title: An observational study of Donor Ex Vivo Lung Perfusion in UK lung transplantation: DEVELOP-UK.
abstract: Many patients awaiting lung transplantation die before a donor organ becomes available. Ex vivo lung perfusion (EVLP) allows initially unusable donor lungs to be assessed and reconditioned for clinical use.
  
  
  
  The objective of the Donor Ex Vivo Lung Perfusion in UK lung transplantation study was to evaluate the clinical effectiveness and cost-effectiveness of EVLP in increasing UK lung transplant activity.
  
  
  
  A multicentre, unblinded, non-randomised, non-inferiority observational study to compare transplant outcomes between EVLP-assessed and standard donor lungs.
  
  
  
  Multicentre study involving all five UK officially designated NHS adult lung transplant centres.
  
  
  
  Patients aged ≥ 18 years with advanced lung disease accepted onto the lung transplant waiting list.
  
  
  
  The study intervention was EVLP assessment of donor lungs before determining suitability for transplantation.
  
  
  
  The primary outcome measure was survival during the first 12 months following lung transplantation. Secondary outcome measures were patient-centred outcomes that are influenced by the effectiveness of lung transplantation and that contribute to the health-care costs.
  
  
  
  Lungs from 53 donors unsuitable for standard transplant were assessed with EVLP, of which 18 (34%) were subsequently transplanted. A total of 184 participants received standard donor lungs. Owing to the early closure of the study, a non-inferiority analysis was not conducted. The Kaplan-Meier estimate of survival at 12 months was 0.67 [95% confidence interval (CI) 0.40 to 0.83] for the EVLP arm and 0.80 (95% CI 0.74 to 0.85) for the standard arm. The hazard ratio for overall 12-month survival in the EVLP arm relative to the standard arm was 1.96 (95% CI 0.83 to 4.67). Patients in the EVLP arm required ventilation for a longer period and stayed longer in an intensive therapy unit (ITU) than patients in the standard arm, but duration of overall hospital stay was similar in both groups. There was a higher rate of very early grade 3 primary graft dysfunction (PGD) in the EVLP arm, but rates of PGD did not differ between groups after 72 hours. The requirement for extracorporeal membrane oxygenation (ECMO) support was higher in the EVLP arm (7/18, 38.8%) than in the standard arm (6/184, 3.2%). There were no major differences in rates of chest radiograph abnormalities, infection, lung function or rejection by 12 months. The cost of EVLP transplants is approximately £35,000 higher than the cost of standard transplants, as a result of the cost of the EVLP procedure, and the increased ECMO use and ITU stay. Predictors of cost were quality of life on joining the waiting list, type of transplant and number of lungs transplanted. An exploratory model comparing a NHS lung transplant service that includes EVLP and standard lung transplants with one including only standard lung transplants resulted in an incremental cost-effectiveness ratio of £73,000. Interviews showed that patients had a good understanding of the need for, and the processes of, EVLP. If EVLP can increase the number of usable donor lungs and reduce waiting, it is likely to be acceptable to those waiting for lung transplantation. Study limitations include small numbers in the EVLP arm, limiting analysis to descriptive statistics and the EVLP protocol change during the study.
  
  
  
  Overall, one-third of donor lungs subjected to EVLP were deemed suitable for transplant. Estimated survival over 12 months was lower than in the standard group, but the data were also consistent with no difference in survival between groups. Patients receiving these additional transplants experience a higher rate of early graft injury and need for unplanned ECMO support, at increased cost. The small number of participants in the EVLP arm because of early study termination limits the robustness of these conclusions. The reason for the increased PGD rates, high ECMO requirement and possible differences in lung injury between EVLP protocols needs evaluation.
  
  
  
  Current Controlled Trials ISRCTN44922411.
  
  
  
  This project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 85. See the NIHR Journals Library website for further project information.
authors.affiliation: Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.|Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Fisher
authors.affiliation: Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.|Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Anders
authors.initials: A
authors.lastname: Andreasson
authors.affiliation: Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Chrysos
authors.affiliation: Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: Lally
authors.affiliation: Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Chrysovalanto
authors.initials: C
authors.lastname: Mamasoula
authors.affiliation: Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Exley
authors.affiliation: Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wilkinson
authors.affiliation: Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Jessica
authors.initials: J
authors.lastname: Qian
authors.affiliation: Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Gillian
authors.initials: G
authors.lastname: Watson
authors.affiliation: Service user and lay member of study research team.
authors.forename: Oli
authors.initials: O
authors.lastname: Lewington
authors.affiliation: Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Chadwick
authors.affiliation: Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK.|Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Elaine
authors.initials: E
authors.lastname: McColl
authors.affiliation: Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Pearce
authors.affiliation: Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Kay
authors.initials: K
authors.lastname: Mann
authors.affiliation: Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: McMeekin
authors.affiliation: Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Luke
authors.initials: L
authors.lastname: Vale
authors.affiliation: Papworth Hospital NHS Foundation Trust, Cambridge, UK.
authors.forename: Steven
authors.initials: S
authors.lastname: Tsui
authors.affiliation: University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
authors.forename: Nizar
authors.initials: N
authors.lastname: Yonan
authors.affiliation: Royal Brompton and Harefield Hospital NHS Foundation Trust, London, UK.
authors.forename: Andre
authors.initials: A
authors.lastname: Simon
authors.affiliation: Royal Brompton and Harefield Hospital NHS Foundation Trust, London, UK.
authors.forename: Nandor
authors.initials: N
authors.lastname: Marczin
authors.affiliation: Queen Elizabeth Hospital NHS Foundation Trust, Birmingham, UK.
authors.forename: Jorge
authors.initials: J
authors.lastname: Mascaro
authors.affiliation: Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.|Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: John
authors.initials: J
authors.lastname: Dark
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003362:Cost-Benefit Analysis; D015199:Extracorporeal Membrane Oxygenation / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007902:Length of Stay / Q000706:statistics & numerical data; D008168:Lung / Q000473:pathology*; D008171:Lung Diseases / Q000601:surgery*; D016040:Lung Transplantation / Q000191:economics / Q000379:methods* / Q000523:psychology; D008297:Male; D008875:Middle Aged; D010477:Perfusion / Q000191:economics / Q000379:methods*; D055031:Primary Graft Dysfunction / Q000453:epidemiology; D011788:Quality of Life; D012121:Respiration, Artificial / Q000706:statistics & numerical data; D013222:State Medicine; D020858:Tissue and Organ Harvesting / Q000191:economics / Q000379:methods* / Q000523:psychology; D006113:United Kingdom; D014850:Waiting Lists; D055815:Young Adult