Clinical Trials

❘❙❚■ Chapter 27 | InteractionTable 1. Mean reduction in systolic blood pressure (in mm Hg) by hypertensive drug treatment and smokingstatus in a hypothetical trial on 800 hypertension patients (200 in each group).Smoking statusHypertensive drug treatmentPlaceboDrugSmoker –2.07 –2.60Nonsmoker –1.94 –4.65What is an interaction effect?In a clinical trial, an interaction effect occurs when a treatment effect is dependenton another factor (eg, gender). For example, suppose a clinical study is carried outto investigate the effect of vitamin A supplements on childhood growth in adeveloping country. Vitamin A supplements might have a greater effect on growthin children from more deprived areas compared with children from less deprivedareas. In this example, the effect of the treatment (vitamin A supplementation) onthe primary outcome (height during childhood) varies according to the levels ofa third pre-existing factor (the prior nutritional status of the child). Therefore, thetreatment effect is dependent on nutritional status at baseline. In epidemiology,this phenomenon is often referred to as effect modification because the thirdvariable modifies the treatment effect on outcome.Example 1Table 1 presents the results of a hypothetical clinical trial assessing the effect ofa new antihypertensive drug on systolic blood pressure (SBP) among 800 patientswith hypertension. The results show that the antihypertensive drug reduces SBP,but the drug’s benefit appears to be greater for nonsmokers (a reduction in SBPof –2.71 mm Hg) than for smokers (a reduction in SBP of –0.53 mm Hg).When to look for an interaction effectDuring the design or analysis of a clinical trial, investigators are often interested inknowing whether the treatment effect of a study drug or therapy varies according topatient characteristics. For example, a treatment effect might decrease with age, orbe larger in subjects in a particular diagnostic category. To address this, statisticaltests of interactions between treatments and relevant covariates are often plannedand performed. If such interactions are anticipated, or are of particular priorinterest, then the planned confirmatory analysis will include a subgroup analysis, orwill use a statistical model including interactions. In most cases, subgroup orinteraction analyses are exploratory in nature and carried out after data collection.306