A critical appraisal of analyzing nasal provocation test results in allergen immunotherapy trials

Background: The statistical analysis of nasal provocation tests is very complex. We compared the conventional analysis with the maximally selected test statistics and the hierarchical ordered logistic model. Methods: We re-analyzed data from a trial with 112 patients suffering from grass pollen allergy. The patients had been randomized to receive either intralymphatic immunotherapy (ILIT) or subcutaneous immunotherapy (SCIT). Results: The conventional analysis indicated that the logarithmized ratio between the pre- and the post-treatment threshold concentration was significantly lower for ILIT than for SCIT. The maximally selected test statistics was used to test different threshold symptom scores that would imply positive clinical symptoms at the given allergen concentration. A threshold score of 3 maximised the difference in improvement between the ILIT and the SCIT groups. The hierarchical ordered logistic model does not take threshold allergen concentrations as the basis for analysis, but the single scores measured at each concentration. This approach simultaneously considers the treatment effect (ILIT versus SCIT), the time effect (pre- versus post-treatment), and the dose effect (different allergen concentrations). The hierarchical ordered logistic model revealed that the clinical improvement was greater after ILIT than after SCIT. Conclusion: As the choice of method can affect the outcome, guidelines for analysis are highly needed.