Study Design
A pre-post, waitlist control, pragmatic randomised controlled trial design will be employed. Comparison will be made with a cross over waitlist group (TAP with wait group) (18).
Study Setting.
Participants will be patients referred to the Gold Coast Interdisciplinary Persistent Pain Centre (IPPC; a tertiary-referral public pain centre).
Participants and eligibility criteria
Participants will be eligible to be included in the study if they are greater than 18 years of age, with persistent non-cancer pain lasting longer than 3 months, have proficient written and spoken English, non-urgent referral (i.e to be seen within 12 months), and be deemed suitable for TAP by their GP. Patients will be excluded if they have a medical/psychiatric condition that would prevent TAP engagement, be scheduled for surgical treatment related to their pain condition within next 6 months or have engaged with a pain service within the last 12 months at the time of recruitment.
Recruitment, Blinding and Randomization
By way of a measure against research bias, an independent research assistant will be used to contact potential participants from the IPPC waitlist, consent them to the research, and complete randomization. This will ensure that clinicians who are associated with the delivery of TAP are blinded to participant group allocation. The research assistant will record socio-demographic variables and collect outcome measures (Time 1 (T1)). Participants will then be randomized to either the treatment (TAP without wait) or control (TAP with wait) group. Randomization will be achieved through independent external automated randomization service(19).
Participants are provided a $20 AUD gift certificate for their time. Participants can withdraw from the research or from treatment at any point. At time of consent, participants are provided details to the Gold Coast Hospital and Health Service research should they wish to make a complaint independent from the study.
Procedure
The TAP without wait group will enter the TAP pathway (Figure 1) from referral (bypassing waitlist) and will have access to available treatments (Appendix A). Participants allocated to the Waitlist group, will remain on the waitlist at T1 and wait 6 months (standard waitlist time) before entering the TAP pathway. At six months (T2), outcome measures will be re-collected for both groups. At this point, participants in the Waitlist group will have access to the treatment program. At 12 months post T1 (T3) the Brief Pain Inventory outcome measure will be re-administered to both groups (Figure 2).
Treatment Measures
Patient outcomes at T1 and T2 will be recorded using a battery of objective and self-report measures that are aligned with the Initiative on Methods, Measurement and Pain Assessment in Clinical Trials (IMMPACT) recommended core outcome domains for clinical trials investigating the efficacy and effectiveness of treatments for persistent pain(20). The Brief Pain Inventory outcome measure will be recorded at T3.
Objective Measures
This study will use the National Institutes of Health (NIH) Toolbox for Assessment of Neurological and Behavioural Function, a standard set of valid, reliable and royalty-free tools for objectively assessing cognitive, emotional, motor and sensory function (Table 1)(21).
Self-Report Measures
Data will be collected and stored using REDCap (Research Electronic Data Capture)(22). REDCap is a secure web application designed to support data capture for research studies. Self-report measures collected at T1 and T2 are listed in Table 2. Only the Brief Pain Inventory will be collected at T3.
DASS(23) PCS(24) PGIC(25) PSQ(26) CPAQ(27) PROMIS(28)
Statistical Considerations and Data Analysis
Power analysis
The G*Power statistical package was used to complete A-priori power analysis to determine the necessary sample size (N) of the study(29). Preliminary clinical data (unpublished) of the outcome measures shows a range of effect size between 0.3 (Depression) and 0.68 (Pain Acceptance) (Figure 3). Using a one tail t-test of independent groups at a significance level of p < 0.05 and a power of 80% with an effect size of 0.4 (moderate range) a sample size of N = 156 (78 in each group) will be required to reject the null hypothesis. A total of 196 patients will be recruited for the study (treatment group, n=98 and control group, n=98) to allow a 20% attrition rate to gain 156 participants for the study.
Statistical Methods
The analyst will be masked to group allocation. Comparisons will be made between pre-post changes in outcomes (see pre/post measures) for the two groups (i.e. ‘TAP without wait’ vs ‘TAP with wait’). Measures at 6 months will be analysed using a linear mixed model(30) (choice based on Akaike Information Criteria),(31) with group, subjects and baseline measures as fixed factors, a random effect and covariate, respectively. SPSS (v22) will be used to analyse by intention to treat with two-tailed alpha set at 0.05 (32). A t-test (alpha=0.05) will be used to test whether mean pre-post changes in outcome variables are different between groups (i.e. TAP without wait’ vs ‘TAP with wait’). A t-test of independent groups will be used to examine whether the mean TAP costs/QALY gained is significantly different to $73,000 (inflation adjusted value). REDCap and the NIH tool box require complete data sets from participates as a measure against missing data.