A safety estimand for late phase clinical trials where the analysis period varies over the subjects.
Background/Aims: Evaluating safety is as important as evaluating efficacy in a clinical trial, yet the tradition for safety analysis is rudimentary. This article explores more complex methodologies for safety evaluation, with the aim of improving the interpretability, as well as generalizability, of...
| Publicado en: | Clinical Trials Vol. 21; no. 4; pp. 483 - 491 |
|---|---|
| Autores principales: | , , |
| Formato: | tables/charts Journal Article |
| Publicado: |
Sage Publications, Ltd.
Aug2024
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=178879720&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 178879720 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 17407745 AB6 jtl: Clinical Trials issn: 17407745 maglogo: N pubinfo: dt: Aug2024 vid: 21 iid: 4 pid: 33180 pub: Sage Publications, Ltd. place: <Blank> artinfo: ui: 178879720 175742687 178879720 178879720 10.1177/17407745241230933 178879720 ppf: 483 ppct: 8 formats: tig: atl: A safety estimand for late phase clinical trials where the analysis period varies over the subjects. aug: au: Hedman, Katarina Lisovskaja, Vera Nyström, Per affil: Biometrics, Late-stage Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca Gothenburg, Mölndal, Sweden sug: subj: Clinical Trials Research Subjects Patient Safety Evaluation Research Methodology Quality Improvement Data Analysis, Statistical Conceptual Framework Adverse Drug Event Risk Factors Cardiovascular Diseases Metabolic Diseases Treatment Termination Kaplan-Meier Estimator ab: Background/Aims: Evaluating safety is as important as evaluating efficacy in a clinical trial, yet the tradition for safety analysis is rudimentary. This article explores more complex methodologies for safety evaluation, with the aim of improving the interpretability, as well as generalizability, of the results. Methods: For studies where the analysis periods vary over the subjects, using the International Council for Harmonisation estimand framework, we construct a formal estimand that could be used in the setting of safety surveillance that answers the clinical question of 'What is the magnitude of the increase in risk of experiencing an adverse event if the treatment is taken, as prescribed, for a specific period of time?'. Estimation methodologies for this estimand are also discussed. Results: The proposed estimand is similar to that found in the efficacy analyses of time to event data (e.g. in outcome studies), with the key difference of utilization of hypothetical intercurrent event strategy for the intercurrent event of treatment discontinuation. This is motivated by what we perceive to be a key difference for the safety objective compared to efficacy objectives, namely a desire for sensitivity (i.e. greater possibility of detecting a negative impact of the drug, if such exists) as opposed to the need to prove a positive effect of the drug in a conservative manner. Conclusion: It is valuable, and possible, to use the International Council for Harmonisation estimand framework not only for efficacy but also for safety evaluation, with the estimand driven by an interpretable, and relevant, clinical question. pubtype: Academic Journal doctype: tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|