Class 1 Outline:

Data as Evidence
1. Data as Evidence
2. Schools of Statistical Thinking
3. The Scientific Method
4. Biostatistics
• What is biostatistics?
• Role of biostatistics in public health
• Key ideas in statistical reasoning
• Biostatistics and the scientific method
5. The Biostatistics Paradigm
6. A Statistical Perspective on Cause
7. Example of Scientific Evidence from Studies:
Aceh Vitamin A Trial

1. Data as Evidence
• Associations between air pollution and mortality

• Benefits of clinical and community trials

• Drug approval decisions

• Descriptions of relationships between attitudes and

behaviors

• Which gene pathways regulate amyloid deposition?

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 2. Schools of Statistical Thinking
• Frequentist statistics
What is the probability of a wrong decision about the treatment
effect? What should we conclude from the observed data given a
specified null hypothesis?

• Bayesian statistics
What should we believe about the treatment effect
given the data that are observed?

• Likelihood inference
What is the evidence about the treatment effect
given the data that are observed?

3. The Scientific Method

Popper (1934) paradigm:
• Competing hypotheses about nature

• H0,H1,H2,H3, …., Hn
• Design a study and generate data

• Science is a process of eliminating hypotheses whose predictions

are inconsistent with observation.

Other paradigms
• Kuhn (1970): “Normal” science; paradigm shifts
• Big data: Science as description

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 3. The Scientific Method (cont’d)
• Often guided by “models”
– Simplifications of the world
– “Hypotheses”; Conceptual frameworks
– Example: Geocentric vs heliocentric models of the solar system
– Example: Dynamical systems view of physiology

Varadhan, Seplaki, Bandeen-Roche,

Xue, Mech Ageing Dev, 2008

Few models are “true” but

some are useful! (Box, 1976)

4. Biostatistics
• Biostatistics --
application of statistical reasoning and methods to the solution of
biological, medical and public health problems

• Biostatistics -- scientific use of quantitative

information to describe or draw inferences about
natural phenomena
– scientific -- accepted theory (ideas) and practice; ethical
standards
– quantitative information -- data reflecting variation in
populations
– inference -- to conclude or surmise from evidence

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 4.1 Role of Biostatistics in Science
1. Generate hypotheses: ask questions.

2. Design and conduct studies to generate evidence;

collect data.

3. Descriptive statistics: describe the distributions of

observations.

4. Statistical inference: assess strength of evidence in

favor of competing hypotheses; use data to update
beliefs and make decisions.

4.2 How Do Hypotheses Originate?

Act of creativity, informed by:

• Scientific background

• Prior observations

• Results of prior studies

• Scientific intuition

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 4.3 Design of a Study

• Ask a precise, testable and appropriate question

• Choose a research approach and design

• Define outcome of interest

• Define comparison groups

• Choose a population to study

4.4 Descriptive Statistics

• Also known as Exploratory Data Analysis (EDA)

• Organization and summarization of data

• Graphical display to visualize important patterns and

variation

• Hypothesis generating

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 4.5 Statistical Inference
• Also known as Confirmatory Data Analysis (CDA)

• Draw conclusions about a population (whole group; true

mechanism) from a sample (representative part of a
group; “trials”)

• Assess strength of evidence in support of competing

hypotheses

• Make comparisons
• Make decisions
• Make predictions

• Statistical inference uses data to surmise what is true or 11

likely to be true.

4.5 Statistical Inference (cont'd)

Probability

Observed Value for

Truth for
a Representative
Population
Sample

Statistical inference

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 4.6 Key Ideas in Statistical Reasoning

1. Natural laws do not perfectly predict all phenomena --

e.g., coin tossing, disease incidence.

2. Probability models are useful tools for representing

“tendencies” in the presence of variation.

3. Variation across people, over time and space, is itself a

natural phenomenon.

4. Variation leads to uncertainty about a particular event.

5. There are important patterns (tendencies, signals, laws)

to be discovered in the midst of variation.

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4.6 Key Ideas in Statistical Reasoning (cont’d)

Combination of data with models is key to human

progress… (R Fisher, 1952 IBS address)

… and even freedom (R Kass, 2017 Fisher Lecture)

Real World Theoretical World

Scientific models
Data
Statistical models

Conclusions
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 4.7 Biostatistics and the Scientific Method

• Competing hypotheses:
H0 - coin has two tails (0 heads)
H1 - coin has one head and one tail
H2 - coin has two heads

• Study and data:

Toss the coin fairly
Data: Heads

• Data as evidence:
– “Heads” is impossible under H0; it is ruled out
– “Heads” is twice as likely under H2 than under H1;
data favor H2 over H1
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4.8. Schools of Statistical Thinking, Revisited

• Frequentist statistics
How frequently would we observe data like ours if the coin were fair
(i.e. a particular hypothesis were true)?

• Bayesian statistics
How do the observed data alter my belief on the probability that the
coin is fair (i.e. a particular hypothesis is true)?

• Likelihood inference
“Evidence” of a fair coin given my toss is measured by the probability
of getting a heads if the coin is fair

Likelihood principle: All evidence regarding a hypothesis is contained

in the “likelihood function”--the probability model, under each possible
hypothesis, for the data actually observed.

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 5. Biostatistics Paradigm

Public health research attempts to discover simple

explanations for “how the world works”; in particular, the
inter-relationships among variables.

