PMID- 37638445
OWN - NLM
STAT- MEDLINE
DCOM- 20231003
LR  - 20231003
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 95
IP  - 3
DP  - 2023
TI  - Unleashing the Power of Bayesian Re-Analysis: Enhancing Insights into Lecanemab 
      (Clarity AD) Phase III Trial Through Informed t-Test.
PG  - 1059-1065
LID - 10.3233/JAD-230589 [doi]
AB  - 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 Abeta 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.
FAU - Costa, Tommaso
AU  - Costa T
AD  - GCS-fMRI, Koelliker Hospital and Department of Psychology, University of Turin, 
      Turin, Italy.
AD  - FOCUSLAB, Department of Psychology, University of Turin, Turin, Italy.
AD  - Neuroscience Institute of Turin, Turin, Italy.
FAU - Premi, Enrico
AU  - Premi E
AD  - Stroke Unit, Department of Neurological and Vision Sciences, ASST Spedali Civili, 
      Brescia, Italy.
FAU - Liloia, Donato
AU  - Liloia D
AD  - GCS-fMRI, Koelliker Hospital and Department of Psychology, University of Turin, 
      Turin, Italy.
AD  - FOCUSLAB, Department of Psychology, University of Turin, Turin, Italy.
FAU - Cauda, Franco
AU  - Cauda F
AD  - GCS-fMRI, Koelliker Hospital and Department of Psychology, University of Turin, 
      Turin, Italy.
AD  - FOCUSLAB, Department of Psychology, University of Turin, Turin, Italy.
AD  - Neuroscience Institute of Turin, Turin, Italy.
FAU - Manuello, Jordi
AU  - Manuello J
AD  - GCS-fMRI, Koelliker Hospital and Department of Psychology, University of Turin, 
      Turin, Italy.
AD  - FOCUSLAB, Department of Psychology, University of Turin, Turin, Italy.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 12PYH0FTU9 (lecanemab)
RN  - 0 (Antibodies, Monoclonal, Humanized)
SB  - IM
MH  - Humans
MH  - *Alzheimer Disease/drug therapy
MH  - Bayes Theorem
MH  - Research Design
MH  - Treatment Outcome
MH  - Antibodies, Monoclonal, Humanized/therapeutic use
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Bayes Factor
OT  - Clarity AD
OT  - clinical trial
OT  - drug development
OT  - informed t priors
EDAT- 2023/08/28 06:42
MHDA- 2023/10/03 06:47
CRDT- 2023/08/28 05:27
PHST- 2023/10/03 06:47 [medline]
PHST- 2023/08/28 06:42 [pubmed]
PHST- 2023/08/28 05:27 [entrez]
AID - JAD230589 [pii]
AID - 10.3233/JAD-230589 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2023;95(3):1059-1065. doi: 10.3233/JAD-230589.