Sheehan-Suicidality Tracking Scale (Sheehan-STS) in Predementia … · 2017. 10. 26. ·...
Transcript of Sheehan-Suicidality Tracking Scale (Sheehan-STS) in Predementia … · 2017. 10. 26. ·...
Sheehan-Suicidality Tracking Scale (Sheehan-STS) in Predementia Alzheimer’s Disease
Vlad Coric MD1, Robert M. Berman MD1, Jesse M. Cedarbaum MD PhD1 and David Sheehan MD2 1Research & Development, Bristol-Myers Squibb, Wallingford Connecticut
2University of South Florida, Tampa, Florida
February 21, 2013
Disclosure: Full-time, paid employee of Bristol-Myers Squibb Own stock in Bristol-Myers Squibb
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Assessment of Suicidal Ideation/Behavior in Alzheimer’s Disease (AD) Populations
Limited published data regarding ideation/behavior in AD trials
No validated scale in Predementia AD – BMS Predementia AD study (CN156-018) initiated 2009
Challenges in AD clinical trial populations – patients with impaired MMSE and progressive decline over time – reliability of assessments over disease course unknown – high burden of psychometric testing (often several hours) – difficulty of obtaining reliable caregiver input (SI internal thoughts not
always expressed; preparatory behaviors often hidden from others)
Sheehan-STS incorporated in CN156-018 trial to assess its utility in a Predementia AD population
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Sheehan-STS
Evolved from the Suicidality Module of the MINI Structured Diagnostic Interview for DSM-IV
Prospective, self-report or clinician-administered rating scale
Eight-item scale assesses – treatment-emergent suicidal ideations – treatment-emergent suicidal behaviors
Items scored on a 5-point Likert scale:
(0=not at all, 1=a little, 2=moderately, 3=very, and 4=extremely)
Efficient administration (completed in 1-2 minutes)
Maps to C-CASA 2010
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Sheehan-STS
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Sheehan-STS Data Analysis
Individual item scores
Suicidal ideation subscale score – sum of scores from items 2, 3, and 4, plus score from item 5 if ≤1
Suicidal behavior subscale score – sum of scores from items 6, 7a, and 8, plus score from item 5 if >1
Sheehan STS-total score – sum of ideation and behavior subscales
Change over time and assess for drug effects on treatment emergent ideation and behavior
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Avagacestat Prodromal (Predementia) AD Study Design
Avagacestat
Placebo
aMCI
Observational cohort (not randomized) Nonpathologic
CSF n=100a
Pathologic CSF
n=270a
Treatment period (104 weeks minimum) 1:1 randomization
Screening to identify predementia patients
LP
aTarget
Sheehan-STS performed at ALL visits: -every 2 weeks for the first 3 months -then every 3 months thereafter
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Key Entry Criteria
Clinical • Ages 45-90 • MMSE 24-30 • CDR-global 0.5
and CDR memory score ≥ 0.5
• MRI/other medical workup do not suggest non-AD causes of impairment
• Stable ChEIs or memantine allowed
• GDS < 6
Cognitive • Memory complaint by
subject or study partner
• Objective impairment on: • Logical Memory II
(WMS) test of Delayed Paragraph Recall or
• Free Cued Selective Reminding Test (total recall, free recall, or delayed free recall)
Biomarker • Cerebrospinal fluid
consistent with Alzheimer’s Disease pathology: • Aβ42 ≤ 200pg/ml
or • t-tau/Aβ42 ≥ 0.39 *CSF analyzed at a central
laboratory using LuminexxMAPtechnique
(INNO-BIA AlzBio3 kit; Innogenetics).
