, so that sources of recruitment difficulties can be identified and suggestions made to change aspects of design, conduct, organisation or training that could then lead on to improvements in recruitment. b) Quantitative: A small randomised surgical trial of 30 patients to compare laryngeal reinnervation to thyroplasty. Patients will be randomised in a 1:1 ratio using a web-based system. Target population Patients aged 18-70 years with UVFP due to unilateral recurrent laryngeal nerve paralysis of traumatic, iatrogenic or idiopathic origin of between 6 and 36 months duration. Patients will have a significant voice disorder as measured by perceptual rating (&ge;2Grade) and VHI (>16 score) e) Common EMG (neurophysiological) criteria (Koufman Grades 2-5: (3)). Intervention The two main surgical approaches are (a) medialisation/augmentation (thyroplasty), which aims to improve the positioning of the paralysed vocal fold, and (b) reinnervation, which is designed to improve muscle tone and bulk. Surgical approaches will be standardised by common training (BLA Manchester course including cadaveric hand s on teaching, Birchall and Karagama) and regular QA audits of operation notes. Primary Outcome Percentage of patients randomised and successfully receiving the operation so allocated. Secondary Outcomes a) Qualitative assessments of; i) whether recruiters are in equipoise with the treatment arms; ii) surgeon and speech therapist positions in relation to clinical equipoise between the two treatments; iii) patient views and beliefs on randomisation, recruitment and retention processes including the reasons for not accepting randomisation/their randomised operation and dropping out of follow up (i.e. reasons for primary outcomes) iv) patient and surgeon/speech therapist views on utility of chosen outcome measures; b) Quantitative assessments; All 30 patients will be evaluated at baseline and 6 months postoperatively with the aim of evaluation at 12 months as well. Efficacy outcome measures are voice handicap index (VHI, principal outcome measure as selected by patients), acoustic and perceptual voice evaluation, videostroboscopy evaluation of laryngeal mechanics, electromyography, and EQ-5D health outcome questionnaire. Percentage of patients dropping out of follow-up will also be measured. Statistical analysis of quantitative data resulting will be combined with recruitment and retention data to inform the future full trial size and design. Sample size 30 patients (15 in each arm) based on experience with successful similar surgery-focused feasibility studies in the UK, and on known rates of presentation. Statistics Qualitative and quantitative analysis will be performed by the highly experienced analysis teams in Bristol (Jepson) and UCL (Ambler, Morris, Schilder, Carding) respectively. Economic benefit Restoration of voice quality and strength increases employment opportunities for patients. If reinnervation is shown to provide longer term benefit, this would significantly reduce further NHS and patient costs. Restoration of voice quality long-term returns patients to both employment (80% of people regard their voice as the major tool of their work, despite the progress of IT) and society. Here, we will calculate costings of laryngeal reinnervation and thyroplasty and confirm the utility of EQ5D.

Lay abstract: The voice is the most important human communication tool. A good voice requires two moving vocal cords. If one cord is paralysed (unilateral vocal cord paralysis-UVFP) people suffer from a breathy, weak voice that tires easily and can cause choking and becoming out of breathe easily. UVFP can be caused by damage to the nerve during a neck operation or by a virus, but often the cause is unknown. The preferred treatment for UVFP is speech therapy. If this does not improve the voice sufficiently, a surgeon can inject a substance into the paralysed cord to increase its size, but often this only helps temporarily. For more permanent results, the surgeon can either; re-route the nerve that supplies the cord (laryngeal reinnervation) or place a synthetic implant into the cord (type 1 thyroplasty). Currently, there is insufficient evidence to prove which operation is better. When questioned, both patients with UVFP and their surgeons feel a trial comparing the two operations is important. 40% of UVFP patients agreed they would be willing to enter a trial that would involve being randomly allocated to one of the two surgical operations. Whilst this is positive, it does not yet provide enough proof that a large-scale trial to find which operation is best can be run successfully. Here, we firstly propose to run a smaller study to see if UVFP patients can be recruited to a clinical trial where they will be randomly allocated to either reinnervation or thyroplasty. We will analyse communication between clinical teams and patients about the operations, test how to best run the trial and collect results, record patients views and check we can collect information important to the NHS. Once the exploratory study is complete we will use this information to plan a large-scale trial of the two operations.

Research activity codes: 6.4 SURGERY
Health categories: ORAL AND GASTROINTESTINAL