Evaluating differential item functioning in the EQ-5D-5L in acute ischemic stroke

Evaluating differential item functioning in the EQ-5D-5L in acute ischemic stroke | medRxiv Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Evaluating differential item functioning in the EQ-5D-5L in acute ischemic stroke View ORCID Profile Olayinka I. Arimoro , View ORCID Profile Ayoola Ademola , View ORCID Profile Michael D. Hill , View ORCID Profile Bijoy K. Menon , View ORCID Profile Tolulope T. Sajobi doi: https://doi.org/10.64898/2026.03.10.26348094 Olayinka I. Arimoro 1 Department of Community Health Sciences & O’Brien Institute for Public Health, Cumming School of Medicine, University of Calgary , Calgary, AB, Canada MSc Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Olayinka I. Arimoro Ayoola Ademola 2 Cancer Analytics Division, Alberta Health Services , Calgary, AB, Canada 3 Department of Surgery, Cumming School of Medicine, University of Calgary , Calgary, AB, Canada PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Ayoola Ademola Michael D. Hill 1 Department of Community Health Sciences & O’Brien Institute for Public Health, Cumming School of Medicine, University of Calgary , Calgary, AB, Canada 4 Department of Clinical Neurosciences & Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary , Calgary, AB, Canada MD, MSc Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Michael D. Hill Bijoy K. Menon 1 Department of Community Health Sciences & O’Brien Institute for Public Health, Cumming School of Medicine, University of Calgary , Calgary, AB, Canada 4 Department of Clinical Neurosciences & Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary , Calgary, AB, Canada MD, MSc Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Bijoy K. Menon Tolulope T. Sajobi 1 Department of Community Health Sciences & O’Brien Institute for Public Health, Cumming School of Medicine, University of Calgary , Calgary, AB, Canada 4 Department of Clinical Neurosciences & Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary , Calgary, AB, Canada PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Tolulope T. Sajobi For correspondence: ttsajobi{at}ucalgary.ca Abstract Full Text Info/History Metrics Data/Code Preview PDF Abstract Background Health-related quality of life is a key secondary endpoint in stroke trials. Differential item functioning (DIF) occurs when individuals with the same underlying HRQOL interpret and respond differently to questionnaire items due to group characteristics, potentially biasing treatment comparisons. This study evaluates DIF in the patient-reported five-level EuroQOL (EQ-5D-5L) among patients with acute ischemic stroke across age, sex, and treatment groups. Methods Data were obtained from the AcT trial, a registry-based randomized comparison of alteplase and tenecteplase. Patients completed the EQ-5D-5L at 90 days post-stroke. DIF was assessed using multigroup graded response models with the Wald-based sweep procedure, which accounts for between-group differences in latent trait distributions. We quantified effect sizes using signed weighted area between curves (sWABC), considering |sWABC| <0.10 as negligible. Results Among 1,264 patients (51.2% tenecteplase; 46.5% female; 30.1% aged ≥80). Omnibus testing revealed significant DIF only for age ( X ² = 86.9, p < 0.001); neither sex ( X ² = 31.7, p = 0.063) nor treatment ( X ² = 22.4, p = 0.379) showed evidence of DIF. At the item level, four items flagged for age-related DIF: self-care, usual activities, pain/discomfort, and anxiety/depression. However, only self-care (sWABC = -0.46) and usual activities (sWABC = - 0.34) showed moderate effects, while pain/discomfort (sWABC = -0.002) and anxiety/depression (sWABC = 0.09) were negligible. Importantly, factor scores from models with and without DIF adjustment correlated (correlation coefficient = 0.98). Conclusions The EQ-5D-5L appears to function equivalently across sex and treatment groups in this stroke population. Age-related DIF, though statistically detectable in physical functioning items, had little practical consequence for individual scores, findings that support the instrument’s use for HRQOL comparisons in stroke trials. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03889249 . Competing Interest Statement Dr. Menon reports stock in Circle NVI and patents for systems of triage in acute stroke. Dr. Sajobi reports consulting fees received from Circle NVI and employment at the University of Calgary. Dr Hill reports employment with the University of Calgary; consulting fees from Brainsgate Ltd; grants/contracts from Biogen, Inc, Boehringer Ingelheim, Canadian Institutes of Health Research, Medtronic, MicroVention, Inc, and NoNO, Inc; being part of the endpoint review committee at Merck; stock in Circle NVI; and patents for systems of triage in acute stroke. The other authors report no conflicts. Clinical Trial NCT03889249 Funding Statement This study was supported by the Canadian Institute for Health Research, the Heart and Stroke Foundation of Alberta/University of Calgary, and the Alberta SPOR SUPPORT Unit. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The trial was regulated by Health Canada (Clinical Trials Application number 231509) and by research ethics boards at participating centres. The datasets used in your study had been de-identified prior to use in this study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request and with appropriate permission from the AcT trial team. Nonstandard abbreviations and acronyms AcT Alteplase Compared to Tenecteplase DIF differential item functioning DTF differential test functioning EQ-5D-5L five-level EuroQOL questionnaire GRM graded response model HRQOL health-related quality of life IRT item response theory mRS modified Rankin Scale NIHSS National Institutes of Health Stroke Scale PROMs patient-reported outcome measures sWABC signed weighted area between curves sDTF signed differential test functioning uDTF unsigned differential test functioning Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Back to top Previous Next Posted March 19, 2026. 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Sajobi medRxiv 2026.03.10.26348094; doi: https://doi.org/10.64898/2026.03.10.26348094 Share This Article: Copy Citation Tools Evaluating differential item functioning in the EQ-5D-5L in acute ischemic stroke Olayinka I. Arimoro , Ayoola Ademola , Michael D. Hill , Bijoy K. Menon , Tolulope T. 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