Title: A randomised controlled feasibility trial comparing the clinical and cost effectiveness of cognitive behavioural therapy (CBT) and selective serotonin reuptake inhibitors (SSRI) and their combination in the management of obsessive compulsive disorder
Funder: Department of Health (England)

Abstract: OCD constitutes a major health-research priority4. Ranked tenth by the WHO in the leading neuropsychiatric causes of disability3, OCD causes serious social and occupational impairment2. NICE5 recommends monotherapy with either CBT or SSRI as the standard first-line treatment, with combined therapy (CBT + SSRI) reserved for those with more severe or enduring illness. However, the stepwise model is not necessarily optimally effective or cost-efficient. Robust evidence exists to support the use of SSRIs or CBT with exposure and response prevention (ERP) as monotherapies, but the evidence supporting the use of combined therapy has been inadequate to allow a true estimate of the effect-size. NICE recommends that a robust, large-scale randomised controlled trial be conducted, including a health-economic analysis, to assess whether combination therapy is more clinically effective and economically viable within the NHS5. To conduct such a trial, it is important that aspects relating to the feasibility of the methodology are first addressed, so that time and money are not wasted1. We therefore propose a multi-centre, partially-blinded, randomised controlled feasibility trial in adults with OCD, assessing three treatments; SSRI, CBT and (SSRI and CBT) combined. The feasibility trial assesses participants over 52 weeks, with systematic evaluation at weeks 0, 2, 4, 8, 16, 32 and 52. The objectives of the feasibility trial are to: 1) assess recruitment rates across the three treatment-arms and the three participating centres according to referral source and treatment history 2) evaluate the ascertainment ratio, i.e. the proportion of eligible cases consenting to randomisation, using a screening/randomisation log 3) investigate premature discontinuation rates across the three treatment-arms and the three participating centres and their reasons 4) evaluate methods to confirm conformity to the study protocol, including fidelity to CBT models and rater-blindness 5) estimate the variation of the primary outcome measure (Y-BOCS) (measures OCD severity), within and between the 3 treatment-arms, to estimate a suitable sample-size for the full trial 6) evaluate treatment-related adverse effects and tolerability across the treatment-arms 7) monitor resource-use and quality of life changes, so as to conduct a preliminary cost-effectiveness analysis To achieve these aims, the principal study outcomes for this trial will be: 1) Number of participants recruited to each treatment-arm in each centre according to referral source and treatment history 2) Ascertainment ratio (numbers screened for eligibility, treatment history and proportion recruited) 3) Number of participants discontinuing treatment prematurely according to treatment-allocation 4) Number of participants lost during follow-up in each treatment-arm in each centre and their reasons 5) Means and standard deviations of study measures at baseline and follow-up across all treatment-groups 6) Adverse events systematically evaluated using meDRA terminology 7) Completion-rates for study instruments 8) Preliminary estimate of cost-effectiveness using EuroQol (EQ-5D) and resource-use questionnaire (Client Services Receipt Inventory; CSRI) The reliability of potentially vulnerable aspects of the design will also be tested e.g. therapist-concordance with the CBT-protocol and adherence to measures designed to preserve rater-blindness, through audio-assessment of randomly selected research-interactions. Although the feasibility trial is not powered to investigate the relative effectiveness of combination therapy in OCD-treatment, it will provide the necessary data to formulate an adequately constituted full trial which could. Therefore, by using the information gained from this feasibility trial, the Health Technology Assessment (HTA) Clinical Evaluation and Trials programme will have the necessary material to guide judgement on the possible conduct of a future, definitive study in a larger clinical population. From this, we can reasonably expect that UK clinical practice regarding OCD treatment will be refined, thereby more cost-effectively improving clinical outcomes for adults with OCD and maximising their quality of life.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL;6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH