Development, validation and clinical usefulness of a prognostic model for relapse in relapsing-remitting multiple sclerosis
Abstract Background Prognosis for the occurrence of relapses in individuals with relapsing-remitting multiple sclerosis (RRMS), the most common subtype of multiple sclerosis (MS), could support individualized decisions and disease management and could be helpful for efficiently selecting patients fo...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-10-01
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| Series: | Diagnostic and Prognostic Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s41512-021-00106-6 |
| _version_ | 1819011203606773760 |
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| author | Konstantina Chalkou Ewout Steyerberg Patrick Bossuyt Suvitha Subramaniam Pascal Benkert Jens Kuhle Giulio Disanto Ludwig Kappos Chiara Zecca Matthias Egger Georgia Salanti |
| author_facet | Konstantina Chalkou Ewout Steyerberg Patrick Bossuyt Suvitha Subramaniam Pascal Benkert Jens Kuhle Giulio Disanto Ludwig Kappos Chiara Zecca Matthias Egger Georgia Salanti |
| author_sort | Konstantina Chalkou |
| collection | DOAJ |
| description | Abstract Background Prognosis for the occurrence of relapses in individuals with relapsing-remitting multiple sclerosis (RRMS), the most common subtype of multiple sclerosis (MS), could support individualized decisions and disease management and could be helpful for efficiently selecting patients for future randomized clinical trials. There are only three previously published prognostic models on this, all of them with important methodological shortcomings. Objectives We aim to present the development, internal validation, and evaluation of the potential clinical benefit of a prognostic model for relapses for individuals with RRMS using real-world data. Methods We followed seven steps to develop and validate the prognostic model: (1) selection of prognostic factors via a review of the literature, (2) development of a generalized linear mixed-effects model in a Bayesian framework, (3) examination of sample size efficiency, (4) shrinkage of the coefficients, (5) dealing with missing data using multiple imputations, (6) internal validation of the model. Finally, we evaluated the potential clinical benefit of the developed prognostic model using decision curve analysis. For the development and the validation of our prognostic model, we followed the TRIPOD statement. Results We selected eight baseline prognostic factors: age, sex, prior MS treatment, months since last relapse, disease duration, number of prior relapses, expanded disability status scale (EDSS) score, and number of gadolinium-enhanced lesions. We also developed a web application that calculates an individual’s probability of relapsing within the next 2 years. The optimism-corrected c-statistic is 0.65 and the optimism-corrected calibration slope is 0.92. For threshold probabilities between 15 and 30%, the “treat based on the prognostic model” strategy leads to the highest net benefit and hence is considered the most clinically useful strategy. Conclusions The prognostic model we developed offers several advantages in comparison to previously published prognostic models on RRMS. Importantly, we assessed the potential clinical benefit to better quantify the clinical impact of the model. Our web application, once externally validated in the future, could be used by patients and doctors to calculate the individualized probability of relapsing within 2 years and to inform the management of their disease. |
| first_indexed | 2024-12-21T01:24:26Z |
| format | Article |
| id | doaj.art-ca11ba385a2347f18bb5721fc4b6ac1d |
| institution | Directory Open Access Journal |
| issn | 2397-7523 |
| language | English |
| last_indexed | 2024-12-21T01:24:26Z |
| publishDate | 2021-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Diagnostic and Prognostic Research |
| spelling | doaj.art-ca11ba385a2347f18bb5721fc4b6ac1d2022-12-21T19:20:34ZengBMCDiagnostic and Prognostic Research2397-75232021-10-015111610.1186/s41512-021-00106-6Development, validation and clinical usefulness of a prognostic model for relapse in relapsing-remitting multiple sclerosisKonstantina Chalkou0Ewout Steyerberg1Patrick Bossuyt2Suvitha Subramaniam3Pascal Benkert4Jens Kuhle5Giulio Disanto6Ludwig Kappos7Chiara Zecca8Matthias Egger9Georgia Salanti10Institute of Social and Preventive Medicine, University of BernLeiden University Medical CenterDepartment Epidemiology and Data Science, Amsterdam University Medical Centres, University of AmsterdamClinical Trial Unit, Department of Clinical Research,, University Hospital Basel, University of BaselClinical Trial Unit, Department of Clinical