Application of response surface methodology and factorial designs to clinical trials for drug combination development.
The use of response surface methodology in the analysis of a factorial trial in the development of a combination treatment for hypertension is discussed. The analysis plan and efficacy results are reviewed with special attention to the quadratic response surface methods that were applied. A key issue is how to test to establish the existence of an effective dose combination. This issue also impacts current designs for combination drugs at fixed doses. Several direct approaches using quadratic response surface methods are discussed. Estimating the combination dose that maximizes the minimum gain of combination over each monotherapy seems most promising.
Stewart
W H
WH
Hoechst Marion Roussel, Inc., Kansas City, Missouri 64134-0627, USA.
D000959:Antihypertensive Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000379:methods*; D003627:Data Interpretation, Statistical; D004110:Diltiazem / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy; D013223:Statistics as Topic / Q000379:methods*
D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D004110:Diltiazem