A tailored, cognitive behavioural approach intervention for mild to moderate anxiety and/or depression in people with chronic obstructive pulmonary disease (COPD): A randomised controlled trial (TANDEM Tailored intervention for ANxiety and DEpression Management in COPD)

Design: Seamless three phase study (Phase I preparation, Phase II pilot, Phase III contingent on funder’s approval of progress report submitted six months before completion of Phase II). Phases I&II: include qualitative studies to refine the intervention and a two centre (Leicester, London) pilot randomised controlled trial (RCT). Phase III: a fully powered multi-centre (London and the Midlands), individually randomised controlled trial to determine the clinical and cost effectiveness of the intervention with a parallel process evaluation. (There is the potential to use the Phase II pilot RCT as an internal pilot if no significant changes in the intervention or study design are required between Phases II and III.) Target population: adults with moderate to severe COPD recruited from primary care, community clinics, secondary care clinics or following referral to PR services, who have symptoms of mild to moderate co-morbid anxiety or depression on screening. Where eligible patients have a caregiver we will invite them to be included in a sub-study of carers. Inclusion/Exclusion Criteria, patients: • Adults with a confirmed diagnosis of COPD, post bronchodilator FEV1:FVC ratio <70% • Moderate or severe COPD severity on spirometry, FEV1 30-80% predicted • Probable mild or moderate anxiety as identified by Hospital Anxiety and Depression Scale Anxiety Subscale (HADS-A) scores of 8 to 15; and/or probable mild or moderate depression as identified by Hospital Anxiety and Depression Scale Depression Subscale (HADS-D) scores of 8 to 15 • Eligible for attendance at their local pulmonary rehabilitation (PR) service at time of randomisation Exclusion criteria, patients: • With HADS-A score and a HADS-D score 15 (suggesting severe anxiety/depression) • With a current severe psychological or psychiatric disorder • Not eligible for pulmonary rehabilitation at their local PR service at the time of randomisation • With a co-morbidity so severe it would prevent the patient from engaging fully in the trial • With moderate or severe cognitive impairment • In receipt of a psychological intervention primarily directed at helping to manage anxiety or depression in the last 6 months (NB those on antidepressants/ anxiolytics are not excluded) • Currently involved in another clinical trial related to COPD • Not sufficiently fluent in English to be able to complete the questionnaires Health technologies being assessed: Tailored, one to one psychological intervention combined with practical problem solving components based on: • our Self-Management Programme of Activity Coping and Education (SPACE), a COPD self-management programme, and • The Lung Manual - a nurse led intervention based on cognitive behavioural principles and self-management, and developed to address mood disorders of anxiety in COPD. This psychological intervention links into, and interdigitates with, usual PR, but is independent of it. Measurement of trial costs and outcomes: All quantitative data collected via a questionnaire completed prior to randomisation and at six and 12 months (supervised self-complete in the presence of a research assistant). Co-primary outcomes: HADS-A and HADS-D at 6 months (also collected as a secondary outcome at 12 months). Other outcomes collected at six and 12 months: Beck Depression Inventory (BDI-II); Beck Anxiety Inventory (BAI); Illness Perception Questionnaire (IPQ-R); MRC breathlessness score; health related quality of life(CRQ-SRS); pulmonary function related activity (PFSDQ-M); smoking status; social engagement (HEQI social engagement subscale); Office for National Statistics social capital questions; health-related quality of life (EQ-5D-5L); and information on the use of health and social care services from the Client Service Receipt Inventory and primary and care administrative data). NB: final selection of secondary outcomes for the main trial to be informed by the pre-pilot and pilot studies. Sample sizes: Phase II Pilot RCT: 45 participants, randomised 1:1.25 control: intervention Phase III Main trial 430 participants, randomised 1:1.25 control: intervention Sample size calculations are based on two primary outcomes (HADS-A, anxiety, subscale at 6 months, and HADS-D, depression, subscale at 6 months). Based on a significance level of 2.5% and 90% power, recruiting 153 participants would allow us to detect a difference of 1.7 points on the HADS anxiety subscale, and 1.5 points on the HADS depression subscale (based on an SD of 4.2 for anxiety and 3.6 for depression): these are equivalent to a standardised mean difference of about 0.4, and are similar to the minimum clinically important difference of 1.5 for HADS in COPD. We increased the sample size due to clustering by therapist in the intervention arm . Assuming an intraclass correlation coefficient between therapists of 0.01 and 24 patients per therapist leads to a design effect of 1.23, which required increasing the number of participants in the intervention arm to 189 (342 overall) using Moerbeek’s method. Assuming a dropout rate of 20%, we would require 428 participants overall. This has been rounded up to 430. Using an allocation ratio of 1.25 vs. 1, this would lead to approximately 240 participants in the intervention arm and 190 in the control arm. We have chosen this unbalanced allocation ratio as it will maximise power compared to a 1:1 ratio due to the presence of clustering by therapist in the intervention arm only. Health economics: An economic evaluation will be carried out as part of the main trial, with unit costs and instrumentation (i.e. the adapted Client Service Receipt Inventory) required for the measurement of resource use developed during the Phase l. The economic analysis will assess whether the addition of a tailored psychological intervention, combined with the availability of standard PR, is likely to be a cost-effective use of resources. The economic evaluation will take an NHS and Personal Social Services Perspective as currently preferred by the National Institute for Health and Care Excellence (NICE). Intervntion sessions and subsequent HCP facilitator support will be centrally recorded and the costs of HCP facilitators will be calculated in line with the methods used for production of unit costs by the University of Kent. This source will be used to generate costs of other services recorded in the Client Service Receipt Inventory, supplemented where possible with administrative data. Total health and social care costs will be compared between the groups using a regression model with baseline costs controlled for. Cost data are usually skewed and so bootstrapped confidence intervals will be generated around the cost difference. Incremental cost-effectiveness will be evaluated based on the primary outcome measures and on quality-adjusted life years gained (QALYs). The latter will be derived from the EQ-5D-5L using area under the curve methods. Point estimates of cost and outcome differences between the groups will be used to produce incremental cost-effectiveness ratios (ICERs). Uncertainty around these estimates will be explored using cost-effectiveness planes generated from 1000 bootstrapped re-samples of the data. Further interpretation of the results will use cost-effectiveness acceptability curves (CEACs) which will provide information on the likelihood that the addition of a tailored psychological intervention will offer a cost-effective addition to patient rehabilitation under different assumptions regarding the value that decision makers attach to quality-adjusted life years gained or a unit improvement in the HADS-D or HADS-A or BDI or BAI. Avoidance of bias: Randomisation will be performed using a central internet or telephone service, using minimisation with a random element, balanced for important participant characteristics to ensure treatment groups are well matched at baseline. Allocation concealment will be maintained through the use of a centralised service. HCPs delivering the intervention will not be involved in delivering routine PR to control or intervention patients to avoid any contamination. Healthcare providers will be aware that individuals are in the study but not aware of their allocation arm (although patients may tell them). Research staff collecting outcome data directly from patients will not be involved in the delivery of the intervention but it will probably not be possible to blind them to patients’ allocation group. During Phase II we will develop training and quality control measures to try to minimise the risk of outcome collection bias. Data extraction from primary care records will be done by masked study personnel as will data entry. A detailed statistical analysis plan will be produced and signed off (i.e. pre-specified) before any outcome data are accessed for analysis.