Estimation case study: total hip replacement

Dr Alberto Corrias

Department of Biomedical Engineering. National University of Singapore

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The problem of total hip replacement

644
operations in
Primary causes Singapore in
inflammatory arthritis 2015-2016
osteoarthritis
avascular necrosis
hip dysplasia
post-traumatic osteoarthritis ∼131
procedure/100K
population
worldwide

†
Sources:
Liu YEB et al. Singapore Med J. 2009; 50 (1) : 15
Kurtz SM et al. 56th Annual Meeting of the Orthopaedic Research Society. March 6-9, 2010. New Orleans.
Ministry of Health website: https://www.moh.gov.sg/content/moh_web/home/costs_and_financing/
hospital-charges/Total-Hospital-Bills-By-condition-procedure/hip_replacement_surgery.html

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The problem of total hip replacement

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The problem of total hip replacement

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The problem of total hip replacement

Youtube link: https://www.youtube.com/watch?v=0-O8IFzV8Nc

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Fatigue testing of the stem (ISO 7206-4)

ISO 7206-4 standard prescribes (among many other things):

minimum of 5X 106 testing cycle without fracture or deformation
6 unbroken specimens and 95% confidence required

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Our first scenario

You are employed as an engineer by Stryker

Your first task is to make sure the hip replacement
system complies with ISO 7206-4 standards
You ordered the R&D lab to test 12 stems for
fatigue until fracture occurs

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The data

Stem # Cycles (X 106 )

Pn
1 5.5587 Xi
X = i=1
2 5.5997 n
s
3 6.5256 Pn 2
i=1 (Xi − X )
4 5.2257 s=
n−1
5 7.4256
In our case, n = 12 and the Xi values are
6 6.2361 the number of cycles before the hip stem
7 5.2254 fractured.
8 4.8783
9 4.9145 Sample Sample
10 5.8256 Mean (X ) standard deviation (s)
11 6.2145 5.9045 0.8432
12 7.2239

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Median and quartiles (q1 , q2 and q3 )
Sorted data In a sorted sample of size n, q1 is the
Stem # Cycles (X 106 ) value at position 0.25(n + 1)† , q3 is the
8 4.8783 value at position 0.75(n + 1)† . q2 is the
9 4.9145 median.
7 5.2254 5.2254+5.2257
q1 = 2
4 5.2257
1 5.5587
2 5.5997 5.5997+5.8256
Median = 2
10 5.8256
11 6.2145
6 6.2361 6.2361+6.5256
q3 = 2
3 6.5256
12 7.2239
5 7.4256

†
If 0.25(n + 1) and 0.75(n + 1) are not integers, then the average of the values
at the two neighbouring positions is calculated
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Box plot to visualize data

†
This is only one possible way of drawing boxplots. It was chosen because it is the way that Python uses by default.
See https://matplotlib.org/3.1.1/api/_as_gen/matplotlib.pyplot.boxplot.html under the ”whis” option
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Our collected data are a sample

If the sample size is large enough

What distribution do the sample means follow?
Which theorem is telling us the answer to the above question?
Answer:
The normal distribution with mean = µ (population mean) and
2
standard deviation = √σn . X ∼ N (µ, σn )
The Central Limit Theorem

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Follow-up question

In the previous question, we saw that

σ2
X ∼ N (µ, )
n
Then,
X −µ
σ/√n
∼ N (a, b)

a =?, b =?

Answer: a = 0, b = 1

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The distribution of the means for small samples
Our 12 stems constitute just one of the many possible samples.
5.9045 − µ
t= √
0.8432/ 12

This area is the proba- This area is the proba-

bility of picking a value bility of picking a value
t ≤ −tcrit t ≥ tcrit

X√−µ
t= s/ 12 ∼ T (11)

−tcrit
−tcrit is the value that
leaves an area of 0.025
(2.5%) to its left
BN2102 Bioengineering Data Analysis
0 tcrit
tcrit is the value that
leaves an area of 0.025
(2.5%) to its right
Estimation case study: total hip replacement 13 / 30
Determination of tcrit using tables

We are asked 95%

confidence interval,
α = 0.05. tcrit = 2.201

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Computation of the confidence interval for the mean
5.9045−µ
√
0.8432/ 12 ∼ T (11)

−tcrit 0 tcrit

5.9045 − µ
−tcrit < √
0.8432/ 12
< tcrit

Hence
√ √
5.9045 − tcrit 0.8432/ 12 < µ < 5.9045 + tcrit 0.8432/ 12

Considering tcrit = 2.201, the 95% confidence interval is given by

5.369 < µ < 6.44

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Looking at the Student t distribution

k1 degrees of freedom
k2 degrees of freedom

−6 −3 0 3 6
Do you think k1 > k2 or k2 > k1 or k1 = k2 ?
Answer: k1 > k2 because smaller degrees of freedom means smaller
sample size, greater uncertainty and bigger tail areas. Practically
speaking, the k2 curve will have a bigger tcrit for the same choice of α
and hence larger confidence intervals (more uncertainty).

