Dataset Information

External validity of docetaxel triplet trials in advanced gastric cancer: are there patients who still benefit?

ABSTRACT:

Background

The purpose of our study was to develop an online calculator to estimate the effect of docetaxel triplets (DPF) in first line of advanced gastric cancer (AGC), and to assess the external validity of docetaxel trials in individual patients.

Methods

The study includes patients with HER2(-) AGC treated with platin and fluoropyrimidine (PF) or with DPF in first line. Treatment effect and interactions were assessed using Bayesian accelerated failure time models.

Result

The series comprises 1376 patients; 238 treated with DPF and 1138 with PF between 2008 and 2019. DPF was associated with increased progression-free survival (PFS) and overall survival (OS) with time ratio (TR) 1.27 (95% credible interval [CrI], 1.15-1.40), and TR 1.19 (95% CrI, 1.09-1.27), respectively. Serious adverse events were more common with DPF, particularly hematological effects (32% vs 22%). Younger participants received greater DPF dose density without achieving greater disease control, while severe toxicity was likewise higher. DPF yielded superior OS in Lauren intestinal (TR 1.27, 95% CrI, 1.08-1.11) vs diffuse subtype (TR 1.17, 95% CrI, 1.09-1.24) and the probability of increasing OS?>?15% was 90% vs 67% in each subtype, respectively. The effect dwindles over time, which can be attributed to pathological changes and clinical practice changes.

Conclusion

Our study confirms the effect of DPF is highly dependent on several clinical-pathological variables, with discreet and gradually declining benefit over platinum doublets in later years, at the expense of increased toxicity. These results may help to underpin the idea that external validity of AGC trials should be revised regularly.

SUBMITTER: Jimenez-Fonseca P

PROVIDER: S-EPMC7902567 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

External validity of docetaxel triplet trials in advanced gastric cancer: are there patients who still benefit?

Jimenez-Fonseca Paula P Carmona-Bayonas Alberto A Martínez de Castro Eva E Custodio Ana A Pericay Pijaume Carles C Hernandez Raquel R Aguado Gema G Castro Unanua Natalia N Cano Juana María JM López Flora F Garrido Marcelo M Fernández Montes Ana A Visa Laura L Sánchez Cánovas Manuel M Limón María Luisa ML Martínez Lago Nieves N Pimentel Paola P Hurtado Alicia A Azkárate Aitor A Longo Federico F Diez Marc M Arias-Martinez Aranzazu A Sauri Tamara T Martín Carnicero Alfonso A Mangas Monserrat M Martín Richard Marta M Granja Mónica M Ramchandani Avinash A Hernández Pérez Carolina C Cerdá Paula P Gil-Negrete Aitziber A Calvo Mariona M Vidal Tocino Rosario R Gallego Javier J

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 20200924 2

<h4>Background</h4>The purpose of our study was to develop an online calculator to estimate the effect of docetaxel triplets (DPF) in first line of advanced gastric cancer (AGC), and to assess the external validity of docetaxel trials in individual patients.<h4>Methods</h4>The study includes patients with HER2(-) AGC treated with platin and fluoropyrimidine (PF) or with DPF in first line. Treatment effect and interactions were assessed using Bayesian accelerated failure time models.<h4>Result</h ...[more]

PMID: 32970266

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Project description:ObjectivesTo assess aspects of the internal validity of recently published cluster randomised trials and explore the reporting of information useful in assessing the external validity of these trials.DesignReview of 34 cluster randomised trials in primary care published in 2004 and 2005 in seven journals (British Medical Journal, British Journal of General Practice, Family Practice, Preventive Medicine, Annals of Internal Medicine, Journal of General Internal Medicine, Pediatrics).Data sourcesNational Library of Medicine (Medline) via PubMed.Data extractionTo assess aspects of internal validity we extracted data on appropriateness of sample size calculations and analyses, methods of identifying and recruiting individual participants, and blinding. To explore reporting of information useful in assessing external validity we extracted data on cluster eligibility, cluster inclusion and retention, cluster generalisability, and the feasibility and acceptability of the intervention to health providers in clusters.Results21 (62%) trials accounted for clustering in sample size calculations and 30 (88%) in the analysis; about a quarter were potentially biased because of procedures surrounding recruitment and identification of patients; individual participants were blind to allocation status in 19 (56%) and outcome assessors were blind in 15 (44%). In almost half the reports, information relating to generalisability of clusters was poorly reported, and in two fifths there was no information about the feasibility and acceptability of the intervention.ConclusionsCluster randomised trials are essential for evaluating certain types of interventions. Issues affecting their internal validity, such as appropriate sample size calculations and analysis, have been widely disseminated and are now better addressed by researchers. Blinding of those identifying and recruiting patients to allocation status is recommended but is not always carried out. There may be fewer barriers to internal validity in trials in which individual participants are not recruited. External validity seems poorly addressed in many trials, yet is arguably as important as internal validity in judging quality as a basis for healthcare intervention.

Project description:BACKGROUND: Controlled clinical trials of health care interventions are either explanatory or pragmatic. Explanatory trials test whether an intervention is efficacious; that is, whether it can have a beneficial effect in an ideal situation. Pragmatic trials measure effectiveness; they measure the degree of beneficial effect in real clinical practice. In pragmatic trials, a balance between external validity (generalizability of the results) and internal validity (reliability or accuracy of the results) needs to be achieved. The explanatory trial seeks to maximize the internal validity by assuring rigorous control of all variables other than the intervention. The pragmatic trial seeks to maximize external validity to ensure that the results can be generalized. However the danger of pragmatic trials is that internal validity may be overly compromised in the effort to ensure generalizability. We are conducting two pragmatic randomized controlled trials on interventions in the management of hypertension in primary care. We describe the design of the trials and the steps taken to deal with the competing demands of external and internal validity. DISCUSSION: External validity is maximized by having few exclusion criteria and by allowing flexibility in the interpretation of the intervention and in management decisions. Internal validity is maximized by decreasing contamination bias through cluster randomization, and decreasing observer and assessment bias, in these non-blinded trials, through baseline data collection prior to randomization, automating the outcomes assessment with 24 hour ambulatory blood pressure monitors, and blinding the data analysis. SUMMARY: Clinical trials conducted in community practices present investigators with difficult methodological choices related to maintaining a balance between internal validity (reliability of the results) and external validity (generalizability). The attempt to achieve methodological purity can result in clinically meaningless results, while attempting to achieve full generalizability can result in invalid and unreliable results. Achieving a creative tension between the two is crucial.

Dataset Information

External validity of docetaxel triplet trials in advanced gastric cancer: are there patients who still benefit?

Background

Methods

Result

Conclusion

Publications

External validity of docetaxel triplet trials in advanced gastric cancer: are there patients who still benefit?

Similar Datasets

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