Bhatt AS, Varshney AS, Nekoui M, Moscone A, Cunningham JW, Jering KS, Patel PN, Sinnenberg LE, Bernier TD, Buckley LF, Cook B, Dempsey J, Kelly J, Knowles DM, Lupi K, Malloy R, Matta LS, Rhoten MN, Sharma K, Snyder CA, Ting C, McElrath EE, Amato MG, Alobaidly M, Ulbricht CE, Choudhry NK, Adler DS, Vaduganathan M. Virtual Optimization of Guideline-Directed Medical Therapy in Hospitalized Patients with Heart Failure with Reduced Ejection Fraction: the IMPLEMENT-HF Pilot Study. Eur J Heart Fail 2021;Abstract
AIMS: HFrEF GDMT implementation remains incomplete. Non-cardiovascular hospitalization may present opportunities for GDMT optimization. We assessed the efficacy and durability of a virtual, multidisciplinary "GDMT Team" on medical therapy prescription for HFrEF. METHODS AND RESULTS: Consecutive hospitalizations in patients with HFrEF≤40% were prospectively identified from February 3 to March 1, 2020 (usual care group) and March 2 to August 28, 2020 (intervention group). Patients with critical illness, de-novo HF, and SBP<90mmHg were excluded. In the intervention group, a pharmacist-physician GDMT Team provided optimization suggestions to treating teams based on an evidence-based algorithm. The primary outcome was a GDMT optimization score, the net of positive (+1 for new initiations or up-titrations) & negative therapeutic changes (-1 for discontinuations or down-titrations) at hospital discharge. Serious in-hospital safety events were assessed. Among 278 consecutive encounters with HFrEF, 118 met eligibility criteria; 29 (25%) received usual care and 89 (75%) received the GDMT Team intervention. Among usual care encounters, there were no changes in GDMT prescription during hospitalization. In the intervention group, β-blocker (72% to 88%; P=0.01), ARNI (6% to 17%; P=0.03), MRA (16% to 29%; P=0.05), and triple therapy (9% to 26%; P<0.01) prescriptions increased during hospitalization. After adjustment, the GDMT Team was associated with an increase in GDMT optimization score (+0.58; 95% CI: +0.09 to +1.07; P=0.02). There were no serious in-hospital adverse events. CONCLUSIONS: Non-cardiovascular hospitalizations are a potentially safe and effective setting for GDMT optimization. A virtual GDMT Team was associated with improved HF therapeutic optimization. This implementation strategy warrants testing in a prospective randomized controlled trial. This article is protected by copyright. All rights reserved.
Lauffenburger JC, Isaac T, Trippa L, Keller P, Robertson T, Glynn RJ, Sequist TD, Kim DH, Fontanet CP, Castonguay EWB, Haff N, Barlev RA, Mahesri M, Gopalakrishnan C, Choudhry NK. Rationale and design of the Novel Uses of adaptive Designs to Guide provider Engagement in Electronic Health Records (NUDGE-EHR) pragmatic adaptive randomized trial: a trial protocol. Implementation Science 2021;16:9.Abstract
The prescribing of high-risk medications to older adults remains extremely common and results in potentially avoidable health consequences. Efforts to reduce prescribing have had limited success, in part because they have been sub-optimally timed, poorly designed, or not provided actionable information. Electronic health record (EHR)-based tools are commonly used but have had limited application in facilitating deprescribing in older adults. The objective is to determine whether designing EHR tools using behavioral science principles reduces inappropriate prescribing and clinical outcomes in older adults.
