<p><strong>PURPOSE: </strong>Use electronic health record (EHR) data to (1) estimate the risk of arrhythmia associated with inhaled short-acting beta-2 agonists (SABA) in pediatric patients and (2) determine whether risk varied by on-label versus off-label prescribing.</p>

<p><strong>METHODS: </strong>Retrospective cohort study of 335&nbsp;041 children ≤18&nbsp;years using EHR primary care data from 2 pediatric health systems (2011-2013). A series of monthly pseudotrials were created, using propensity score methodology to balance baseline characteristics between SABA-exposed (identified by prescription) and SABA-unexposed children. Association between SABA and subsequent arrhythmia for each health system was estimated through pooled logistic regression with separate estimates for children initiating under and over 4&nbsp;years old (off-label and on-label, respectively).</p>

<p><strong>RESULTS: </strong>Eleven percent of the cohort received a SABA prescription, 57% occurred under the age of 4&nbsp;years (off-label). During the follow-up period, there were 283 first arrhythmia events, most commonly atrial tachyarrhythmias and premature ventricular/atrial contractions. In 1 health system, adjusted risk for arrhythmia was increased among exposed children (OR 1.89, 95% CI 1.31-2.73) without evidence of interaction between label status and risk. The absolute adjusted rate difference was 3.6/10&nbsp;000 person-years of SABA exposure. The association between SABA exposure and arrhythmias was less strong in the second system (OR 1.26, 95% CI 0.30-5.33).</p>

<p><strong>CONCLUSION: </strong>Using EHR data, we could estimate the risk of a rare event associated with medication use and determine difference in risk related to on-label versus off-label status. These findings support the value of EHR-based data for postmarketing drug studies in the pediatric population.</p>

<p><strong>BACKGROUND AND OBJECTIVES: </strong>Pediatric hypertension predisposes children to adult hypertension and early markers of cardiovascular disease. No large-scale studies have examined diagnosis and initial medication management of pediatric hypertension and prehypertension. The objective of this study was to evaluate diagnosis and initial medication management of pediatric hypertension and prehypertension in primary care.</p>

<p><strong>METHODS: </strong>Retrospective cohort study aggregating electronic health record data on &gt;1.2 million pediatric patients from 196 ambulatory clinics across 27 states. Demographic, diagnosis, blood pressure (BP), height, weight, and medication prescription data extracted. Main outcome measures include proportion of pediatric patients with ≥3 visits with abnormal BPs, documented hypertension and prehypertension diagnoses, and prescribed antihypertensive medications. Marginal standardization via logistic regression produced adjusted diagnosis rates.</p>

<p><strong>RESULTS: </strong>Three hundred ninety-eight thousand seventy-nine patients, ages 3 to 18, had ≥3 visits with BP measurements (48.9% girls, 58.6% &lt;10 years old). Of these, 3.3% met criteria for hypertension and 10.1% for prehypertension. Among practices with ≥50 eligible patients, 2813 of 12 138 patients with hypertension (23.2%; 95% confidence interval, 18.2%-28.2%) and 3990 of 38 874 prehypertensive patients (10.2%; 95% confidence interval, 8.2%-12.2%) were diagnosed. Age, weight, height, sex, and number and magnitude of abnormal BPs were associated with diagnosis rates. Of 2813 diagnosed, persistently hypertensive patients, 158 (5.6%) were prescribed antihypertensive medication within 12 months of diagnosis (angiotensin-converting enzyme inhibitors/angiotensin receptive blockers [35%], diuretics [22%], calcium channel blockers [17%], and β-blockers [10%]).</p>

<p><strong>CONCLUSIONS: </strong>Hypertension and prehypertension were infrequently diagnosed among pediatric patients. Guidelines for diagnosis and initial medication management of abnormal BP in pediatric patients are not routinely followed.</p>

<p>The United States lacks a system to use routinely collected electronic health record (EHR) clinical data to conduct comparative effectiveness research (CER) on pediatric drug therapeutics and other child health topics. This Special Article describes the creation and details of a network of EHR networks devised to use clinical data in EHRs for conducting CER, led by the American Academy of Pediatrics Pediatric Research in Office Settings (PROS). To achieve this goal, PROS has linked data from its own EHR-based "ePROS" network with data from independent practices and health systems across the United States. Beginning with 4 of proof-of-concept retrospective CER studies on psychotropic and asthma medication use and side effects with a planned full-scale prospective CER study on treatment of pediatric hypertension, the Comparative Effectiveness Research Through Collaborative Electronic Reporting (CER(2)) collaborators are developing a platform to advance the methodology of pediatric pharmacoepidemiology. CER(2) will provide a resource for future CER studies in pediatric drug therapeutics and other child health topics. This article outlines the vision for and present composition of this network, governance, and challenges and opportunities for using the network to advance child health and health care. The goal of this network is to engage child health researchers from around the United States in participating in collaborative research using the CER(2) database.</p>