Clinical Trials

Clinical Trials: A Practical Guide ■❚❙❘Table 1. Treatment groups after randomization in a 2 × 2 factorial study comparing the effects of vitaminsupplements on pregnancy outcomes in 1,075 Tanzanian women infected with HIV-1 [1].MultivitaminsVitamin AYes No OverallYes Vitamin A + multivitamins Multivitamins Treated with multivitamins(n = 270) (n = 269) (n = 539)No Vitamin A Placebo No multivitamins(n = 269) (n = 267) (n = 536)Overall Treated with vitamin A No vitamin A Total women(n = 539) (n = 536) (n = 1075)comparing column margins. Similarly, by comparing row totals, it is possible toevaluate the effect of using multivitamins during pregnancy (see Table 1).It is also possible to analyze this as a four-way study by investigating each cellof the contingency table separately; however, the number of individuals includedin each comparison is reduced, and consequently the study loses power. All 2 × 2factorial studies can be laid out in the same format as Table 1.Why should we consider a factorial design?A factorial design allows two treatments to be evaluated with a trial budgetfor a single comparison, providing both treatments have similar expectedbenefits. This is important because trials are becoming increasingly expensive ashigher standards are expected and larger trials are needed. A trial involving1,000 patients currently costs approximately US$4 million, assuming the trialinvestigates a new agent, involves evaluations every 6 months, and is partlyconducted in Western countries.Such an expense is unlikely to be spared to answer questions concerning relativelycheap treatments that could never hope to recoup the investment from profits.For example, no commercial company would finance a trial for aspirin becausethere is no profit to be made from aspirin and such expenditure could not beregained. Therefore, questions about the benefits of cheap, traditional agents areoften appended onto trials of more commercially viable agents.A factorial design presents the opportunity for an investigator to answer a questionfrom both commercial and noncommercial angles. For example, in the ISIS-4(Fourth International Study of Infarct Survival) trial, investigators assessed thebenefits of captopril (a new blood-pressure–lowering agent), oral mononitrate103