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**University of York
Department of Health Sciences
**

**Applied Biostatistics**

**Suggested Answer to the Sample Assessment
**This suggested answer was not used in the marking of the assessment but has been produced
especially for current students. Text in square brackets [ ] are my explanatory comments, not
part of the suggested answer.

**Applied Biostatistics Assignment 2005/2006
1. Produce charts (or use some other method) to show the distribution of age and years
since diagnosis. Briefly describe what those charts show you about the distribution of the
variables.
**

These are both quantitative variables. The best way to show the distribution of a quantitative variable is a histogram. We could also use a box and whisker plot, or a Normal quantile plot.

The histogram of age is as follows:

800700600500400300 Age (months)

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[Note that I have edited the graph to give bigger fonts and reduced the size of the graph so that the font is of similar size to my text. I have altered the interval size to 50 from the default width of 33.333, and changed the scale on the Age axis. I have also used Variables View to give age a label with units.]

There are no obvious outliers. This appears to be a bimodal distribution, with one mode around 400 months and another around 700 months. This suggests that there are two distinct populations of patients.

The histogram of years since diagnosis is as follows:

50403020100 Years since diagnosis

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This distribution is positively skew, the tail on the right being much longer than the tail on the left. There are no obvious outliers. Some of these patients have had psoriasis for a very long time.

**2. The people should have been randomly allocated to each of the two groups (treatment
and control). Carry out a test, to compare the mean age of the people in each group.
What is the result? What do you conclude?
**

**Carry out a test to compare the proportions of males and females in each group. What is
the result? What do you conclude?
**

Age is a quantitative variable, so a comparison of means is indicated. There were 67 subjects in the treated group and 78 in the control group. [This information was obtained by the Frequencies command.] As there are more than 50 subjects in each group, we can use the large sample z method to compare means. This means we can ignore the awkward shape of the age distribution. The results are:

Mean and standard deviation for each group

Group Number Mean Standard deviation

Standard error of the

mean

Treated 67 532 147 17

Control 78 547 146 18

[I did this using the two sample t test command. This is the SPSS output:
** Group Statistics
**

group N Mean Std. Deviation Std. Error Mean

0 78 547.53 146.123 16.545 Age (months) 1 67 532.43 146.902 17.947

I have given the mean and standard deviation to three significant figures, which seemed enough. We do not need all the figures SPSS produces.]

The mean age of control subjects exceeded the mean age of treated subjects by 15 months, 95% confidence interval –33 to +63 months, P = 0.5.

There is no evidence that in the population from which these subjects come there is any difference in mean age between treated and control subjects. We can conclude that there is nothing to suggested that subjects were not allocated randomly to treatment group.

[This was the output:
** Independent Samples Test
**

Levene's Test for Equality of Variances t-test for Equality of Means

F Sig. T df Sig. (2- tailed)

Mean Difference

Std. Error Difference

95% Confidence Interval of the Difference

Lower Upper Age (months)

Equal variances assumed

.240 .625 .619 143 .537 15.093 24.400 -33.138 63.324

Equal variances not assumed

.618 139.494 .537 15.093 24.410 -33.168 63.354

The large sample z method corresponds to the ‘equal variance not assumed’ row. We do not need any assumptions about variance, so we ignore the Levene test.]

Male or female is a dichotomous, qualitative variable, so a chi-squared test or Fisher’s exact test would be appropriate.

The two by two cross-tabulation of sex by group is as follows:

Treated Control Total

Female 37 (47.4%) 35 (52.2%) 72 (49.7%)

Male 41 (52.6%) 32 (47.8%) 73 (50.3%)

Total 78 (100.0%) 67 (100.0%) 145 (100.0%)

The percentage of females in each group was similar and the difference was not significant (chi- squared = 0.33, 1 degree of freedom, P = 0.5). Hence there is no evidence that in this population sex differed between the treatment groups and the data are consistent with the groups being allocated to treatment group randomly.

[This was the output:
** sex * group Crosstabulation
**

group 0 1 Total

Count 37 35 72 Expected Count 38.7 33.3 72.0

0

% within group 47.4% 52.2% 49.7% Count 41 32 73 Expected Count 39.3 33.7 73.0

Sex

1

% within group 52.6% 47.8% 50.3% Count 78 67 145 Expected Count 78.0 67.0 145.0

Total

% within group 100.0% 100.0% 100.0%
** Chi-Square Tests
**

Value df Asymp. Sig.