Lauffenburger JC, Mahesri M, Choudhry NK. Use of Data-Driven Methods to Predict Long-term Patterns of Health Care Spending for Medicare Patients. JAMA network open 2020;3:e2020291-e2020291.Abstract
IMPORTANCE: Current approaches to predicting health care costs generally rely on a single composite value of spending and focus on short time horizons. By contrast, examining patients' spending patterns using dynamic measures applied over longer periods may better identify patients with different spending and help target interventions to those with the greatest need. OBJECTIVE: To classify patients by their long-term, dynamic health care spending patterns using a data-driven approach and assess the ability to predict spending patterns, particularly using characteristics that are potentially modifiable through intervention. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used a retrospective cohort design from a random nationwide sample of Medicare fee-for-service administrative claims data to identify beneficiaries aged 65 years or older with continuous eligibility from 2011 to 2013. Statistical analysis was performed from August 2018 to December 2019. MAIN OUTCOMES AND MEASURES: Group-based trajectory modeling was applied to the claims data to classify the Medicare beneficiaries by their total health care spending patterns over a 2-year period. The ability to predict membership in each trajectory spending group was assessed using generalized boosted regression, a data mining approach to model building and prediction, with split-sample validation. Models were estimated using (1) prior-year predictors and (2) prior-year predictors potentially modifiable through intervention measured in the claims data. These models were evaluated using validated C-statistics. The relative influence of individual predictors in the models was evaluated. RESULTS: Among the 329 476 beneficiaries, the mean (SD) age was 76.0 (7.2) years and 190 346 (57.8%) were female. This final 5-group model included a minimal-user group (group 1, 37 572 individuals [11.4%]), a low-cost group (group 2, 48 575 individuals [14.7%]), a rising-cost group (group 3, 24 736 individuals [7.5%]), a moderate-cost group (group 4, 83 338 individuals [25.3%]), and a high-cost group (group 5, 135 255 individuals [41.2%]). Potentially modifiable characteristics strongly predicted these patterns (C-statistics range: 0.68-0.94). For groups with progressively increasing spending in particular, the most influential factors were number of medications (relative influence: 29.2), number of office visits (relative influence: 30.3), and mean medication adherence (relative influence: 33.6). CONCLUSIONS AND RELEVANCE: Using a data-driven approach, distinct spending patterns were identified with high accuracy. The potentially modifiable predictors of membership in the rising-cost group represent important levers for early interventions that may prevent later spending increases. This approach could be adapted by organizations to target quality improvement interventions, particularly because numerous health care organizations are increasingly using these routinely collected data.
Lauffenburger JC, Mahesri M, Choudhry NK. Not there yet: using data-driven methods to predict who becomes costly among low-cost patients with type 2 diabetes. BMC Endocr Disord 2020;20:125.Abstract
BACKGROUND: Diabetes is a leading cause of Medicare spending; predicting which individuals are likely to be costly is essential for targeting interventions. Current approaches generally focus on composite measures, short time-horizons, or patients who are already high utilizers, whose costs may be harder to modify. Thus, we used data-driven methods to classify unique clusters in Medicare claims who were initially low utilizers by their diabetes spending patterns in subsequent years and used machine learning to predict these patterns. METHODS: We identified beneficiaries with type 2 diabetes whose spending was in the bottom 90% of diabetes care spending in a one-year baseline period in Medicare fee-for-service data. We used group-based trajectory modeling to classify unique clusters of patients by diabetes-related spending patterns over a two-year follow-up. Prediction models were estimated with generalized boosted regression, a machine learning method, using sets of all baseline predictors, diabetes predictors, and predictors that are potentially-modifiable through interventions. Each model was evaluated through C-statistics and 5-fold cross-validation. RESULTS: Among 33,789 beneficiaries (baseline median diabetes spending: $4153), we identified 5 distinct spending patterns that could largely be predicted; of these, 68.1% of patients had consistent spending, 25.3% had spending that rose quickly, and 6.6% of patients had spending that rose progressively. The ability to predict these groups was moderate (validated C-statistics: 0.63 to 0.87). The most influential factors for those with progressively rising spending were age, generosity of coverage, prior spending, and medication adherence. CONCLUSIONS: Patients with type 2 diabetes who were initially low spenders exhibit distinct subsequent long-term patterns of diabetes spending; membership in these patterns can be largely predicted with data-driven methods. These findings as well as applications of the overall approach could potentially inform the design and timing of diabetes or cost-containment interventions, such as medication adherence or interventions that enhance access to care, among patients with type 2 diabetes.
