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Updated: Feb 15, 2026

Synthetic Antigen Controls for Immunohistochemistry
Published on: August 23, 2021
Combining synthetic controls and interrupted time series analysis to improve causal inference in program evaluation
1Linden Consulting Group, LLC, San Francisco, CA, USA.
Rationale, Aims And Objectives:
Interrupted time series analysis (ITSA) is an evaluation methodology in which a single treatment unit's outcome is studied over time and the intervention is expected to "interrupt" the level and/or trend of the outcome. The internal validity is strengthened considerably when the treated unit is contrasted with a comparable control group. In this paper, we introduce a robust evaluation framework that combines the synthetic controls method (SYNTH) to generate a comparable control group and ITSA regression to assess covariate balance and estimate treatment effects.
Methods:
We evaluate the effect of California's Proposition 99 for reducing cigarette sales, by comparing California to other states not exposed to smoking reduction initiatives. SYNTH is used to reweight nontreated units to make them comparable to the treated unit. These weights are then used in ITSA regression models to assess covariate balance and estimate treatment effects.
Results:
Covariate balance was achieved for all but one covariate. While California experienced a significant decrease in the annual trend of cigarette sales after Proposition 99, there was no statistically significant treatment effect when compared to synthetic controls.
Conclusions:
The advantage of using this framework over regression alone is that it ensures that a comparable control group is generated. Additionally, it offers a common set of statistical measures familiar to investigators, the capability for assessing covariate balance, and enhancement of the evaluation with a comprehensive set of postestimation measures. Therefore, this robust framework should be considered as a primary approach for evaluating treatment effects in multiple group time series analysis.
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