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BUILDING A DOSE TOXO-EQUIVALENCE MODEL FROM A BAYESIAN META-ANALYSIS OF PUBLISHED CLINICAL TRIALS.

ABSTRACT: In clinical practice medications are often interchanged in treatment protocols when a patient negatively reacts to their first line of therapy. Although switching between medications is common, clinicians often lack structured guidance when choosing the initial dose and frequency of a new medication, given the former with respect to risk of adverse events. In this paper we propose to establish this dose toxo-equivalence relationship using published clinical trial results with one or both drugs of interest via a Bayesian meta-analysis model that accounts for both within- and between-study variances. With the posterior parameter samples from this model, we compute median and 95% credible intervals for equivalent dose pairs of the two drugs that are predicted to produce equal rates of an adverse outcome, relying solely on study-level information. Via extensive simulations, we show that this approach approximates well the true dose toxo-equivalence relationship, considering different study designs, levels of between-study variance, and the inclusion/exclusion of nonconfounder/nonmodifier subject-level covariates in addition to study-level covariates. We compare the performance of this study-level meta-analysis estimate to the equivalent individual patient data meta-analysis model and find comparable bias and minimal efficiency loss in the study-level coefficients used in the dose toxo-equivalence relationship. Finally, we present the findings of our dose toxo-equivalence model applied to two chemotherapy drugs, based on data from 169 published clinical trials.

SUBMITTER: Sigworth EA

PROVIDER: S-EPMC11299894 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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BUILDING A DOSE TOXO-EQUIVALENCE MODEL FROM A BAYESIAN META-ANALYSIS OF PUBLISHED CLINICAL TRIALS.

Sigworth Elizabeth A EA Rubinstein Samuel M SM Warner Jeremy L JL Chen Yong Y Chen Qingxia Q

The annals of applied statistics 20231030 4

In clinical practice medications are often interchanged in treatment protocols when a patient negatively reacts to their first line of therapy. Although switching between medications is common, clinicians often lack structured guidance when choosing the initial dose and frequency of a new medication, given the former with respect to risk of adverse events. In this paper we propose to establish this dose toxo-equivalence relationship using published clinical trial results with one or both drugs o ...[more]

PMID: 39104542

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Project description:BackgroundWith the second largest tuberculosis (TB) burden globally, China is committed to actively engage in international TB clinical trials to contribute to global TB research. However, lack of research capacity among local sites has been identified as a barrier.Main textThe China Tuberculosis Clinical Trials Consortium (CTCTC) was initiated by Beijing Chest Hospital with investment from the US National Institutes of Health and technical support from Family Health International 360 in 2013, as a nationwide collaborative clinical trial network to strengthen selected clinical site research capacity and attract TB clinical trials. The program aims to: 1) recruit leading hospitals that care for TB patients; 2) conduct on-site assessment to identify capacity gaps and needs for improvement; 3) design and deliver capacity building activities; 4) attract and deliver high quality results for TB clinical trials. A total of 24 sites have joined CTCTC, covering 20 provinces in China. Twenty-two sites have been accredited by the National Medical Products Administration (NMPA) to be qualified to conduct TB clinical trials. The onsite assessment, extensive trainings among the CTCTC sites and young investigators have resulted in better understanding and improvement of the site capacity in conducting TB clinical trials. The establishment and growth of the CTCTC network has benefited from the good leadership, effective international cooperation and local commitment. Issues in human resources, regulatory environment and sustainability have been challenging the network from continuing growth. Clinical researchers have full-time clinical responsibilities in China and it is thus important to build a cadre of other human resources to assist. The regulatory environment is becoming friendlier in China to introduce international clinical trials to the CTCTC network.ConclusionsThe CTCTC, with mature management structure and sustainable development model, which are distilled five key lessons for other developing countries or investigators of interest. They are the respectively using assessment-based approach to design tailored training package, understanding the availability of clinical researchers, providing solutions to maintain sustainability, understanding local regulatory environments and working with an international organization with local on-site team, respectively. Although, the experiences and capacity of China's TB hospitals in conducting clinical research vary. Considerable efforts to continue building the capacity are still needed, although the gap is smaller for a few top-tier hospitals.

Dataset Information

BUILDING A DOSE TOXO-EQUIVALENCE MODEL FROM A BAYESIAN META-ANALYSIS OF PUBLISHED CLINICAL TRIALS.

Publications

BUILDING A DOSE TOXO-EQUIVALENCE MODEL FROM A BAYESIAN META-ANALYSIS OF PUBLISHED CLINICAL TRIALS.

Similar Datasets

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