(2-sided) Exact Sig. (2-sided)

Exact Sig. (1-sided)

Pearson Chi-Square .333(b) 1 .564 Continuity Correction(a) .168 1 .682

Likelihood Ratio .333 1 .564 Fisher's Exact Test .619 .341 Linear-by-Linear Association .330 1 .565

N of Valid Cases 145 a Computed only for a 2x2 table b 0 cells (.0%) have expected count less than 5. The minimum expected count is 33.27. Note that I have not used the SPSS table, but produced my own from the SPSS output and that I have lined up the table neatly in columns. The expected frequencies are all large enough for the chi-squared test.]

We can conclude that there is no evidence from either the age or the sex distribution to suggest that the patients were not allocated to the two groups randomly.

**3. Was the treatment successful at reducing the PASI?
**

PASI is a quantitative variable, so we want to compare means. We want to compare the mean PASI six months after treatment. The PASI after treatment is likely to be related to the baseline PASI and we should take this into account in the analysis. There are two ways to do this. We could calculate the change in PASI and use that, or we could do a multiple regression and use baseline PASI as a predicting variable or covariate.

[I shall do both, for illustration. People lost marks for not using the baseline measurement, but simply comparing the post-treatment PASI between the two groups.]

Plotting the data before and after treatment will show whether we need to take the baseline PASI into account. Baseline and post-treatment PASI scores are clearly related, as the scatter diagram shows:

140120100806040200 PASI before treatment

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P A

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[As usual, I have edited the graph to make the text bigger, etc. I have made the two scales the same, because this is the same variable measured twice. It would have been nice to use a different symbol for each group and to draw a line of equality, where the baseline and six-month PASI would be equal, but I am not an SPSS user and this defeated me.]

Inspection of the graph suggests that both PASI variables are positively skew, as histograms confirm:

140120100806040200 PASI before treatment

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140120100806040200 PASI six months post treatment

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Although the histogram of PASI at six months suggests that there may be an outlier, inspection of the scatter diagram shows that this subject had the highest PASI on both occasions and so there is no reason to reject this measurement.

The distribution of the differences, six-month PASI minus baseline, was as follows:

6040200-20-40-60 PASI, six-month minus baseline

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[I used Transform, Compute to calculate the difference, then labelled it in Variable View. As usual, I edited the histogram.]

The distribution of the differences appears approximately Normal, with no obvious outliers. We can compare the two groups using a box plot:

TreatedControl Group

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P A

S I,

si x-

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in us

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4

This suggests that the differences are more negative for the treated group. We can compare these differences using either a two sample t test or a z test, because the data appear approximately Normal with similar variances in the two groups and the samples are larger than 50. I shall use the two sample t test.

The mean and standard deviation of the change in PASI for each group were:

Group Number Mean Standard deviation

Standard error of the

mean

Treated 67 –8.70 17.1 2.1

Control 78 1.62 14.9 1.7

[I did this using the two sample t test command. This is the SPSS output:
** Group Statistics
**

Group N Mean Std. Deviation Std. Error

Mean Control 78 1.6282 14.89714 1.68677 PASI, six-month

minus baseline Treated 67 -8.7015 17.06939 2.08536

**Independent Samples Test
**

Levene's Test for Equality of

Variances t-test for Equality of Means

F Sig. t df Sig. (2- tailed)

Mean Difference

Std. Error Differenc

e

95% Confidence Interval of the

Difference

Lower Upper PASI, six- month minus baseline

Equal variances assumed .971 .326 3.891 143 .000 10.32970 2.65457 5.08244 15.57696

Equal variances not assumed

3.851 132.134 .000 10.32970 2.68215 5.02420 15.63520

]

The difference was highly significant (P < 0.001) and the mean difference in PASI in the treated group was less than the mean in the control group by 10.3 units, 95% confidence interval 5.0 units to 15.6 units. Hence there is strong evidence that the treatment reduced mean PASI, by between 5.1 and 15.8 units.

We can also use multiple regression. The effect of being in the treated group was –10.3, 95% confidence interval –15.6 to –5.1, P < 0.001.

[I used linear regression with PASI at six months as the dependent variable and group and PASI at baseline as the independent variables. The output was:

**Coefficients(a)
**

Model Unstandardized

Coefficients Standardized Coefficients t Sig.