Lauffenburger JC, Fontanet CP, Isaac T, Gopalakrishnan C, Sequist TD, Gagne JJ, Jackevicius CA, Fischer MA, Solomon DH, Choudhry NK. Comparison of a new 3-item self-reported measure of adherence to medication with pharmacy claims data in patients with cardiometabolic disease. Am Heart J 2020;228:36-43.Abstract
BACKGROUND: Less than half of patients with cardiometabolic disease consistently take prescribed medications. While health insurers and some delivery organizations use claims to measure adherence, most clinicians do not have access during routine interactions. Self-reported scales exist, but their practical utility is often limited by length or cost. By contrast, the accuracy of a new 3-item self-reported measure has been demonstrated in individuals with HIV. We evaluated its concordance with claims-based adherence measures in cardiometabolic disease. METHODS: We used data from a recently-completed pragmatic trial of patients with cardiometabolic conditions. After 12 months of follow-up, intervention subjects were mailed a survey with the 3-item measure that queries about medication use in the prior 30 days. Responses were linearly transformed and averaged. Adherence was also measured in claims in month 12 and months 1-12 of the trial using proportion of days covered (PDC) metrics. We compared validation metrics for non-adherence for self-report (average <0.80) compared with claims (PDC <0.80). RESULTS: Of 459 patients returning the survey (response rate: 43.5%), 50.1% were non-adherent in claims in month 12 while 20.9% were non-adherent based on the survey. Specificity of the 3-item metric for non-adherence was high (month 12: 0.83). Sensitivity was relatively poor (month 12: 0.25). Month 12 positive and negative predictive values were 0.59 and 0.52, respectively. CONCLUSIONS: A 3-item self-reported measure has high specificity but poor sensitivity for non-adherence versus claims in cardiometabolic disease. Despite this, the tool could help target those needing adherence support, particularly in the absence of claims data.
Doll JA, Kaltenbach LA, Anstrom KJ, Cannon CP, Henry TD, Fonarow GC, Choudhry NK, Fonseca E, Bhalla N, Eudicone JM, Peterson ED, Wang TY. Impact of a Copayment Reduction Intervention on Medication Persistence and Cardiovascular Events in Hospitals With and Without Prior Medication Financial Assistance Programs. J Am Heart Assoc 2020;:e014975.Abstract


Hospitals commonly provide a short-term supply of free P2Y12 inhibitors at discharge after myocardial infarction, but it is unclear if these programs improve medication persistence and outcomes. The ARTEMIS (Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study) trial randomized hospitals to usual care versus waived P2Y12 inhibitor copayment costs for 1-year post-myocardial infarction. Whether the impact of this intervention differed between hospitals with and without pre-existing medication assistance programs is unknown.

Methods and Results

In this post hoc analysis of the ARTEMIS trial, we examined the associations of pre-study free medication programs and the randomized copayment voucher intervention with P2Y12 inhibitor persistence (measured by pharmacy fills and patient report) and major adverse cardiovascular events using logistic regression models including a propensity score. Among 262 hospitals, 129 (49%) offered pre-study free medication assistance. One-year P2Y12 inhibitor persistence and major adverse cardiovascular events risks were similar between patients treated at hospitals with and without free medication programs (adjusted odds ratio 0.93, 95% CI, 0.82-1.05 and hazard ratio 0.92, 95% CI, 0.80-1.07, respectively). The randomized copayment voucher intervention improved persistence, assessed by pharmacy fills, in both hospitals with (53.6% versus 44.0%, adjusted odds ratio 1.45, 95% CI, 1.20-1.75) and without (59.0% versus 48.3%, adjusted odds ratio 1.46, 95% CI, 1.25-1.70) free medication programs (Pinteraction=0.71). Differences in patient-reported persistence were not significant after adjustment.


While hospitals commonly report the ability to provide free short-term P2Y12 inhibitors, we did not find association of this with medication persistence or major adverse cardiovascular events among patients with insurance coverage for prescription medication enrolled in the ARTEMIS trial. An intervention that provided copayment assistance vouchers for 1 year was successful in improving medication persistence in hospitals with and without pre-existing short-term medication programs. Registration URL: Unique identifier: NCT02406677.

