Prioritising outcomes for evaluating eosinophil-guided corticosteroid therapy among patients with acute COPD exacerbations requiring hospitalisation: a Delphi consensus study

Abstract

Objectives: Presently, those outcomes that should be prioritised for chronic obstructive pulmonary disease (COPD) exacerbation studies remain unclear. In order to coordinate multicentre studies on eosinophilia-driven corticosteroid therapy for patients hospitalised for acute exacerbation of COPD (AECOPD), we aimed to find consensus among experts in the domain regarding the prioritisation of outcomes.

Design: A modified Delphi study was proposed to recognised COPD experts. Two brainstorming questionnaires were used to collect potential outcomes. Four subsequent rounds of questionnaires were used to rank items according to a six-point Likert scale for their importance in the protocol, as well as for being the primary outcome. Priority outcome criteria were predefined as those for which ≥70% of experts indicated that the outcome was essential for interpreting study results.

Setting: COPD exacerbation management in France.

Participants: 34 experts recommended by the French Language Pulmonology Society were invited to participate. Of the latter, 21 experts participated in brainstorming, and 19 participated in all four ranking rounds.

Results: 105 outcomes were ranked. Two achieved consensus as candidate primary outcomes: (1) treatment failure defined as death from any cause or the need for intubation and mechanical ventilation, readmission because of COPD or intensification of pharmacologic therapy, and (2) the time required to meet predefined discharge criteria. The 10 secondary priority outcomes included survival, time with no sign of improvement, episodes of hospitalisation, exacerbation, pneumonia, mechanical or non-invasive ventilation and oxygen use, as well as comorbidities during the initial hospitalisation.

Conclusions: This Delphi consensus project generated and prioritised a great many outcomes, documenting current expert views concerning a diversity of COPD endpoints. Among the latter, 12 reached consensus as priority outcomes for evaluating the efficacy of eosinophil-driven corticosteroid therapy in AECOPD inpatients.

Study registration: The eo-Delphi project/protocol was registered on 23 January 2018 at https://osf.io/4ahqw/.

Keywords: chronic airways disease; respiratory medicine (see thoracic medicine); therapeutics.

