P110: Establishing a Hybrid Control in Conjunctival Allergen Challenge Studies for Allergic Conjunctivitis
Senior Vice President, Biostatistics and Strategic Consulting
Statistics & Data Corporation (SDC) United States
Randomized, controlled and blinded conjunctival allergen challenge studies using standardized methodology have been used to support approvals for allergic conjunctivitis indication. The hybrid control is to expose fewer subjects to allergens for whom there will be no benefit from treatment.
The hybrid control is to pool the trial control subjects and certain historical control subjects based on adequate statistical matching, such as propensity score (PS). The PS matching incorporates prognostic factors such as age, sex, and baseline post-challenge itchiness and redness.
Among three completed Phase II and III CAC studies for the allergic conjunctivitis indication, two are used as historical control and one is selected as a reference. We compare the outcomes between the historical control and the reference trial control, after controlling PS, to evaluate the similarity in vehicle treatment responses. We construct a hybrid control arm for the reference trial using PS matching between the trial treatment group and the historical control. The results of the treatment effect using the hybrid control are compared with the results using the trial control.
The reference study was randomized in a 2:1 ratio to treatment (91 subjects) or control (47 subjects). The combined historical control includes 75 subjects from the two studies. Figure 1 shows the post-challenge mean scores of itchiness and redness for the baseline, 16 hours post treatment time points, and 15-minutes post treatment, displayed by individual study and matched groups using PS matching. The mean differences between the two matched groups are reduced to less than or equal to 0.24. The results show that the conclusions on treatment effect are unchanged using the hybrid control in the reference trial. The least squares mean differences are less than or equal to 0.17 between the trial and hybrid controls.
Introducing hybrid control arms in randomized, vehicle-controlled, and double-masked conjunctival allergen challenge studies may still maintain study integrity and validity. The use of a hybrid control could potentially reduce costs and improve subject safety.