Effect Size Analyses of Souvenaid in Patients with Alzheimer's Disease

Jeffrey Cummings, Philip Scheltens, Ian McKeith, Rafael Blesa, John E Harrison, Paulo H F Bertolucci, Kenneth Rockwood, David Wilkinson, Wouter Wijker, David A Bennett, Raj C Shah, Jeffrey Cummings, Philip Scheltens, Ian McKeith, Rafael Blesa, John E Harrison, Paulo H F Bertolucci, Kenneth Rockwood, David Wilkinson, Wouter Wijker, David A Bennett, Raj C Shah

Abstract

Background: Souvenaid® (uridine monophosphate, docosahexaenoic acid, eicosapentaenoic acid, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium), was developed to support the formation and function of neuronal membranes.

Objective: To determine effect sizes observed in clinical trials of Souvenaid and to calculate the number needed to treat to show benefit or harm.

Methods: Data from all three reported randomized controlled trials of Souvenaid in Alzheimer's disease (AD) dementia (Souvenir I, Souvenir II, and S-Connect) and an open-label extension study were included in analyses of effect size for cognitive, functional, and behavioral outcomes. Effect size was determined by calculating Cohen's d statistic (or Cramér's V method for nominal data), number needed to treat and number needed to harm. Statistical calculations were performed for the intent-to-treat populations.

Results: In patients with mild AD, effect sizes were 0.21 (95% confidence intervals: -0.06, 0.49) for the primary outcome in Souvenir II (neuropsychological test battery memory z-score) and 0.20 (0.10, 0.34) for the co-primary outcome of Souvenir I (Wechsler memory scale delayed recall). No effect was shown on cognition in patients with mild-to-moderate AD (S-Connect). The number needed to treat (6 and 21 for Souvenir I and II, respectively) and high number needed to harm values indicate a favorable harm:benefit ratio for Souvenaid versus control in patients with mild AD.

Conclusions: The favorable safety profile and impact on outcome measures converge to corroborate the putative mode of action and demonstrate that Souvenaid can achieve clinically detectable effects in patients with early AD.

Keywords: Alzheimer’s disease; Souvenaid; effect size; number-needed-to-treat.

Figures

Fig.1
Fig.1
Effect sizes (point estimate and 95% CI) for the main primary and secondary outcome measures in the Souvenir I (•), Souvenir II (■), open-label extension (OLE) (♦), and S-Connect (▴) studies in patients with mild and mild to moderate Alzheimer’s disease. Mean baseline values of the Mini-Mental State Examination (MMSE) score of the total study populations are shown in the figure. Effect sizes were calculated using Cohen’s d [18] (red) for change from baseline values, except for CIBIC-plus (values at week 12 were used), and Cramér’s V [19] (blue) for nominal data. Cohen’s d values range from –∞ to +∞, with a positive effect size indicating improvement in the active (Souvenaid) group versus control and vice versa. Cramér’s V values range from 0 (no association) to 1 (perfect association).

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Source: PubMed

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