ESMO Guidance for Reporting Oncology real-World evidence (GROW)

Annals of Oncology, Год журнала: 2023, Номер 34(12), С. 1097 - 1112

Опубликована: Окт. 15, 2023

Язык: Английский

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Effectively Leveraging RWD for External Controls: A Systematic Literature Review of Regulatory and HTA Decisions

Clinical Pharmacology & Therapeutics, Год журнала: 2023, Номер 114(2), С. 325 - 355

Опубликована: Апрель 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.

Язык: Английский

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ESMO Guidance for Reporting Oncology real-World evidence (GROW)

ESMO Real World Data and Digital Oncology, Год журнала: 2023, Номер 1, С. 100003 - 100003

Опубликована: Ноя. 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.

Язык: Английский

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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

The International Journal of Neuropsychopharmacology, Год журнала: 2024, Номер 27(2)

Опубликована: Фев. 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

Язык: Английский

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The Next Horizon of Drug Development: External Control Arms and Innovative Tools to Enrich Clinical Trial Data

Therapeutic Innovation & Regulatory Science, Год журнала: 2024, Номер 58(3), С. 443 - 455

Опубликована: Март 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.

Язык: Английский

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Enriching single-arm clinical trials with external controls: possibilities and pitfalls

Blood Advances, Год журнала: 2022, Номер 7(19), С. 5680 - 5690

Опубликована: Дек. 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.

Язык: Английский

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Augmenting randomized clinical trial data with historical control data: Precision medicine applications

JNCI Journal of the National Cancer Institute, Год журнала: 2022, Номер 115(1), С. 14 - 20

Опубликована: Сен. 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.

Язык: Английский

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Framework for the Use of External Controls to Evaluate Treatment Outcomes in Precision Oncology Trials

JCO Precision Oncology, Год журнала: 2024, Номер 8

Опубликована: Янв. 8, 2024

Advances in genomics have enabled anticancer therapies to be tailored target specific genomic alterations. Single-arm trials (SATs), including those incorporated within umbrella, basket, and platform trials, are widely adopted when it is not feasible conduct randomized controlled rare biomarker-defined subpopulations. External controls (ECs), defined as control arm data derived outside the clinical trial, gained renewed interest a strategy supplement evidence generated from SATs allow comparative analysis. There increasing examples demonstrating application of EC precision oncology trials. The prospective conducting studies associated with distinct methodological challenges, considerations for use subpopulations been adequately discussed, formal framework yet established. In this review, we present analysis using EC. Key steps (1) defining purpose address study question, (2) determining if external fit purpose, (3) developing transparent protocol statistical plan, (iv) interpreting results drawing conclusions on basis prespecified hypothesis. We specify required subpopulations, which include specifying comparator biomarker status group, lines treatment, assessment testing panels used, (4) cohort stratification tumor-agnostic studies. further discuss novel trial designs techniques leveraging propose future directions advance generation facilitate drug development oncology.

Язык: Английский

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The Swedish initiative for the study of Primary sclerosing cholangitis (SUPRIM)

EClinicalMedicine, Год журнала: 2024, Номер 70, С. 102526 - 102526

Опубликована: Март 11, 2024

BackgroundDespite more than 50 years of research and parallel improvements in hepatology oncology, there is still today neither a treatment to prevent disease progression primary sclerosing cholangitis (PSC), nor reliable early diagnostic tools for the associated hepatobiliary cancers. Importantly, limited understanding underlying biological mechanisms PSC its natural history not only affects identification new drug targets but implies lack surrogate markers that hampers design clinical trials evaluation efficacy. The easy access large representative well-characterised prospective resources an important contributing factor current situation.MethodsWe here present SUPRIM cohort, national multicentre longitudinal study unselected patients capturing diversity phenotypes. We describe 10-year effort inclusion follow-up, intermediate analysis report including original results, resource. All included gave written informed consent (recruitment: November 2011–April 2016).FindingsOut 512 patients, 452 completed five-year follow-up without endpoint outcomes. Liver transplantation was performed 54 (10%) malignancy diagnosed 15 (3%). draw comprehensive landscape multidimensional heterogeneity illustrating Performances available predictive scores are compared perspectives on continuation cohort provided.InterpretationWe envision as open-access collaborative resource accelerate generation knowledge independent validations promising ones with aim uncover diagnostics, prognostic tools, markers, by 2040.FundingThis work supported Swedish Cancer Society, Stockholm County Council, Research Funds Radiumhemmet.

Язык: Английский

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Comparison of Synthetic Data Generation Techniques for Control Group Survival Data in Oncology Clinical Trials: Simulation Study

JMIR Medical Informatics, Год журнала: 2024, Номер 12, С. e55118 - e55118

Опубликована: Май 8, 2024

Synthetic patient data (SPD) generation for survival analysis in oncology trials holds significant potential accelerating clinical development. Various machine learning methods, including classification and regression trees (CART), random forest (RF), Bayesian network (BN), conditional tabular generative adversarial (CTGAN), have been used this purpose, but their performance reflecting actual remains under investigation.

Язык: Английский

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