1. Sample Size and Statistical Power Epidemiology 655 Winter 1999 Jennifer Beebe

2. Determining Sufficient Sample Size Purpose: To provide an understanding of the concepts of sample size and statistical power; to provide tools for sample size calculation

3. Why do we worry about Sample Size and Power? Sample size too big; too much power wastes money and resources on extra subjects without improving statistical results Sample size too small; having too little power to detect meaningful differences –exposure (treatment) discarded as not important when in fact it is useful Improving your research design Improving chances for funding

4. Review of Statistical Concepts Hypothesis testing –Null hypothesis H o : No difference between groups; no effect of the covariate on the outcome –Alternative hypothesis H a : The researcher’s theory –Decision rule: Reject H o if a test statistic is in the critical region (p<.05)

5. Hypothesis Testing: Example H o : Diabetes is not associated with endometrial cancer in postmenopausal women H a : –Diabetes is associated with endometrial cancer; direction of association not specified (two-sided test) –Women with diabetes have an increased risk of developing endometrial cancer (one-sided test) –Women with diabetes have a decreased risk of developing endometrial cancer (one-sided test)

6. Under optimal conditions, we would examine all postmenopausal women with and without diabetes to determine if diabetes is associated with endometrial cancer –Instead, we collect data on a sample of postmenopausal women –Based on sample data, we would conduct a statistical test to determine whether or not to reject the null hypothesis

7. Errors Our sample may not accurately reflect the target population and we may draw an incorrect conclusion about all postmenopausal women based on the data obtained from our sample Type I and Type II errors

8. Two Types of Error Type I: Rejecting the H o when H o is true –The probability of a Type I error is called  –  is the designated significance level of the test –Usually we set the critical value so  =0.05 In our example, we could conclude based on our sample, that diabetes is associated with endometrial cancer when there really is no association

9. P-values Measure of a Type I error (random error) Probability that you have obtained your study results by chance alone, given that your null hypothesis is true If p=0.05, there is just a 5% chance that an observed association in your sample is due to random error

10. Example:Diabetes and Endometrial Cancer From our sample data, we found that women who have diabetes are 2 times more likely to develop endometrial cancer when compared to women without diabetes (p=0.01) If diabetes and endometrial cancer are not associated, there is a 1% probability that we would find this association by chance if we set the critical value as 0.05; 0.01<0.05; we would reject H o in favor of H a

11. Type II Error Type II: Accept H o when H a is true The probability of a type II error is called   depends on the effect size (How far from H o are we?) If we are far from H o, then  is small If we are close to H o, then  is large In our example, we could conclude that there is no association between diabetes and endometrial cancer when in fact there is an association

12. Truth in the Population AssociationNo association Studyb/w predictorb/w predictor Resultsand outcomeand outcome Reject HoCorrectType I error Fail to Type II errorCorrect Reject Ho

13. Power Power is the probability of observing an effect of a particular magnitude in the sample if one of a specified effect size or greater actually exists in the population Power = 1-  if  =.20 then power =.80; we will accept a 20% chance of missing an association of a particular size b/w an exposure and an outcome if one really exists

14.  and  Levels Usually range from 0.01-.10 (  ) and from 0.05-.20 (  ) Convention  =0.05 and  =0.20 Use low alpha’s to avoid false positives Use low beta’s to avoid false negatives Increased sample size will reduce type I and type II errors

15. Asking the sample size question? What sample size do I need to have adequate power to detect a particular effect size (or difference)? I only have N subjects available. What power will I have to detect a particular effect size (or difference) with that sample size?

16. Preparing to Calculate Sample Size What kind of study are you doing? –Case-control, cross-sectional, cohort What is the main purpose of the study? –What question(s) are you asking? What is your outcome measure? –Is it continuous, dichotomous, ordinal? The prevalence of exposure(s) in study population?

17. Preparing to Calculate Sample Size What statistical tests will be used? –(t-test, ANOVA, chi-square, regression etc) Will the test be one or two tailed? What  level will you use? –  =0.05 The hard one: How small an effect size (or difference) is important to detect? –What difference would you not want to miss? With what degree of certainty (power) do you want to detect the effect? (80-95%)

18. Tradeoffs with Sample Size Sample size is affected by effect size, , , power If detected effect size is  (Big OR or RR) then sample size  If detected effect size is  (Small OR or RR) then sample size  If the effect size is fixed; –  ;  ; (1-  )  ; sample size 

19. Tradeoffs with Power Power affected by sample size, prevalence of exposure, , , effect size  sample size;  power  effect size to detect;  power  ;  power Power of study is optimal usually when prevalence of the exposure in the control or referent group is b/w 40-60% Equal numbers of subjects in each group will increase power

20. Sample Size Requirements in a Cohort / Cross-sectional Study In addition to specified  and power, sample size depends on the – Incidence or probability of outcome among the unexposed –Ratio of exposed / unexposed –Relative risk/prevalence ratio that one regards as important to detect

21. Sample Size Requirements for a Case-control Study In addition to specified  and power, sample size depends on the –Ratio of cases to controls –Proportion of controls exposed –Odds ratio that one regards as important to detect

22. Sample Size and Power Software EpiInfo –Programs  Statcalc  Sample size and Power –User-friendly; easily accessible nQuery –More sophisticated, lots of options, you need to supply program with more information PASS, Power and Precision, GPower

23. Helpful Hints Choose an effect size reasonable for observational studies (this may be based on previous literature) Knowledge of prevalence of exposures of interest (also based on previous literature) Increase sample size 10-20% for each major confounder