A calibration approach to transportability and data-fusion with observational data

Two important considerations in clinical research studies are proper evaluations of internal and external validity. While randomized clinical trials can overcome several threats to internal validity, they may be prone to poor external validity. Conversely, large prospective observational studies sampled from a broadly generalizable population may be externally valid, yet susceptible to threats to internal validity, particularly confounding. Thus, methods that address confounding and enhance transportability of study results across populations are essential for internally and externally valid causal inference, respectively. These issues persist for another problem closely related to transportability known as data-fusion. We develop a calibration method to generate balancing weights that address confounding and sampling bias, thereby enabling valid estimation of the target population average treatment effect. We compare the calibration approach to two additional doubly robust methods that estimate the effect of an intervention on an outcome within a second, possibly unrelated target population. The proposed methodologies can be extended to resolve data-fusion problems that seek to evaluate the effects of an intervention using data from two related studies sampled from different populations. A simulation study is conducted to demonstrate the advantages and similarities of the different techniques. We also test the performance of the calibration approach in a motivating real data example comparing whether the effect of biguanides vs sulfonylureas-the two most common oral diabetes medication classes for initial treatment-on all-cause mortality described in a historical cohort applies to a contemporary cohort of US Veterans with diabetes.

Automated summary

Proper evaluations of internal and external validity are important in clinical research studies. Randomized clinical trials can address internal validity but may lack external validity. Large prospective observational studies may have external validity but are susceptible to threats to internal validity. Methods that address confounding and enhance transportability of study results across populations are crucial for valid causal inference.