Utility of an effect size analysis for communicating treatment effectiveness: a case study of cholinesterase inhibitors for Alzheimer's disease

Objectives: To highlight the utility of using an effect size analysis to communicate the effectiveness of treatment interventions.

Design: Secondary analysis.

Setting: Previously published systematic review on cholinesterase inhibitors (ChEIs) in Alzheimer's disease.

Participants: Individuals with mild to moderate Alzheimer's disease.

Intervention: Six-month randomized controlled trials involving a placebo group and a ChEI group (donepezil, galantamine, or rivastigmine).

Measurements: Cognitive function was assessed according to performance on the cognition subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog). Global Function was quantified using the Clinician's Interview-Based Impression of Change-Plus (CIBIC-Plus). Harm was defined as withdrawal from a trial because of an adverse event. Several effect size indices were computed based on these domains: the success rate difference (SRD), the harm rate difference (HRD), the number needed to treat (NNT) or harm (NNH), and the area under the curve (AUC). Harm:benefit ratios were also computed to compare effect size indices across domains of function.

Results: In terms of benefit, the NNT for cognition ranged from 4 to 14 (corresponding AUC values: 0.64-0.54), and the NNT for global function ranged from 6 to 100 (corresponding AUC 0.59-0.51). In terms of harm, the NNH ranged from 6 to 20 (corresponding AUC 0.58-0.53). Only one of the four studies had favorable harm:benefit ratios in both the cognition and global function domains.

Conclusion: Effect size indices should be reported in clinical trials because they provide important insight into the clinical meaningfulness of results. Additional benefit is gained by comparing effect size indices across domains of function to reveal harm:benefit ratios.