Fanaroff AC, Peterson ED, Kaltenbach LA, Cannon CP, Choudhry NK, Henry TD, Anstrom KJ, Cohen DJ, Fonseca E, Khan ND, Fonarow GC, Wang TY. Agreement and Accuracy of Medication Persistence Identified by Patient Self-report vs Pharmacy Fill: A Secondary Analysis of the Cluster Randomized ARTEMIS Trial. JAMA Cardiology 2020;Abstract
Pharmacy fill data are increasingly accessible to clinicians and researchers to evaluate longitudinal medication persistence beyond patient self-report.To assess the agreement and accuracy of patient-reported and pharmacy fill–based medication persistence.This post hoc analysis of the cluster randomized clinical trial ARTEMIS (Affordability and Real-world Antiplatelet Treatment Effectiveness After Myocardial Infarction Study) enrolled patients at 287 US hospitals (131 randomized to intervention and 156 to usual care) from June 5, 2015, to September 30, 2016, with 1-year follow-up and blinded adjudication of major adverse cardiovascular events. In total, 8373 patients with myocardial infarction and measurement of P2Y12 inhibitor persistence by both patient self-report and pharmacy data were included. Serum P2Y12 inhibitor drug levels were measured for 944 randomly selected patients. Data were analyzed from May 2018 to November 2019.Patients treated at intervention-arm hospitals received study vouchers to offset copayments at each P2Y12 inhibitor fill for 1 year after myocardial infarction.Nonpersistence was defined as a gap of 30 days or more in P2Y12 inhibitor use (patient report) or supply (pharmacy fill) and as serum P2Y12 inhibitor levels below the lower limit of quantification (drug level). Among patients in the intervention arm, a “criterion standard” definition of nonpersistence was a gap of 30 days or more in P2Y12 inhibitor use by both voucher use and pharmacy fill. Major adverse cardiovascular events were defined as adjudicated death, recurrent myocardial infarction, or stroke.Of 8373 patients included in this analysis, the median age was 62 years (interquartile range, 54-70 years), 5664 were men (67.7%), and 990 (11.8%) self-reported as nonwhite race/ethnicity. One-year estimates of medication nonpersistence rates were higher using pharmacy fills (4042 patients [48.3%]) compared with patient self-report (1277 patients [15.3%]). Overall, 4185 patients (50.0%) were persistent by both pharmacy fill data and patient report, 1131 patients (13.5%) were nonpersistent by both, and 3057 patients (36.5%) were discordant. By application of the criterion standard definition, the 1-year nonpersistence rate was 1184 of 3703 patients (32.0%); 892 of 3318 patients (26.9%) in the intervention arm who self-reported persistence were found to be nonpersistent, and 303 of 1487 patients (20.4%) classified as nonpersistent by pharmacy fill data were actually persistent. Agreement between serum P2Y12 inhibitor drug levels and either patient-reported (κ = 0.11-0.23) or fill-based (κ = 0.00-0.19) persistence was poor. Patients who were nonpersistent by both pharmacy fill data and self-report had the highest 1-year major adverse cardiac event rate (18.3%; 95% CI, 16.0%-20.6%) compared with that for discordant patients (9.7%; 8.7%-10.8%) or concordantly persistent patients (8.2%; 95% CI, 7.4%-9.0%).Patient report overestimated medication persistence rates, and pharmacy fill data underestimated medication persistence rates. Patients who are nonpersistent by both methods have the worst clinical outcomes and should be prioritized for interventions that improve medication-taking Identifier: NCT02406677
Haff N, Lauffenburger JC, Morawski K, Ghazinouri R, Noor N, Kumar S, Juusola J, Choudhry NK. The accuracy of self-reported blood pressure in the Medication adherence Improvement Support App For Engagement-Blood Pressure (MedISAFE-BP) trial: Implications for pragmatic trials. Am Heart J 2020;220:68-72.Abstract
Self-report of health conditions and behaviors is one potential strategy to increase the pace of enrollment into pragmatic clinical trials. In this study, we assessed the accuracy of self-reported poorly controlled hypertension among adults in the community who were screened for participation in the MedISAFE-BP trial. Of individuals who self-reported poorly controlled hypertension using the online trial enrollment platform, 64% had a systolic blood pressure less than 140 mm Hg when measured at home. Although we identified several characteristics associated with accurate self-report including older age (odds ratio [OR] 1.02 per year, 95% CI 1.01-1.03), diabetes (OR 1.59, 95% CI 1.17-2.14), and low health activation (OR 1.56 95% CI 1.17-2.07), we were unable to identify patients for whom self-reported hypertension would be a reliable method for their inclusion in a pragmatic trial.
