Wilson Pace

Improving the efficiency and effectiveness of pragmatic clinical trials in older adults in the United States

Pragmatic clinical trials (PCTs) seek to improve the generalizability and increase the statistical power of traditional explanatory trials. They are a major tenet of comparative effectiveness research. While a powerful study design, PCTs have been limited by high cost, modest efficiency, and limited ability to fill relevant evidence gaps. Based on an American Reinvestment and Recovery Act (ARRA) supported meeting of national stakeholders, we propose several innovations and future research that could improve the efficiency and effectiveness of such studies focused in the U.S. Innovations discussed include optimizing the use of community based practices through partnership with Practice Based Research Networks (PBRNs), using information technology to simplify PCT subject recruitment, consent and randomization processes, and utilizing linkages to large administrative databases, such as Medicare, as a mechanism to capture outcomes and other important PCT variables with lower subject and research team burden. Testing and adaptation of such innovations to PCT are anticipated to improve the public health value of these increasingly important studies.

Diagnosis and Medication Treatment of Pediatric Hypertension: A Retrospective Cohort Study

BACKGROUND AND OBJECTIVES: 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. METHODS: Retrospective cohort study aggregating electronic health record data on >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. RESULTS: Three hundred ninety-eight thousand seventy-nine patients, ages 3 to 18, had ≥3 visits with BP measurements (48.9% girls, 58.6% <10 years old). Of these, 3.3% met criteria for hypertension and 10.1% for prehypertension. Among practices with ≥50 eligible patients, 2813 of 12u2009138 patients with hypertension (23.2%; 95% confidence interval, 18.2%–28.2%) and 3990 of 38u2009874 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%]). CONCLUSIONS: 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.

Effectiveness of 2 Methods of Promoting Physical Activity, Healthy Eating, and Emotional Well-Being With the Americans in Motion—Healthy Interventions Approach

PURPOSE An increasing number of Americans are putting their health at risk from being overweight. We undertook a study to compare patient-level outcomes of 2 methods of implementing the Americans In Motion—Healthy Interventions (AIM-HI) approach to promoting physical activity, healthy eating, and emotional well-being. METHODS We conducted a randomized trial in which 24 family medicine practices were randomized to (1) an enhanced practice approach in which clinicians and office staff used AIM-HI tools to make personal changes and created a healthy environment, or (2) a traditional practice approach in which physicians and staff were trained and asked to use the tools with patients. Of the 610 patients enrolled, 331 were in healthy practices, and 279 were in traditional practices. At 0, 4, and 10 months we assessed blood pressure, body mass index, fasting blood glucose and insulin levels, nuclear magnetic resonance lipoprotein profiles, fitness, dietary intake, physical activity, and emotional well-being. Outcome data were analyzed using linear, mixed-effects multivariate models, adjusting for practices as a random effect. RESULTS Regardless of patient group, 16.2% of patients who completed a 10-month visit (n = 378 patients, 62% of enrollees) and 10% of all patients enrolled lost 5% or more of their body weight; 16.7% of patients who completed a 10-month visit (10.3% of all enrollees) had a 2-point or greater increase in their fitness level; and 29.2% of 10-month completers (18.0% of all enrollees) lost 5% or more of their body weight and/or increased their fitness level by 2 or more points. There were no significant differences in these outcomes between groups. CONCLUSIONS There was no difference between the 2 groups in the primary and most secondary outcomes. Both patient groups were able to show significant before-after improvements in selected patient-level outcomes.

Protocol for the asthma tools study: a pragmatic practice-based research network trial

