Antoine Gavoille, Mikail Nourredine, Fabien Rollot, Romain Casey, Guillaume Mathey, Anne Kerbrat, Jonathan Ciron, Jérôme De Sèze, Bruno Stankoff, Elisabeth Maillart, Aurelie Ruet, Pierre Labauge, Arnaud Kwiatkowski, Helene Zephir, Caroline Papeix, Gilles Defer, Christine Lebrun-Frenay, Thibault Moreau, David-Axel Laplaud, Eric Berger, Pierre Clavelou, Eric Thouvenot, Olivier Heinzlef, Jean Pelletier, Abdullatif Al Khedr, Olivier Casez, Bertrand Bourre, Abir Wahab, Laurent Magy, Solène Moulin, Jean-Philippe Camdessanché, Ines Doghri, Mariana Sarov, Karolina Hankiewicz, Corinne Pottier, Amélie Dos Santos, Eric Manchon, Maia Tchikviladze, Muriel Rabilloud, Fabien Subtil, Sandra Vukusic
{"title":"目标试验模拟复制随机临床试验使用注册数据在多发性硬化症。","authors":"Antoine Gavoille, Mikail Nourredine, Fabien Rollot, Romain Casey, Guillaume Mathey, Anne Kerbrat, Jonathan Ciron, Jérôme De Sèze, Bruno Stankoff, Elisabeth Maillart, Aurelie Ruet, Pierre Labauge, Arnaud Kwiatkowski, Helene Zephir, Caroline Papeix, Gilles Defer, Christine Lebrun-Frenay, Thibault Moreau, David-Axel Laplaud, Eric Berger, Pierre Clavelou, Eric Thouvenot, Olivier Heinzlef, Jean Pelletier, Abdullatif Al Khedr, Olivier Casez, Bertrand Bourre, Abir Wahab, Laurent Magy, Solène Moulin, Jean-Philippe Camdessanché, Ines Doghri, Mariana Sarov, Karolina Hankiewicz, Corinne Pottier, Amélie Dos Santos, Eric Manchon, Maia Tchikviladze, Muriel Rabilloud, Fabien Subtil, Sandra Vukusic","doi":"10.1136/jnnp-2025-336762","DOIUrl":null,"url":null,"abstract":"<p><p>BackgroundTarget trial emulation (TTE) offers a formal framework for causal inference using observational data, but its validity must be evaluated in each research domain by replicating randomised clinical trials (RCTs). We aimed to replicate eight RCTs evaluating the efficacy of disease-modifying therapies (DMTs) in multiple sclerosis (MS) using French registry data.</p><p><strong>Methods: </strong>This multicentre, retrospective, observational study was conducted using data extracted in December 2023 from the <i>Observatoire Français de la Sclérose en Plaques</i> (OFSEP) database. For each emulated trial, patients were included when they initiated one of the DMT evaluated in the corresponding RCT and met its inclusion criteria. Clinical outcomes were the annualised relapse rate and 3-month confirmed Expanded Disability Status Scale progression. Radiological outcomes were new/enlarged T2-lesions and new gadolinium-enhanced T1-lesions on a brain MRI. A targeted maximum likelihood estimator was used to estimate the treatment effect adjusted for confounding factors between groups and corrected for censoring and missing outcome assessment.</p><p><strong>Results: </strong>14 111 patients were included in eight emulated trials: ASSESS (fingolimod vs glatiramer acetate), BEYOND (interferon beta vs glatiramer acetate), CONFIRM (dimethyl fumarate (DMF) vs glatiramer acetate), OPERA (ocrelizumab vs interferon beta), REGARD (interferon beta vs glatiramer acetate), RIFUND-MS (rituximab vs DMF), TENERE (teriflunomide vs interferon beta) and TRANSFORMS (fingolimod vs interferon beta). Treatment effects estimated in emulated trials were concordant with RCT findings in seven of eight trials for relapse rate, and in all six trials assessing disability progression. Radiological outcomes were more challenging to replicate; concordance was achieved in three of five trials for new T2-lesions, and one of four trials for new gadolinium-enhanced T1-lesions.</p><p><strong>Conclusion: </strong>The combined use of a TTE methodology and high-quality registry data is a valid tool to evaluate treatment effectiveness in MS.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":7.5000,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Target trial emulation to replicate randomised clinical trials using registry data in multiple sclerosis.\",\"authors\":\"Antoine Gavoille, Mikail Nourredine, Fabien Rollot, Romain Casey, Guillaume Mathey, Anne Kerbrat, Jonathan Ciron, Jérôme De Sèze, Bruno Stankoff, Elisabeth Maillart, Aurelie Ruet, Pierre Labauge, Arnaud Kwiatkowski, Helene Zephir, Caroline Papeix, Gilles Defer, Christine Lebrun-Frenay, Thibault Moreau, David-Axel Laplaud, Eric Berger, Pierre Clavelou, Eric Thouvenot, Olivier Heinzlef, Jean Pelletier, Abdullatif Al Khedr, Olivier Casez, Bertrand Bourre, Abir Wahab, Laurent Magy, Solène Moulin, Jean-Philippe Camdessanché, Ines Doghri, Mariana Sarov, Karolina Hankiewicz, Corinne Pottier, Amélie Dos Santos, Eric Manchon, Maia Tchikviladze, Muriel Rabilloud, Fabien Subtil, Sandra Vukusic\",\"doi\":\"10.1136/jnnp-2025-336762\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>BackgroundTarget trial emulation (TTE) offers a formal framework for causal inference using observational data, but its validity must be evaluated in each research domain by replicating randomised clinical trials (RCTs). We aimed to replicate eight RCTs evaluating the efficacy of disease-modifying therapies (DMTs) in multiple sclerosis (MS) using French registry data.