Example Section
An unmatched case-control study evaluating the association between smoking and CHD is planned.
If 30% of the population is estimated to be smokers, what is the number of study subjects (assuming an equal number of cases and controls in an unmatched study design) necessary to detect a hypothesized odds ratio of 2.0? Assume 90% power and α=0.05.
Formula Section
Due to the design of unmatched case-control studies, where unequal sampling rates are used for the exposed and unexposed, we cannot estimate relative risks for case-control studies, and must instead estimate odds ratios. The hypothesis we wish to test is slightly altered
\(\begin{array}{l}
\mathrm{H}_{0}^{*}\colon \pi_{1}^{*}=\pi_{2}^{*} \\
\mathrm{H}_{1}^{*}\colon \pi_{1}^{*} / \pi_{2}^{*}=\lambda^{*}
\end{array}\)
Where
\(\begin{array}{l}
\pi_{1}^{*}=p(\text { Exposed } \mid \text { Disease })=p(\text { Exposed } \mid \text { Case }) \\
\pi_{2}^{*}=p(\text { Exposed } \mid \text { No disease })=p(\text { Exposed } \mid \text { Control })
\end{array}\)
The formulas are similar to the formula for relative risk, but with additional parameters.
\(\begin{aligned}
n=\frac{(r+1)(1+(\lambda-1) P)^{2}}{r P^{2}(P-1)^{2}(\lambda-1)^{2}}[ & z_{\alpha} \sqrt{(r+1) p_{c}^{*}\left(1-p_{c}^{*}\right)} \\
& \left.+z_{\beta} \sqrt{\frac{\lambda P(1-P)}{[1+(\lambda-1) P]^{2}}+r P(1-P)}\right]^{2}
\end{aligned}\)
and
\(\displaystyle{p_{c}^{*}=\frac{P}{r+1}\left(\frac{r \lambda}{1+(\lambda-1) P}+1\right)}\)
Where
- \(\mathrm{P}=\) exposure prevalence
- \(\lambda=\) estimated relative risk
- r = ratio of cases to controls
For our example, \(p_{c}{ }^{*}=0.3808\) and n= 375.6 total patients - that is 188 cases and 188 controls.
These tables give requirements for a one-sided test directly. For two-sided tests, use the table corresponding to half the required significance level. Note that \(P\) is the prevalence of the risk factor in the entire population and \(\lambda\) is the appropriate relative risk to be tested. | |||||||||
---|---|---|---|---|---|---|---|---|---|
(a) 5% significance, 90% power \(P\) |
|||||||||
\(\lambda\) | 0.010 | 0.050 | 0.100 | 0.200 | 0.300 | 0.400 | 0.500 | 0.700 | 0.900 |
0.10 | 2 318 | 456 | 224 | 108 | 70 | 50 | 40 | 30 | 38 |
0.20 | 3 206 | 638 | 316 | 158 | 104 | 80 | 66 | 56 | 88 |
0.30 | 4 546 | 912 | 458 | 232 | 160 | 124 | 106 | 98 | 176 |
0.40 | 6 676 | 1 348 | 684 | 356 | 248 | 200 | 176 | 172 | 330 |
0.50 | 10 318 | 2 098 | 1 074 | 566 | 404 | 332 | 296 | 306 | 616 |
0.60 | 17 220 | 3 522 | 1 816 | 974 | 706 | 588 | 536 | 576 | 1 206 |
0.70 | 32 570 | 6 698 | 3 476 | 1 890 | 1 390 | 1 174 | 1 088 | 1 206 | 2 612 |
0.80 | 77 686 | 16 052 | 8 382 | 4 614 | 3 438 | 2 944 | 2 764 | 3 146 | 7 012 |
0.90 | 328 374 | 68 156 | 35 786 | 19 922 | 15 020 | 13 006 | 12 354 | 14 400 | 32 892 |
1.10 | 363 666 | 76 090 | 40 352 | 22 918 | 17 630 | 15 574 | 15 096 | 18 316 | 43 550 |
1.20 | 95 332 | 20 020 | 10 664 | 6 112 | 4 744 | 4 228 | 4 134 | 5 102 | 12 340 |
1.30 | 44 334 | 9 342 | 4 998 | 2 888 | 2 260 | 2 032 | 2 002 | 2 510 | 6 166 |
1.40 | 26 044 | 5 506 | 2 958 | 1 722 | 1 358 | 1 230 | 1 222 | 1 554 | 3 870 |
1.50 | 17 376 | 3 684 | 1 986 | 1 166 | 926 | 846 | 846 | 1 090 | 2 748 |
1.60 | 12 558 | 2 672 | 1 446 | 854 | 684 | 628 | 632 | 826 | 2 106 |
1.80 | 7 618 | 1 630 | 888 | 532 | 432 | 400 | 408 | 546 | 1 420 |
2.00 | 5 230 | 1 124 | 616 | 374 | 306 | 288 | 296 | 404 | 1 074 |
3.00 | 1 754 | 386 | 218 | 138 | 120 | 118 | 126 | 184 | 522 |
4.00 | 978 | 220 | 126 | 84 | 74 | 76 | 84 | 130 | 380 |
5.00 | 664 | 150 | 88 | 60 | 56 | 58 | 66 | 104 | 316 |
10.00 | 244 | 60 | 38 | 30 | 30 | 34 | 40 | 70 | 224 |
20.00 | 108 | 30 | 20 | 18 | 20 | 24 | 30 | 56 | 190 |
(Tables from Woodward, M. Epidemiology Study Design and Analysis. Boca Raton: Chapman and Hall, 2013)
Stop and Think!
- Prevalence of the risk factor increases (P)?
- Odds ratio decreases (\(\lambda\))?
- For many \(\lambda\), 0.5 has the smallest sample size requirement
- largest sample sizes with OR closest to 1; 1.1 requires greater n than 0.9