Lauffenburger JC, Lewey J, Jan S, Lee J, Ghazinouri R, Choudhry NK. Association of Potentially Modifiable Diabetes Care Factors With Glycemic Control in Patients With Insulin-Treated Type 2 Diabetes. JAMA Network Open 2020;3:e1919645-e1919645.Abstract
Numerous factors are associated with the ability of patients with type 2 diabetes to achieve optimal glycemic control. However, many of these factors are not modifiable by quality improvement interventions. In contrast, the structure of how diabetes care is delivered, such as whether patients visit an endocrinologist or how prescriptions are filled, is potentially modifiable, yet its associations with glycemic control have not been rigorously evaluated.To investigate the association of diabetes care delivery with glycemic control in patients with type 2 diabetes using insulin.This retrospective cohort study used baseline claims and laboratory insurer data within a large pragmatic trial to identify individuals with type 2 diabetes using insulin with data for at least 1 hemoglobin A1c (HbA1c) test result from before trial randomization (July 1, 2014, to October 5, 2016) and for key nonmodifiable patient factors as well as diabetes care delivery and behavioral factors measured before the HbA1c test. Analyses were conducted from February 4, 2017, to November 13, 2018.Multivariable modified Poisson regression was used to evaluate the independent associations of nonmodifiable patient factors and potentially modifiable diabetes care delivery and patient behavioral factors with achieving adequate diabetes control (ie, HbA1c level <8%). The extent of measured variation explained in glycemic control by these factors was also explored using pseudo R2 and C statistics.Of 1423 patients included, 565 (39.7%) were women, and the mean (SD) age was 56.4 (9.0) years. In total, 690 (48.5%) had HbA1c levels less than 8%. Age (relative risk [RR] per 1-unit increase, 1.01; 95% CI, 1.00-1.02), persistent use of basal insulin (RR, 1.20; 95% CI, 1.00-1.43), more frequent filling of glucose self-testing supplies (RR, 1.01; 95% CI, 1.01-1.02), visiting an endocrinologist (RR, 1.41; 95% CI, 1.19-1.67), and receipt of insulin prescriptions by mail order (RR, 1.23; 95% CI, 1.03-1.48) were all independently associated with adequate control. Measured potentially modifiable diabetes care factors explained more variation in adequate glycemic control than measured nonmodifiable patient factors (C statistic, 0.661 vs 0.598; pseudo R2 = 0.11 vs 0.04).These findings suggest that for patients with type 2 diabetes using insulin, the way in which care is delivered may be more strongly associated with achieving adequate control of HbA1c levels than patient factors that cannot be altered are. Given the potential for intervention, these care delivery factors could be the focus of efforts to improve diabetes outcomes.
Lauffenburger JC, Isaac T, Bhattacharya R, Sequist TD, Gopalakrishnan C, Choudhry NK. Prevalence and Impact of Having Multiple Barriers to Medication Adherence in Non-adherent Patients with Poorly-controlled Cardiometabolic Disease. The American Journal of Cardiology 2020;125(3):376-382.Abstract
ABSTRACT Adherence to medications remains poor despite numerous efforts to identify and intervene upon non-adherence. One potential explanation is the limited focus of many interventions on one barrier. Little is known about the prevalence and impact of having multiple barriers in contemporary practice. Our objective was to quantify adherence barriers for patients with poorly-controlled cardiometabolic condition, identify patient characteristics associated with having multiple barriers, and determine its impact on adherence. We used a linked electronic health records and insurer claims dataset from a large health system from a recent pragmatic trial. Barriers to medication-taking before the start of the intervention were elicited by clinical pharmacists using structured interviews. We used multivariable modified Poisson regression models to examine the association between patient factors and multiple barriers and multivariable linear regression to evaluate the relationship between multiple barriers and claims-based adherence. Of the 1,069 patients (mean: 61 years of age) in this study, 25.1% had multiple barriers to adherence; the most common co-occurring barriers were forgetfulness and health beliefs (31%, n=268). Patients with multiple barriers were more likely to be non-white (Relative Risk [RR]:1.57, 95%CI: 1.21-1.74), be single/unpartnered (RR:1.36, 95%CI: 1.06-1.74), use tobacco (RR:1.54, 95%CI: 1.13-2.11), and have poor glycemic control (RR:1.77, 95%CI: 1.31-2.39) versus those with 0 or 1 barrier. Each additional barrier worsened average adherence by 3.1% (95%CI: -4.6%, -1.5%). In conclusion, >25% of non-adherent patients present with multiple barriers to optimal use, leading to meaningful differences in adherence. These findings should inform quality improvement interventions aimed at non-adherence.
