J Clark1, R Schall. 1. Biostatistics, Quintiles South Africa, Centurion, South Africa.
Abstract
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. CONCLUSION: 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.
RCT Entities:
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. CONCLUSION: 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.
Authors: G Walter Canonica; Jean Bousquet; Thomas Casale; Richard F Lockey; Carlos E Baena-Cagnani; Ruby Pawankar; Paul C Potter; Philippe J Bousquet; Linda S Cox; Stephen R Durham; Harold S Nelson; Giovanni Passalacqua; Dermot P Ryan; Jan L Brozek; Enrico Compalati; Ronald Dahl; Luis Delgado; Roy Gerth van Wijk; Richard G Gower; Dennis K Ledford; Nelson Rosario Filho; Erkka J Valovirta; Osman M Yusuf; Torsten Zuberbier Journal: World Allergy Organ J Date: 2009-11-19 Impact factor: 4.084
Authors: Oliver Pfaar; Claus Bachert; Albrecht Bufe; Roland Buhl; Christof Ebner; Peter Eng; Frank Friedrichs; Thomas Fuchs; Eckard Hamelmann; Doris Hartwig-Bade; Thomas Hering; Isidor Huttegger; Kirsten Jung; Ludger Klimek; Matthias Volkmar Kopp; Hans Merk; Uta Rabe; Joachim Saloga; Peter Schmid-Grendelmeier; Antje Schuster; Nicolaus Schwerk; Helmut Sitter; Ulrich Umpfenbach; Bettina Wedi; Stefan Wöhrl; Margitta Worm; Jörg Kleine-Tebbe; Susanne Kaul; Anja Schwalfenberg Journal: Allergo J Int Date: 2014