Clinical Trials

❘❙❚■ Chapter 23 | Subgroup AnalysisWhat is a subgroup analysis?A clinical study is usually concerned with the overall impact of a treatment on anentire trial population. However, individuals within this population can differ inmany ways with respect to their age, gender, other medical problems, and riskof side-effects. These factors can influence their response to treatments. Byunderstanding the relationship between these characteristics and the treatmenteffect, clinicians can make more accurate treatment decisions for specific patientsusing knowledge gained through subgroup analyses.Subgroups can be identified on the basis of patients having specific features notshared by the whole trial population. These features might be patient characteristics(eg, male gender or age >75 years), risk factors (eg, high blood pressure for heartdisease, asbestos exposure for lung cancer), specific procedures (eg, keyhole surgeryrather than a traditional procedure) or specific tests (eg, a new assay test tomeasure amylase). Subgroups can also be defined by the level of compliance in thetrial (eg, fully compliant) or by the occurrence of a specific outcome (eg, theoccurrence of a stroke or survival to 5 years).Example 1For example, in a trial of adjuvant chemotherapy for breast cancer, survival wasassessed according to nodal status (two categories) and by age group (twocategories). Ascertaining survival according to these subgroups provided foursurvival curves and, consequently, better estimates of survival for individualpatients [1]. Using these data, physicians and patients were able to have a moreinformed discussion about whether chemotherapy would be likely to have benefitsor disadvantages in their specific situation.What is an appropriate subgroup?An appropriate subgroup consists of subjects with one or more characteristics thathave rational relationships to the disease or treatment. For example, consider atrial where patients are being prescribed a novel beta-blocker to reduce highblood pressure. Within this population, examining the treatment effect insubgroups of patients with and without heart failure or minor cardiac rhythmdisturbances would be appropriate. Raised blood pressure can lead to heartfailure and may therefore be associated with a greater benefit from beta-blockers.However, beta-blockers also reduce the rate at which the heart contracts and maymake some patients with slow heart rhythm disturbances worse, therebydecreasing the treatment effect. It would be rational to examine both of theseexample subgroups in the above trial. Subgroups of subjects recruited on a266