Utilization of anonymization techniques to create an external control arm for clinical trial data DOI Creative Commons
Juha Mehtälä, Mehreen Ali, Timo Miettinen

et al.

BMC Medical Research Methodology, Journal Year: 2023, Volume and Issue: 23(1)

Published: Nov. 4, 2023

Subject-level real-world data (RWD) collected during daily healthcare practices are increasingly used in medical research to assess questions that cannot be addressed the context of a randomized controlled trial (RCT). A novel application RWD arises from need create external control arms (ECAs) for single-arm RCTs. In analysis ECAs against RCT data, there is an evident manage and analyze same technical environment. Nordic countries, legal requirements may require original subject-level anonymized, i.e., modified so risk identify any individual minimal. The aim this study was conduct initial exploration on how well pseudonymized anonymized perform creation ECA RCT.This hybrid observational cohort using clinical arm completed phase II (PACIFIC-AF) Finnish sources. were within (k, ε)-anonymity framework (a model protecting individuals identification). Propensity score matching weighting methods applied RWD, balance potential confounders data. Descriptive statistics overall survival analyses conducted prior after weighting, both sets.Anonymization affected baseline characteristics only marginally. greatest difference prevalence chronic obstructive pulmonary disease (4.6% vs. 5.4% compared respectively). Moreover, changed anonymization by 8% (95% CI 4-22%). Both able produce matched Anonymization impacted 22% -21-87%).Anonymization viable technique cases where flexible transfer sharing required. As necessarily affects some aspects further careful consideration strategies needed.

Language: Английский

ESMO Guidance for Reporting Oncology real-World evidence (GROW) DOI Creative Commons
Luis Castelo‐Branco, Anna Pellat, Diogo Martins-Branco

et al.

Annals of Oncology, Journal Year: 2023, Volume and Issue: 34(12), P. 1097 - 1112

Published: Oct. 15, 2023

Language: Английский

Citations

104
Effectively Leveraging RWD for External Controls: A Systematic Literature Review of Regulatory and HTA Decisions DOI Creative Commons
Oriol Solà-Morales, Lesley H. Curtis, Julien Heidt

et al.

Clinical Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 114(2), P. 325 - 355

Published: April 20, 2023

Real‐world data (RWD)‐derived external controls can be used to contextualize efficacy findings for investigational therapies evaluated in uncontrolled trials. As the number of submissions regulatory and health technology assessment (HTA) bodies using rises, light recent HTA guidance on appropriate use RWD, there is a need address operational methodological challenges impeding quality real‐world evidence (RWE) generation consistency evaluation RWE across agencies. This systematic review summarizes publicly available information outcomes from trials all indications January 1, 2015, through August 20, 2021, that were submitted European Medicines Agency, US Food Drug Administration, and/or select major (National Institute Health Care Excellence (NICE), Haute Autorité de Santé (HAS), Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG), Gemeinsamer Bundesausschuss (G‐BA)). By systematically reviewing context guidance, this study provides quantitative qualitative insights into how control design analytic choices may viewed by different agencies practice. The primary aspects identified discussion include, but are not limited to, engagement regulators bodies, approaches handling missing (a component quality), selection endpoints. Continued collaboration these other will inform assist stakeholders attempting generate controls.

Language: Английский

Citations

19
ESMO Guidance for Reporting Oncology real-World evidence (GROW) DOI Creative Commons
Luis Castelo‐Branco, Anna Pellat, Diogo Martins-Branco

et al.

ESMO Real World Data and Digital Oncology, Journal Year: 2023, Volume and Issue: 1, P. 100003 - 100003

Published: Nov. 1, 2023

•Real-world evidence in oncology is evolving rapidly with many particularities.•This guidance provides key recommendations for reporting real-world studies oncology.•Recommendations are based on a review of current and the authors' collective expert opinion.•Authors multidisciplinary group experts from different institutions countries.•Guidance provided full article development, including title, introduction, methods, results, discussion, conclusion.

