0:00
Okay in this section we're going to take a look at some practice problems designed
to highlight some of the ideas at least that we covered in lecture eight.
And so, as usual, I'll go through the problem
set-ups first then advise you to pause the recording, work
on them at your leisure, and then resume whenever the
fancy strikes, and you can compare your solutions to mine.
0:23
So the first couple exercises I'm going to ask
you three scenarios and ask you these are scenarios
extensively where we'll be carrying continuous outcomes between two groups.
Just want you to think about the study design.
Whether it's an example of a paired or unpaired design.
And if it's paired what is the unit of pairing.
0:43
So this first one, this first scenario in Baltimore, a real
estate practice known as flipping has elicited concerns from local and
Federal government officials.
Flipping occurs when real estate investor buys
a property for a low price, makes little
or no improvement to this property, and then
resell, resells it quickly at a higher price.
This practice has raised concern, because the properties involved in
flipping are generally in disrepair and the victim's generally low income.
1:20
As part of this suit, the advocates have collected data on all houses purchased by
these three corporations which were sold in
less than one year after they were purchased.
Data were collected on the purchase price and
the resale price for each of these properties.
These data were collected to investigate whether the resale
prices, were on average, higher than the initial purchase price.
And a confidence interval was constructed for
the average profit in these quick turnover sales.
1:48
So was this an example of a paired or unpaired study design.
In the second scenario, researchers are
testing a new blood pressure reducing drug.
Or a drug that potentially reduces blood pressure.
Participants in this study are randomized to
either the drug group or a placebo group.
And, the baseline,
meaning pre-randomization measurements are taken on both groups.
On everyone who's going to participate in the study.
And another measurement is taken three months after
the administration of the drug, or the placebo.
Researchers are curious as to whether the drug is
more effective in lowering blood pressure than the placebo.
2:28
Then finally in this third study, researchers are
interested in the impact of a vegan diet
on risk factors for coronary heart disease, CHD.
In subjects with a family history of such coronary heart disease.
So, researchers randomly select a 100 such families with more than one child And
randomized two siblings from each family to either a vegan diet or omnivorous diet.
2:58
And then what they do is they, measure before
randomization, they measure baseline coronary
heart disease risk factor measurements.
they take these things like blood pressure, blood pressure,
cholesterol level, and percent body fat on each participant.
And then they do this again after six weeks of the diet or,
or the diet period, whether it be the vegan or the omnivore diet.
And then changes in the risk factor levels are
to be compared between those on the vegan diet and those on the omnivorous diet.
3:28
Okay.
In this next section, we'll practice doing some hand computations.
Not because hand computations are that important in this computer age.
But because it helps you think about what
aspects of the concepts gets translated into the mathematics.
And help you think about what goes
into computing the uncertainty, for sample mean differences,
differences in proportion, etcetera.
So this first question and we'll talk about
it at a high school in the United States.
A dietary counseling program is being tested to
measure the program's long-term impact on student's fat intake.
Of the 300 students at the school, 150 are
randomized to receive five one-hour sessions of dietary counseling.
And the other 150
students receive no counseling.
4:16
Six months after the last counseling session, all students
are asked to keep a food diary for one week.
And each student's average fat, daily fat
intake in grams for the week is calculated.
And then the results of this exercise as follows.
4:32
So the average daily fat intake, for the group of 146 of the 150 students who were
in the intervention group, four were lost to follow up.
The average daily fat intake was 54.8 grams but there was
a fair amount of person to person variability in this intake.
The standard deviation was 28.1 grams. In the group, the 142 who, who were
followed up in the control group, the average daily fat intake was 62.8 grams.
But the standard deviation of 34.7 grams.
So I'd like you to estimate using these
sample results, a 95% confidence interval for the true
mean difference in average fat intake, between the group
that received counseling and the group that did not.
And interpret the observed mean difference in the 95% confidence interval.
And finally we'll talk about a study that was performed on
a representative sample of 258 intravenous drug users
from a larger population of such drug users.
And now particularly interest to the researchers were factors which
may influence the risk of
contracting Tuberculosis amongst intravenous drug users.
5:47
So 97 of the study subjects admitted to sharing needles to shoot
drugs, and of these 97, 24 had a positive tuberculin test result.