• explanations - hypotheses about mechanisms

• variable- a characteristic taking on different values
• simple - scientists prefer simple, rather than complex
explanations; Occam's razor; principle of parsimony
• inter-relationships- associations; causal connections
• Causal graphs as short-hand notation

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5.1 Variables
• Variable - a characteristics taking on different values

• Random variable - a variable for which the values

obtained are usually thought of as arising partly as a
result of chance factors

• Response variable (Y) - the outcome measure; that

which is affected or caused; often a health measure

• Explanatory variables (X) - those which affect or cause

the response:
– Treatment (intervention) – explanatory variable that can be
controlled by the scientist.
– Risk factors - explanatory variables which influence the risk of
the outcome; scientific interest (e.g. smoking; salt intake); usually
cannot be controlled.
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 5.2 Kinds of Variables and Measurement
Scales
• Quantitative: concept of amount; numerical
– Discrete Variables: gaps in values; e.g., number of
births, number of drinks per week

– Continuous Variables: no gaps in values; e.g., blood

pressure, age, height, time to seroconversion

Special case: time to event data in which we need to

deal with “censoring”

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5.2 Kinds of Variables and Measurement

Scales (cont’d)

• Qualitative: concept of attribute; categorical

– Nominal scale
• Binary or dichotomous: e.g., gender, alive or dead
• Polychotomous or polytomous: e.g., marital status

– Ordinal or ordered scale: e.g., ratings, preferences

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 5.3 Measurement Properties of Data
• “Variation” refers to the differences among a set of
measurements

• Where do these differences come from; why aren't all the

measurements the same?

• Natural vs. measurement variation

– Natural variation - Differences among persons
(experimental units) in the “true” values of the variable
of interest
– Measurement variation (or error) - Differences
between the measured and true values

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5.4 Bias and Variance

• Bias - difference between the average (expected) value
of a measurement (variable) and the true value that it
targets

• Variance - variation among measurements about their

average or mean value, even if that mean differs from
the true targeted value

• In science and statistics, we continually balance bias and

variance.

• Mean squared error (MSE) = Variance + Bias2

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 6.0 Statistical Perspective on Cause
• When we say “Smoking causes lung cancer”, what do
we mean?

• Webster's New Collegiate Dictionary:

– Cause: something that brings about an effect or result

• Sir Bradford Hill's criteria:

– Strength of association
– Consistency
– Specificity
– Temporality
– Dose-response
– Plausibility

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6.1 Counterfactual Definition of Cause

• Xi = 1 if person i is a smoker, 0 if not

• Yi(X) = 1 if person i has lung cancer, 0 if not

• Causal effect of smoking on lung cancer for person i

Yi(Xi=1) - Yi(Xi=0)

• Difference in lung cancer state if person i is a smoker

relative to if he is not

• Cannot observe both Yi(Xi=1) and Yi(Xi=0)  counter-

factual
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• Missing data problem (Rubin, 1974)

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 6.1 Counterfactual Definition of Cause (cont’d)

Person X Y(X=0) Y(X=1) =Y(1)-Y(0)

1 0 0 ? ?
2 0 0 ? ?
3 0 1 ? ?
. . . . .
50 0 1 ? ?
51 1 ? 0 ?
52 1 ? 1 ?
. . . . .
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100 1 ? 0 ?

6.1 Counterfactual Definition of Cause (cont’d)

• Use available data to “fill-in” or “impute missing
information

• Since a person cannot be used as his/her own control,

use another person who is as similar as possible
– Compare like-to-like

• Quality of data can be assessed by how accurately we

can “impute” missing information

• How similar are comparison groups for measured and

unmeasured other factors?
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 6.2 Approximating Causality
• Taking into account the factors (variables) that may differ
between comparison groups which may influence the
outcome.

• Confounders - other variables which need to be taken

into account when assessing the association of
treatments or risk factors with a response or outcome.

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6.3 Effect Modification

• Taking into account that there may be an interaction
between two variables on an outcome (e.g. the effect of
a variable on an outcome is modified by the value of a
second variable).

• Effect modifiers - variables which identify subgroups of

people (units) across which the relationship of a
treatment (risk factor) and outcome will differ.

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 7. Example: Scientific Evidence in a Study
• Aceh Vitamin A Trial

• 25,939 preschool children in 450 Indonesian villages in

northern Sumatra

• 200,000 IU vitamin A given at 1-3 months after the

baseline census and again 6-8 months later

• Consider 23,682 out of 25,939 who were visited on a

pre-designed schedule

References
1. Sommer A, Djunaedi E, Loeden A et al. Lancet 1986
2. Sommer A, Zeger S: Statistics in Medicine 1991
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7.1 Data as Scientific Evidence

• Randomized Community Trial of Children in 450 Villages

Alive at Alive at
12 mos. 12 mos.
Vit A Yes No Total
No 11,514 74 11,588

Yes 12,048 46 12,094

Total 23,562 120 23,682

• Does Vitamin A reduce mortality?
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 7.2 Data as Scientific Evidence (cont'd)

• Mortality Rates per 1,000 child-years

Mortality
Vitamin A Deaths/Child-Years Rate

No 74/11,588 6.4
Yes 46/12,094 3.8
Total 120/23,682 5.1
• Does Vitamin A reduce mortality?
• Calculate a risk ratio or “relative risk”: 3.8/6.4 = 0.59
• 40 percent reduction in mortality in the study group!
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7.3 Remaining Questions

• There appears to be an association between Vitamin A

and reduced mortality.

• Does Vitamin A cause this reduction?

– The role of randomization is to balance other
observed and unobserved factors.
– The Aceh study is only one small part of the
Indonesian population.
– If the study was performed again, would we get the
same or similar results?
– Do we believe Vit A works? Should we declare this?
– How strong is this evidence that Vitamin A works?

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 7.4 Inference vs. Prediction

• Inference: Estimate the association between the

outcome of mortality and treatment, and characterize the
estimate’s uncertainty

• Prediction: Best predict the outcome of mortality based

on available data of treatment and other factors, and
characterize the prediction’s accuracy

• More later to distinguish these!

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