Clinical Trials

Clinical Trials: A Practical Guide ■❚❙❘example, we would need to increase our original sample size by a factor of four toinvestigate whether women on vitamin A and multivitamins have improved birthoutcomes compared with either intervention separately.What are the limitations of a factorial design?InteractionsThe main disadvantage of factorial trials is that the possibility of interactioneffects can usually only be determined at the end of the study. If such aninteraction effect is present then the usual way of analysis – ignoring the othertreatment assignment by summing up over the table margins – becomes invalid,since each cell by itself is meaningful.Since factorial trials are often designed with the assumption of the absence ofa treatment interaction, they are not powered to detect interactions, unless theyare substantially over-powered or the initial assumptions were very conservative.It follows that, in order to test the validity of assumptions of the analysis,interactions need to be tested for, but often they cannot be completely excluded.A more detailed description of power associated with a test for interaction infactorial design can be found elsewhere [11,12].ComplianceAnother notable disadvantage is that individuals randomized to only one or twointerventions will find it easier to comply with treatment than individualsrandomized to several different interventions. In the analysis of a factorial design,individuals are combined across treatment groups and then compared to calculatethe effect of each intervention at a time. Therefore, if adherence is reduced in animbalanced way, it could strongly influence the overall findings. A possible practicalsolution is to manufacture study medication that contains all the different drugcombinations/placebo within a single pill; however, this might not be economicalor profitable if certain biochemical interactions occur by combining the differentdrug formulations in the manufacturing process.ConclusionMost trials consider a single treatment factor where an intervention is comparedwith one or more alternatives or placebo. Factorial studies are an efficient andeconomical way of comparing multiple interventions because they combine two ormore trials into a single study for little more than the cost of the first study.Participants are randomly allocated to one or more overlapping intervention111