The clinical effectiveness and cost-effectiveness of a ‘stepping into day treatment’ approach versus inpatient treatment as usual for anorexia nervosa in adult specialist eating disorder services (DAISIES trial): a study protocol of a randomised controlled multi-centre open-label parallel group non-inferiority trial
Authors: Irish Madeleine , Dalton Bethan , Potts Laura , McCombie Catherine , Shearer James , Au Katie , Kern Nikola , Clark-Stone Sam , Connan Frances , Johnston A. Louise , Lazarova Stanimira , Macdonald Shiona , Newell Ciarán , Pathan Tayeem , Wales Jackie , Cashmore Rebecca , Marshall Sandra , Arcelus Jon , Robinson Paul , Himmerich Hubertus , Lawrence Vanessa C. , Treasure Janet , Byford Sarah , Landau Sabine , Schmidt Ulrike 
Published: June 2022

Abstract
Background
Anorexia nervosa (AN) is a serious and disabling mental disorder with a high disease burden. In a proportion of cases, intensive hospital-based treatments, i.e. inpatient or day patient treatment, are required, with day patient treatment often being used as a ‘step-down’ treatment after a period of inpatient treatment. Demand for such treatment approaches has seen a sharp rise. Despite this, the relative merits of these approaches for patients, their families, and the NHS and wider society are relatively unknown. This paper describes the rationale for, and protocol of, a two-arm multi-centre open-label parallel group non-inferiority randomised controlled trial, evaluating the effectiveness and cost-effectiveness of these two intensive treatments for adults with severe AN: inpatient treatment as usual and a stepped care day patient approach (the combination of day patient treatment with the option of initial inpatient treatment for medical stabilisation). The main aim of this trial is to establish whether, in adults with severe AN, a stepped care day patient approach is non-inferior to inpatient treatment as usual in relation to improving body mass index (BMI) at 12 months post-randomisation.

Methods
386 patients with a Diagnostic and Statistical Manual 5th edition diagnosis of severe AN or related disorder, with a BMI of ≤16 kg/m2 and in need of intensive treatment will be randomly allocated to either inpatient treatment as usual or a stepped care day patient approach. Patients in both groups will receive treatment until they reach a healthy weight or get as close to this point as possible. Assessments will be conducted at baseline (prior to randomisation), and at 6 and 12 months post-randomisation, with additional monthly symptom monitoring. The primary outcome will be BMI at the 12-month post-randomisation assessment. Other outcomes will include psychosocial adjustment; treatment motivation, expectations and experiences; cost-effectiveness; and carer burden.

Discussion
The results of this study will provide a rigorous evaluation of two intensive treatment approaches which will inform future national and international treatment guidelines and service provision.

Trial registration
ISRCTN ISRCTN10166784. Registered 28 February 2020. ISRCTN is a primary registry of the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) network and includes all items from the WHO Trial Registration Data Set.