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Sheehan-STS in Predementia AD Population (CN156-018)
3,348 administrations of Sheehan-STS in 263 subjects treated up to 152 weeks (interim analysis Nov-2012)
Randomization completed September 2011
24 month recruitment period
72 sites in North America and Europe
Study terminated November 2012 and subjects remain in follow-up phase
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Demographics and Baseline Evaluation, randomized sample with baseline Sheehan-STS
Randomized (n=263)
Age, mean (range) 71.8 (49-90) Gender, % male 56 APOE4 Status, % carrier 68 MMSE (range) 27.0 (24-30) Baseline Sheehan-STS: Total Score = 0 94.7% (n=248) Total Score = 1 3.8% (n=10) Total Score > 1 1.5% (n=4) Suicidal Ideation Subscale 5% (n=14) Suicidal Behavior Subscale 0% (n=0)
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Completion of Sheehan-STS in Predementia AD Visit Number records (%)
≥ 1 missing item Baseline 0/263
Week 2 1/258 (0.4%)
Week 4 0/248
Week 6 0/239
Week 8 0/248
Week 12 0/229
Week 16 0/223
Week 20 0/216
Week 24 1/219 (0.5%)
Week 32 0/203
Week 44 2/188 (1.1%)
Week 56 0/179
Week 68 0/163
Week 80 0/137
Week 92 0/119
Week 104 0/91
Week 116-152 0/125
TOTAL ACROSS WEEKS
4/3,348 (0.12%) (safety sample)
99.88% completion rate
without missing data
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Observed Changes from baseline Sheehan-STS total score
Week < -1 -1 No Change 1 > 1 Week 2 3 9 240 2 1
Week 4 3 7 229 5 2
Week 6 3 6 221 7 1
Week 8 3 7 228 1 1
Week 12 3 6 213 3 1
Week 16 3 7 204 2 1
Week 20 3 8 198 4 1
Week 24 2 8 198 2 1
Week 32 1 7 189 4 1
Week 44 2 7 174 1 1
Week 56 1 7 166 1 2
Week 68 1 7 150 2 1
Week 80 1 6 127 1 2
Week 92 4 112 1 1
Week 104 3 88
(treatments pooled OC data set)
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Agreement Between Sheehan-STS Suicidal Ideation Subscale and Treatment Emergent AEs
(cohort randomized to study treatment)
Agreement between
Sheehan-STS and TEAE reporting
STS
Idea
tion
Subs
cale
Sco
re
2,990 (98.3%)
52 (1.7%)
0
1 (0.03%)
No Yes
0
≥1
Treatment Emergent AE of SUICIDAL IDEATION
Sheehan-STS more sensitive than AE/SAE assessed SI
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Agreement Between Sheehan-STS Suicidal Behavior Subscale and Treatment Emergent AEs
STS
Beh
avio
rs S
ubsc
ale
3,032 (99.6%)
11 (0.4%)
0
0
No
0
≥1
Treatment Emergent AE of SUICIDE ATTEMPT
Yes
(cohort randomized to study treatment)
Agreement between
Sheehan-STS and TEAE reporting
Sheehan-STS more sensitive than AE/SAE assessed SB
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Sheehan-STS in Predementia AD Very low rates of missing data
Sensitive to change from baseline
High rates of agreement between Sheehan-STS and review of TEAE/SAEs
More sensitive than AE/SAE reporting of ideations/behaviors – Sheehan-STS ideation subscale identified 52 incidences of suicidal ideations
– Sheehan-STS behavior subscale identified 11 incidences of suicidal behaviors
Administrations did not fail to capture occurrences of SI/SB
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Sheehan-STS in Predementia AD Sheehan-STS demonstrated significant utility during this
study and advantages include: – can be administered either via self report or clinicians
– more sensitive than AE/SAE reporting
– efficient (completed in only 1 to 2 minutes)
– assesses multiple domains of suicidal thoughts/behaviors (passive suicidal ideation, active suicidal ideation, suicidal behaviors, self-injurious behaviors, accidents)
– multiple analyses (individual item scores, total score, suicidal ideation subscale, suicidal behaviors subscale, treatment emergent changes)
– maps to the C-CASA (suicidality classification/coding system )
Future work needed: assess other AD populations, reliability over entire disease course, correlation with other scales, ↑ sample size, assess caregiver report
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Acknowledgements
The authors acknowledge with deep appreciation all the patients and study partners who participated in the CN156-018 trial
We also recognize the efforts of the principal investigators and their clinical staff
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Back-up Slides
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Agreement Between Sheehan-STS and GDS-short form
(Administrations of cohort randomized to study treatment)
STS
Tota
l Sco
re 1,561
(93.9%)
51 (3.1%)
40 (2.4%)
11 (0.67%)
≤ 5 > 5 (mild depressive sx’s)
0
≥1
GDS-short form total score