Abstract
Background Valid outcome measures are imperative to evaluate treatment response, yet the suitability of existing endpoints for severe asthma is unclear. This review aimed to identify outcome measures for severe asthma and appraise the quality of their measurement properties.
Methods A literature search was performed to identify “candidate” outcome measures published between 2018–2020 (PROSPERO, CRD42020204437). A modified Delphi exercise was conducted to select “key” outcome measures within healthcare professional, patient, pharmaceutical, and regulatory stakeholder groups. Initial validation studies for “key” measures were rated against modified quality criteria from COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN). The evidence was discussed at multi-stakeholder meetings to ratify “priority” outcome measures. Subsequently, four bibliographic databases were searched from inception to identify development and validation studies for these endpoints. Two reviewers screened records, extracted data, assessed their methodological quality, and graded the evidence according to COSMIN.
Results 96 outcome measures were identified as “candidates”, 55 as “key”, and 24 as “priority” for severe asthma; including clinical, healthcare utilisation, quality of life, asthma control, and composite. 32 studies reported measurement properties of 17 “priority” endpoints from the latter three domains. Only SAQ and C-ACT were developed with input from severe asthma patients. The certainty of evidence was “low” to “very low” for most “priority” endpoints across all measurement properties, and none fulfilled all quality standards.
Conclusion Only two outcome measures had robust developmental data for severe asthma. This review informed development of core outcome measures sets for severe asthma.
Footnotes
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Conflict of interest: Anna Rattu and Ekaterina Khaleva declare funding from the European Commission”s Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No. 831434 (3TR) for this manuscript.
Conflict of interest: Chris Brightling declares grants from GSK, AZ, Novartis, Chiesi, BI, Genentech, Roche, Sanofi, Mologic, 4DPharma; consulting fees from GSK, AZ, Novartis, Chiesi, BI, Genentech, Roche, Sanofi, Mologic, 4DPharma, TEVA and support from the 3TR project.
Conflict of interest: Sven-Erik Dahlén declares 3TR IMI Grant; consulting fees for AZ, Cayman Co, GSK, Novartis, Regeneron, Sanofi and Teva; payment for lectures from AZ and Sanofi. Sven-Erik Dahlén declares 3TR IMI Grant; consulting fees for AZ, Cayman Co, GSK, Novartis, Regeneron, Sanofi and Teva; payment for lectures from AZ and Sanofi.
Conflict of interest: Apostolos Bossios declares honoraria for lectures from GSK, AZ, Teva and Novartis; support for attending meetings from AZ and Novartis; honoraria for Advisory Board Meetings from GSK, AZ, Teva, Novartis and Sanofi; being a member of the steering Committee of SHARP, Secretary of Assembly 5 (Airway diseases, asthma, COPD, and chronic cough), European Respiratory Society; Vice-chair of Nordic Severe Asthma Network (NSAN).
Conflict of interest: Louise J Fleming declares participation in advisory boards and honoraria for lectures from Sanofi, Respiri UK, AZ, Novartis and Teva outside of submitted work. All payments were made to her institution.
Conflict of interest: Kian Fan Chung has received honoraria for participating in Advisory Board meetings of GSK, AZ, Roche, Novartis, Merck, and Shionogi regarding treatments for asthma, chronic obstructive pulmonary disease and chronic cough and has also been renumerated for speaking engagements for Novartis & AZ; received MRC grant on Precision Medicine for severe asthma, EPSRC grant on air pollution and asthma and GSK grant on mepolizumab and eosinophils in asthma.
Conflict of interest: Erik Melén declares consulting fees from AZ, Chiesi, Novartis and Sanofi outside the submitted work. Rekha Chaudhuri has received lecture fees from GSK, AZ, Teva, Chiesi, Sanofi and Novartis; honoraria for Advisory Board Meetings from GSK, AZ, Teva, Chiesi, Novartis; sponsorship to attend international scientific meetings from Chiesi, Napp, Sanofi and GSK and a research grant to her Institute from AZ for a UK multi-centre study.
Conflict of interest: Ratko Djukanovic declares funding from ERS, TEVA, GSK, Novartis, Sanofi and Chiesi for the SHARP CRC; consulting fees for Synairgen; honorarium for a lecture from GSK; participation on a Data Safety Monitoring Board or Advisory Board for Kymab (Cambridge) and shares in Synairgen outside of the submitted work.
Conflict of interest: Rekha Chaudhuri has received lecture fees from GSK, AZ, Teva, Chiesi, Sanofi and Novartis; honoraria for Advisory Board Meetings from GSK, AZ, Teva, Chiesi, Novartis; sponsorship to attend international scientific meetings from Chiesi, Napp, Sanofi and GSK and a research grant to her Institute from AZ for a UK multi-centre study.
Conflict of interest: Andrew Exley declares being a minority shareholder in GlaxoSmithKline PLC.
Conflict of interest: Gerard H Koppelman reports receiving research grants from Lung Foundation of the Netherlands, Ubbo Emmius Foundation, H2020 European Union, TEVA the Netherlands, GSK, Vertex, outside this work (money to institution); he reports memberships of advisory boards to GSK and PURE-IMS, outside this work (money to institution).
Conflict of interest: Arnaud Bourdin declares unrestricted grants from AZ and Boeringher Ingelheim to his institute; consulting fees, honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, and support for attending meetings and travel from AZ, Boeringher Ingelheim, GSK, Novartis, Sanofi; participation on a Data Safety Monitoring Board or Advisory Board for AZ, Boeringher Ingelheim, GSK, Novartis, Sanofi; Abs science.
Conflict of interest: Celeste Porsbjerg declares grants (paid to institution), consulting fees (paid to institution and personal honoraria) and honoraria for lectures (paid to institution and personal honoraria) from AZ, GSK, Novartis, TEVA, Sanofi, Chiesi and ALK; participation in the Advisory Board (paid to institution and personal honoraria) for AZ, Novartis, TEVA, Sanofi and ALK.
Conflict of interest: Courtney Coleman and Clare Williams declare funding received to support this work by European Lung Foundation from European Commission”s Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No. 831434 (3TR).
Conflict of interest: Elizabeth Davin bought and sold shares on public market during 2021–22 in Regeneron, Roche, and ICON Plc, and declares no current holdings.
Conflict of interest: Phil Taverner declares honorarium for being a lay member of Asthma and Lung UK's research funding panel, and chairing a Patient and Community Oversight Group for two NIHR health protection research units on environmental and chemical hazards; and payment for chairing a NICE guideline committee on Advocacy Services.
Conflict of interest: Sofia Romagosa Vilarnau declares unrestricted educational grants paid to the organisation from Novartis, Pfizer, Astra Zeneca, Chiesi Farmaceutici, GSK, AbbVie, LeoPharma, Boehringer Ingelheim, Sanofi, Regeneron, OM Pharma, MSD, Roche and DBV Technologies.
Conflict of interest: Graham Roberts declares EU IMI funding and AZ paid to the institution. No other author has any conflict of interest to declare.
- Received June 16, 2022.
- Accepted November 30, 2022.
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