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Anti-Amyloid Treatment in Asymptomatic           Alzheimer’s (A4):      Composite outcome measure Michael Donohue∗ , Reisa...
A4 study design   Age 70-85, MMSE 27-30, CDR-G 0, LM II 15-9 with >12 years education
Composite components    • Components selected, a priori, based on literature    • Sum of baseline-standardized Z-scores:  ...
ADNI amyloid group differences                                                                                 * p = 0.018 ...
Smallest detectable effect with N = 500 per group                                                                          ...
Australian Imaging, Biomarker & Lifestyle (AIBL) Study    Composite change from baseline                                  ...
ADCS Prevention Instrument (PI) Study                                                                      *              ...
Thank you!    • Alzheimer’s Research Forum    • Reisa Sperling, Rema Raman, Ronald Thomas,      Chung-Kai Sun, Anthony Gam...
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Donohue Alzforum Webinar Feb 28 2013

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Donohue Alzforum Webinar Feb 28 2013

  1. 1. Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4): Composite outcome measure Michael Donohue∗ , Reisa Sperling, Chung-Kai Sun, Rema Raman, Ronald Thomas, Paul Aisen ∗ Alzheimer’s Disease Cooperative Study Division of Biostatistics & Bioinformatics Department of Family & Preventive Medicine University of California, San Diego Alzheimer’s Research Forum February 28, 2013
  2. 2. A4 study design Age 70-85, MMSE 27-30, CDR-G 0, LM II 15-9 with >12 years education
  3. 3. Composite components • Components selected, a priori, based on literature • Sum of baseline-standardized Z-scores: • Mini-Mental State Exam (MMSE) (0-30 points) • ADAS Delayed Word List Recall (0-10 words) • Logical Memory Delayed Paragraph Recall (0-25 story units) • WAIS-R Digit Symbol Substitution (0-93 symbols) − • Zt = (Yt σ Y0 ) , where σ0 is standard deviation of Y at baseline. 0 • 25%σ0 change on each component Z-score → 1 point change on total composite.
  4. 4. ADNI amyloid group differences * p = 0.018 Composite change from baseline 1 0 −1 amyloid− n=60 59 58 53 52 amyloid+ −2 n=37 36 34 34 27 0 10 20 30 Month area between curves p = 0.052 Mixed model estimates adjusted for age and composite score at baseline.
  5. 5. Smallest detectable effect with N = 500 per group * Composite change from baseline 1 0 −1 (solanezumab) n=500 459 435 410 386 361 337 amyloid− n=60 59 58 53 52 amyloid+ −2 n=37 36 34 34 27 0 10 20 30 Month 80% power to detect 0.53/1.24 = 43% of 2 year amyloid group difference (d = 0.21) (α=5%, attrition=30%).
  6. 6. Australian Imaging, Biomarker & Lifestyle (AIBL) Study Composite change from baseline 1 *p = 0.010 0 −1 (solanezumab) n=500 459 435 410 386 361 337 amyloid− n=114 109 amyloid+ −2 n=50 47 0 10 20 30 Month 80% power to detect 0.46/1.07 = 43% of 1.5 year amyloid group difference (d = 0.21) (α=5%, attrition=30%).
  7. 7. ADCS Prevention Instrument (PI) Study * * *p < 0.001 0 Composite change from baseline −2 −4 (solanezumab) n=500 459 435 410 386 361 337 CDR−G stable n=478 422 381 335 CDR−G progressor n=27 27 24 21 0 10 20 30 Month area between curves p < 0.001 80% power to detect 0.65/4.47 = 15% of 3 year progressor group difference (d = 0.21) (α=5%, attrition=30%).
  8. 8. Thank you! • Alzheimer’s Research Forum • Reisa Sperling, Rema Raman, Ronald Thomas, Chung-Kai Sun, Anthony Gamst, Chris Rowe, Paul Aisen • Alzheimer’s Disease Cooperative Study (ADCS) • Alzheimer’s Disease Neuroimaging Initiative (ADNI) • Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL) • UCSD Clinical & Translational Research Institute 8KL2TR000099-03 • Study volunteers and their families

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