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Estimating Similarity of Dose-Response Relationships in Phase I Clinical Trials-Case Study in Bridging Data Package.

ABSTRACT: Bridging studies are designed to fill the gap between two populations in terms of clinical trial data, such as toxicity, efficacy, comorbidities and doses. According to ICH-E5 guidelines, clinical data can be extrapolated from one region to another if dose-reponse curves are similar between two populations. For instance, in Japan, Phase I clinical trials are often repeated due to this physiological/metabolic paradigm: the maximum tolerated dose (MTD) for Japanese patients is assumed to be lower than that for Caucasian patients, but not necessarily for all molecules. Therefore, proposing a statistical tool evaluating the similarity between two populations dose-response curves is of most interest. The aim of our work is to propose several indicators to evaluate the distance and the similarity of dose-toxicity curves and MTD distributions at the end of some of the Phase I trials, conducted on two populations or regions. For this purpose, we extended and adapted the commensurability criterion, initially proposed by Ollier et al. (2019), in the setting of completed phase I clinical trials. We evaluated their performance using three synthetic sets, built as examples, and six case studies found in the literature. Visualization plots and guidelines on the way to interpret the results are proposed.

SUBMITTER: Ollier A

PROVIDER: S-EPMC7916097 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Estimating Similarity of Dose-Response Relationships in Phase I Clinical Trials-Case Study in Bridging Data Package.

Ollier Adrien A Zohar Sarah S Morita Satoshi S Ursino Moreno M

International journal of environmental research and public health 20210209 4

Bridging studies are designed to fill the gap between two populations in terms of clinical trial data, such as toxicity, efficacy, comorbidities and doses. According to ICH-E5 guidelines, clinical data can be extrapolated from one region to another if dose-reponse curves are similar between two populations. For instance, in Japan, Phase I clinical trials are often repeated due to this physiological/metabolic paradigm: the maximum tolerated dose (MTD) for Japanese patients is assumed to be lower ...[more]

PMID: 33572323

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Project description:ABSTRACT Elagolix, a gonadotrophin?releasing hormone antagonist, is used in premenopausal women with endometriosis. There is a risk of bone loss with elagolix, but the long?term effects of BMD loss later in life cannot be directly assessed and has not been quantified. To address this gap in knowledge, this study indirectly estimated the impact of elagolix on postmenopausal fracture risk. BMD change in premenopausal women with endometriosis treated with elagolix was modeled from the phase III program data (elagolix group) and used to simulate treatment effects on (fracture risk assessment tool estimated) 10?year risks of hip and major osteoporotic fracture in women ages 50 to 79?years from the 2005–2010 National Health and Nutrition Examination Survey (NHANES; N = 2303). Change in the proportion of women reaching risk?based antiosteoporotic treatment thresholds was also estimated. For elagolix versus NHANES, median 10?year risk of major osteoporotic fracture was 4.73% versus 4.70% in women ages 50 to 59?years, 7.03% versus 6.97% in women ages 60 to 69?years, and 10.83% versus 10.68% in women ages 70 to 79?years. Median 10?year risk of hip fracture in these same groups was 0.19% versus 0.18% for women ages 50 to 59?years, 0.51% versus 0.49% for women 60 to 69?years, and 2.22% versus 2.14% for women 70 to 79?years. The proportion of women reaching risk?based antiosteoporotic treatment thresholds caused by elagolix 150?mg daily for 12?months was 0.36% higher at age 50 to 59?years, 0.23% at age 60 to 69?years, and 1.79% at age 70 to 79?years. The number needed to harm was 643 for one additional hip fracture and 454 for one additional major osteoporotic fracture. Results were similar for elagolix 200?mg twice a day for 3?months. In the modeled scenarios, elagolix had minimal impact on long?term risk of fracture and reaching risk?based treatment thresholds. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Dataset Information

Estimating Similarity of Dose-Response Relationships in Phase I Clinical Trials-Case Study in Bridging Data Package.

Publications

Estimating Similarity of Dose-Response Relationships in Phase I Clinical Trials-Case Study in Bridging Data Package.

Similar Datasets

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