The FREQ Procedure

## Example 3.8 Cochran-Armitage Trend Test

The data set Pain contains hypothetical data for a clinical trial of a drug therapy to control pain. The clinical trial investigates whether adverse responses increase with larger drug doses. Subjects receive either a placebo or one of four drug doses. An adverse response is recorded as Adverse='Yes'; otherwise, it is recorded as Adverse='No'. The number of subjects for each drug dose and response combination is contained in the variable Count.

```data pain;
input Dose Adverse \$ Count @@;
datalines;
0 No 26   0 Yes  6
1 No 26   1 Yes  7
2 No 23   2 Yes  9
3 No 18   3 Yes 14
4 No  9   4 Yes 23
;
```

The following PROC FREQ statements provide a trend analysis. The TABLES statement requests a table of Adverse by Dose. The MEASURES option produces measures of association, and the CL option produces confidence limits for these measures. The TREND option tests for a trend across the ordinal values of the variable Dose with the Cochran-Armitage test. The EXACT statement produces exact -values for this test, and the MAXTIME= option terminates the exact computations if they do not complete within 60 seconds. The TEST statement computes an asymptotic test for Somers’ .

The PLOTS= option requests a frequency plot for the table of Adverse by Dose. By default, PROC FREQ provides a bar chart for the frequency plot. The TWOWAY=STACKED option requests a stacked layout, where the bars correspond to the column variable (Dose) values, and the row variable (Adverse) frequencies are stacked within each bar.

```ods graphics on;
proc freq data=Pain;
tables Adverse*Dose / trend measures cl
plots=freqplot(twoway=stacked);
test smdrc;
exact trend / maxtime=60;
weight Count;
title 'Clinical Trial for Treatment of Pain';
run;
ods graphics off;
```

Output 3.8.1 through Output 3.8.4 display the results of the analysis. The "Col Pct" values in Output 3.8.1 show the expected increasing trend in the proportion of adverse effects with the increasing dosage (from 18.75% to 71.88%). The corresponding frequency bar chart (Output 3.8.2) also shows this increasing trend.

Output 3.8.1 Contingency Table
 Clinical Trial for Treatment of Pain

The FREQ Procedure

Frequency
Percent
Row Pct
Col Pct
0 1 2 3 4 Total
No
 26 16.15 25.49 81.25
 26 16.15 25.49 78.79
 23 14.29 22.55 71.88
 18 11.18 17.65 56.25
 9 5.59 8.82 28.13
 102 63.35
Yes
 6 3.73 10.17 18.75
 7 4.35 11.86 21.21
 9 5.59 15.25 28.13
 14 8.7 23.73 43.75
 23 14.29 38.98 71.88
 59 36.65
Total
 32 19.88
 33 20.5
 32 19.88
 32 19.88
 32 19.88
 161 100

Output 3.8.2 Stacked Bar Chart of Frequencies

Output 3.8.3 displays the measures of association produced by the MEASURES option. Somers’ measures the association treating the row variable (Adverse) as the response and the column variable (Dose) as a predictor. Because the asymptotic 95% confidence limits do not contain zero, this indicates a strong positive association. Similarly, the Pearson and Spearman correlation coefficients show evidence of a strong positive association, as hypothesized.

The Cochran-Armitage test (Output 3.8.4) supports the trend hypothesis. The small left-sided -values for the Cochran-Armitage test indicate that the probability of the Row 1 level (Adverse='No') decreases as Dose increases or, equivalently, that the probability of the Row 2 level (Adverse='Yes') increases as Dose increases. The two-sided -value tests against either an increasing or decreasing alternative. This is an appropriate hypothesis when you want to determine whether the drug has progressive effects on the probability of adverse effects but the direction is unknown.

Output 3.8.3 Measures of Association
Statistic Value ASE 95%
Confidence Limits
Gamma 0.5313 0.0935 0.3480 0.7146
Kendall's Tau-b 0.3373 0.0642 0.2114 0.4631
Stuart's Tau-c 0.4111 0.0798 0.2547 0.5675
Somers' D C|R 0.4427 0.0837 0.2786 0.6068
Somers' D R|C 0.2569 0.0499 0.1592 0.3547
Pearson Correlation 0.3776 0.0714 0.2378 0.5175
Spearman Correlation 0.3771 0.0718 0.2363 0.5178
Lambda Asymmetric C|R 0.1250 0.0662 0.0000 0.2547
Lambda Asymmetric R|C 0.2373 0.0837 0.0732 0.4014
Lambda Symmetric 0.1604 0.0621 0.0388 0.2821
Uncertainty Coefficient C|R 0.0515 0.0191 0.0140 0.0890
Uncertainty Coefficient R|C 0.1261 0.0467 0.0346 0.2175
Uncertainty Coefficient Symmetric 0.0731 0.0271 0.0199 0.1262

Somers' D R|C
Somers' D R|C 0.2569
ASE 0.0499
95% Lower Conf Limit 0.1592
95% Upper Conf Limit 0.3547

Test of H0: Somers' D R|C = 0
ASE under H0 0.0499
Z 5.1511
One-sided Pr > Z <.0001
Two-sided Pr > |Z| <.0001

Output 3.8.4 Trend Test
Cochran-Armitage Trend Test
Statistic (Z) -4.7918

Asymptotic Test
One-sided Pr < Z <.0001
Two-sided Pr > |Z| <.0001

Exact Test
One-sided Pr <= Z 7.237E-07
Two-sided Pr >= |Z| 1.324E-06

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