Assessing Minimal Clinically Important Differenceestimates for the Rett Syndrome Behavior Questionnaire (RSBQ) using Data from the Trofinetide Clinical Program
Author(s)
Mirko V. Sikirica, PharmD1, Nazia Rashid, PharmD, MS2, Ratna Revankar, PhD3, James M. Youakim, MD4;
1Acadia Pharmaceuticals, Medical Affairs, San Diego, CA, USA, 2Acadia Pharmacueticals, Medical Affairs, San Diego, CA, USA, 3Acadia Pharmacueticals, Biostats, San Diego, CA, USA, 4Acadia Pharmaceuticals, Clinical Development, San Diego, CA, USA
1Acadia Pharmaceuticals, Medical Affairs, San Diego, CA, USA, 2Acadia Pharmacueticals, Medical Affairs, San Diego, CA, USA, 3Acadia Pharmacueticals, Biostats, San Diego, CA, USA, 4Acadia Pharmaceuticals, Clinical Development, San Diego, CA, USA
Presentation Documents
OBJECTIVES: Research is needed to guide the interpretation of change measured by the caregiver-reported Rett Syndrome Behavior Questionnaire (RSBQ). We aimed to estimate the Minimal Clinically Important Difference (MCID) of the 45-item RSBQ using the Trofinetide clinical studies.
METHODS: Data from the 6-week, double-blind, randomized, placebo-controlled Phase II (ACP-2566-002, Study-002; NCT02715115) and the 12-week, double-blind, randomized, placebo-controlled, Phase III (ACP-2566-003, LAVENDER; NCT04181723) studies were used. We applied the distribution-based method using the pooled standard deviation (SD) from both treatment arms for each trial. The baseline RSBQ mean total score and mean change from baseline values were used to approximate a range of MCIDs at the 0.4 and 0.5 SD threshold.
RESULTS: There were 82 females in Study-002 and 187 females in the LAVENDER study across both treatment arms at baseline. The pooled SD (Standard Error (SE)) at baseline was 11.39 (0.84) and 11.87 (0.87) for the two studies, respectively. At baseline, using the 0.4 and 0.5 SD thresholds, the RSBQ MCIDs ranged from 4.56 to 5.93. At the end of study assessments, the MCIDs based on total score change from baseline ranged from 3.23 to 4.03 for the 6-week Study-002 and 3.55 to 4.44 for the 12-week LAVENDER study.
CONCLUSIONS: These findings suggest that an estimated MCID for the RSBQ across the Trofinetide clinical trial program is likely to be within a 3- to 6-point difference. Changes in outcomes above this range are likely clinically important, based on natural variability observed in the data; smaller changes likely reflect measurement error rather than true clinical changes. These analyses should be confirmed via further investigation and expert consultation.
METHODS: Data from the 6-week, double-blind, randomized, placebo-controlled Phase II (ACP-2566-002, Study-002; NCT02715115) and the 12-week, double-blind, randomized, placebo-controlled, Phase III (ACP-2566-003, LAVENDER; NCT04181723) studies were used. We applied the distribution-based method using the pooled standard deviation (SD) from both treatment arms for each trial. The baseline RSBQ mean total score and mean change from baseline values were used to approximate a range of MCIDs at the 0.4 and 0.5 SD threshold.
RESULTS: There were 82 females in Study-002 and 187 females in the LAVENDER study across both treatment arms at baseline. The pooled SD (Standard Error (SE)) at baseline was 11.39 (0.84) and 11.87 (0.87) for the two studies, respectively. At baseline, using the 0.4 and 0.5 SD thresholds, the RSBQ MCIDs ranged from 4.56 to 5.93. At the end of study assessments, the MCIDs based on total score change from baseline ranged from 3.23 to 4.03 for the 6-week Study-002 and 3.55 to 4.44 for the 12-week LAVENDER study.
CONCLUSIONS: These findings suggest that an estimated MCID for the RSBQ across the Trofinetide clinical trial program is likely to be within a 3- to 6-point difference. Changes in outcomes above this range are likely clinically important, based on natural variability observed in the data; smaller changes likely reflect measurement error rather than true clinical changes. These analyses should be confirmed via further investigation and expert consultation.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
PT15
Topic
Clinical Outcomes
Disease
SDC: Rare & Orphan Diseases