Language: Английский

Citations

18
Relapse Rates With Paliperidone Palmitate in Adult Patients With Schizophrenia: Results for the 6-Month Formulation From an Open-label Extension Study Compared to Real-World Data for the 1-Month and 3-Month Formulations DOI Creative Commons
Ibrahim Turkoz, Mehmet Daskiran,

Uzma Nasim Siddiqui

et al.

The International Journal of Neuropsychopharmacology, Journal Year: 2024, Volume and Issue: 27(2)

Published: Feb. 1, 2024

Abstract Background The 3 paliperidone palmitate (PP) long-acting injectable antipsychotic formulations, PP 1-month (PP1M), 3-month (PP3M), and 6-month (PP6M), have shown to reduce the risk of relapse in schizophrenia. current phase-4 study constructed external comparator arms (ECAs) using real-world data for PP3M PP1M compared prevention rates with PP6M from an open-label extension (OLE) adult patients Methods were derived a single-arm, 24-month, OLE (NCT04072575), which included schizophrenia who completed 12-month randomized, double-blind, noninferiority, phase-3 (NCT03345342) without relapse. Patients ECAs identified IBM® MarketScan® Multistate Medicaid Database based on similar eligibility criteria as cohort. Results A total 178 each cohort following propensity score matching. Most men (>70%; mean age: 39–41 years). Time (primary analysis Kaplan-Meier estimates) was significantly delayed (P < .001, log-rank test). rate lower (3.9%) vs (20.2%) (29.8%) cohorts. Risk decreased .001) by 82% (HR = 0.18 [95% CI 0.08 0.40]), 89% 0.11 [0.05 0.25]), 35% 0.65 [0.42 0.99]; P .043). Sensitivity confirmed findings primary analysis. Although matched mimic characteristics cohort, heterogeneity between groups could exist due factors including prior participation, unmeasured confounders, variations capture quality, completeness clinical information. Conclusions In trial setting, time demonstrated treatments settings among Trial registration ClinicalTrials.gov Identifier: NCT04072575; EudraCT number: 2018-004532-30

Language: Английский

Citations

6
Enriching single-arm clinical trials with external controls: possibilities and pitfalls DOI Creative Commons
Jérôme Lambert, Étienne Lengliné, Raphaël Porcher

et al.

Blood Advances, Journal Year: 2022, Volume and Issue: 7(19), P. 5680 - 5690

Published: Dec. 19, 2022

For the past decade, it has become commonplace to provide rapid answers and early patient access innovative treatments in absence of randomized clinical trials (RCT), with benefits estimated from single-arm trials. This trend is important oncology, notably when assessing new targeted therapies. Some those uncontrolled further include an external/synthetic control group as way indirect comparison a pertinent group. We aimed some guidelines comprehensive tool for (1) critical appraisal comparisons or (2) performing trial. used example ciltacabtagene autoleucel treatment adult patients relapsed refractory multiple myeloma after 3 more lines illustrative example. propose 3-step guidance. The first step includes definition estimand, which encompasses effect population (whole restricted trial external controls), reflecting question. second relies on adequate selection controls previous RCTs real-world data cohorts, registries, electronic files. third consists choosing statistical approach targeting defined above depends available (individual-level aggregated data). validity derived heavily careful methodological considerations included proposed procedure. Because level evidence well-conducted RCT cannot be guaranteed, evaluation than standard settings.

Language: Английский

Citations

21
The Next Horizon of Drug Development: External Control Arms and Innovative Tools to Enrich Clinical Trial Data DOI Creative Commons
Kelly H. Zou,

Chelsea Vigna,

Aniketh Talwai

et al.

