What is the significance of the non-inferiority rate in a clinical study?

From the Guidelines

The noninferiority rate in a study is a critical threshold that determines whether a new treatment is considered not worse than a standard treatment by a clinically acceptable margin, and it is expressed as a percentage or ratio that is determined before the study begins. When designing a noninferiority trial, researchers must pre-define a noninferiority margin, commonly called delta, for the primary endpoint, which is the smallest treatment difference that would mean the new treatment is declared inferior 1. The choice of margin requires a realistic balancing of scientific goals with an achievable sample size, and it is sometimes related to prior knowledge of the efficacy of the active control compared with placebo 1.

The noninferiority margin can be expressed as a relative risk or hazard ratio, and it is essential to consider the clinical relevance and historical data about the standard treatment's effectiveness when determining this margin 1. For instance, in the ACUITY trial, the noninferiority margin was set at a relative risk of 1.25, and the trial's findings revealed that the new treatment was noninferior to the standard treatment because the upper bound of the 95% CI was less than the pre-declared delta 1.

Key considerations when interpreting noninferiority trials include the choice of margin, the sample size, and the analysis of the results, and the study results are then analyzed to determine if the difference between treatments falls within this predetermined margin. Understanding the noninferiority rate is crucial for interpreting study results correctly and making informed clinical decisions, especially when testing treatments that may offer other benefits, such as fewer side effects, easier administration, or lower cost, even if they aren't necessarily more effective than existing options 1.

Some of the challenges in noninferiority trials include the choice of margin, the sample size, and the analysis of the results, and it is essential to carefully consider these factors to ensure that the trial is adequately powered to detect noninferiority. Additionally, the use of composite endpoints, which combine safety and efficacy endpoints, can be challenging to interpret, and it is crucial to carefully examine each component measure to ensure that the results are accurately interpreted 1.

In summary, the noninferiority rate in a study is a critical threshold that determines whether a new treatment is considered not worse than a standard treatment by a clinically acceptable margin, and it is essential to carefully consider the choice of margin, sample size, and analysis of the results to ensure that the trial is adequately powered to detect noninferiority. By understanding the noninferiority rate and its implications, clinicians can make informed decisions about the use of new treatments and ensure that patients receive the best possible care.

From the Research

Noninferiority Rate in a Study

The noninferiority rate in a study refers to the extent to which a new treatment is not significantly worse than an established active control treatment.

• The noninferiority margin is a crucial component in noninferiority trials, as it defines the maximum amount of inferiority that is considered acceptable 2.
• The choice of the noninferiority margin is influenced by several factors, including the baseline risk, type of primary outcome, and benefits of the new treatment 2.
• Noninferiority trials aim to demonstrate that the test product is no worse than the comparator by more than a pre-specified small amount 3.
• The design, execution, and interpretation of noninferiority trials are complex and require careful consideration of several factors, including assay sensitivity, choice of active-control, and analysis of non-inferiority clinical trials 4, 3.

Key Considerations

• Noninferiority trials are important when other aspects of care can be improved, such as convenience, toxicity, costs, and safety (nonefficacy benefits) 4.
• The results of noninferiority studies may be difficult to interpret and can be easily misused 5.
• The US FDA has recommended that non-inferiority designs should not be used for certain indications, such as acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, and acute bacterial otitis media 3.
• The values for noninferiority margins are significantly lower than the differences to be detected in a superiority trial 2.