Statistical Methods for

Biomedical Engineering
BIOMEDE 503
Today’s Goals:
• Introduce course
• Review syllabus Lecture 1: Class Introduction
• Highlight need for statistics
January 6, 2022

Instructor: Tim Bruns, Ph.D.

Tim Bruns – My career timeline

B.S., EE Assistant Prof.

Minor BioEng M.S., BioEng Ph.D., BME BME Associate Prof.
BME

1 2 3 4 5 6 7

2000 2005 2009 2013 2019

Summer Intern R&D Systems Engineer Postdoc, PM&R

2
2020: Grad Chair. Oversee
4 7 56 aspects of grad program w/
1
focus on PhD students
3

BIOMEDE 503 – Winter 2022 January 6, 2022 – 2 Instructor: Tim Bruns

 Tim Bruns, Ph.D.
Associate Professor, Biomedical Engineering
pneurolab.com Peripheral Neural Engineering and Urodynamics Lab #pneurolab

Develop interfaces with the peripheral nervous system to restore

function and examine systems-level neurophysiology
Pelvic organ neuromodulation Anatomical & computational
Clinical modeling
Closed-loop bladder control
electrophysiology Electrode design &
evaluation

Sexual arousal

@tim_bruns
pNEURO Lab
Graduate Student Instructor: Ciara Davis
• Email: ciaradav@umich.edu
• 3 Office Hours: Wednesdays 1PM, Fridays 11AM & 2PM
• Zoom for office hours; by appointment possible
• Zoom link: https://umich.zoom.us/j/9099809646

• About me:
• PhD student working with Dr. Rhima Coleman
• Perform research on cartilage regeneration in older adults
• Took BIOMEDE 503 in Winter 2017

BIOMEDE 503 – Winter 2022 January 6, 2022 – 4 Instructor: Tim Bruns

Course Goals
• Make statistics interesting and practical.
• Show how statistics are applied in real situations, particularly those relevant to BME.
• Teach the underlying principles of statistics that will allow you to develop your own tests
and methods.
• Allow you to use statistical tests to improve your experiments.

From the syllabus:

This course will cover descriptive statistics, probability theory, distributions for discrete and
continuous variables, hypothesis testing, analysis of variance, and more advanced topics.

Who is this course for?

• Designed for MS & PhD students in Biomedical Engineering (fulfills BME graduate
Statistics requirement).
• Students without a prior (solid) background in statistics.
• If you have prior coursework through at least ANOVA and non-parametric testing, you may
want to consider other courses.
BIOMEDE 503 – Winter 2022 January 6, 2022 – 5 Instructor: Tim Bruns
Course Syllabus

https://umich.instructure.com/courses/490497/
BIOMEDE 503 – Winter 2022 January 6, 2022 – 6 Instructor: Tim Bruns
Pre-class Survey: who are the students?
85 enrolled students!
83 completed survey

Research

Graduate Program
• 93% BME
• Cellular & Molecular Biosciences
edwordle.net
• Mechanical Engineering
• Neuroscience

BIOMEDE 503 – Winter 2022 January 6, 2022 – 7 Instructor: Tim Bruns

Pre-class Survey: who are the students?
85 enrolled students!
83 completed survey

Prior tests

edwordle.net

BIOMEDE 503 – Winter 2022 January 6, 2022 – 8 Instructor: Tim Bruns

Pre-class Survey – Statistics knowledge

✓ ✓

✓
✓ ✓
✓

BIOMEDE 503 – Winter 2022 January 6, 2022 – 9 Instructor: Tim Bruns

What is R?
• R is a software language and environment for statistical
computing and graphics.
• It is FREE!
• R has a wide array of statistical techniques (linear and
non-linear modeling, classical statistical tests, clustering,
time-series analysis, etc.) as well as a well-developed set
of graphics functions.
• R will be used for in-class examples and for homework.
• Download at http://www.r-project.org/

• Next class: using R

BIOMEDE 503 – Winter 2022 January 6, 2022 – 10 Instructor: Tim Bruns
What is Statistics?
• Statistics is the science of learning from data.
• It involves the collection, organization, and analysis of data in order
to draw conclusions – or inferences.
• Biology and physiology are becoming much more of quantitative
sciences and are producing “computable” data.
• Our ability to analyze this data and
design experiments that test a
hypothesis are deeply embedded
in proper statistical analysis.