The other 161 subjects denied having shared needles, and of
these 161 subjects, 28 had a positive tuberculin test result.
6:07
So I'd first like you to use the study results, estimate the difference of
proportions for those contracting tuberculosis amongst those
who shared needles and those who didn't.
And construct a 95% confidence interval, the true difference in
the population of IDVUs from which the sample, a sample was taken.
And then interpret this estimated difference
in proportions, and the 95% confidence interval.
Based on what you got in Part A, what, if
anything, can you say about the estimated relative risk and
odds ratios for comparing the tuberculosis outcomes between the needle
sharers and non-needle sharers And the corresponding 95% confidence intervals.
And then finally, I'd like you to go
ahead and now estimate the relative risk of tuberculosis
for those who shared needles compared to those who
didn't and it's 95% confidence interval using these data.
7:28
So which of the following examples involve the comparison of paired data?
Let's go through these three quickly and
we'll talk about the study design for each.
So the first was the slipping example, where the housing advocates collected
data on the purchase price and resale price of a group of properties.
7:47
And names were collected to see if the resale
price was higher, on average, than the purchase price.
And what the degree of the difference was.
So the study design here is that for the unit of observation for
each of the data points was a particular house, on which
two measures were collected on each house. The original price,
8:20
So for each house we could est, investigate the difference in these.
So we can compute the difference for each of
the houses and look at the nature of the differences.
We could average them to see if there was an increase on average and how
large it was, we could compute a
standard deviation on the individual changes in price.
So the unit this was a paired study and the unit of pairing was the house.
We had two measurements per house, that we're comparing.
8:53
So the second situation, researchers are
testing a new blood pressure reducing drug.
Participants in this study group in this study are
randomized to either the drug group or a placebo group.
And, they first took initial blood pressure measurements
prior to randomization on everyone enrolled in the study.
And, then another measurement was taken three months
after the administration of the drug or the placebo.
And researchers are interested as to whether the drug is
more effective in lowering blood pressure than the placebo.
9:39
So this should clue you in right away, that this is going to be
an unpaired analysis ultimately because the outcomes
of interest are compared across these two groups.
But what are the outcomes of interest?
Well, this may throw a little wrench into, into
your thinking, but let's just work through the logic.
So for each person randomized to the drug group,
we collected a pre randomization measurement and a post
randomization measurement in blood pressure.
And so we could compute the difference for each
person enrolled in the drug group, and we could
compute a mean difference, a mean change on average
for those individuals who are enrolled in the drug group.
We could do the same thing for those,
10:41
So within the drug and the placebo group these measurements are paired,
but we're not interested in comparing each person in the drug group to
himself, or each person in the placebo to himself, or interest in comparing these
paired changes on average between the drug in the placebo group.
So the ultimate result is an unpaired comparison.
11:05
In this third scenario we said researchers are interested
in measuring the impact of a vegan diet on
risk factories, for factors for coronary heart disease in
subjects with a family history of coronary heart disease.
So if the researchers randomly select 100 such families with more than one child and
randomize two siblings from each family to receive
either a vegan diet or an omnivorous diet.
One sibling's
randomized to one group and then the other is put in the other group.
So these diets, prescribed by a nutritionist, are to last for six weeks.
11:49
And they compare the changes in the risk factor levels
over the six week period between the two diet groups.
What is the data set up here?
Well, to start what they're doing, the unit of observation is really
at the family level, so for each family, they select two siblings.
12:10
So we'll call 'em Sibling A and Sibling B, so Sibling A from Family One, Sibling B.
Sibling A from Family Two, Sibling B from Family Two.
And then.
[BLANK_AUDIO].
The first sibling is randomized to either be
put in the vegan diet or the omnivorous diet.
12:48
If the first sibling is randomized to the omnivorous group, then
the second sibling will effectively have been randomized to the vegan group.
And, then what they do is, within each diet group for each sibling they
take a pre-diet and post-diet measure on
certain things like blood pressure, cholesterol level etcetera.
And then they look at the change and they
do the same for everyone
13:23
And for each sibling a randomized to that group they looked at the difference.
And they're ultimately interesting, comparing the changes
between the vegan and the omnivorous group.
