Abstract: Conducting Valid Trials

The Critical (and Misunderstood) Roles of Randomization and Complete Follow-Up

The purpose of a randomized clinical trial is to establish a causal relationship between an intervention and outcomes of interest, and the primary role of randomization is to ensure the validity of causal conclusions, not -- as is typically claimed -- to remove bias in treatment assignments or balance baseline characteristics.

Using easily understood examples, interactive activities and minimal mathematics, we will demonstrate how randomization enables us to make valid causal assessments based on trial data, and we will discuss the implications this has for study design, conduct and analysis. For example, we will address how missing data or incomplete follow-up compromise our causal conclusions, including the special case of study designs that encourage suspension of laboratory, adverse event, or other safety assessments following treatment discontinuation.

We will explain how the Intention to Treat (ITT) principle is essential to inference based on randomization and not merely a means to conservatively estimate the “real-world” treatment effect (another popular misconception). Other topics will include the validity of alternatives to ITT analyses and implications for non-inferiority trials.

The Target Audience

Anyone involved in the design or implementation of randomized clinical trials with an interest in ensuring the quality and integrity of those trials. This includes clinicians, clinic coordinators, statisticians, data managers, and others. No formal statistical background is required, and both statisticians and clinicians can expect to benefit.

Goals

To help participants develop a deeper understanding of

Presenters