Background Asthma is common among children, adolescents, and adults. However, management of asthma often fails to follow evidence-based guidelines. Control assessments have been developed, validated against expert opinion, and disseminated. However, in primary care, assessment of control is only one step in asthma management. To facilitate integration of the evidence-based guidelines into practice, tools should also guide the next steps in care. The Asthma APGAR tools do just that, incorporating a control assessment as well as assessment of the most common reasons for inadequate and poor control. The Asthma APGAR tool is also linked to a care algorithm based on the 2007 National Heart, Lung, and Blood Institute asthma guidelines. The objective of this study is to assess the impact of implementation of the Asthma APGAR on patient asthma outcomes in primary care practices. Methods A total of 1400 patients aged 5–60 years with physician-diagnosed asthma are enrolled in 20 practice-based research network (PBRN) practices randomized to intervention or usual care. The primary outcomes are changes in patient self-reported asthma control, asthma-related quality of life, and rates of exacerbations documented in medical records over the 18–24 months of enrollment. Process measures related to implementation of the Asthma APGAR system into daily care will also be assessed using review of medical records. Qualitative assessments will be used to explore barriers to and facilitators for integrating the Asthma APGAR tools into daily practice in primary care. Discussion Data from this pivotal pragmatic study are intended to demonstrate the importance of linking assessment of asthma and management tools to improve asthma-related patient outcomes. The study is an effectiveness trial done in real-world PBRN practices using patient-oriented outcome measures, making it generalizable to the largest possible group of asthma care providers and primary care clinics.

Use of Asthma APGAR Tools in Primary Care Practices: A Cluster-Randomized Controlled Trial

PURPOSE The purpose of this study was to assess patient and practice outcomes after introducing the Asthma APGAR (Activities, Persistent, triGGers, Asthma medications, Response to therapy) tools into primary care practices. METHODS We used a pragmatic cluster-randomized controlled design in 18 US family medicine and pediatric practices to compare outcomes in patients with persistent asthma aged 5 to 45 years after introduction of the Asthma APGAR tools vs usual care. Patient outcomes included asthma control, quality of life, and emergency department (ED), urgent care, and inpatient hospital visits. The practice outcome was adherence to asthma guidelines. RESULTS We enrolled 1,066 patients: 245 children, 174 adolescents, and 647 adults. Sixty-five percent (692 patients) completed both baseline and 12-month questionnaires, allowing analysis for patient-reported outcomes. Electronic health record data were available for 1,063 patients (99.7%) for practice outcomes. The proportion of patients reporting an asthma-related ED, urgent care, or hospital visit in the final 6 months of the study was lower in the APGAR practices vs usual care practices (10.6% vs 20.9%, P = .004). The percentage of patients with “in control” asthma increased more between baseline and 1 year in the APGAR group vs usual care group (13.5% vs 3.4%, P =.0001 vs P =.86) with a trend toward better control scores and asthma-related quality of life in the former at 1 year (P ≤.06 and P = .06, respectively). APGAR practices improved their adherence to 3 or more guideline elements compared with usual care practices (20.7% increase vs 1.9% decrease, P = .001). CONCLUSIONS Introduction of the Asthma APGAR tools improves rates of asthma control; reduces asthma-related ED, urgent care, and hospital visits; and increases practices’ adherence to asthma management guidelines.

A pragmatic randomized trial comparing tablet computer informed consent to traditional paper-based methods for an osteoporosis study

Objective Methods to improve informed consent efficiency and effectiveness are needed for pragmatic clinical trials. We compared informed consent using a tablet computer to a paper approach to assess comprehension and satisfaction of patients and clinic staff for a future osteoporosis clinical trial. Methods Nine community-based practices identified and recruited patients to compare the informed consent processes (tablet vs. paper) in a mock osteoporosis clinical trial. The tablet informed consent included an animation summarizing the trial, complete informed consent document, and questions to assess and reinforce comprehension of the study. Participants were women age ≥55 years with ≥1 year of alendronate use. We surveyed participants to assess comprehension and satisfaction and office staff for satisfaction and perceived time demands. Results The nine practices enrolled 33 participants. There was not a significant difference in comprehension between the tablet vs. paper informed consent [mean (SD) tablet: 12.2 (1.0) vs. paper: 11.4 (1.7)]. Office staff preferred the tablet to the paper informed consent for identifying potential study participants (two-sided t-test p = 0.02) despite an increased perceived time spent to complete the tablet process [tablet: 28.3 min (SD 16.3) vs. paper: 19.0 min (SD 6.9); p = 0.08]. Conclusions Although, there were no significant differences in participant satisfaction and comprehension with the tablet informed consent compared to a paper informed consent, patients and office staff trended towards greater satisfaction with the tablet informed consent. Larger studies are needed to further evaluate the utility of electronic informed consent in pragmatic clinical trials.

