An adjudication algorithm for respiratory-related hospitalisation in idiopathic pulmonary fibrosis

Paul Ford; Michael Kreuter; Kevin K Brown; Wim A Wuyts; Marlies Wijsenbeek; Dominique Israël-Biet; Richard Hubbard; Steven D Nathan; Hilario Nunes; Bjorn Penninckx; Niyati Prasad; Ineke Seghers; Paolo Spagnolo; Nadia Verbruggen; Nik Hirani; Juergen Behr; Robert J Kaner; Toby M Maher

doi:10.1183/23120541.00636-2023

An adjudication algorithm for respiratory-related hospitalisation in idiopathic pulmonary fibrosis

ERJ Open Res. 2024 Jan 29;10(1):00636-2023. doi: 10.1183/23120541.00636-2023. eCollection 2024 Jan.

Authors

Paul Ford¹, Michael Kreuter², Kevin K Brown³, Wim A Wuyts⁴, Marlies Wijsenbeek⁵, Dominique Israël-Biet⁶, Richard Hubbard⁷, Steven D Nathan⁸, Hilario Nunes⁹, Bjorn Penninckx¹, Niyati Prasad¹, Ineke Seghers¹, Paolo Spagnolo¹⁰, Nadia Verbruggen¹, Nik Hirani¹¹, Juergen Behr¹², Robert J Kaner¹³, Toby M Maher^{14

15}

Affiliations

¹ Galapagos NV, Mechelen, Belgium.
² Center for Pulmonary Medicine, Departments of Pneumology, Mainz University Medical Center and of Pulmonary, Critical Care and Sleep Medicine, Marienhaus Clinic Mainz, Mainz, Germany.
³ Department of Medicine, National Jewish Health, Denver, CO, USA.
⁴ Unit for Interstitial Lung Diseases, Department of Respiratory Medicine, University Hospitals Leuven, Leuven, Belgium.
⁵ Centre for Interstitial Lung Disease and Sarcoidosis, Department of Respiratory Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
⁶ Université Paris Cité, Hôpital Européen Georges Pompidou, Paris, France.
⁷ Academic Unit of Population and Lifespan Sciences, School of Medicine, University of Nottingham, Nottingham, UK.
⁸ Inova Advanced Lung Disease and Transplant Program, Inova Fairfax Hospital, Falls Church, VA, USA.
⁹ Department of Pneumology, Centre de Référence des Maladies Pulmonaires Rares, Assistance Publique-Hôpitaux de Paris, Hôpital Avicenne, Université Sorbonne Paris Nord, Bobigny, France.
¹⁰ Respiratory Disease Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy.
¹¹ Edinburgh Lung Fibrosis Clinic, Royal Infirmary Edinburgh and Centre for Inflammation Research, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, UK.
¹² Department of Medicine V, LMU University Hospital, Ludwig Maximilian University Munich, Comprehensive Pneumology Center (member of the German Center for Lung Research), Munich, Germany.
¹³ Division of Pulmonary and Critical Care Medicine and Department of Genetic Medicine, Weill Cornell Medicine, New York, NY, USA.
¹⁴ National Heart and Lung Institute, Imperial College London, London, UK.
¹⁵ Keck Medicine of University of Southern California, Los Angeles, CA, USA.

Abstract

Background: There is no standard definition of respiratory-related hospitalisation, a common end-point in idiopathic pulmonary fibrosis (IPF) clinical trials. As diverse aetiologies and complicating comorbidities can present similarly, external adjudication is sometimes employed to achieve standardisation of these events.

Methods: An algorithm for respiratory-related hospitalisation was developed through a literature review of IPF clinical trials with respiratory-related hospitalisation as an end-point. Experts reviewed the algorithm until a consensus was reached. The algorithm was validated using data from the phase 3 ISABELA trials (clinicaltrials.gov identifiers NCT03711162 and NCT03733444), by assessing concordance between nonadjudicated, investigator-defined, respiratory-related hospitalisations and those defined by the adjudication committee using the algorithm.

Results: The algorithm classifies respiratory-related hospitalisation according to cause: extraparenchymal (worsening respiratory symptoms due to left heart failure, volume overload, pulmonary embolism, pneumothorax or trauma); other (respiratory tract infection, right heart failure or exacerbation of COPD); "definite" acute exacerbation of IPF (AEIPF) (worsening respiratory symptoms within 1 month, with radiological or histological evidence of diffuse alveolar damage); or "suspected" AEIPF (as for "definite" AEIPF, but with no radiological or histological evidence of diffuse alveolar damage). Exacerbations ("definite" or "suspected") with identified triggers (infective, post-procedural or traumatic, drug toxicity- or aspiration-related) are classed as "known AEIPF"; "idiopathic AEIPF" refers to exacerbations with no identified trigger. In the ISABELA programme, there was 94% concordance between investigator- and adjudication committee-determined causes of respiratory-related hospitalisation.

Conclusion: The algorithm could help to ensure consistency in the reporting of respiratory-related hospitalisation in IPF trials, optimising its utility as an end-point.

Associated data

ClinicalTrials.gov/NCT03733444
ClinicalTrials.gov/NCT03711162