95% Confidence Interval for B

B Std. Error Beta

Lower Bound

Upper Bound

1 (Constant) 1.759 4.157 .423 .673 -6.458 9.976 Group -10.327 2.665 -.235 -3.874 .000 -15.596 -5.058 PASI before

treatment .997 .091 .660 10.896 .000 .816 1.178

a Dependent Variable: PASI six months post treatment ]

We should check the assumptions of the regression by residual plots. The histogram and Normal plot of the residuals were as follows:

6040200-20-40-60 Unstandardized Residual

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6040200-20-40-60 Observed Value

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**E
xp
**

**ec
te
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**d
N
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**or
m
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**al
V
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**al
ue
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**Normal Q-Q Plot of Unstandardized Residual
**

The histogram appears to fit a Normal distribution and the Normal plot appears fairly straight. Next we look at the plot of residuals against the predicted value, to assess the uniformity of the variance.

100806040200 Unstandardized Predicted Value

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There may be some slight increase in variability at large predicted values, but not much. The regression analysis appears to be valid.

We can conclude that treatment reduced mean PASI by between 5 and 15 units.

**5. Did a higher proportion of people in the treatment group feel that they had improved
than those in the control group?
**

Feelings of improvement is a dichotomous, qualitative variable so a cross-tabulation and chi- squared or Fisher’s exact test is indicated.

The tabulation of perceived improvement by treatment group is as follows:

Treated Control Total

Improved 49 (73.1%) 41 (52.6%) 90 (62.1%)

Not improved 18 (26.9%) 37 (47.4%) 55 (37.9%)

Total 78 (100.0%) 67 (100.0%) 145 (100.0%)

The difference was statistically significant, chi-squared = 6.48, 1 degree of freedom, P = 0.01. There were no cells with expected frequencies less than five, so the chi-squared test is valid for this table.

We can conclude that there is good evidence that patients in the treated group were more likely to think that they had improved than were patients in the control group.

[The output was:
** improved * Group Crosstabulation
**

Group Control Treated Total

Count 37 18 55 Expected Count 29.6 25.4 55.0

0

% within Group 47.4% 26.9% 37.9% Count 41 49 90 Expected Count 48.4 41.6 90.0

improved

1

% within Group 52.6% 73.1% 62.1% Count 78 67 145 Expected Count 78.0 67.0 145.0

Total

% within Group 100.0% 100.0% 100.0%
** Chi-Square Tests
**

Value df Asymp. Sig.

(2-sided) Exact Sig. (2-sided)

Exact Sig. (1-sided)

Pearson Chi-Square 6.478(b) 1 .011 Continuity Correction(a) 5.633 1 .018

Likelihood Ratio 6.578 1 .010 Fisher's Exact Test .016 .008 Linear-by-Linear Association 6.433 1 .011

N of Valid Cases 145 a Computed only for a 2x2 table b 0 cells (.0%) have expected count less than 5. The minimum expected count is 25.41. ]

The relative risk of reporting improvement for patients in the control group was 1.39 with 95% confidence interval 1.08 to 1.80.

[To do this I had to reverse the order of the groups, to make the order treated then control. I
created a variable grouprev by 1 – group. This was then 0 for treated and 1 for control. I then
had to switch the row and column variables:
** grouprev * improved Crosstabulation
**

Improved 0 1 Total

Count 18 49 67 Expected Count 25.4 41.6 67.0

.00

% within improved 32.7% 54.4% 46.2% Count 37 41 78 Expected Count 29.6 48.4 78.0

grouprev

1.00

% within improved 67.3% 45.6% 53.8% Count 55 90 145 Expected Count 55.0 90.0 145.0

Total

% within improved 100.0% 100.0% 100.0%
** Risk Estimate
**

95% Confidence Interval

Value Lower Upper Odds Ratio for grouprev (.00 / 1.00) .407 .202 .819

For cohort improved = 0 .566 .358 .896 For cohort improved = 1 1.391 1.077 1.797 N of Valid Cases 145

The relative risk we want is for improved = 1. Note that 1.797 rounds up to 1.80. It is a good idea to check that 73.1% / 52.6% =1.39, which it does.]

Hence we can conclude that the treatment lead to increase in the proportion of patients reporting improvement, by a factor estimated to be between 1.08 and 1.80.

Our final conclusions are that there is no reason to think that this trial was not correctly randomised and that patients receiving the new treatment had an improvement in mean PASI score, compared to the control group, which is estimated to be between 5 and 15 units. They were also more likely to report an improvement, by a factor estimated to be between 0.05 and 1.80.

Martin Bland,

11 December 2006

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