The NAtional Trial of Tonsillectomy IN Adults (NATTINA): a clinical and cost effectiveness study

Scientific Abstract Question: What is the clinical and cost effectiveness of tonsillectomy for the management of tonsillitis in adults? Design: A mixed methods study incorporating a feasibility study, internal pilot and a phase III, multicentre trial randomising patients to immediate tonsillectomy versus conservative management. Setting: 29 Ear Nose and Throat outpatient clinics, district and teaching hospital, 4 in Scotland and 23 in England and 2 in Wales. Target Population: Adults (16y+) referred to secondary care because of disabling recurrent sore throats. Interventions (health technologies) compared: Patients will be randomised on a 1:1 basis to: 1. Immediate tonsillectomy - dissection of the palatine tonsils 2. Conservative management. i.e. deferred surgery. Measurement of Costs and Outcomes Feasibility -engage NATTINA patient Forum; assess otolaryngologists’ willingness to randomise and patients’ willingness to be randomised, taking account of predicted variation in severity. Assess the acceptability of Early Maximum Medical Therapy pathway Finalise methods to input weekly sore throat day returns into trial database. Main Trial Set up of study sites and recruitment of 510 participants. Randomly allocate patients over a further 18 months, with 24 months follow-up Main Trial Primary Outcomes. Total number of sore throat days over the 24 months following randomisation. Secondary Outcomes. 1. Number of sore throat episodes and their key characteristics from NATTINA Sore Throat Alert Reports (STARs) i. category (a) mild or (b) moderate/severe ii. use of over-the-counter medication iii. use of any prescription therapy iv. number of days unable to undertake usual activities v. SF-12 general health questionnaire referring to the episode. 2. Tonsil Outcome Inventory 14 (TOI14) total and subscales (Throat, General Health, Resources and Social / Psychological) six monthly 3. SF- 12 general health questionnaire six monthly 4. Nature of any adverse events experienced 5. Evaluation of the impact of alternative sore throat patient pathways by observation and statistical modelling of outcomes against baseline severity, as assessed by total number of sore throat days recalled in the six months prior to recruitment plus TOI14 score at recruitment. Economic evaluation has three components (1) a cost-effectiveness analysis, based on the incremental cost per sore throat day avoided (2) cost-utility analysis, based on incremental cost per quality-adjusted life year (QALY) gained (3) cost-benefit analysis, based on patients’ willingness to pay to avoid a sore throat day. The SF-12 is sensitive to the outcomes of interest – the SF-12 physical subscale has an effect size of 1 from tonsillectomy. Health state utilities will be derived using the SF-6D algorithms and used to estimate QALYs. Costs measured will include those due to hospital visits, primary care visits, days of inability to undertake usual activities, over the counter medicines, the complications of surgery as well as the direct costs of the interventions. Modelling work in collaboration with prescribing data bases in England and Scotland and by direct access to participants’ primary care records will inform longer term and more extensive models of relative efficiency for the trial and the wider population. Qualitative Process Evaluation of pilot and main trial will address acceptability of trial/treatments and unforeseen consequences from the perspective of participants and stakeholders including primary care clinicians. Sample size: The total number recruited will be 510. By recruiting 510 patients we are allowing for a total loss to follow up of 25% over 24 months. Two groups of 191 patients (providing complete data at two years) gives 90% power to detect an effect size of 0.33(corresponding mean intergroup difference of 3.6 days of sore throat based on a pooled estimated standard deviation of 10.8 days) assuming a type 1 error rate of 5%. Project phases (months) -3 to 0 Ethical approval; staff recruitment; NATTINA Patient Forum set-up; 0-5 Feasibility study; 6- 42 main trial recruitment; 42 – 66 main trial follow-up; 66-69 analysis Team expertise - senior academic otolaryngologists, director of the Scottish Primary Care Research Network, clinical lead for the Primary Care Research Network Northern and Yorkshire, chair of the SIGN guideline on sore throat, an expert patient TSC representative and a provisional patient engagement group, the deputy director and senior trial manager of the Newcastle CTU, senior statistician, qualitative researchers, a highly experienced health economist, motivated clinical otolaryngologists with recruitment expertise, collaboration from a senior information analyst and clinical microbiology (Sunderland Royal Infirmary).