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Interpretation

5.369X 106 < µ < 6.44X 106

In statistical terms
We are not guaranteed that the true value of µ is between 5.369X 106
and 6.44X 106 . Of all the possible 95% confidence intervals based on
a sample of size 12, 95% will contain the true mean µ. Hence we are
95% confident that the interval we just computed is one of them and
contains the actual mean µ.

How it is reported
Based on the collected data, we are 95% confident that the true
mean of the number of cycles before fracture of the hip prosthetic
stem is between 5.369X 106 and 6.44X 106 cycles.

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Wear testing of the whole system (ISO 14242-1)

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Wear in hip prosthetics

†
Sources:
Birkett N et al J Surg Case Rep. 2015 Sep; 2015(9):rjv122.
Nine MdJ et al. Materials 2014, 7(2) 980-1016.

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The equivalent circular diameter (ECD)

The equivalent circular diameter (ECD) is the diameter of the circle

with the same area as the non-circular object we are considering.

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Our second scenario

You are still employed as an engineer by Stryker

Now your task is to make sure the hip
replacemenet system complies with ISO 14242-1
standards in terms of wear
You ordered the R&D lab to test for wear and
measure the ECD of the isolated wear particles

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Second scenario: CALCULATION QUESTION (3 points)

Particle # ECD (µm)

1 0.6254 Questions:
2 0.5874
1 Compute the 95% confidence
interval for the mean ECD
3 0.3657
2 Compute the 99% confidence
4 0.9836
interval for the mean ECD
5 0.7812

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Second scenario: solution

Pn
i=1 Xi
X =
n
s
Particle # Size (µm) Pn
− X )2
i=1 (Xi
1 0.6254 s=
n−1
2 0.5874
In this case, n = 5 and the Xi values are
3 0.3657 the particle sizes.
4 0.9836
5 0.7812 Sample Sample
Mean (X ) standard deviation (s)
0.6687 0.2303

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Second scenario: solution

0.6687 − µ
−tcrit < √
0.2303/ 5
< tcrit

where
tcrit = 2.776 for the 95% confidence interval
tcrit = 4.604 for the 99% confidence interval

The 95% confidence interval is The 99% confidence interval is

0.383 < µ < 0.955 0.1945 < µ < 1.1428

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The role of s

You collected two samples S1 and S2 of the same size n. You compute
the sample standard deviations (s1 and s2 respectively) and you found
s1 = 2s2 . A1 and A2 are the amplitudes of the confidence intervals
based on the two samples. Which of the following is correct?
1 A1 = 2A2
2 A2 = 2A1
3 A1 = A2
Answer: A2 = 2tα/2 √s2n , A1 = 2tα/2 √s1n = 2tα/2 √
2s2
n
= 2A2 . Hence,
A1 = 2A2

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Checking assumptions: random independent sampling

In a random sample there must be no bias in selecting the

sample
In a random sample every measurement is independent from the
previous one. If you have consecutive measurements, a scatter
plot may help in identifying trends in the data.
Caution!
Confidence intervals may be invalid if the measurements were not
independent from each other and/or the sample is biased
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Checking assumptions: underlying population is normal (1)

1 check for patterns or asymmetries in the data

Caution!
For small samples, the underlying population must be approximately
normal. We should at least have no reason to suspect non-normality.

†
There is still debate of how small is ”small”.
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Checking assumptions: underlying population is normal (2)
2 check for outliers using boxplots

Caution!
Confidence intervals may be invalid in the presence of outliers!

Outliers and common sense

In many books, any data point outside of the box plot whiskers is
termed ”outlier”. Use common sense, only extreme outliers should be
cause of concern
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What to do with outliers?

Outlier can be
eliminated
yes

Report result with

Check with data
and without out-
collector: was it
lier. The outlier is
a measurement
called influential
error?
point
yes
no
Report result with
Repeat analysis
outlier and report
without outlier:
no outlier makes no
any difference?†
difference

†
What actually ”makes a difference” will become clearer after we look at hypothesis testing
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Lecture Summary

Given a random sample of size n from an unknown population, we

compute the β = 100 ∗ (1 − α)% confidence intervals for the
population mean with:

s s
X − tα/2 √ < µ < X + tα/2 √
n n

We require the assumption that the underlying population is normal.

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