A comprehensive review and shiny application on the matching-adjusted indirect comparison.

Population-adjusted indirect comparison (PAIC) is an increasingly used technique for estimating the comparative effectiveness of different treatments for the health technology assessments when head-to-head trials are unavailable. Three commonly used PAIC methods include matching-adjusted indirect comparison (MAIC), simulated treatment comparison (STC), and multilevel network meta-regression (ML-NMR). MAIC enables researchers to achieve balanced covariate distribution across two independent trials when individual participant data are only available in one trial. In this article, we provide a comprehensive review of the MAIC methods, including their theoretical derivation, implicit assumptions, and connection to calibration estimation in survey sampling. We discuss the nuances between anchored and unanchored MAIC, as well as their required assumptions. Furthermore, we implement various MAIC methods in a user-friendly R Shiny application Shiny-MAIC. To our knowledge, it is the first Shiny application that implements various MAIC methods. The Shiny-MAIC application offers choice between anchored or unanchored MAIC, choice among different types of covariates and outcomes, and two variance estimators including bootstrap and robust standard errors. An example with simulated data is provided to demonstrate the utility of the Shiny-MAIC application, enabling a user-friendly approach conducting MAIC for healthcare decision-making. The Shiny-MAIC is freely available through the link: https://ziren.shinyapps.io/Shiny_MAIC/.

Borrowing Concurrent Information from Non-Concurrent Control to Enhance Statistical Efficiency in Platform Trials.

A platform trial is a trial involving an innovative adaptive design with a single master protocol to efficiently evaluate multiple interventions. It offers flexible features such as dropping interventions for futility and adding new interventions to be evaluated during the course of a trial. Although there is a consensus that platform trials can identify beneficial interventions with fewer patients, less time, and a higher probability of success than traditional trials, there remains debate on certain issues, one of which is whether (and how) the non-concurrent control (NCC) (i.e., patients in the control group recruited prior to the new interventions) can be combined with the current control (CC) in the analysis, especially if there is a change of standard of care during the trial. METHODS: In this paper, considering time-to-event endpoints under the proportional hazard model assumption, we introduce a new concept of NCC concurrent observation time (NCC COT), and propose to borrow NCC COT through left truncation. This assumes that the NCC COT and CC are comparable. If the protocol does not prohibit NCC patients to change the standard of care while on study, NCC COT and CC likely will share the same standard of care. A simulated example is provided to demonstrate the approach. RESULTS: Using exponential distributions, the simulated example assumes that NCC COT and CC have the same hazard, and the treatment group has a lower hazard. The estimated HR comparing treatment to the pooled control group is 0.744 (95% CI 0.575, 0.962), whereas the comparison to the CC group alone is 0.755 (95% CI 0.566, 1.008), with corresponding p-values of 0.024 versus 0.057, respectively. This suggests that borrowing NCC COT can improve statistical efficiency when the exchangeability assumption holds. CONCLUSION: This article proposes an innovative approach of borrowing NCC COT to enhance statistical inference in platform trials under appropriate scenarios.

RIMeta: An R shiny tool for estimating the reference interval from a meta-analysis.

A reference interval, or an interval in which a prespecified proportion of measurements from a healthy population are expected to fall, is used to determine whether a person's measurement is typical of a healthy individual. For a specific biomarker, multiple published studies may provide data collected from healthy participants. A reference interval estimated by combining the data across these studies is typically more generalizable than a reference interval based on a single study. Methods for estimating reference intervals from random effects meta-analysis and fixed-effects meta-analysis have been recently proposed and implemented using R software. We present an R Shiny tool, RIMeta, implementing these methods, which allows users not proficient in R to estimate a reference interval from a meta-analysis using aggregate data (mean, standard deviation, and sample size) from each study. RIMeta (https://cers.shinyapps.io/RIMeta/) provides users a convenient way to estimate a reference interval from a meta-analysis and to generate the reference interval plot to visualize the results. The use of this web-based R Shiny tool does not require the installation of R or any background knowledge of programming. We explain all functions of the R Shiny tool and illustrate how to use it with a real data example.