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Boards and Beyond: Biostatistics and Epidemiology

1. Basic Pharmacology
2. Behavioral Science
3. Biochemistry
4. Biostatistics and Epidemiology
5. Cardiology
6. Cell Biology
7. Dermatology
8. Endocrinology
9. Gastroenterology
10. Genetics
11. Hematology
12. Immunology
13. Infectious Disease
14. Musculoskeletal
15. Neurology
16. Pathology
17. Psychiatry
18. Pulmonology
19. Renal
20. Reproductive
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- Central Tendency
• Middle of the bell curve
• Characterized by (1) mean (2) median (3) mode
Mean is most affected by outliers; mode is least affected

- Standard Error (SE)

• Estimates how much variability exists in a set of sample means around the true population mean
• Statistical accuracy of an estimated mean

- Confidence Interval (CI)

• Range of values within which the true mean of the population is expected to fall
As sample size increases, CI narrows
95% CI corresponds to α = .05
• CI for sample mean = Mean ± Z(SE)
95% CI: Z = 1.96
99% CI: Z = 2.58
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- Null Hypothesis (H0)

• NO difference between groups
• NO relationship between risk factor or treatment and the occurrence of the health outcome
• In research, you should always assume the null hypothesis is correct until it can be rejected

- Alternative Hypothesis (H1)

• There IS a difference between groups
• Relationship between risk factor or treatment and the occurrence of the health outcome EXISTS
• Rejection of the null hypothesis

- Hypothesis Testing
• Stating that there is no effect or difference when none exists (null hypothesis not rejected)
• Stating that there is an effect or difference when one exists (null hypothesis rejected)
• 4 Possibilities:
1) There is a difference, and our experiment detected it.
2) There is NOT a difference, and our experiment also found no difference.
3) There is NO difference in reality, but our study detects a difference. Type 1 error (α)
4) There is a difference in reality, but our study did not detect it. Type 2 error (ß)

↑ Power = Desirable in a study

↑ Power means there is a high likelihood

of finding real differences (associations)

α = Type 1 = False positive

ß = Type 2 = False negative
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- Tests to Compare Groups

• t-Test: Compares 2 means
• ANOVA: Compares >2 means
• Chi-Squared: Compares categorical variables
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- Studies to Determine Association of Exposure/Risk with Disease

1. Cross-Sectional Study
2. Case-Control Study
3. Cohort Study (Prospective/Retrospective)

- Cross-Sectional Study
• Observe frequency of disease and frequency of risk factors in a snapshot of time
Lack of a time frame; may have more than one group in the study
• Asks: “What is happening right now in the present?”
• Measures: Disease prevalence
• Can show risk factor associations with the disease; but does NOT establish causality
Cannot identify RR or RR

- Case Series
• Purely descriptive study (similar to cross-sectional)
• Used when there is a new or bizarre disease with unclear cause
• Ex: New febrile illness occurring in Paris, France
Analyzes the symptoms and patient demographics (age, gender) for clues about the etiology
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- Cohort Study
• Compares a group with an exposure VS another group without the exposure
• Aims to identify if the exposure or risk factor is associated with later development of disease
• Measures: RR (“how much does exposure increase risk of disease?”)
• Cons: Does not work with rare diseases
• Prospective: Monitors group over time; more powerful study
• Retrospective: Looks back in time at the groups; prone to recall bias

- Case-Control Study
• Compares a group of people with the disease VS people without the disease
• Aims to see if odds of prior exposure or risk factor are associated with the disease
Compares odds of exposure-related disease in patients that HAVE THE DISEASE vs
those that DO NOT have the disease
• Good for studying rare diseases
• Measures: OR (“what are the odds of the disease in those exposed vs odds in those unexposed?”)

Case control studies will

always study people that
ALREADY HAVE THE
DISEASE
CohoRt = RR7
Case ContrOl = OR
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- Sensitivity (True-Positive)
• Percentage of people with the disease who test positive
• Probability of a positive test result if the patient HAS the disease
• Sensitivity = A/(A+C)
• If you’re overly sensitive in life, you will always be brought DOWN (ARROW DOWN)

- Specificity (True-Negative)
• Percentage of people that do NOT have the disease who test negative
• Probability of a negative test result if the patient DOES NOT HAVE the disease
• If you’re specific about things in life, you will always be going UP (ARROW UP)
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 • Accuracy (valid ity) is how closely data matches reality
• Pre cision (reliability) is how closely repea ted 11
meas ureme nts mat ch each other
• Can have accura cy withou t precision (or vice versa)
Precision vs accuracy
Precision (reliability)
T he co nsistency an d re p rod uc ibili ty of a Random e rror ! prec ision in a test.
test. T he abse nce of ra ndom va ria tio n in a t prec ision - i standard dev iation .
test. t pr ec ision - t statistical power (1 -
Accuracy (validity)
)
T he closeness of test results to th e true val ues. . System atic error i accuracy in a test.
T he absence of systematic error or bias in a test.

f- - - - Accuracy- - - (- - - - Accu racy - - -

••••• • •
Low High
High

• • •
••• • •
•
•
•• Low Low

High

High
----Precision - - - .., L --- Precision ,)

Receiving op erating
charact eristic curve
ROC curve demonstrates how well a diag nostic Ideal test (AUC = 1)
1

·.
test ca n disti nguish betwee n 2 g rou ps (eg,
I
d isease vs healthy). Plots the true-positive rate
(sensitivity) aga in st the false-positive rate 'I
(1 - specificity). -
T he better perform in g test will have a higher I
<lJ
"§ I I I
area und e r the curve (AUC ), with the curve
g:
.....,. .._- th' uppc lcf mer.
.

• Straight line fro m bott om le ft to top rig ht is a bad

test
• Close r curve is to right angle, better the test FP rate (1 - specificity) 1

• Useless test has 0.5 (50%) area under curve

• Perfect test has 1.0 (100 %) area under curve
• More area under curve = better test
• Mo re a bili ty to discrimin ate individuals wi th d isease fr o m
th ose with out
Likelihood ratio probab ility shifts with (+) or (-) test Li kelihood th at a would be
given test result expected in a
Likelihood ratios tell us how much
 pat ie nt wit h the target LW= sens itivity T P rate FP
disorde r 1 - specific ity rate
co mpa red to the likelihood th
at the sa me result would be LR-= 1 - sensitivit y F rate TN
expected in a patient without specificity rate
the
tar get d isorde r.
LW > 10 i ndicates a highly
specific tes t, wh ile LR- < 0.1 LR Interpre tation
indicates a highly sensitive >10 Large increase probability
test. 1 No change in probability
<0.1 Large decrease in probability
LRs ca n be multiplied with
pretest odd s of d isease to
estimate posttest odd s.
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- Bias
• Selection:
“Volunteers” compared with general population can be a red flag
Berkson’s Bias: Hospitalized patients chosen as a group
• Confounding:
Correct by randomization
Correct by matching (carefully select control subjects to closely match study subjects)
• Hawthorne Effect: Participants change behavior once they know they’re in a study
Correct by blinding
• Observer-Expectancy (Pygmalion) Effect: Researcher
Researcher’s positive beliefs in the efficacy of a treatment can influence the outcome
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- Clinical Trial Phases

1. Safety measured (Is it safe?)
Safety, Toxicity, Pharmacokinetics
Small group of healthy volunteers
2. Efficacy measured (Does it work?)
Efficacy, Dosing, Side Effects
Small group of sick patients
3. Comparison measured (Is it better than the current standard treatment?)
Large group of sick patients
4. Long-term adverse effects measured (Should it stay on the market?)
Post-marketing study, monitor long-term side effects