Randomized controlled trials increasingly recruit patients globally to facilitate recruitment and to improve validity and applicability. However, patients from countries with different developmental status may differ in terms of clinical profiles, adherence to prescribed therapy and access to health care facilities. Further, these differences may impact patient outcomes. In this issue of Heart Professor Prabhakaran and colleagues (see page 279) (figure 1) report the influence of developmental status of individual countries, as defined by the United Nations' Human Development Index (HDI), on clinical outcomes of patients with Acute Coronary Syndrome (ACS) in a multinational study, the Trilogy ACS. Despite uniform study eligibility criteria, baseline characteristics differed significantly among patients from different HDI-classified countries. These baseline differences in turn were associated with differential outcomes. The authors conclude that geographical and other country-level factors variations in study populations need to be taken into account when designing, conducting and analyzing trials.

In the companion editorial, Dr Banerjee (see page 245) systematizes how this heterogeneity in developmental status can influence both internal and …