Yanjanin et al. Figure 2:
Statistical Modeling of NPC Phenotypic Progression
Group members: Lindsay Renz and Madeline Zupan
Acknowledgements:
Dr. Kasturi Haldar, PhD
Barbara Calhoun, RN, MSN, PNP
Background
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Niemann-Pick Type C disease is a neurodegenerative, lysosomal storage disorder
with a broad clinical spectrum and a variable age of onset.
Clinical severity scale created to analyze and track disease progression
o 9 major and 8 minor domains
o Dynamic range from 0-61
o For details see Table I
Total of 37 patients
o 18 current NPC patients
o 19 historical NPC patients
o Demographics of patients- see Table II
Figure 1 - NPC Clinical Progression
o Fig 1A: severity scores vs. age for current cohort
o Fig 1B: severity scores vs. years since onset
o Fig 1C: Longitudinal severity scores vs. age for all historical cohorts
o Fig 1D: Progression slope made from linear regression of Fig 1C lines
o Fig 1E: Contributions of major domains to total score
Data:
Figure 2
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NPC Phenotypic Progression
○ Statistical modeling
○ both cohorts
Range in:
○ Age
○ Visits
○ Scores
Graph shows:
○ Population model
○ Individual model
○ Individual measure
Total Score
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S = -10.7 +1.87x
Age (years)
Strengths
● Shows linear progression of individual scores
● Indicates population averages
o Individuals can compare scores
● Statistical analysis numbers - comparative
o Range, mean, standard deviation
● Both cohorts included in data
o Doubles number of subjects
● Clearly shows progression of disease is independent of
age of onset
Weaknesses
● Inconsistent number of data points per patient
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o Visit range 1-8
Score range
o 1-46 out of max 61
o Massive standard deviation for total score range
Unclear on impact of inclusion of “modifiers” in score
Inclusion of irrelevant domains
o Hearing/sensorineural
o Memory
No indication of which patients were simultaneously receiving treatment
o Treatment/therapy would slow disease progression
Young children unable to fully indicate extent of domains
o E.g. Toddlers cannot communicate memory loss
Inclusion of adults
o Small sample size
o Statistically significant as data or more subjects necessary?
Significance
● Definitive model for mapping progression
● Consistently indicates linear progression of disease
● Provides comparative examples for various ages of
onset
● Increased age of onset is not correlated with higher
scores
● Tool for both healthcare professionals and patients