Conflict of interest statement

Competing interests: As a consensus-building project among COPD experts, there are no specific conflicts of interest for this study. For thoroughness, past collaborations with industry are presented here.AB, as an advisory board member, congress participant or study investigator, has previously received honoraria, grants or other forms of support from Astra Zeneca, GSK, Boeringher Ingelheim, Novartis, Teva, Regeneron, Chiesi Farmaceuticals, Actelion, Gilead and Roche. AD reports past collaborations (affiliation or financial interest or interest of any kind in the past 3 years) with AstraZeneca, GSK, Chiesi, Circassia, ALK, Novartis, Pierre Fabre, Boehringer-Ingelheim, Menarini, Teva, Zambon. CC reports interventions, expertise, grants or congress support from ALK-Abello, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKlein, MEDA Pharma, Medexact, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi, Santelys, TEVA. CR reports board participation, symposiums and congress fees for Astra Zeneca, Boeringher Ingelheim, Chiesi, GSK, Novartis. FC reports having received research grant support from Pfizer and Bristol-Myers Squibb, and fees for board memberships or symposia from Bayer, Bristol-Myers Squibb/Pfizer and Astra Zeneca and having received travel support from Bayer, Bristol-Myers Squibb/Pfizer, Daiichi Sankyo, Boehringer Ingelheim, Leo Pharma, Intermune and Actelion. GaD reports personal fees from Astra Zeneca, Boehringer Ingelheim, Chiesi, Novartis, Nuvaira, BTG/PneumRx. GeD declares being a consultant for Novartis Pharma, Astra-Zeneca, GSK, Boehringer Ingelheim, Mundi Pharma, Vivisol, TEVA, ALK, SANOFI, Menarini, participating at medical meetings for GSK, Astra-Zeneca, Novartis Pharma, Chiesi, MSD, Takeda, AGIR adom, Orkyn, TEVA, Mundi Pharma, ALK, Stallergène, SANOFI, taking part in clinical trails for (investigator)—GSK, ALK, Novartis Pharma, Boehringer-Ingelheim, Vitalair, AB Science, Amgen, Lilly, Astra Zeneca, Sanofi, Roche, TEVA, research fellowship- GSK, Novartis Pharma, MSD, Chiesi; MZ reports grants and personal fees from Novartis, personal fees and non-financial support from Boehringer Ingelheim, personal fees and non financial support from Astra Zeneca, personal fees from Chiesi, personal fees from GSK outside the submitted work. NR reports grants and personal fees from Boehringer Ingelheim, Novartis, Pfizer and personal fees from Teva, GSK, AstraZeneca, Chiesi, Mundipharma, Cipla, Sanofi, Sandoz, 3M, Trudell, Zambon. OLR reports personal fees and non-financial support from AstraZeneca, Boehringer Ingelheim, Chiesi, Lilly and Novartis; non-financial support from ALK, GlaxoSmithKlein, ICOMED, LEO Pharma, MSD, MundiPharma, Pfizer and TEVA. Outside the submitted work, PB declares grants from GSK, Novartis, Boehringer, AstraZeneca, Chiesi; personal fees from GSK, Novartis, Boehringer, AstraZeneca, Circassia, Sanofi and Menarini. PC provided consultancy services for Boehringer Ingelheim, Johnson & Johnson, GSK, Merck Sharp & Dohme, AstraZeneca, Novartis, Teva, Chiesi, and Sanofi; has served on advisory boards for Almirall, Boehringer Ingelheim, Johnson & Johnson, GSK, AstraZeneca, Novartis, Teva, Chiesi, and Sanofi; has received lecture fees from Boehringer Ingelheim, Centocor, GSK, AstraZeneca, Novartis, Teva, Chiesi, Boston Scientific, and ALK-Abelló; and received industry-sponsored grants from Roche, Boston Scientific, Boehringer Ingelheim, Centocor, GSK, AstraZeneca, ALK-Abelló, Novartis, Teva, and Chiesi. PD reports personal fees from Astra Zeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, MundiPharma, Novartis, and Sanofi. During the past 3 years, PRB has received fees for lecturing/advisory boards from Astra Zeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, Pfizer, Teva, Vertex, Zambon. RK reports grants and personal fees from Air Liquide, Elivie, personal fees from Astra-Zeneca, Novartis, Boehringer Ingelheim. TC reports past collaborations (affiliation or financial interest or interest of any kind in the past 3 years) with AstraZeneca, GSK, Chiesi, Novartis and Boehringer-Ingelheim. YM reports past collaborations (as a national board member) with: Astra-Zeneca, Chiese, GSK, and Menarini. CB, CMS and MM report no conflicts of interest.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Methodology flow chart for the eo-Delphi project. The expert panel was invited to participate in six sequentially administered questionnaires. Only those experts who responded to an invitation were subsequently invited to participate in the next questionnaire. The first questionnaire included questions describing the demographics of the expert panel, as well as opinion-type questions. It ended with an open-ended brainstorming question. The second questionnaire corresponded to a second round of brainstorming. The final four questionnaires were ranking questionnaires, where outcomes proposed by the expert panel during the brainstorming process were evaluated according to a Likert scale specifically designed for prioritising outcomes in research trials (table 1).

Figure 2

COPD expert opinions concerning current guidelines (GOLD in gold and French national guidelines (SPLF) in blue) as well as local hospital discharge criteria (light grey). Panel A: %Response rates when asked how familiar experts were with a given guideline. Panel B: Visual analogue scale scores for how often experts applied a given guideline (ranging from 0 (never) to 100 (all the time)) in their practice and then how they would rate that guideline (score ranging from 0 (completely inadequate) to 100 (perfect)). Experts were also asked how they rated their local hospital discharge criteria (score ranging from 0 (completely inadequate) to 100 (perfect)). Medians are presented as horizontal lines, first to third quartiles as boxes, 1.5× the IQR as whiskers and outliers as points. COPD, chronic obstructive pulmonary disease; SPLF, the Société de Pneumologie de Langue Française.