dr alan winston - bhivaalan winston has received honoraria or research grants, or been a consultant...
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![Page 1: Dr Alan Winston - BHIVAAlan Winston has received honoraria or research grants, or been a consultant or investigator, in clinical trials sponsored by Abbott, Boehringer Ingelheim, Bristol-Myers](https://reader034.vdocuments.net/reader034/viewer/2022051812/602ae9fb0c4606316d739fdd/html5/thumbnails/1.jpg)
Dr Alan Winston Imperial College Healthcare NHS Trust, London
16-19 April 2013, Manchester Central Convention Complex
19th Annual Conference of the British HIV Association (BHIVA)
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16-19 April 2013, Manchester Central Convention Complex
19th Annual Conference of the British HIV Association (BHIVA)
COMPETING INTEREST OF FINANCIAL VALUE > £1,000:
Speaker Name Statement
Alan Winston
Alan Winston has received honoraria or research grants, or been a consultant or
investigator, in clinical trials sponsored by Abbott, Boehringer Ingelheim, Bristol-Myers
Squibb, Gilead Sciences, GlaxoSmithKline, Janssen Cilag, Roche, Pfizer and ViiV
Healthcare.
Date April 2013
Dr Alan Winston Imperial College Healthcare NHS Trust, London
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Neurocognitive testing in clinical trials: luxury or necessity?
Alan Winston Imperial College, London
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Luxury or necessity
0102030405060708090
100
Regimen A
Regimen B
Pro
port
ion
undet
ecta
ble
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Luxury or necessity
Where next?
•Non-infectious co-morbidities
•Patient acceptability and QOL
•Implications for cost and healthcare utilisation
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Technicalities of cognitive testing
Screening battery Cognitive testing in clinical practice
Cognitive testing in research studies
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Technicalities of cognitive testing
Screening battery Cognitive testing in clinical practice
Cognitive testing in research studies
Problems: •Ease of administration •Decision to administer to all or selected populations •Sensitive and specific •Reproducible
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Technicalities of cognitive testing
Screening battery Cognitive testing in clinical practice
Cognitive testing in research studies
Problems: •Ease of administration •Decision to administer to all or selected populations •Sensitive and specific •Reproducible
Problems: •Populations to target •Time consuming •Appropriate control population •Interpretation of patient’s symptomatology
![Page 9: Dr Alan Winston - BHIVAAlan Winston has received honoraria or research grants, or been a consultant or investigator, in clinical trials sponsored by Abbott, Boehringer Ingelheim, Bristol-Myers](https://reader034.vdocuments.net/reader034/viewer/2022051812/602ae9fb0c4606316d739fdd/html5/thumbnails/9.jpg)
Technicalities of cognitive testing
Screening battery Cognitive testing in clinical practice
Cognitive testing in research studies
Problems: •Ease of administration •Decision to administer to all or selected populations •Sensitive and specific •Reproducible
Problems: •Populations to target •Time consuming •Appropriate control population •Interpretation of patient’s symptomatology
The way forward: •Allows an accurate assessment of end-organ disease within an already selected cohort •Often permits longitudinal data •May offer the opportunity to obtain appropriate control data
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Which battery?
Domain
Attention
Executive function
Verbal learning
Verbal memory
Fine motor
Speed of information processing
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Which battery?
Domain Study (PIVOT) Study (POPPY)
Attention Colour Trails Test 1 Cog State (card)
Executive function Colour Trails Test 2 Cog State (maze)
Verbal learning Hopkins Verbal Learning Test, learning Cog State (words)
Verbal memory Hopkins Verbal Learning Test, recall Cog State (words)
Fine motor Grooved Pegboard -
Speed of information processing - Cog State (card)
Does it matter which battery for longitudinal studies?