https://www.lynda.com/Business-Intelligence-tutorials/Statistics-Fundamentals-Part-2-Intermediate/495322-2.html

BIOMEDE 503 – Winter 2022 January 6, 2022 – 11 Instructor: Tim Bruns

Statistics vs. Probability
• Statistics and probability are
complementary.
• Statistics tries to draw conclusions about
a population based on knowledge of a
sample drawn from that population.
• Probability is the study of randomness. It
uses knowledge about the population to https://www.omniconvert.com/what-is/sample-size/

make estimates about samples taken

from that population. Probability: Given model → predict data
• Probability forms the theoretical Statistics: Given data → predict model
underpinnings of statistical analysis.

BIOMEDE 503 – Winter 2022 January 6, 2022 – 12 Instructor: Tim Bruns

Is Statistics Intuitive?
• If all data was continuous and normally distributed, there would be no need
for statistics courses.
• Unfortunately, much of our thinking and approach to a given problem is
based on our knowledge of the normal distribution, and this strongly affects
how we think.

mean

standard normal distribution

deviations
from the
mean

https://analystprep.com/cfa-level-1-exam/quantitative-methods/key-properties-normal-distribution/

• Data can be categorical or quantitative. Quantitative data can be discrete or

continuous. The analysis methods for each case are different.
BIOMEDE 503 – Winter 2022 January 6, 2022 – 13 Instructor: Tim Bruns
Is Statistics Intuitive?
https://www.pnas.org/content/105/13/5012

An interesting study where infants were tested to see if they could:

• Make inferences about the population based on a sample
• Make inferences about a sample based on knowledge of the
population

Infants could recognize the unexpected outcome

BIOMEDE 503 – Winter 2022 January 6, 2022 – 14 Instructor: Tim Bruns
Defining a Confidence Interval
• One of the most common statistical exercises is calculating a
confidence interval. This is typically a range within which you are
90% (or 95%, etc.) confident the true answer lies.

• Consider estimating the 90% confidence interval for…

• Length of the Nile river
• Distance from London to Tokyo
• Weight of an empty Boeing 747
• Charge storage capability of the battery for an implantable
neurostimulator
• Coverage estimate for dosing of a vaccine
BIOMEDE 503 – Winter 2022 January 6, 2022 – 15 Instructor: Tim Bruns
Confidence Interval
• Here is data on 50 independent
trials where a coin is flipped 20
times.
• Each bar indicates a 90%
confidence interval on the
probability of one side being
seen.
• All should have a 0.50
probability, right?

BIOMEDE 503 – Winter 2022 January 6, 2022 – 16 Instructor: Tim Bruns

Using Statistics for Decisions
We often make illogical decisions because of how we feel about
probabilities.

• Imagine 2 bowls of marbles: one with 9 white and 1 red, the

other with 93 white and 7 red. You can pick 1 marble from 1
bowl, and you win a prize if it is red. Which bowl do you choose?

• Which prognosis is worse? – A virus that kills 129 people out of

10,000 or one that only kills 2.4 out of 100?

BIOMEDE 503 – Winter 2022 January 6, 2022 – 17 Instructor: Tim Bruns

Using Statistics for Decisions
We have great difficulty combining probabilities or calculating
conditional probabilities.

A classic example is the Monty Hall problem.

You are a contestant on a game show and are presented with 3
doors. A great prize is behind one of the doors but the other two
have worthless items. You choose a door and the host, who knows
what is behind the doors, then opens one of the two other doors to
show you there is no prize. You are now given the chance to change
your mind and choose the other door.

Should you switch? Does it matter?

https://en.wikipedia.org/wiki/Monty_Hall_problem
BIOMEDE 503 – Winter 2022 January 6, 2022 – 18 Instructor: Tim Bruns
Using Statistics for Decisions
Contestant chooses door 1

Before host opens a door After host opens an other door

Most people are bad at
accounting for the
conditional probability
BIOMEDE 503 – Winter 2022 January 6, 2022 – 19 Instructor: Tim Bruns
Using Statistics for Decisions
We also have difficulty with Bayesian logic.

