"Noninferiority or Equivalence Trials: Design Concepts, Issues, and Considerations"

Conducting a randomized clinical trial of a novel treatment intervention with a rural, remote population poses a number of unique methodological challenges. In this seminar, the presenters will discuss procedural and design challenges that researchers commonly face and will draw from their experiences conducting a 4-year, VA funded RCT using an equivalency design to evaluate the effectiveness of a telemental health intervention with PTSD veterans in the Hawaiian Islands.

Part I of the seminar will focus on methodological issues related to participant recruitment, assessment, and retention. The presenters will discuss challenges that researchers face in working with a culturally diverse, research-naïve, remote population with limited access to care. This population is often difficult to reach and researchers have limited support from clinical providers and minimal infrastructure upon which to draw. The presenters will share their experiences and specific strategies and techniques they have used in their ongoing RCT.

Part II of the seminar will focus on use of an equivalency or noninferiority design. This non-traditional design is becoming increasingly common in RCTs as the use of placebos with ill participants is seen as unethical. This design is especially appropriate when evaluating novel interventions designed to increase access to care for remote populations. In such studies, the true question is whether a less costly or more convenient novel intervention is as effective as the more expensive or inconvenient standard intervention. Despite the design’s recent popularity, it is often poorly understood and improperly applied leading to misleading research findings. This presentation will identify when an equivalency design can be used, how it is similar and dissimilar to standard superiority trials, and what are the key statistical considerations. It will address difficult decision points in using this design, such as choosing an appropriate control condition and determining the equivalence limit or noninferiority margin. The presenters will use examples from published studies as well as hypothetical scenarios to demonstrate how data would be interpreted differently based on design decisions and the implications of the differing findings.