Immunotherapy: clinical trials--optimal trial and clinical outcomes

The methodology of randomized clinical trials is essential to assess and register treatment interventions. Although specific immunotherapy was introduced a century ago, very few trials meet the criteria for pivotal studies. The paper reviews the methods which should be used to investigate specific immunotherapy.

Large pivotal trials on specific immunotherapy were published within the last year and made sublingual immunotherapy an accepted treatment in Europe. Moreover, a study proposed the guidelines for conducting trials on immunotherapy. Phase I studies were also published on sublingual immunotherapy. A large trial on subcutaneous immunotherapy confirmed its efficacy, but showed that this form of treatment is associated with side effects.

The clinical efficacy of subcutaneous and sublingual immunotherapy with pollen and mites is well established for both rhinitis and asthma, but the methodology of many specific immunotherapy trials was found to be insufficient until recent large pivotal studies. The present paper reviews the requirements for conducting trials in allergen-specific immunotherapy including allergen standardization, patient inclusion and exclusion criteria, phase I trials to assess safety, dose-ranging studies, and pivotal trials. These need to be randomized, parallel group, placebo-controlled designs. The number of patients should be sufficient. Primary and secondary outcome measures are listed. Trials for asthma need specific requirements. In all trials, safety should be carefully monitored. Studies in children are required.