Trials of antihypertensive therapies in children.

Clinical trials assessing the safety, effectiveness and pharmacokinetics of new antihypertensive medications have been numerous as new classes of medications have been developed and brought to market over the past two decades. However, very few clinical trials have been initiated and completed in children with hypertension. Excluding diuretics, only one antihypertensive medication marketed within the past 20 years has any pediatric pharmacokinetic or dosing information published in the drug label and none have a pediatric indication. There are many reasons that these studies have not been done. Summation of the data collected in large epidemiologic studies that establish normal blood pressure and define hypertension using casual measurements have been a relatively recent event in pediatrics. Although ambulatory blood pressure measurement has been studied for the past decade there is still uncertainty with respect to the standardization of devices, measurement technique and normal values in a multi-racial pediatric population. As a result, no large scale, industry-sponsored clinical trials involving antihypertensive therapy have employed this measurement technique in children. In recognition of this problem, US Congress passed the Food and Drug Administration Modernization Act in 1997. Among the many provisions of this law, the US Food and Drug Administration (FDA) is required to publish a list of approved drugs for which additional information may prove beneficial for children. This law and subsequent action by the FDA also provides a mechanism by which manufacturers may gain six months of additional market exclusivity if adequate and well-controlled pediatric trials are completed and submitted to the FDA in response to a formal written request for these studies. Because such studies have not been previously undertaken and the new rules provide a significant financial incentive, written requests have been issued for pediatric studies involving more than a dozen antihypertensive agents. The FDA published a sample written request for oral antihypertensives in children and several potential study designs were presented.