Abstract
Background Valid outcome measures are imperative to evaluate treatment response, yet the suitability of existing end-points 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 and 2020. 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 20 July 2020 to identify development and validation studies for these end-points. 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” end-points from the latter three domains. Only the Severe Asthma Questionnaire and Childhood Asthma Control Test were developed with input from severe asthma patients. The certainty of evidence was “low” to “very low” for most “priority” end-points across all measurement properties and none fulfilled all quality standards.
Conclusions Only two outcome measures had robust developmental data for severe asthma. This review informed development of core outcome measures sets for severe asthma.
Abstract
This study identified and appraised the validity of selected outcome measures for severe asthma with input from key stakeholders. Only the Severe Asthma Questionnaire and Childhood Asthma Control Test had robust developmental data for severe asthma. https://bit.ly/3F7Xwcn
Footnotes
This study is registered at PROSPERO with identifier number CRD42020204437.
Disclaimer: The content of this publication reflects only the authors’ views and the Joint Undertaking is not responsible for any use that may be made of the information it contains.
This article has an editorial commentary: https://doi.org/10.1183/13993003.02107-2022
Authors contributions: Study concept and design: G. Roberts and A. Rattu. Conduct and analysis of modified Delphi exercise, multi-stakeholder meetings and online voting: A. Rattu and E. Khaleva. Literature searches, data extraction and COSMIN assessments: A. Rattu and E. Khaleva. Drafting of the original manuscript: A. Rattu, E. Khaleva and G. Roberts. All authors provided critical review of the manuscript and approved the final version.
Conflict of interest: A. Rattu and E. Khaleva declare funding from the European Commission's Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement number 831434 (3TR) for this manuscript. C. Brightling declares grants from GlaxoSmithKline, AstraZeneca, Novartis, Chiesi, Boehringer Ingelheim, Genentech, Roche, Sanofi, Mologic and 4DPharma, consulting fees from GlaxoSmithKline, AstraZeneca, Novartis, Chiesi, Boehringer Ingelheim, Genentech, Roche, Sanofi, Mologic, 4DPharma and Teva, and support from the 3TR project. S-E. Dahlén declares a 3TR IMI grant, consulting fees from AstraZeneca, Cayman Co., GlaxoSmithKline, Novartis, Regeneron, Sanofi and Teva, and payment for lectures from AstraZeneca and Sanofi. A. Bossios declares honoraria for lectures from GlaxoSmithKline, AstraZeneca, Teva and Novartis, support for attending meetings from AstraZeneca and Novartis, honoraria for advisory board meetings from GlaxoSmithKline, AstraZeneca, Teva, Novartis and Sanofi, and being a member of the Steering Committee of SHARP, Secretary of Assembly 5 (Airway Diseases, Asthma, COPD and Chronic Cough) of the European Respiratory Society, and Vice-chair of the Nordic Severe Asthma Network (NSAN). L. Fleming declares participation in advisory boards and honoraria for lectures from Sanofi, Respiri UK, AstraZeneca, Novartis and Teva, outside the submitted work; all payments were made to her institution. K.F. Chung has received honoraria for participating in advisory board meetings of GlaxoSmithKline, AstraZeneca, Roche, Novartis, Merck and Shionogi regarding treatments for asthma, COPD and chronic cough, and has also been remunerated for speaking engagements for Novartis and AstraZeneca; has received an MRC grant on precision medicine for severe asthma, an EPSRC grant on air pollution and asthma, and a GlaxoSmithKline grant on mepolizumab and eosinophils in asthma. E. Melén declares consulting fees from AstraZeneca, Chiesi, Novartis and Sanofi, outside the submitted work. R. Chaudhuri has received lecture fees from GlaxoSmithKline, AstraZeneca, Teva, Chiesi, Sanofi and Novartis, honoraria for advisory board meetings from GlaxoSmithKline, AstraZeneca, Teva, Chiesi and Novartis, sponsorship to attend international scientific meetings from Chiesi, Napp, Sanofi and GlaxoSmithKline, and a research grant to her institute from AstraZeneca for a UK multicentre study. R. Djukanovic declares funding from the European Respiratory Society, Teva, GlaxoSmithKline, Novartis, Sanofi and Chiesi for the SHARP CRC, consulting fees for Synairgen, honorarium for a lecture from GlaxoSmithKline, participation on a data safety monitoring board or advisory board for Kymab (Cambridge), and shares in Synairgen, outside the submitted work. A. Exley declares being a minority shareholder in GlaxoSmithKline PLC. G.H. Koppelman reports receiving research grants from the Lung Foundation of the Netherlands, Ubbo Emmius Foundation, H2020 European Union, Teva, GlaxoSmithKline and Vertex, outside this work (money to institution); he reports memberships of advisory boards to GlaxoSmithKline and PURE-IMS, outside this work (money to institution). A. Bourdin declares unrestricted grants from AstraZeneca and Boehringer 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 AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis and Sanofi; participation on a data safety monitoring board or advisory board for AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Sanofi and Abs science. C. 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 AstraZeneca, GlaxoSmithKline, Novartis, Teva, Sanofi, Chiesi and ALK; participation on an advisory board (paid to institution and personal honoraria) for AstraZeneca, Novartis, Teva, Sanofi and ALK. C. Coleman and C. Williams declare funding received to support this work by the European Lung Foundation (ELF) from the European Commission's Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement number 831434 (3TR), and are employees of the ELF. E. Davin bought and sold shares on the public market during 2021–2022 in Regeneron, Roche and ICON Plc, and declares no current holdings. P. 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. S. Romagosa Vilarnau declares unrestricted educational grants paid to the organisation from Novartis, Pfizer, AstraZeneca, Chiesi Farmaceutici, GlaxoSmithKline, AbbVie, LeoPharma, Boehringer Ingelheim, Sanofi, Regeneron, OM Pharma, MSD, Roche and DBV Technologies. G. Roberts declares EU IMI funding and consulting fees from AstraZeneca paid to his institution. No other author has any conflict of interest to declare.
Support statement: A. Rattu and E. Khaleva were supported by the European Union Innovative Medicines Initiative 2 (IMI2) 3TR project. G. Roberts is funded by University of Southampton and National Institutes of Health Research via Southampton's Biomedical Research Centre. This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement number 831434 (3TR). The JU receives support from the European Union's Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). Funding information for this article has been deposited with the Crossref Funder Registry.
- Received June 16, 2022.
- Accepted November 30, 2022.
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