This sounds very similar to the last study
except, except, the two diet groups are inherently linked.
Because there's one person from each family
represented in each of the two groups.
And so this is an example, ultimately, of a paired comparison,
where co-, because we are comparing the changes
between those who get the vegan and omnivorous diet.
But those who got the vegan diet, for every person who
got the vegan diet he or she is linked to his
[INAUDIBLE],
a specific person in the omnivorous diet group.
So, this is an example of a paired comparison ultimately.
14:10
All right in the second question I asked
you to do some computations and interpret the results.
So we had, in a high school in the United States, a dietary counseling program is
being tested to measure the potential long term impact on student's fat intake.
Of the 300
students at the school, 150 were randomized to
receive five one hour sessions of dietary counseling.
The other 150 students received no such counseling.
14:36
Six months after the last counseling session, all students
are asked to keep a food diary for one week.
Each student's average fat intake, in grams, is calculated at
the end of the week; and the results are as follows.
So the average daily intake
for each student during that follow-up week,
in the intervention group, was 54.8 grams.
Standard deviation of the individual values is
28.1 and there were 146 people followed up.
In the control group the average hot or daily fat intake was higher, 62.8 grams.
Here's the standard deviation. And there were 142 people in this group.
15:17
So
I wanted you to estimate using the sample
results on a 95% confidence interval for the
true mean difference in average fat intake between
those that received counseling and those that did not.
And then interpret the results.
So let's see what we got.
Let's lay out the data. So we said the counseling group, the mean
15:37
average that intake was 54.8 grams with the standard deviation of 28.1 and
there were 146 people. And then in the.
[BLANK_AUDIO]
No counseling group it was 62.8 Standard
deviation of 34.7, and 142 people.
So this observed mean difference, the observed
mean difference between these two groups, the
mean plan intake for the counseling group
minus the mean intake for the non counseling
group was negative eight grams.
So they consumed eight grams less, on average per day, than
those who got the couns- who did, did not receive the counseling.
16:57
So we take the standard deviation of the individual.
Daily fat intakes for those in the counseling group, square
it, divide it by the number of people in that group.
So this essentially turns
out to be the standard error of that first sample mean, square,
then we add it to the same thing done for the group
that did not receive counseling and then the uncertainty in our difference
means is basically an additive function of the uncertainty in each mean.
And if you do the math on this, this turns out
to be about 3.7 grams, a 95% confidence interval for the
true mean difference among all high school students.
You can think of that as the population under study.
It was negative 8 plus or minus 2 times
3.7, where it goes from negative
15.4 grams to negative 0.6 grams.
So what do you notice about this confidence interval?
Well, you probably notice it does not
include 0, so this result is statistically significant.
18:09
Meaning that all possibilities show a reduced average
fat intake for those who got the dietary counseling.
But the range of values leaves little bit to the interpretation.
On the one hand, this would be a pretty impressive effect.
If those who actually receive the program,
got consumed over 15 calories. 15 fat grams less per day on average.
On the other end, we're talking about a
negligible effect of average difference of negative 0.6 grams.
So there's a lot of uncertainty in this confidence interval.
I think given that the sample results were so large, and average intake,
reduced intake of eight grams and the fact that this is statistically significant,
though, shows credible evidence that this program was effective at lowering
the average daily fat intake in this population of high school students.
19:04
Okay, finally this study that we looked at
the representative sample of 258 intravenous drug users.
And I'll just jump to the problems here.
So the first thing I asked you to do
was look at the difference of proportions of those,
who had tuberculosis, amongst those who shared needles, and those who didn't.
So we just do this straight up the
proportion who had tuberculosis amongst those who shared needles,
19:50
or said they didn't share needles, this proportion was 28 out of
161. So that's 17%.
So this difference here, the difference between
those proportion who shared, and those who didn't
was 8%. 8% greater proportion of persons
with tuberculosis than those amongst those
who'd share needles than those that didn't.
This is the difference in proportions but of course this
estimate is based on relatively small to medium sized samples so
we want to account for the uncertainty in it so we
have to estimate the standard error of this difference in proportions.
And this formula is very similar
in spirit to the estimated standard error for difference in
unpaired means, we take the uncertainty associated with the first proportion
20:53
and functionally square it, and then add it
to the uncertainty in the second estimated proportion.
