Clinical Trials

Clinical Trials: A Practical Guide ■❚❙❘Table 1. CHARM (Candesartan in Heart failure – Assessment of Reduction in Mortality and morbidity)eligibility criteria [1].InclusionExclusionAge ≥18 yearsSymptomatic heart failure (NYHA class II–IV for at least 4 weeks’ duration)Serum creatinine ≥265 μmol/LSerum potassium ≥5.5 mmol/LKnown bilateral renal artery stenosisSymptomatic hypotensionWomen of childbearing potential who are not using adequate contraceptionCritical aortic or mitral stenosisMyocardial infarctionStrokeOpen heart surgery in previous 4 weeksUse of angiotensin receptor blocker in previous 2 weeksAny noncardiac disease limiting 2-year survivalNYHA = New York Heart Association.many patients with the disease as possible (in this example, patients with heartfailure), but to exclude those with co-morbidities that might affect outcome (inthis example, stroke, severe aortic, or mitral stenosis) and those in whom safetymay be compromised (in this example, existing severe renal impairment ascandesartan can worsen renal function in certain circumstances).If particular tests or measurements are to be performed as part of the eligibilitycriteria, it is essential to ensure that the results of these investigations are availableprior to randomization of the patient into the study. Stratification or minimizationtechniques can be employed at the randomization stage to ensure balancebetween groups in important variables that may affect outcome; therefore, it isimportant to ensure that these data are available in a timely fashion. For example,in a study of cystic fibrosis, patients were stratified by their breathing capacity(as measured by forced expiratory volume in 1 second) and their atopy status,so it was essential that the results of the lung function and skin prick tests wereavailable at randomization.Disease statusSome diseases are subject to seasonal factors that affect the timing of patientselection (eg, immunotherapy studies of hay fever). Other diseases are subject tovariability, and repeated measurements are often required to confirm diagnosis inthese conditions (eg, repeat blood pressure measurements for the diagnosis ofhypertension). It is important to select patients who are ill enough to improve withthe intervention, but some patients might be too ill to participate in the study.51