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

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 community-acquired bacterial pneumonia (CABP).

Understanding Noninferiority Trial Design

In noninferiority trials like DEFINE-CABP, the statistical framework is structured differently from superiority trials:

• The null hypothesis states that the new treatment (delafloxacin) is inferior to the standard treatment (moxifloxacin) by at least the prespecified noninferiority margin (12.5% in this case) 1
• The alternative hypothesis is that the new treatment is not inferior to the standard treatment by more than the noninferiority margin

Key Elements of the DEFINE-CABP Trial

• Phase 3 noninferiority study comparing delafloxacin with moxifloxacin for CABP treatment 2
• Primary endpoint: Early clinical response (symptom improvement 96 hours after first dose)
• Noninferiority margin: 12.5% (FDA-directed)
• Results: Early clinical response rates were 88.9% in the delafloxacin group and 89.0% in the moxifloxacin group 2

Statistical Framework in Noninferiority Trials

Noninferiority trials follow this logical structure:

1. Null hypothesis (H₀): The new treatment is inferior to the standard treatment by at least the noninferiority margin

   • In mathematical terms: H₀: δ ≤ -NI margin (where δ is the difference between treatments)

2. Alternative hypothesis (H₁): The new treatment is not inferior to the standard treatment by more than the noninferiority margin

   • In mathematical terms: H₁: δ > -NI margin

Clinical Implications of the DEFINE-CABP Results

The trial demonstrated that delafloxacin was noninferior to moxifloxacin for the treatment of CABP 2. This has important clinical implications:

• Delafloxacin provides an alternative fluoroquinolone option for CABP treatment
• It demonstrates efficacy against Gram-positive, Gram-negative, and atypical pathogens 3
• It may be particularly beneficial in patients with comorbidities like asthma or COPD 4

Common Pitfalls in Interpreting Noninferiority Trials

• Misinterpreting the null hypothesis: The null hypothesis in noninferiority trials is that the new treatment is inferior, not that there is no difference
• Confusing with equivalence trials: Noninferiority trials only test whether the new treatment is not worse than the standard by a prespecified margin, not whether they are equivalent
• Overlooking the noninferiority margin: The selection of the 12.5% margin is critical to interpreting the results and was specifically directed by the FDA

By rejecting the null hypothesis, the DEFINE-CABP trial demonstrated that delafloxacin is not worse than moxifloxacin by more than the prespecified margin for early clinical response in CABP patients.