[SOUND]
Which is also squared.
And then, take the square root of that sum.
So, again, the uncertainty in this difference in proportions,
21:12
is a function of the uncertainty in each proportion, itself.
And if you do this, this turns out to be about .05.
5%. So.
[SOUND]
And then all the dust settles.
Sorry, was trying to draw a barrier here, since it's for organization.
We observed an 8% greater proportion in the group
that shared needles, but when I account for the uncertainty.
And if we do this, we get a
confidence interval that goes from negative 2% to 18%.
So this, you'll notice that zero is in this interval, includes zero.
21:57
After accounting for the uncertainty, it's not
clear what the direction of association is,
although most values in the confidence interval
show an increase amongst those who shared needles.
But the literal interpretation is that the absolute difference
of proportions in those who shared needles and those who
didn't in this population could by anywhere from a reduction
up to 2% or and increase up to 80 18%.
22:25
And I said, before you do any estimation based
on these results, what can you say about the
estimated relative risk and odds ratios for comparing tuberculosis
outcomes between the two groups and their corresponding confidence level.
So, the risk difference between the sharers and those
who didn't share Was positive, indicating a higher proportion.
Well, we know there were higher proportion of share tuberculosis
outcomes amongst those who shared than those who didn't.
And hence, even though, I mean, we knew proportion was higher in the top group.
But if all we had was this risk
difference, we, we could still say that the
estimated relative risk of tuberculosis for those who
shared and those who didn't is greater than one.
And so it would be estimated, odds ratio.
And then the fact that the 95% confidence interval for the
population level difference of proportions, included zero.
We know that the confidence intervals for the relative risk
and odds ratios would concur in terms of the null value.
And their respective null value is one, so they're 95% CI's will include one.
We can ascertain that without actually computing them.
23:41
But just to full steam ahead and give this is a full on treatment why don't
we go ahead and estimate the relative and
compute a 95% confidence interval from these data.
So the easiest way to get this started is to set up a
two by two table, and there's certain arbitrariness about how you set these up.
But, in order for the formulae that I've given you
for standard errors with a relative risk to work it's advantageous
to set it up.
It makes things easier to keep track of if you put the outcome
status in the rows, and then those with the outcome in the first row.
24:17
And those who don't have the outcome in the
second row and in the columns you have the exposures.
And those with the exposures those who share needles in
the first and those who didn't share in the second.
24:32
fill this table out. We're good, almost good to go, so
there are estimated relative risks to start.
Sorry, all of a sudden I'm having a lot more trouble with the pen.
And I'm used to having trouble with the pen,
but all of a sudden I'm really having trouble.
Here's the 25% we observed amongst the sharers.
25:04
We have the 17% amongst those who didn't share.
This is approximately equal to 1.4. We know we're going to have to put
this on the log scale, to start to estimate the confidence interval.
A log of 1.4 is roughly equal to 0.34.
And now to get the standard error of the log of this estimated relative risk, we
have to just run through our formula, which
involves some counts from the two by two table.
So we'd take the square root of 1 over the number of outcomes TB positive results in
the exposed group, the sharers, minus 1 over the number of people in that group.
And then we add 1 over
the number of TB positive outcomes in the group who didn't share needles.
Minus 1 over the total number in that group.
26:01
And if you do the math out on this you get something approximately equal
to 0.24. And so the 95% confidence
interval for the log of the true relative risk
goes from 0.34 log of estimated relative risk
plus or minus 2 times 0.24. And when all the
dust settles we get a confidence interval and a log relative risk scale.
Negative 0.14 to 0.82, so you see that
we knew, heads up that this confidence interval for
the log relative risk includes zero, which means
when we exponentiate the results to get the confidence
interval for the actual relative risk, we get an interval that goes
from 0.87 to 2.27 and it includes the null value of one.
27:06
So you suggest that an individuals risk of con,
having Tuberculosis being Tuberculosis positive is 13% anywhere from
13% less to 127% greater amongst any individual who
shares needles versus an individual who does not share needles.
And so the results are statistically un, inconclusive about the association at the
population level between sharing needles and
increased or decreased risk to tuberculosis.