As real world evidence on drug efficacy involves non-randomised studies, statistical methods
adjusting for confounding are needed. In this context, prognostic score (PGS) analysis has
recently been proposed as a method for causal inference. It aims to restore balance across the
different treatment groups by identifying subjects with a similar prognosis for a given reference
exposure ('control'). This requires the development of a multivariable prognostic model in the
control arm of the study sample, which is then extrapolated to the different treatment arms.
Unfortunately, large cohorts for developing prognostic models are not always available.
Prognostic models are therefore subject to a dilemma between overfitting and parsimony; the
latter being prone to a violation of the assumption of no unmeasured confounders when
important covariates are ignored. Although it is possible to limit overfitting by using
penalization strategies, an alternative approach is to adopt evidence synthesis. Aggregating
previously published prognostic models may improve the generalizability of PGS, while taking
account of a large set of covariates - even when limited individual participant data are available.
In this article, we extend a method for prediction model aggregation to PGS analysis in non-
randomised studies. We conduct extensive simulations to assess the validity of model
aggregation, compared with other methods of PGS analysis for estimating marginal treatment
effects. We show that aggregating existing PGS into a 'meta-score' is robust to
misspecification, even when elementary scores wrongfully omit confounders or focus on
different outcomes. We illustrate our methods in a setting of treatments for asthma.