Research,, University Hospital Basel, University of BaselMultiple Sclerosis Centre, Neurologic Clinic and Policlinic, Departments of Head, Spine and Neuromedicine, Biomedicine and Clinical Research, University Hospital Basel and University of BaselNeurocenter of Southern Switzerland, Civic HospitalMultiple Sclerosis Centre, Neurologic Clinic and Policlinic, Departments of Head, Spine and Neuromedicine, Biomedicine and Clinical Research, University Hospital Basel and University of BaselMultiple Sclerosis Center, Neurocenter of Southern Switzerland, EOCInstitute of Social and Preventive Medicine, University of BernInstitute of Social and Preventive Medicine, University of BernAbstract Background Prognosis for the occurrence of relapses in individuals with relapsing-remitting multiple sclerosis (RRMS), the most common subtype of multiple sclerosis (MS), could support individualized decisions and disease management and could be helpful for efficiently selecting patients for future randomized clinical trials. There are only three previously published prognostic models on this, all of them with important methodological shortcomings. Objectives We aim to present the development, internal validation, and evaluation of the potential clinical benefit of a prognostic model for relapses for individuals with RRMS using real-world data. Methods We followed seven steps to develop and validate the prognostic model: (1) selection of prognostic factors via a review of the literature, (2) development of a generalized linear mixed-effects model in a Bayesian framework, (3) examination of sample size efficiency, (4) shrinkage of the coefficients, (5) dealing with missing data using multiple imputations, (6) internal validation of the model. Finally, we evaluated the potential clinical benefit of the developed prognostic model using decision curve analysis. For the development and the validation of our prognostic model, we followed the TRIPOD statement. Results We selected eight baseline prognostic factors: age, sex, prior MS treatment, months since last relapse, disease duration, number of prior relapses, expanded disability status scale (EDSS) score, and number of gadolinium-enhanced lesions. We also developed a web application that calculates an individual’s probability of relapsing within the next 2 years. The optimism-corrected c-statistic is 0.65 and the optimism-corrected calibration slope is 0.92. For threshold probabilities between 15 and 30%, the “treat based on the prognostic model” strategy leads to the highest net benefit and hence is considered the most clinically useful strategy. Conclusions The prognostic model we developed offers several advantages in comparison to previously published prognostic models on RRMS. Importantly, we assessed the potential clinical benefit to better quantify the clinical impact of the model. Our web application, once externally validated in the future, could be used by patients and doctors to calculate the individualized probability of relapsing within 2 years and to inform the management of their disease.https://doi.org/10.1186/s41512-021-00106-6PrognosisPrognostic modelRelapsing-remitting multiple sclerosisClinical benefitClinical usefulness |
| spellingShingle | Konstantina Chalkou Ewout Steyerberg Patrick Bossuyt Suvitha Subramaniam Pascal Benkert Jens Kuhle Giulio Disanto Ludwig Kappos Chiara Zecca Matthias Egger Georgia Salanti Development, validation and clinical usefulness of a prognostic model for relapse in relapsing-remitting multiple sclerosis Diagnostic and Prognostic Research Prognosis Prognostic model Relapsing-remitting multiple sclerosis Clinical benefit Clinical usefulness |
| title | Development, validation and clinical usefulness of a prognostic model for relapse in relapsing-remitting multiple sclerosis |
| title_full | Development, validation and clinical usefulness of a prognostic model for relapse in relapsing-remitting multiple sclerosis |
| title_fullStr | Development, validation and clinical usefulness of a prognostic model for relapse in relapsing-remitting multiple sclerosis |
| title_full_unstemmed | Development, validation and clinical usefulness of a prognostic model for relapse in relapsing-remitting multiple sclerosis |
| title_short | Development, validation and clinical usefulness of a prognostic model for relapse in relapsing-remitting multiple sclerosis |
| title_sort | development validation and clinical usefulness of a prognostic model for relapse in relapsing remitting multiple sclerosis |
| topic | Prognosis Prognostic model Relapsing-remitting multiple sclerosis Clinical benefit Clinical usefulness |
| url | https://doi.org/10.1186/s41512-021-00106-6 |
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