Dataset Information

Decision rules for identifying combination therapies in open-entry, randomized controlled platform trials.

ABSTRACT: Platform trials have become increasingly popular for drug development programs, attracting interest from statisticians, clinicians and regulatory agencies. Many statistical questions related to designing platform trials-such as the impact of decision rules, sharing of information across cohorts, and allocation ratios on operating characteristics and error rates-remain unanswered. In many platform trials, the definition of error rates is not straightforward as classical error rate concepts are not applicable. For an open-entry, exploratory platform trial design comparing combination therapies to the respective monotherapies and standard-of-care, we define a set of error rates and operating characteristics and then use these to compare a set of design parameters under a range of simulation assumptions. When setting up the simulations, we aimed for realistic trial trajectories, such that for example, a priori we do not know the exact number of treatments that will be included over time in a specific simulation run as this follows a stochastic mechanism. Our results indicate that the method of data sharing, exact specification of decision rules and a priori assumptions regarding the treatment efficacy all strongly contribute to the operating characteristics of the platform trial. Furthermore, different operating characteristics might be of importance to different stakeholders. Together with the potential flexibility and complexity of a platform trial, which also impact the achieved operating characteristics via, for example, the degree of efficiency of data sharing this implies that utmost care needs to be given to evaluation of different assumptions and design parameters at the design stage.

SUBMITTER: Meyer EL

PROVIDER: S-EPMC9304586 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ObjectiveTo evaluate the effects of four drug (quadruple) versus three drug (triple) combination antiretroviral therapies in treatment naive people with HIV, and explore the implications of existing trials for clinical practice and research.DesignSystematic review and meta-analysis of randomised controlled trials.Data sourcesPubMed, EMBASE, CENTRAL, Web of Science, and the Cumulative Index to Nursing and Allied Health Literature from March 2001 to December 2016 (updated search in PubMed and EMBASE up to June 2018); and reference lists of eligible studies and related reviews.Study selectionRandomised controlled trials comparing quadruple with triple combination antiretroviral therapies in treatment naive people with HIV and evaluating at least one effectiveness or safety outcome.Review methodsOutcomes of interest included undetectable HIV-1 RNA, CD4 T cell count, virological failure, new AIDS defining events, death, and severe adverse effects. Random effects meta-analyses were conducted.ResultsTwelve trials (including 4251 people with HIV) were eligible. Quadruple and triple combination antiretroviral therapies had similar effects on all relevant effectiveness and safety outcomes, with no point estimates favouring quadruple therapy. With the triple therapy as the reference group, the risk ratio was 0.99 (95% confidence interval 0.93 to 1.05) for undetectable HIV-1 RNA, 1.00 (0.90 to 1.11) for virological failure, 1.17 (0.84 to 1.63) for new AIDS defining events, 1.23 (0.74 to 2.05) for death, and 1.09 (0.89 to 1.33) for severe adverse effects. The mean difference in CD4 T cell count increase between the two groups was -19.55 cells/?L (-43.02 to 3.92). In general, the results were similar, regardless of the specific regimens of combination antiretroviral therapies, and were robust in all subgroup and sensitivity analyses.ConclusionIn this study, effects of quadruple combination antiretroviral therapy were not better than triple combination antiretroviral therapy in treatment naive people with HIV. This finding lends support to current guidelines recommending the triple regimen as first line treatment. Further trials on this topic should be conducted only when new research is justified by adequate systematic reviews of the existing evidence. However, this study cannot exclude the possibility that quadruple cART would be better than triple cART when new classes of antiretroviral drugs are made available.

Dataset Information

Decision rules for identifying combination therapies in open-entry, randomized controlled platform trials.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets