What is the null hypothesis in the DEFINE-CABP (Community-Acquired Bacterial Pneumonia) trial comparing delafloxacin (Baxdela) to moxifloxacin (Avelox)?

Understanding the Null Hypothesis in the DEFINE-CABP Trial

The null hypothesis in the DEFINE-CABP trial is that delafloxacin is not noninferior to moxifloxacin for providing an early clinical response in patients with CABP.

Explanation of Noninferiority Trial Design

In noninferiority trials like DEFINE-CABP, the null hypothesis is structured differently from superiority trials. The goal is to determine whether a new treatment (delafloxacin) is not unacceptably worse than an established treatment (moxifloxacin).

The DEFINE-CABP trial was designed with the following key elements:

• Phase 3 noninferiority study comparing delafloxacin with moxifloxacin
• Primary endpoint: early clinical response (symptom improvement 96 hours after first dose)
• FDA-directed noninferiority margin of 12.5%
• Results showed early clinical response rates of 88.9% in delafloxacin group vs 89.0% in moxifloxacin group

Statistical Framework of Noninferiority Trials

For noninferiority trials, the statistical framework works as follows:

1. Null hypothesis (H₀): The new treatment is inferior to the standard treatment by at least the prespecified noninferiority margin (delafloxacin is worse than moxifloxacin by at least 12.5%)

2. Alternative hypothesis (H₁): The new treatment is not inferior to the standard treatment by more than the prespecified noninferiority margin (delafloxacin is not worse than moxifloxacin by more than 12.5%)

Evidence Supporting This Interpretation

According to established guidelines for noninferiority trials, several conditions must be met for valid noninferiority testing 1:

1. There must be reliable evidence of the effect of the control regimen compared to no therapy
2. The trial design must conform closely to previous studies that established the effect of the control
3. The selected margin of potential inferiority must be smaller than the effect of the control compared to no intervention

The DEFINE-CABP trial met these conditions by:

• Using moxifloxacin as an established effective treatment for CABP
• Following a similar design to previous CABP studies
• Setting a noninferiority margin (12.5%) that was less than the established treatment effect

Clinical Implications

The results of the DEFINE-CABP trial (difference of -0.1% with 95% CI within the noninferiority margin) allowed rejection of the null hypothesis, establishing that delafloxacin is noninferior to moxifloxacin for early clinical response in CABP 2.

This finding has important clinical implications:

• Delafloxacin provides another treatment option for CABP
• It demonstrates efficacy against Gram-positive, Gram-negative, and atypical pathogens
• The availability of both IV and oral formulations allows for flexible treatment approaches 3

Common Misconceptions About Noninferiority Trials

It's important to understand that:

• Noninferiority does not mean equivalence (which would require proving both noninferiority and non-superiority)
• The null hypothesis in noninferiority trials is the opposite of what many clinicians expect (we assume inferiority until proven otherwise)
• The noninferiority margin (12.5% in this case) represents the maximum clinically acceptable difference

By correctly identifying the null hypothesis as "delafloxacin is not noninferior to moxifloxacin," we recognize the statistical framework that guided this important clinical trial.