Speaker
Description
Randomized trials often utilize a select group of study participants. This group does not typically represent the general population. Furthermore, sample sizes are often small to reduce cost. To improve power and generalizability, external control groups may be added to the randomized study. It is possible to incorporate a suitably selected external control group into a randomized clinical trial to improve efficiency.
A clinical trial was conducted to study a novel drug treatment for Spinal Muscular Atrophy. The study randomized trial participants at baseline to treatment or control and followed up for one year. The study used an external control group, obtained from a study of another novel drug for the same disease, conducted at a different center. During year one of the follow up the external controls served as additional controls to increase power. At the end of year 1 the drug was found to be effective. Subsequently, all trial participants were switched to treatment. This group was then followed for another year and at the end of the trial the effectiveness of the drug was assessed by comparison with the external controls. We discuss how the available data can be used to assess potential biases between external controls and study participants. We develop a flexible model to incorporate dependencies between observations on the same subject and demonstrate how difference-in-difference comparisons can be used to assess the assumption of ignorability in assignment top trial.
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