Effect of 2 Clinical Decision Support Strategies on Chronic Kidney Disease Outcomes in Primary Care: A Cluster Randomized Trial

Key Points Question Can clinical decision support plus practice facilitation improve treatment of chronic kidney disease (CKD) in primary care, with the goal of delaying progression of CKD from stages 3 and 4? Findings This cluster randomized clinical trial of 30 primary care practices comprising 6699 patients showed a significant effect in the intervention group compared with the control group in slowing the annualized loss of estimated glomerular filtration rate in patients with stages 3 and 4 CKD. There was significant improvement in hemoglobin A1c over time among patients in the intervention group compared with patients in the control group, with an imbalance between groups resulting from practice dropout posing a significant limitation. Meaning Findings suggest that a multimodal intervention in primary care can slow the progression of stages 3 and 4 CKD.

The asthma Symptom Free Days Questionnaire: how reliable are patient responses?

Abstract Objective: Symptom free days are a widely used patient-reported outcome (PRO) in asthma clinical trials. We assessed the internal consistency of one instrument for this PRO, the Symptom Free Days Questionnaire (SFDQ), in a population of Black adults with asthma enrolled in the Blacks and Exacerbations on Long-acting beta agonists and Tiotropium (BELT) trial. Methods: We assessed responses to the SFDQ collected at baseline, 6 and 12u2009months as part of the BELT trial. The internal consistency of responses, specifically number of patient-reported days with symptoms in 14u2009days were compared to the number of patient-reported days with no symptoms in the same 14u2009days. Lin concordance correlation coefficients (Lin ccc) were calculated over time to assess “learning” and by age, sex, geographic location, and annual family income. Results: The internal consistency of the responses of the 1070 enrolled patients was consistently low over the 12u2009months of the study; varying from 43.8% at baseline to 52.1% at 12u2009months. This corresponded to Lin cccs of 0.33–0.32 over the study period. Internal consistency and the Lin ccc did not vary by age group, sex, geographic location or percent poverty. Concordance was slightly but not significantly higher at all time points in those with family annual income of ≥

Susceptibility to Exacerbations in Black Adults with Asthma

50,000 compared to those with lower annual incomes. Conclusions: The SFDQ did not work well in the BELT population of Black adults with asthma. Further validation is required before the SFDQ is used in other large clinical trials with any population.

Spirometry Can Be Done in Family Physicians’ Offices and Alters Clinical Decisions in Management of Asthma and COPD

Abstract Objective: Exacerbations account for much of the morbidity in asthma. In a large intervention study, we sought to test the hypothesis that a Black adult exacerbation-prone phenotype – a group of Black people with asthma who are at high risk of repeat exacerbation within one year – exists in asthma independent of clinical control. Methods: We analyzed exacerbation risk factors in 536 self-identified Black Americans with asthma eligible for, or on, Step 3 National Asthma Education and Prevention Program (NAEPP) therapy who participated in a randomized 6–18u2009month trial of tiotropium versus long acting beta agonist as add-on therapy to inhaled corticosteroids. Exacerbations were defined as events treated by oral or systemic corticosteroids. Clinical control was assessed by a validated asthma control questionnaire (ACQ5). Results: Exacerbations became more likely with loss of clinical control. The mean baseline ACQs for exacerbators and non-exacerbators were 2.41 and 1.91, respectively (pu2009<u20090.001). The strongest independent factor associated with exacerbations across all ACQ levels was an exacerbation in the preceding year (adjusted OR 3.26; pu2009<u20090.001). The severity of prior exacerbations did not correlate with the likelihood of a future exacerbation. Lower baseline FEV1/FVC was also associated with increased risk of exacerbations. Conclusions: Even though exacerbations increase with loss of clinical control, an exacerbation susceptibility phenotype exists in Black adults with asthma, independent of clinical control. This phenotype requires precision therapeutic targeting.