A comparison of the key features that differ between conventional randomised controlled trials (RCTs) and effectiveness trials

Conventional RCTsRandomised effectiveness trials
Trial settingOften academic/research centres specially equipped for clinical research, which patients may have to travel considerable distance to attend [5].
Trial patients often attend frequent, regular study visits with a specialist investigator [5].
Patients are provided with regular training during study visits to ensure optimal medication use and adherence [6]. Adherence to study medication is monitored.
Routine care practices and hospitals.
Patients treated by their (local) regular healthcare provider in accordance with usual clinical care; limited or no study-specific visits required.
Training and medication guidance is given as part of usual clinical care. This varies between sites and countries.
Patients may change their treatment at physician or patient discretion.
Patient selectionNarrow population due to strict inclusion and exclusion criteria [7, 8]; recruitment of patients with comorbid conditions and concomitant medications is limited [5, 7–9].Enrolment of a broader patient population creates high external validity as patients are more representative of the population seen in usual practice [8, 10].
Key differences between protocol-defined study treatments and those given in clinical practiceOften employ a placebo group or strictly controlled comparator group to enable direct comparison of pure drug effects providing high internal validity [10].Comparator treatments are aligned with physician and country usual standard of care.
Measurement of outcomesOutcomes often those required by regulatory authority, which may not be used in the routine care of patients, such as physiological end-points or biomarkers [11].Selected end-points are relevant to usual practice and include a more patient-centred focus [8].
Safety monitoringExclusion of “high-risk” patients most likely to experience safety issues [5, 9].
Safety is closely monitored by investigators at each study visit.
Enrolment of a wider population of patients allows collection of more generalisable safety data [10].
Patient safety is ensured through treating physicians during routine study visits or planned telephone calls.