Probably not
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Domain Test Standard normative data Adjusted normative data
Attention Colour Trails Test 1 n=1528, 70% Caucasian, [1]
n=182, inc. African American, [1]
Executive function Colour Trails Test 2
as above as above
Verbal learning Hopkins Verbal Learning Test (HVLT), learning
n=1179, [2] n=246, 42% African American, [4]
Verbal memory Hopkins Verbal Learning Test (HVLT), recall
as above as above
Fine motor Grooved Pegboard
[3] -
Methods
• Neurocognitive testing undertaken prospectively in all subjects • Baseline test results available for this analysis • Raw scores for each test were transformed to z-scores using normative data (age matched all
tests and education matched CTT)
1. D’Elia LF et al. Color Trails Test. 1996 Odessa, FL: PAR 2. Brandt J and Benedict RHB. Hopkins Verbal Learning test-Revised. 2001 Odessa, FL:PAR 3. Trites R. Neuropsychological test manual. Ottawa, Ontario 1997 4. Journal of Clinical and Experimental Neuropsychology, Volume 33, Issue 7, 2011)
PIVOT – Control populations
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PIVOT – describing cognitive results
Description of neurocognitive results
Global score • composite score / average • NPZ-5 Categorise this score • example < 1 SD mean • expect approximately 16% of healthy
population < 1 SD mean
Categorical score (such as Frascati score) • Impaired versus non-impaired (yes/no) • below 1 SD in at least 2 domains • result normal or abnormal • expect approximately 20% of healthy population
abnormal • no Instrumental Activities of Daily Living Scale
assessed – therefore can’t categorise ANI, MCD, HAD
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Global scores (NPZ-5)
NC results - overall Standard normative data
84
69
83
34
16
31
17
66
0
20
40
60
80
100
Estimated control population
Overall Caucasian Black ethnicity
Within normal range > 1SD below mean
p<0.001
%
PIVOT
PLOS One (in press)
N=560
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Global scores (NPZ-5)
Categorical Score (Frascati)
NC results - overall Standard normative data
84
69
83
34
16
31
17
66
0
20
40
60
80
100
Estimated control population
Overall Caucasian Black ethnicity
Within normal range > 1SD below mean
p<0.001
%
80
49
62
1920
51
38
81
0
20
40
60
80
100
Estimated control population
Overall Caucasian Black ethnicity
Normal > 1SD below mean in at least 2 domains
p<0.001
%
PIVOT
PLOS One (in press)
N=560
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0
20
40
60
80
100Overall Caucasian Black ethnicity
%
Drivers of findings
Association between global (NPZ-5) and categorical (Frascati) scores
PLOS One (in press)
PIVOT
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80
38 3831
20
64 6269
0
20
40
60
80
100
Estimated control population
Overall Caucasian Black ethnicity
Normal > 1SD below mean in at least 2 domains
84
5862
45
16
4238
55
0
20
40
60
80
100
Estimated control population
Overall Caucasian Black ethnicity
Within normal range > 1SD below mean
NC results – adjusted
Global scores (NPZ-5)
Categorical Score (Frascati)
p=0.001
p=0.156
Adjusted normative data
%
%
84
69
83
34
16
31
17
66
0
20
40
60
80
100
Estimated control population
Overall Caucasian Black ethnicity
Within normal range > 1SD below mean
80
49
62
1920
51
38
81
0
20
40
60
80
100
Estimated control population
Overall Caucasian Black ethnicity
Normal > 1SD below mean in at least 2 domains
PLOS One (in press)
PIVOT
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A tale of 2 studies
PIVOT
Baseline results: • need for population control data to interpret results • need to challenge current diagnostic criteria
PI OT
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A tale of 2 studies
PIVOT
Baseline results: • need for population control data to interpret results • need to challenge current diagnostic criteria
Follow up results: • differences in any changes in cognitive function between two treatment approaches • factors associated with cognitive function (implications for screening etc. in different populations)
POPPY
Baseline results will include cognitive function in: • 1000 HIV infected subjects over 50 • 500 HIV infected subjects under 50 • 500 HIV un-infected subjects over 50
Follow up results: • differences in any changes in cognitive function between these groups
PI OT
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#BHIVA2013