Affiliations: [a] GCS-fMRI, Koelliker Hospital and Department of Psychology, University of Turin, Turin, Italy
| [b] FOCUSLAB, Department of Psychology, University of Turin, Turin, Italy
| [c] Neuroscience Institute of Turin, Turin, Italy
| [d] Stroke Unit, Department of Neurological and Vision Sciences, ASST Spedali Civili, Brescia, Italy
Correspondence:
[*]
Correspondence to: Dr. Donato Liloia, PhD, Department of Psychology, Via Verdi 10, 10124 Turin, Italy. Tel.: +39 011 670 39 24; E-mail: [email protected]; ORCID: 0000-0002-9481-8510.
Note: [1] These authors contributed equally to this work.
Abstract: Background: Clinical trials targeting Alzheimer’s disease (AD) aim to alleviate clinical symptoms and alter the course of this complex neurodegenerative disorder. However, the conventional approach of null hypothesis significance testing (NHST) commonly employed in such trials has inherent limitations in assessing clinical significance and capturing nuanced evidence of effectiveness on a continuous scale. Objective: In this study, we conducted a re-analysis of the phase III trial of lecanemab, a recently proposed humanized IgG1 monoclonal antibody with high affinity for Aβ soluble protofibrils, using a Bayesian approach with informed t-test priors. Methods: To achieve this, we carefully selected trial data and derived effect size estimates for the primary endpoint, the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB). Subsequently, a series of Bayes Factor analyses were performed to compare evidence supporting the null hypothesis (no treatment effect) versus the alternative hypothesis (presence of an effect). Drawing on relevant literature and the lecanemab phase III trial, we incorporated different minimal clinically important difference (MCID) values for the primary endpoint CDR-SB as prior information. Results: Our findings, based on a standard prior, revealed anecdotal evidence favoring the null hypothesis. Additional robustness checks yielded consistent results. However, when employing informed priors, we observed varying evidence across different MCID values, ultimately indicating no support for the effectiveness of lecanemab over placebo. Conclusion: Our study underscores the value of Bayesian analysis in clinical trials while emphasizing the importance of incorporating MCID and effect size granularity to accurately assess treatment efficacy.
Keywords: Alzheimer’s disease, Bayes Factor, Clarity AD, clinical trial, drug development, informed t priors
