Emulation of a randomized controlled trial in ulcerative colitis with <scp>US</scp> and French claims data: Infliximab with thiopurines compared to infliximab monotherapy

Kirchgesner, Julien; Desai, Rishi; Schneeweiss, Maria C.; Beaugerie, Laurent; Kim, Seo Young; Schneeweiß, Sebastian

doi:10.1002/pds.5356

Cited by 7 publications

(23 citation statements)

References 21 publications

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“…The emulation of RCTs by RWE studies may help to calibrate an effectiveness outcome measurable in RWD that could be applied to other treatment comparisons within the same indication. Thus, we first developed an effectiveness outcome measure and a methodological approach for confounding adjustment, which allowed us to successfully replicate findings of the SONIC and the SUCCESS trials using the same databases included in this study 9 10. The same data and analytic framework were applied in this study.…”

Section: Methodsmentioning

confidence: 99%

“…Based on the previously emulated trials of SONIC and SUCCESS,9 10 we excluded patients with tuberculosis, opportunistic infections within the previous 6 months and patients with a previous history of cancer (excluding nonmelanoma skin cancer) any time prior. Since vedolizumab was only available in patients previously treated with or intolerant to anti-TNF in France during the study period and the majority of patients initiating vedolizumab are previously exposed to immunosuppressants,17 we could not limit the study to immunosuppressants and biologic-naïve patients.…”

Section: Methodsmentioning

confidence: 99%

“…In order to select patients treated with only thiopurines combined with vedolizumab, we excluded patients exposed to methotrexate within 60 days prior to cohort entry. Finally, the exclusion criteria related to IBD disease activity applied in the replicated trials of SONIC and SUCCESS were considered,9 10 to minimise differences regarding IBD disease activity across these studies. For both CD and UC cohorts, patients with an ostomy, stricture, abscess, abdominal surgery within the previous 6 months were excluded.…”

Section: Methodsmentioning

confidence: 99%

“…In the French databases, patients were considered as being exposed to thiopurines for 1 month following delivery, as thiopurines are dispensed by French pharmacies, which are authorised to deliver 1-month supply of treatment. These definitions were previously used 9 10 15 19…”

Section: Methodsmentioning

confidence: 99%

“…In the absence of RCT evidence, real-world evidence (RWE) derived from real-world data (RWD) can provide valuable information on treatment effectiveness based on the head-to-head comparison 8. We recently successfully conducted an RWD cohort study in the USA and French claims databases and replicated the findings of the SONIC and SUCCESS trials for the effectiveness of infliximab and thiopurines compared with infliximab monotherapy by emulating the RCTs as closely as possible 9 10. This highlights the opportunities of principled RWE analysis by emulating RCT designs to study treatment effectiveness in patients with IBD in clinical practice when corresponding RCT data are lacking 11 12…”

Section: Introductionmentioning

confidence: 99%

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Decreased risk of treatment failure with vedolizumab and thiopurines combined compared with vedolizumab monotherapy in Crohn’s disease

Kirchgesner

Desai

Schneeweiss

et al. 2022

Gut

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ObjectiveWhile infliximab combined to thiopurines is more effective than infliximab monotherapy in patients with Crohn’s disease (CD) and UC, the impact of adding thiopurines to vedolizumab remains controversial. We emulated two target trials comparing the effectiveness of combination therapy versus vedolizumab monotherapy in CD and UC.DesignBased on two US and the French nationwide healthcare databases, patients with CD and UC who initiated vedolizumab were identified. The study methodology, including confounding adjustment and outcome definitions, were previously validated in successful emulations of the SONIC and SUCCESS trials. Risk ratios for treatment failure based on hospitalisation or surgery related to disease activity, treatment switch, or prolonged corticosteroids use, were estimated after 1:1 propensity score (PS) matching.ResultsAmong a total of 10 299 vedolizumab users, 804 CD and 1088 UC pairs of combination therapy versus vedolizumab monotherapy users were PS matched. Treatment failure occurred at week 26 in 236 (29.3%) and 376 (34.3%) patients with CD and at week 16 in 236 (21.7%) and 263 (24.2%) patients with UC initiating combination therapy and vedolizumab monotherapy, respectively. The risk of treatment failure was decreased with combination therapy compared with vedolizumab monotherapy in CD (RR 0.85, 95% CI: 0.74 to 0.98) and to a lesser extent in UC (RR 0.90, 95% CI: 0.77 to 1.05). Findings were consistent across databases.ConclusionUsing validated methodologies, combination therapy with vedolizumab and thiopurines was associated with lower treatment failure compared with vedolizumab monotherapy in CD but not UC across the USA and France.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Decreased risk of treatment failure with vedolizumab and thiopurines combined compared with vedolizumab monotherapy in Crohn’s disease

Kirchgesner

Desai

Schneeweiss

et al. 2022

Gut

Self Cite

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Reporting of Observational Studies Explicitly Aiming to Emulate Randomized Trials

