Pragmatic controlled clinical trials in primary care: the struggle between external and internal validity

External validity is maximized by having few exclusion criteria and by allowing flexibility in the interpretation of the intervention and in management decisions. Internal validity is maximized by decreasing contamination bias through cluster randomization, and decreasing observer and assessment bias, in these non-blinded trials, through baseline data collection prior to randomization, automating the outcomes assessment with 24 hour ambulatory blood pressure monitors, and blinding the data analysis.Clinical trials conducted in community practices present investigators with difficult methodological choices related to maintaining a balance between internal validity (reliability of the results) and external validity (generalizability). The attempt to achieve methodological purity can result in clinically meaningless results, while attempting to achieve full generalizability can result in invalid and unreliable results. Achieving a creative tension between the two is crucial.Controlled clinical trials of health care interventions are either explanatory or pragmatic. [1-8] Explanatory trials test whether an intervention is efficacious; that is, whether it can have a beneficial effect in an ideal situation. These trials are often conducted in large tertiary care, referral-based, health centres on a homogenous group of patients, who have demonstrated compliance, who are likely to remain in the study, and who often have no medical condition other than the one under treatment.Pragmatic trials measure effectiveness; they measure the degree of beneficial effect in real clinical practice. Pragmatic trials are conducted on patients who represent the full spectrum of the population to which the treatment might be applied. These patients may demonstrate variable compliance, have a number of co-morbid conditions, and use other medications. If an intervention is shown to have a significant beneficial effect in a pragmatic trial then it has been shown not only that it can work, but a