title: The clinical effectiveness and cost-effectiveness of treatments for idiopathic pulmonary fibrosis: a systematic review and economic evaluation.
abstract: BACKGROUND
  Idiopathic pulmonary fibrosis (IPF) is a life-limiting lung disease that generally affects people over 60 years old. The main symptoms are shortness of breath and cough, and as the disease progresses there is a considerable impact on day-to-day life. Few treatments are currently available.
  
  
  OBJECTIVE
  To conduct a systematic review of clinical effectiveness and an analysis of cost-effectiveness of treatments for IPF based on an economic model informed by systematic reviews of cost-effectiveness and quality of life.
  
  
  METHODS
  Eleven electronic bibliographic databases, including MEDLINE, EMBASE, Web of Science, and The Cochrane Library and the Centre for Reviews and Dissemination databases, were searched from database inception to July 2013. Reference lists of relevant publications were also checked and experts consulted.
  
  
  METHODS
  Two reviewers independently screened references for the systematic reviews, extracted and checked data from the included studies and appraised their risk of bias. An advisory group was consulted about the choice of interventions until consensus was reached about eligibility. A narrative review with meta-analysis was undertaken, and a network meta-analysis (NMA) was performed. A decision-analytic Markov model was developed to estimate cost-effectiveness of pharmacological treatments for IPF. Parameter values were obtained from NMA and systematic reviews. Univariate and probabilistic sensitivity analyses were undertaken. The model perspective is NHS and Personal Social Services, and discount rate is 3.5% for costs and health benefits.
  
  
  RESULTS
  Fourteen studies were included in the review of clinical effectiveness, of which one evaluated azathioprine, three N-acetylcysteine (NAC) (alone or in combination), four pirfenidone, one BIBF 1120, one sildenafil, one thalidomide, two pulmonary rehabilitation, and one a disease management programme. Study quality was generally good, with a low risk of bias. The current evidence suggests that some treatments appear to be clinically effective. The model base-case results show increased survival for five pharmacological treatments, compared with best supportive care, at increased cost. General recommendations cannot be made of their cost-effectiveness owing to limitations in the evidence base.
  
  
  CONCLUSIONS
  Few direct comparisons of treatments were identified. An indirect comparison through a NMA was performed; however, caution is recommended in the interpretation of these results. In relation to the economic model, there is an assumption that pharmacological treatments have a constant effect on the relative rate of per cent predicted forced vital capacity decline.
  
  
  CONCLUSIONS
  Few interventions have any statistically significant effect on IPF and a lack of studies on palliative care approaches was identified. Research is required into the effects of symptom control interventions, in particular pulmonary rehabilitation and thalidomide. Other research priorities include a well-conducted randomised controlled trial on inhaled NAC therapy and an updated evidence synthesis once the results of ongoing studies are reported.
  
  
  BACKGROUND
  This study is registered as PROSPERO CRD42012002116.
  
  
  BACKGROUND
  The National Institute for Health Research Health Technology Assessment programme.
authors.affiliation: Southampton Health Technology Assessments Centre, University of Southampton, Southampton, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Loveman
authors.affiliation: Southampton Health Technology Assessments Centre, University of Southampton, Southampton, UK.
authors.forename: Vicky R
authors.initials: VR
authors.lastname: Copley
authors.affiliation: Southampton Health Technology Assessments Centre, University of Southampton, Southampton, UK.
authors.forename: Jill
authors.initials: J
authors.lastname: Colquitt
authors.affiliation: Oxford Outcomes, Oxford, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Scott
authors.affiliation: Southampton Health Technology Assessments Centre, University of Southampton, Southampton, UK.
authors.forename: Andy
authors.initials: A
authors.lastname: Clegg
authors.affiliation: Southampton Health Technology Assessments Centre, University of Southampton, Southampton, UK.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Jones
authors.affiliation: Department of Respiratory Medicine, Mater Misericordiae University Hospital, Dublin, Ireland.
authors.forename: Katherine M A
authors.initials: KM
authors.lastname: O'Reilly
authors.affiliation: Cardiac and Pulmonary Rehabilitation, University Hospitals of Leicester NHS Trust, Leicester, UK.
authors.forename: Sally
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Palliative Medicine, University Hospital of Munich, Munich, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bausewein
authors.affiliation: Interstitial Lung Disease Unit, Royal Brompton and Harefield NHS Trust, London, UK.
authors.forename: Athol
authors.initials: A
authors.lastname: Wells
mesh_terms: D006801:Humans; D003362:Cost-Benefit Analysis; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy / Q000191:economics; D018803:Models, Economic; D016896:Treatment Outcome