Hansford,

Cashin,

Jones

et al. 2023

JAMA Netw Open

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ImportanceObservational (nonexperimental) studies that aim to emulate a randomized trial (ie, the target trial) are increasingly informing medical and policy decision-making, but it is unclear how these studies are reported in the literature. Consistent reporting is essential for quality appraisal, evidence synthesis, and translation of evidence to policy and practice.ObjectiveTo assess the reporting of observational studies that explicitly aimed to emulate a target trial.Evidence ReviewWe searched Medline, Embase, PsycINFO, and Web of Science for observational studies published between March 2012 and October 2022 that explicitly aimed to emulate a target trial of a health or medical intervention. Two reviewers double-screened and -extracted data on study characteristics, key predefined components of the target trial protocol and its emulation (eligibility criteria, treatment strategies, treatment assignment, outcome[s], follow-up, causal contrast[s], and analysis plan), and other items related to the target trial emulation.FindingsA total of 200 studies that explicitly aimed to emulate a target trial were included. These studies included 26 subfields of medicine, and 168 (84%) were published from January 2020 to October 2022. The aim to emulate a target trial was explicit in 70 study titles (35%). Forty-three studies (22%) reported use of a published reporting guideline (eg, Strengthening the Reporting of Observational Studies in Epidemiology). Eighty-five studies (43%) did not describe all key items of how the target trial was emulated and 113 (57%) did not describe the protocol of the target trial and its emulation.Conclusion and RelevanceIn this systematic review of 200 studies that explicitly aimed to emulate a target trial, reporting of how the target trial was emulated was inconsistent. A reporting guideline for studies explicitly aiming to emulate a target trial may improve the reporting of the target trial protocols and other aspects of these emulation attempts.

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Arzneimittelepidemiologie und Arzneimittelverbrauchsforschung auf der Basis von Krankenkassendaten: zentrale Untersuchungsfragen und methodische Hinweise

Schubert

2022

Präv Gesundheitsf

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Zusammenfassung Hintergrund Seit Ende der 1970er-Jahren werden Arzneimitteldaten der Krankenkassen zur Darstellung der Entwicklung der Verbrauchsmengen und Kosten herangezogen. Ziel des Beitrags ist es, das Spektrum an Fragestellungen von Studien der Arzneimittelverbrauchsforschung und Pharmakoepidemiologie, die auf der Basis von Krankenkassendaten bearbeitet wurden, aufzuzeigen. Material und Methode Ausgangspunkt sind international referenzierte Publikationen (MEDLINE) seit 1975 mit Daten aus Deutschland, die in Bezug auf die bearbeiteten Fragestellungen, das gewählte Studiendesign und Methodik ausgewertet wurden. Ergebnisse Es werden die in 235 arzneimittelbezogenen Studien herangezogenen Datenprofile und Variablen skizziert sowie methodische Anforderungen bei der Nutzung von Arzneimitteldaten aufgezeigt. Bei deskriptiven Studien beziehen sich diese auf Aspekte der Datenquelle, der Festlegung der Studienpopulation und auf Fragen, die bei Nutzung der Arzneimitteldaten vorab zu klären sind. Bei analytischen Studien wird auf Besonderheiten hinsichtlich der Festlegung der Exposition, der Indikation und der Outcomes eingegangen sowie auf relevante Literatur zu Forschungsdesign und Kontrolle von Bias und Confoundern hingewiesen. Diskussion und Schlussfolgerung Studien zur Arzneimittelverbrauchsforschung wurden bislang vorwiegend auf den Datensätzen einzelner Krankenkasse durchgeführt. Eine Verbesserung der Datenlage könnte das im Aufbau befindliche Forschungsdatenzentrum Gesundheit des Bundesinstituts für Arzneimittel und Medizinprodukte (BfArM) mit Daten aller GKV-Versicherten bewirken, da dadurch krankenkassenspezifische Besonderheiten vermieden werden. Auch seltene Ereignisse, die große Datensätze erfordern, könnten auf diesem Datensatz untersucht werden. Eine Linkage mit anderen Datenquellen sollte vorgesehen werden.

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Emulation of a randomized controlled trial in ulcerative colitis with US and French claims data: Infliximab with thiopurines compared to infliximab monotherapy

Cited by 7 publications

References 21 publications

Decreased risk of treatment failure with vedolizumab and thiopurines combined compared with vedolizumab monotherapy in Crohn’s disease

Decreased risk of treatment failure with vedolizumab and thiopurines combined compared with vedolizumab monotherapy in Crohn’s disease

Reporting of Observational Studies Explicitly Aiming to Emulate Randomized Trials

Arzneimittelepidemiologie und Arzneimittelverbrauchsforschung auf der Basis von Krankenkassendaten: zentrale Untersuchungsfragen und methodische Hinweise

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