• Suppose we have a test for COVID-19 that is 99% accurate, but

has an error rate of 1%.
• We also have prior information that COVID-19 occurs in about
0.01% of the population (~10 cases per 100,000 people).

With these assumptions, if a person gets a positive test result,

what are the chances that this person is really COVID-19 positive?

Numbers are fictional, for illustrative purposes only

BIOMEDE 503 – Winter 2022 January 6, 2022 – 20 Instructor: Tim Bruns
Using Statistics for Decisions
Given 100,000 people: 99,990 COVID-19 negative; 10 COVID-19
positive. All take test.
Among COVID-19 negative: 99,990 * 0.01 = 1000 positive results (999.9)
Among COVID-19 positive: 10 * 0.99 = 10 positive results (9.9)
Chances that positive result is really COVID-19:
10
𝑃 𝐶𝑂𝑉𝐼𝐷 + +𝑡𝑒𝑠𝑡 = = 0.99%
10 + 1000

For a 0.1% error rate: 𝑃 𝐶𝑂𝑉𝐼𝐷 + +𝑡𝑒𝑠𝑡 = 9.1%

For a 0.01% error rate: 𝑃 𝐶𝑂𝑉𝐼𝐷 + +𝑡𝑒𝑠𝑡 = 50%
Numbers are fictional, for illustrative purposes only
BIOMEDE 503 – Winter 2022 January 6, 2022 – 21 Instructor: Tim Bruns
Multiple Comparisons Confuse Us

• In this study the authors examined the health records of 10 million

Ontario residents to show how multiple hypothesis testing can
produce associations with no clinical plausibility.
• 223 most common hospitalization diagnoses compared to
astrological sign: 72 diseases statistically more frequent under one
sign (p<0.05) in derivation cohort (half of population).
BIOMEDE 503 – Winter 2022 January 6, 2022 – 22 Instructor: Tim Bruns
Multiple Comparisons Confuse Us
• The authors looked at 223 diseases and individually related them to
12 astrological signs: 223 x 12 = 2,676 distinct comparisons.
• If two elements are unrelated (which they should be here), then
purely by chance 5% will have p-values less than 0.05.
• 5% of 2,676 = 134, so 72 significant associations is not surprising.
• Of 24 significant associations tested in derivation cohort (top 2 per
sign), only 2 were still significant in validation cohort.

• If correctly adjust tests for multiple comparisons, no relationships

are significant. https://www.sciencedirect.com/science/article/pii/S0895435606001247
BIOMEDE 503 – Winter 2022 January 6, 2022 – 23 Instructor: Tim Bruns
How do we collect data?
Suppose we wish to evaluate the effect of a new treatment for high
blood pressure. We bring in 20 patients and treat those with “high”
blood pressure.

Data selection matters!

BIOMEDE 503 – Winter 2022 January 6, 2022 – 24 Instructor: Tim Bruns
How do we collect data?
Suppose you need to find the average length of an
earthworm. How do you approach this problem?

• How do you collect your data?

• How do you control for environment?
• How do you control for the population?

https://www.nynjtc.org/news/worms-woods

BIOMEDE 503 – Winter 2022 January 6, 2022 – 25 Instructor: Tim Bruns

Why we need Statistics

• Our brains are trained to pick out patterns, even if they are not
there.
• We are too confident in our conclusions.
• Data are complex, and often follow non-normal distributions.
• We need to consider alternate hypotheses and alternative
explanations.
• We need to (should) consider what form of statistical analysis we
will use before we conduct an experiment.

BIOMEDE 503 – Winter 2022 January 6, 2022 – 26 Instructor: Tim Bruns

Good practice in scientific research

https://arriveguidelines.org/

If you do animal research, I

encourage you to follow this. Non-
animal research has significant
overlap in many categories.

Clinical studies: see CONSORT

http://www.consort-statement.org/

BIOMEDE 503 – Winter 2022 January 6, 2022 – 27 Instructor: Tim Bruns

For Upcoming Classes
• Next class
1. Introduction to R
2. Graphing
3. Descriptive statistics

• I encourage you to use R to try examples from lectures. Next class

will walk through using it. Data files will be posted to Canvas.

• Homework 1 will be due January 15th. It will be posted within 3

days.

BIOMEDE 503 – Winter 2022 January 6, 2022 – 28 Instructor: Tim Bruns