The impact of different censoring methods for analyzing survival using real-world data with linked mortality information: a simulation study DOI Creative Commons

Wei‐Chun Hsu,

Aaron Crowley, Craig S. Parzynski

и другие.

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Окт. 5, 2023

Abstract Background Evaluating outcome reliability is critical in real-world evidence studies. Overall survival a common clinical these studies; however, its capture data sources incomplete and often supplemented with linked mortality information from external sources. There are conflicting recommendations for censoring overall We conducted simulation study to understand the impact of different methods on estimating median log hazard ratios when not fully captured. Methods used Monte Carlo emulate non-randomized comparative effectiveness two treatments electronic health records data. simulated time death, last database activity cutoff. attributed death events after randomly set them missing reflect sensitivity specificity contemporary Two schemes were evaluated: (1) censor at date without an observed (2) end availability (data cutoff). bias, coverage, rejection rate assess performance each method under varying amounts treatment effects, length follow-up, sample size. Results When was captured, estimates unbiased cutoff underestimated activity. missing, survival, while overestimated it. As increased, bias decreased increased data-off. Conclusions Researchers should completeness choosing how analysis using Substantial can occur if inappropriate scheme selected. advocate providers perform validation studies their publish findings inform methodological decisions better.

Язык: Английский

PMDA Perspective on Use of Real‐World Data and Real‐World Evidence as an External Control: Recent Examples and Considerations DOI Creative Commons
Junichi Asano,

Hajime Sugano,

Hiroyuki Murakami

и другие.

Clinical Pharmacology & Therapeutics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 3, 2025

Recent discussions about the utilization of real-world data (RWD) and evidence (RWE) have been more focused on drug development for regulatory approval rather than during post-marketing stage. In Japan, RWD/RWE practically utilized as an external control approval. Most cases were related to orphan diseases where feasibility conducting randomized controlled clinical trials was generally low. The provides additional information that can support review However, many points should be taken into consideration through all stages a study is based RWD/RWE, including planning, analysis, interpretation. this article, we present our recent experience focusing efficacy evaluations with submitted part new applications in describe evaluation Points described article promote appropriate facilitate proper discussion PMDA. Further accumulation PMDA will enhance knowledge contribute better decision making approvals RWD/RWE.

Язык: Английский

Процитировано

1
External Controls to Study Treatment Effects in Rare Diseases: Challenges and Future Directions DOI
Janick Weberpals, Shirley Wang

Clinical Pharmacology & Therapeutics, Год журнала: 2024, Номер unknown

Опубликована: Сен. 17, 2024

Regulators increasingly rely on real‐world evidence generated from routine‐care health data to evaluate novel therapies. Particularly, external control arms are used supplement and contextualize efficacy safety claims of single arm clinical trials for rare disease However, there a number methodological issues that may affect the validity results derived such comparisons. In this mini‐review, we briefly summarize frequently approaches outline some most important criticisms paths forward.

Язык: Английский

Процитировано

5
Analytical Methods for Comparing Uncontrolled Trials with External Controls from Real-World Data: a Systematic Literature Review and Comparison to European Regulatory and Health Technology Assessment Practice DOI Creative Commons
Milou A. Hogervorst, Kanaka V Soman, Helga Gardarsdóttir

и другие.

Value in Health, Год журнала: 2024, Номер unknown

Опубликована: Сен. 1, 2024

Язык: Английский

Процитировано

3
Comparability of external and internal control patients for the prospective randomized HOVON‐103 trial in older AML patients DOI Creative Commons
Sjoerd J. F. Hermans, Jurjen Versluis, Erik van Werkhoven

и другие.

British Journal of Haematology, Год журнала: 2025, Номер unknown

Опубликована: Май 26, 2025

Summary Real‐world data (RWD) previously contributed to post‐marketing regulatory decision‐making, but are currently also considered as external controls single‐arm trials. The use of RWD control may be compromised by methodological issues, urging validation cohorts. Two cohorts newly diagnosed acute myeloid leukaemia patients, one registered the HARMONY Alliance (HA) and Netherlands Cancer Registry (NCR), were compared arm randomized HOVON‐103 trial (H103 controls). All aged >65 years with a WHO performance score 0–2 (or missing), received standard induction chemotherapy. 1:1 propensity calliper matching (PSM) was applied improve comparability, overall (OS) relapse‐free survival (RFS) assessed. Fewer elements available in H103 controls, specifically NCR cohort. Baseline characteristics differed from controls; missing more frequent predominantly concerned score. After PSM, HA patients demonstrated non‐significantly different OS RFS at 2 (26 ± 4% vs. 31 5%, p = 0.59; 24 5% 30 6%, 0.52), while had 12% lower (28 40 4%, 0.21). Validation is needed before incorporating into comparative analyses, data, comorbidities, residual confounding limit comparability.

Язык: Английский

Процитировано

0
Application of the target trial emulation framework to external comparator studies DOI Creative Commons
Kellyn F Arnold,

Luis Antunes,

Briana Coles

и другие.

