A simple sample size formula for analysis of covariance in randomized clinical trials.
OBJECTIVE
Randomized clinical trials that compare two treatments on a continuous outcome can be analyzed using analysis of covariance (ANCOVA) or a t-test approach. We present a method for the sample size calculation when ANCOVA is used.


METHODS
We derived an approximate sample size formula. Simulations were used to verify the accuracy of the formula and to improve the approximation for small trials. The sample size calculations are illustrated in a clinical trial in rheumatoid arthritis.


RESULTS
If the correlation between the outcome measured at baseline and at follow-up is rho, ANCOVA comparing groups of (1-rho(2))n subjects has the same power as t-test comparing groups of n subjects. When on the same data, ANCOVA is used instead of t-test, the precision of the treatment estimate is increased, and the length of the confidence interval is reduced by a factor 1-rho(2).


CONCLUSIONS
ANCOVA may considerably reduce the number of patients required for a trial.
Borm
George F
GF
Department of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Centre, Geert Grooteplein 21, PO Box 9101, NL-6500 HB Nijmegen, The Netherlands. G.Borm@epid.umcn.nl
Fransen
Jaap
J
Lemmens
Wim A J G
WA
D000704:Analysis of Variance; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D004359:Drug Therapy, Combination; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use; D000077339:Leflunomide; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D018401:Sample Size; D012460:Sulfasalazine / Q000627:therapeutic use; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D007555:Isoxazoles; D012460:Sulfasalazine; D000077339:Leflunomide