title: The clinical and cost effectiveness of a Breathlessness Intervention Service for patients with advanced non-malignant disease and their informal carers: mixed findings of a mixed method randomised controlled trial.
abstract: BACKGROUND
  Breathlessness is the most common and intrusive symptom of advanced non-malignant respiratory and cardiac conditions. The Breathlessness Intervention Service (BIS) is a multi-disciplinary complex intervention, theoretically underpinned by a palliative care approach, utilising evidence-based non-pharmacological and pharmacological interventions to support patients with advanced disease in managing their breathlessness. Having published the effectiveness and cost effectiveness of BIS for patients with advanced cancer and their carers, we sought to establish its effectiveness, and cost effectiveness, in advanced non-malignant conditions.
  
  
  METHODS
  This was a single-centre Phase III fast-track single-blind mixed method RCT of BIS versus standard care for breathless patients with non-malignant conditions and their carers. Randomisation was to one of two groups (randomly permuted blocks). Eighty-seven patients referred to BIS were randomised (intervention arm n = 44; control arm n = 43 received BIS after four-week wait); 79 (91 %) completed to key outcome measurement. The primary outcome measure was 0-10 numeric rating scale for patient distress due to breathlessness at four weeks. Secondary outcome measures were Chronic Respiratory Questionnaire, Hospital Anxiety and Depression Scale, Client Service Receipt Inventory, EQ-5D and topic-guided interviews.
  
  
  RESULTS
  Qualitative analyses showed the positive impact of BIS on patients with non-malignant conditions and their carers; quantitative analyses showed a non-significant greater reduction in the primary outcome ('distress due to breathlessness'), when compared to standard care, of -0.24 (95 % CI: -1.30, 0.82). BIS resulted in extra mean costs of £799, reducing to £100 when outliers were excluded; neither difference was statistically significant. The quantitative findings contrasted with those previously reported for patients with cancer and their carers, which showed BIS to be both clinically and cost effective. For patients with non-malignant conditions there was a notable trend of improvement over both trial arms to the key measurement point; participants may have experienced a therapeutic effect from the research interviews, diluting the intervention's impact.
  
  
  CONCLUSIONS
  BIS had a statistically non-significant effect for patients with non-malignant conditions, and slightly increased service costs, but had a qualitatively positive impact consistent with findings for advanced cancer. Trials of palliative care interventions should consider multiple, mixed method, primary outcomes and ensure that protocols limit potential contaminating therapeutic effects in study designs.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN04119516 (December 2008); ClinicalTrials.gov NCT00678405 (May 2008).
authors.affiliation: Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Institute of Public Health, Robinson Way, Cambridge, CB2 0SR, UK. mcf22@medschl.cam.ac.uk.
authors.forename: Morag C
authors.initials: MC
authors.lastname: Farquhar
authors.affiliation: Imperial Clinical Trials Unit, School of Public Health, Imperial College London, Stadium House, 68 Wood Lane, London, W12 7RH, UK.
authors.forename: A Toby
authors.initials: AT
authors.lastname: Prevost
authors.affiliation: Institute of Psychiatry, King's College London, De Crespigny Park, London, SE5 8AF, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: McCrone
authors.affiliation: Formerly of Palliative Care Service, Cambridge University Hospitals' NHS Foundation Trust, Addenbrooke's Hospital, Hills Rd, Cambridge, CB2 0QQ, UK.
authors.forename: Barbara
authors.initials: B
authors.lastname: Brafman-Price
authors.affiliation: Formerly of Palliative Care Service, Cambridge University Hospitals' NHS Foundation Trust, Addenbrooke's Hospital, Hills Rd, Cambridge, CB2 0QQ, UK.
authors.forename: Allison
authors.initials: A
authors.lastname: Bentley
authors.affiliation: Department of Palliative Care, Policy & Rehabilitation, King's College London, Cicely Saunders Institute, Denmark Hill, London, SE5 9PJ, UK.
authors.forename: Irene J
authors.initials: IJ
authors.lastname: Higginson
authors.affiliation: School of Nursing, Midwifery and Social Work, Jean McFarlane Building, University of Manchester, Oxford Rd, Manchester, M13 9PL, UK.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Todd
authors.affiliation: Formerly of Palliative Care Service, Cambridge University Hospitals' NHS Foundation Trust, Addenbrooke's Hospital, Hills Rd, Cambridge, CB2 0QQ, UK.|Department of Oncology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Booth
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017028:Caregivers / Q000191:economics*; D003131:Combined Modality Therapy; D003362:Cost-Benefit Analysis; D004417:Dyspnea / Q000191:economics* / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D004739:England; D005260:Female; D017048:Health Care Costs; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010166:Palliative Care / Q000191:economics*; D010348:Patient Care Team / Q000191:economics; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000191:economics* / Q000503:physiopathology / Q000628:therapy*; D036301:Qualitative Research; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D012119:Respiration; D016037:Single-Blind Method; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
keywords: Advanced disease; Breathlessness; Chronic obstructive pulmonary disease; Complex intervention; Mixed methods; Non-malignant disease; Palliative care; Randomised controlled trial