Assessment of combined symptom and medication scores for rhinoconjunctivitis immunotherapy clinical trials.
BACKGROUND
In randomized, double-blind, placebo-controlled clinical trials the efficacy of immunotherapy for allergic rhinoconjunctivitis is evaluated using the Average Rhinoconjunctivitis Total Symptom Score (ARTSS). Effective treatment is associated with lower ARTSS relative to placebo. For ethical reasons patients are provided with registered rescue medication, which may alleviate symptoms and thus reduce symptom scores. This effect biases the mean difference in ARTSS between effective treatment and placebo towards zero. Therefore, when rescue medication is taken by a patient, the ARTSS needs to be adjusted appropriately.


METHODS
We considered five outcome measures: ARTSS, Average Rescue Medication Score (ARMS), and three combined symptom and RMSs. To assess the different outcome measures regarding their power to discriminate between effective treatment and placebo, we calculated their effect size when applied to data from a clinical trial of immunotherapy for allergic rhinoconjunctivitis.


RESULTS
Of the five outcome measures considered, the average of the ARTSS and ARMS was associated with the largest effect size, and thus with the highest power to show treatment efficacy. Discriminant and multivariate analyses suggest that this average is approximately optimal among all weighted sums of ARTSS and ARMS.


CONCLUSIONS
Our findings support recommendations made in a World Allergy Organisation document on methodological aspects of immunotherapy trials. The average of the ARTSS and ARMS should be considered as a primary efficacy variable in clinical trials of immunotherapy for allergic rhinoconjunctivitis.
Clark
J
J
Biostatistics, Quintiles South Africa, Centurion, South Africa.
Schall
R
R
D000286:Administration, Sublingual; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000485:Allergens / Q000009:adverse effects*; D003233:Conjunctivitis, Allergic / Q000209:etiology / Q000628:therapy*; D004311:Double-Blind Method; D006634:Histamine H1 Antagonists / Q000627:therapeutic use; D006801:Humans; D007167:Immunotherapy; D011058:Pollen / Q000009:adverse effects*; D012107:Research Design; D006255:Rhinitis, Allergic, Seasonal / Q000209:etiology / Q000628:therapy*; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000485:Allergens; D006634:Histamine H1 Antagonists