</p><p><strong>Methods: </strong>This multicentre, retrospective, observational study was conducted using data extracted in December 2023 from the <i>Observatoire Français de la Sclérose en Plaques</i> (OFSEP) database. For each emulated trial, patients were included when they initiated one of the DMT evaluated in the corresponding RCT and met its inclusion criteria. Clinical outcomes were the annualised relapse rate and 3-month confirmed Expanded Disability Status Scale progression. Radiological outcomes were new/enlarged T2-lesions and new gadolinium-enhanced T1-lesions on a brain MRI. A targeted maximum likelihood estimator was used to estimate the treatment effect adjusted for confounding factors between groups and corrected for censoring and missing outcome assessment.</p><p><strong>Results: </strong>14 111 patients were included in eight emulated trials: ASSESS (fingolimod vs glatiramer acetate), BEYOND (interferon beta vs glatiramer acetate), CONFIRM (dimethyl fumarate (DMF) vs glatiramer acetate), OPERA (ocrelizumab vs interferon beta), REGARD (interferon beta vs glatiramer acetate), RIFUND-MS (rituximab vs DMF), TENERE (teriflunomide vs interferon beta) and TRANSFORMS (fingolimod vs interferon beta). Treatment effects estimated in emulated trials were concordant with RCT findings in seven of eight trials for relapse rate, and in all six trials assessing disability progression. Radiological outcomes were more challenging to replicate; concordance was achieved in three of five trials for new T2-lesions, and one of four trials for new gadolinium-enhanced T1-lesions.</p><p><strong>Conclusion: </strong>The combined use of a TTE methodology and high-quality registry data is a valid tool to evaluate treatment effectiveness in MS.</p>\",\"PeriodicalId\":16418,\"journal\":{\"name\":\"Journal of Neurology, Neurosurgery, and Psychiatry\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":7.5000,\"publicationDate\":\"2025-09-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Neurology, Neurosurgery, and Psychiatry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/jnnp-2025-336762\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neurology, Neurosurgery, and Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/jnnp-2025-336762","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Target trial emulation to replicate randomised clinical trials using registry data in multiple sclerosis.
BackgroundTarget trial emulation (TTE) offers a formal framework for causal inference using observational data, but its validity must be evaluated in each research domain by replicating randomised clinical trials (RCTs). We aimed to replicate eight RCTs evaluating the efficacy of disease-modifying therapies (DMTs) in multiple sclerosis (MS) using French registry data.
Methods: This multicentre, retrospective, observational study was conducted using data extracted in December 2023 from the Observatoire Français de la Sclérose en Plaques (OFSEP) database. For each emulated trial, patients were included when they initiated one of the DMT evaluated in the corresponding RCT and met its inclusion criteria. Clinical outcomes were the annualised relapse rate and 3-month confirmed Expanded Disability Status Scale progression. Radiological outcomes were new/enlarged T2-lesions and new gadolinium-enhanced T1-lesions on a brain MRI. A targeted maximum likelihood estimator was used to estimate the treatment effect adjusted for confounding factors between groups and corrected for censoring and missing outcome assessment.
Results: 14 111 patients were included in eight emulated trials: ASSESS (fingolimod vs glatiramer acetate), BEYOND (interferon beta vs glatiramer acetate), CONFIRM (dimethyl fumarate (DMF) vs glatiramer acetate), OPERA (ocrelizumab vs interferon beta), REGARD (interferon beta vs glatiramer acetate), RIFUND-MS (rituximab vs DMF), TENERE (teriflunomide vs interferon beta) and TRANSFORMS (fingolimod vs interferon beta). Treatment effects estimated in emulated trials were concordant with RCT findings in seven of eight trials for relapse rate, and in all six trials assessing disability progression. Radiological outcomes were more challenging to replicate; concordance was achieved in three of five trials for new T2-lesions, and one of four trials for new gadolinium-enhanced T1-lesions.
Conclusion: The combined use of a TTE methodology and high-quality registry data is a valid tool to evaluate treatment effectiveness in MS.
期刊介绍：
The Journal of Neurology, Neurosurgery & Psychiatry (JNNP) aspires to publish groundbreaking and cutting-edge research worldwide. Covering the entire spectrum of neurological sciences, the journal focuses on common disorders like stroke, multiple sclerosis, Parkinson’s disease, epilepsy, peripheral neuropathy, subarachnoid haemorrhage, and neuropsychiatry, while also addressing complex challenges such as ALS. With early online publication, regular podcasts, and an extensive archive collection boasting the longest half-life in clinical neuroscience journals, JNNP aims to be a trailblazer in the field.
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