Frontiers in Drug Safety and Regulation, Год журнала: 2024, Номер 4

Опубликована: Апрель 11, 2024

External comparator (EC) studies are increasingly being used to generate evidence that supports the evaluation of emerging pharmacological treatments for regulatory and health technology assessment (HTA) purposes. However, reliability generated from EC can vary. In this paper, we outline how an existing framework causal inference, target trial emulation (TTE) framework, be appropriately applied improve design analysis studies. Applying TTE involves specifying protocol ideal which would answer question interest, then emulating its key elements under real-world (RW) settings. We describe each component original explain it studies, supplemented with practical recommendations. also highlight special considerations limitations in applying clarity, transparency,

Язык: Английский

Процитировано

3
Generalizability in real‐world trials DOI Creative Commons
Anatol‐Fiete Näher, Marvin Kopka, Felix Balzer

и другие.

Clinical and Translational Science, Год журнала: 2024, Номер 17(7)

Опубликована: Июль 1, 2024

Abstract Real‐world evidence (RWE) trials have a key advantage over conventional randomized controlled (RCTs) due to their potentially better generalizability. High generalizability of study results facilitates new biological insights and enables targeted therapeutic strategies. Random sampling RWE trial participants is regarded as the gold standard for Additionally, use sample correction procedures can increase results, even when using nonrandomly sampled real‐world data (RWD). This presents descriptive on extent which design currently planned or already conducted takes into account. It also examines whether random correcting nonrandom samples are considered. Based text mining publicly available metadata provided during registrations clinicaltrials.gov, EU‐PAS, OSF‐RWE registry, it shown that share with information increased from 65.27% in 2002 97.43% 2022, corresponding 14.79% 28.30% samples. For samples, there an 0.00% 0.95% used. We conclude potential benefits RWD terms generalizing not yet being fully realized.

Язык: Английский

Процитировано

3
EU HTA Joint Clinical Assessment: are patients with rare disease going to lose out? DOI Creative Commons
Alejandra Castañón,

Rebecca Sloan,

Luisamanda Selle Arocha

и другие.

Journal of Comparative Effectiveness Research, Год журнала: 2024, Номер 13(6)

Опубликована: Май 2, 2024

Язык: Английский

Процитировано

2
Enhancing External Control Arm Analyses through Data Calibration and Hybrid Designs DOI
Sebastian Schneeweiß

Clinical Pharmacology & Therapeutics, Год журнала: 2024, Номер unknown

Опубликована: Июль 2, 2024

Almost all external control arm analyses to contextualize findings of a single trial struggle with two key issues: the lack baseline randomization, and equally important, difference in data collection between experimental its primary collection, using secondary data. We illustrate calibration design remedy issues arising from differential measurements arms, discuss hybrid that expands an underpowered randomized internal real-world mitigate randomization arm. show how approaches fit into evidence-development strategy naturally builds on incremental insights gained.

Язык: Английский

Процитировано

2
A Framework for the Use and Likelihood of Regulatory Acceptance of Single-Arm Trials DOI Creative Commons

Disha Subramaniam,

Colin Anderson‐Smits, Rebecca Rubinstein

и другие.

Therapeutic Innovation & Regulatory Science, Год журнала: 2024, Номер 58(6), С. 1214 - 1232

Опубликована: Сен. 16, 2024

Single-arm clinical trials (SAT) are common in drug and biologic submissions for rare or life-threatening conditions, especially when no therapeutic options exist. External control arms (ECAs) improve interpretation of SATs but pose methodological regulatory challenges.

Язык: Английский

Процитировано

2
Regulatory and HTA Considerations for Development of Real‐World Data Derived External Controls DOI Creative Commons
Lesley H. Curtis, Oriol Solà-Morales, Julien Heidt

и другие.

Clinical Pharmacology & Therapeutics, Год журнала: 2023, Номер 114(2), С. 303 - 315

Опубликована: Апрель 20, 2023

Regulators and Health Technology Assessment (HTA) bodies are increasingly familiar with, publishing guidance on, external controls derived from real-world data (RWD) to generate evidence (RWE). We recently conducted a systematic literature review (SLR) evaluating publicly available information on the use of RWD-derived contextualize outcomes uncontrolled trials submitted European Medicines Agency (EMA), US Food Drug Administration (FDA), and/or select HTA bodies. The identified several key operational methodological aspects for which more detailed alignment within between regulatory agencies is necessary. This paper builds SLR findings by delineating set takeaways responsible generation fit-for-purpose RWE. Practical guidelines designing, conducting, reporting control studies explored discussed. These considerations include: (i) early engagement with regulators during study planning phase; (ii) consideration appropriateness comparability across multiple dimensions, including eligibility criteria, temporality, population representation, clinical evaluation; (iii) ensuring adequate sample sizes, hypothesis testing considerations; (iv) implementation clear transparent strategy assessing addressing quality, missingness RWD; (v) selection comparable meaningful endpoints that operationalized analyzed using appropriate analytic methods; (vi) conduct sensitivity analyses assess robustness in context uncertainty sources potential bias.

Язык: Английский

Процитировано

5