Therapeutic Innovation & Regulatory Science, Journal Year: 2024, Volume and Issue: 58(3), P. 443 - 455

Published: March 25, 2024

Abstract Conducting clinical trials (CTs) has become increasingly costly and complex in terms of designing operationalizing. These challenges exist running CTs on novel therapies, particularly oncology rare diseases, where target narrower patient groups. In this study, we describe external control arms (ECA) other relevant tools, such as virtualization decentralized (DCTs), the ability to follow trial subjects real world using tokenization. ECAs are typically constructed by identifying appropriate sources data, then cleaning standardizing it create an analysis-ready data file, finally, matching with CT interest. addition, ECA tools also include subject-level meta-analysis simulated subjects’ for analyses. By implementing recent advances digital health technologies devices, virtualization, DCTs, realigning from site-centric designs virtual, decentralized, patient-centric can be done, which reduces burden participate encourages diversity. Tokenization technology allows linking real-world (RWD), creating more comprehensive longitudinal outcome measures. provide robust ways enrich informed decision-making, reduce costs operations, augment insights gained data.

Language: Английский

Citations

4
Augmenting randomized clinical trial data with historical control data: Precision medicine applications DOI Creative Commons
Boris Freidlin, Edward L. Korn

JNCI Journal of the National Cancer Institute, Journal Year: 2022, Volume and Issue: 115(1), P. 14 - 20

Published: Sept. 26, 2022

Abstract As precision medicine becomes more precise, the sizes of molecularly targeted subpopulations become increasingly smaller. This can make it challenging to conduct randomized clinical trials therapies in a timely manner. To help with this problem small patient subpopulation, study design that is frequently proposed trial (RCT) intent augmenting RCT control arm data historical from set patients who have received treatment outside (historical data). In particular, strategies been developed compare outcomes across cohorts treated standard (control) guide use analysis; lessen potential well-known biases using controls without any randomization. Using some simple examples and completed studies, we demonstrate commentary these are unlikely be useful applications.

Language: Английский

Citations

15
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

et al.

Value in Health, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

Citations

3
rdborrow: an R package for causal inference incorporating external controls in randomized controlled trials with longitudinal outcomes DOI
Lei Shi, Herbert Pang, Chen Chen

et al.

Journal of Biopharmaceutical Statistics, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 24

Published: April 28, 2025

Randomized controlled trials (RCTs) are considered the gold standard for treatment effect evaluation in clinical development. However, designing and analyzing RCTs poses many challenges such as how to ensure validity improve power hypothesis testing with a limited sample size or account crossover allocation. One promising approach circumvent these problems is incorporate external controls from additional data sources. This manuscript introduces new R package called rdborrow, which implements several control borrowing methods under causal inference framework facilitate design analysis of longitudinal outcomes. More concretely, our provides an Analysis module, weighting proposed Zhou et al. (2024), well difference-in-differences synthetic (2024) borrowing. Meanwhile, features Simulation module can be used simulate trial study implementation, evaluate performance different estimators, conduct analysis. In reproducible code examples, we generate simulated sets mimicking real illustrate process users follow simulation based on randomized incorporating data.

Language: Английский

Citations

0
Keeping the End in Mind: Reviewing U.S. FDA Inspections of Submissions including Real-World Data DOI Creative Commons

Cheryl Grandinetti,

Donna R. Rivera,

Lee H. Pai-Scherf

et al.

Therapeutic Innovation & Regulatory Science, Journal Year: 2025, Volume and Issue: unknown

Published: May 24, 2025

Abstract The increasing use of real-world data (RWD) to generate evidence (RWE) presents unique opportunities and challenges for drug development regulatory decision-making, particularly in the area good clinical practice inspections. FDA typically focuses their application review-based inspections on pivotal studies that submitted support new biological product applications. This focus applies regardless sources used those studies. In this article, we discuss fundamental role verifying quality, integrity, reliability RWD submissions. Through case examples, highlight specific related accessing source records, assessing evaluating processes curation, transformation, analysis. Our experience underscores importance early engagement with agencies as well implementation robust quality management practices throughout study lifecycle. As continues shape landscape, these examples provide insights navigating complexities associated submissions utilizing RWE approval.

Language: Английский

Citations

0