What type of study should be performed first to determine if Drug X is as efficacious as Drug Y?

From the Guidelines

A non-inferiority trial should be performed first to determine if Drug X is as efficacious as Drug Y. When researchers want to determine if a new drug (drug X) is as efficacious as an existing drug (drug Y), a non-inferiority trial is the most suitable study design, as it is specifically designed to demonstrate that the new treatment is not worse than the standard treatment by more than a pre-specified margin, known as the noninferiority margin or delta 1. This type of study is essential in situations where the new treatment has some other advantages, such as fewer side effects, ease of administration, or lower cost, making it worthwhile to demonstrate noninferiority in respect to efficacy. Some key points to consider when designing a noninferiority trial include:

• Pre-defining a noninferiority margin for the primary endpoint
• Ensuring that the trial's conclusions depend on where the 95% confidence interval (CI) for the treatment effect lies
• Understanding that the goal is to demonstrate that the new treatment is not unacceptably worse than the standard treatment, which aligns with the question's premise that drug X should be "as efficacious as" drug Y. Other study designs, such as case-control, cohort, or cross-sectional studies, are not suitable as the first choice when directly comparing the efficacy of two drugs, as they do not provide a direct comparison of the treatments and are more focused on examining risk factors, observing outcomes over time, or providing a snapshot at a single point in time, respectively.

From the Research

Study Design for Comparing Drug X and Drug Y

To determine if Drug X is as efficacious as Drug Y, a non-inferiority trial should be performed first. The primary objective of a non-inferiority trial is to demonstrate that a new treatment (in this case, Drug X) is not significantly less effective than an existing treatment (Drug Y) [ 2, 3, 4, 5 ].

Key Considerations for Non-Inferiority Trials

Some key considerations for non-inferiority trials include:

• Determining the non-inferiority margin before the study commences [ 2 ]
• Choosing an appropriate standard therapy for comparison [ 2 ]
• Considering the rationale for the choice of non-inferiority margin [ 2 ]
• Evaluating the assumed benefit of the new treatment [ 2 ]
• Using intention-to-treat and per-protocol analyses [ 4 ]

Advantages of Non-Inferiority Trials

Non-inferiority trials are useful when a new treatment has advantages over the standard treatment, such as reduced cost, lower toxicity, or improved convenience [ 6, 3, 4 ]. These trials can provide valuable information on the efficacy of Drug X compared to Drug Y, while also considering other important factors.

Potential Pitfalls of Non-Inferiority Trials

Some potential pitfalls of non-inferiority trials include:

• Inherent assumptions that may not be correct [ 4 ]
• Introduction of less effective treatments through successive non-inferiority trials [ 4 ]
• Poor quality trials that favor non-inferior results [ 4 ]
• Overreliance on p-values rather than effect size and confidence limits [ 4 ]