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Sivem Afach

Publications and source records attributed to Sivem Afach.

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Integration of aggregated data in causally interpretable meta-analysis by inverse weighting

Obtaining causally interpretable meta-analysis results is challenging when there are differences in the distribution of effect modifiers between eligible trials. To overcome this, recent work on transportability methods has considered standardizing results of individual studies over the case-mix of a target population, prior to pooling them as in a classical random-effect meta-analysis. One practical challenge, however, is that case-mix standardization often requires individual participant data (IPD) on outcome, treatments and case-mix characteristics to be fully accessible in every eligible study, along with IPD case-mix characteristics for a random sample from the target population. In this paper, we aim to develop novel strategies to integrate aggregated-level data from eligible trials with non-accessible IPD into a causal meta-analysis, by extending moment-based methods frequently used for population-adjusted indirect comparison in health technology assessment. Since valid inference for these moment-based methods by M-estimation theory requires additional aggregated data that are often unavailable in practice, computational methods to address this concern are also developed. We assess the finite-sample performance of the proposed approaches by simulated data, and then apply these on real-world clinical data to investigate the effectiveness of risankizumab versus ustekinumab among patients with moderate to severe psoriasis.

stat.ME

Transportability of aggregate trial results to an external environment in causally interpretable meta-analysis

In evidence synthesis, multilevel modeling approaches (MMAs) are commonly employed to combine aggregate data (AD) and individual participant data (IPD). These approaches rely on an aggregate outcome model that is ideally obtained by integrating the prespecified individual- level outcome model over the covariate distribution observed in each eligible study. In non- linear settings, such an integration may however be analytically intractable and requires ap- proximations. In this paper, we propose a novel method for incorporating AD into causal meta-analysis of IPD studies that can overcome this challenge. Rather than relying on an ag- gregate outcome model that is difficult to be correctly formulated, we propose modeling the trial membership as a function of baseline covariates. This model allows one to estimate the individual-level outcome model in each AD study by leveraging IPD available in other trials, and then to transport the treatment effects estimated from both AD and IPD trials to an external target population, even when only aggregate covariate data are available for that population. Unlike previous proposals, we do not require pseudo-IPD to be generated from the aggregate data, which helps minimize bias due to incomplete information on the covariate distribution in each AD trial and in the target population.

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Network meta-analysis of rare events using penalized likelihood regression

Network meta-analysis (NMA) of rare events has attracted little attention in the literature. Until recently, networks of interventions with rare events were analyzed using the inverse-variance NMA approach. However, when events are rare the normal approximation made by this model can be poor and effect estimates are potentially biased. Other methods for the synthesis of such data are the recent extension of the Mantel-Haenszel approach to NMA or the use of the non-central hypergeometric distribution. In this article, we suggest a new common-effect NMA approach that can be applied even in networks of interventions with extremely low or even zero number of events without requiring study exclusion or arbitrary imputations. Our method is based on the implementation of the penalized likelihood function proposed by Firth for bias reduction of the maximum likelihood estimate to the logistic expression of the NMA model. A limitation of our method is that heterogeneity cannot be taken into account as an additive parameter as in most meta-analytical models. However, we account for heterogeneity by incorporating a multiplicative overdispersion term using a two-stage approach. We show through simulations that our method performs consistently well across all tested scenarios and most often results in smaller bias than other available methods. We also illustrate the use of our method through two clinical examples. We conclude that our "penalized likelihood NMA" approach is promising for the analysis of binary outcomes with rare events especially for networks with very few studies per comparison and very low control group risks.

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