Fanaroff AC, Peterson ED, Kaltenbach LA, Cannon CP, Choudhry NK, Henry TD, Anstrom KJ, Cohen DJ, Fonseca E, Khan ND, Fonarow GC, Wang TY. Association of a P2Y12 Inhibitor Copayment Reduction Intervention With Persistence and Adherence With Other Secondary Prevention Medications: A Post Hoc Analysis of the ARTEMIS Cluster-Randomized Clinical Trial. JAMA Cardiology 2019;Abstract
The Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study (ARTEMIS) cluster-randomized trial found that copayment reduction for P2Y12 inhibitors improved 1-year patient persistence in taking that medication.To assess whether providing copayment reduction for P2Y12 inhibitors increases patient persistence in taking other secondary prevention cardiovascular medications.This post hoc analysis of the ARTEMIS trial includes data from 287 hospitals that enrolled patients between June 2015 and September 2016. Patients hospitalized with acute myocardial infarction were included. Data analysis occurred from May 2018 through August 2019.Hospitals randomized to the intervention provided patients vouchers that waived copayments for P2Y12 inhibitors fills for 1 year. Hospitals randomized to usual care did not provide study vouchers.Persistence in taking β-blocker, statin, and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker medications at 1 year, defined as the absence of a gap in medication supply of 30 or more days by pharmacy fill data in the intervention-arm (intent-to-treat) population.A total of 131 hospitals (with 5109 patients) were randomized to the intervention, and 156 hospitals (with 3264 patients) randomized to the control group. Patients discharged from intervention hospitals had higher persistence in taking statins (2247 [46.1%] vs 1300 [41.9%]; adjusted odds ratio, 1.11 [95% CI, 1.00-1.24]), and β-blockers (2235 [47.6%] vs 1277 [42.5%]; odds ratio, 1.23 [95% CI, 1.10-1.38]), although the association was smaller than that seen for P2Y12 inhibitors (odds ratio, 1.47 [95% CI, 1.29-1.66]). Persistence in taking angiotensin-converting enzyme inhibitors or angiotensin II-receptor blockers were also numerically higher among patients in the intervention arm than in the usual-care arm, but this was not significant after risk adjustment (1520 [43.9%] vs 847 [40.5%]; adjusted odds ratio, 1.10 [95% CI, 0.97-1.24]). Patients in the intervention arm reported greater financial burden associated with medication cost than the patients in the usual-care arm at baseline, but these differences were no longer significant at 1 year.Reducing patient copayments for 1 medication class increased persistence not only to that therapy class but may also have modestly increased persistence to other post–myocardial infarction secondary prevention medications. These findings have important implications for the clinical utility and cost-effectiveness of medication cost-assistance Identifier: NCT02406677
Metes ID, Xue L, Chang C-CH, Huskamp HA, Gellad WF, Lo-Ciganic W-H, Choudhry NK, Richards-Shubik S, Guclu H, Donohue JM. Association between physician adoption of a new oral anti-diabetic medication and Medicare and Medicaid drug spending. BMC Health Services Research 2019;19:703.Abstract


In the United States, there is well-documented regional variation in prescription drug spending. However, the specific role of physician adoption of brand name drugs on the variation in patient-level prescription drug spending is still being investigated across a multitude of drug classes. Our study aims to add to the literature by determining the association between physician adoption of a first-in-class anti-diabetic (AD) drug, sitagliptin, and AD drug spending in the Medicare and Medicaid populations in Pennsylvania.


We obtained physician-level data from QuintilesIMS Xponent™ database for Pennsylvania and constructed county-level measures of time to adoption and share of physicians adopting sitagliptin in its first year post-introduction. We additionally measured total AD drug spending for all Medicare fee-for-service and Part D enrollees (N = 125,264) and all Medicaid (N = 50,836) enrollees with type II diabetes in Pennsylvania for 2011. Finite mixture model regression, adjusting for patient socio-demographic/clinical characteristics, was used to examine the association between physician adoption of sitagliptin and AD drug spending.


Physician adoption of sitagliptin varied from 44 to 99% across the state’s 67 counties. Average per capita AD spending was $1340 (SD $1764) in Medicare and $1291 (SD $1881) in Medicaid. A 10% increase in the share of physicians adopting sitagliptin in a county was associated with a 3.5% (95% CI: 2.0–4.9) and 5.3% (95% CI: 0.3–10.3) increase in drug spending for the Medicare and Medicaid populations, respectively.


In a medication market with many choices, county-level adoption of sitagliptin was positively associated with AD spending in Medicare and Medicaid, two programs with different approaches to formulary management.

Stolpe S, Choudhry NK. Effect of Automated Immunization Registry-Based Telephonic Interventions on Adult Vaccination Rates in Community Pharmacies: A Randomized Controlled Trial. Journal of Managed Care & Specialty Pharmacy 2019;25:989-994.Abstract
BACKGROUND: Pharmacies have a unique opportunity to address suboptimal adult vaccination rates, but few solutions have proven effective. Such strategies are challenged by the lack of access that many pharmacies have to a patient’s complete immunization history; consequently, they are unable to identify which of their patients actually require vaccination. A pharmacy-based strategy that leverages such information could enhance efforts to increase rates of guideline-based vaccination. OBJECTIVE: To determine the effect on vaccination rates of an automated telephonic intervention for adults in need of either pneumococcal vaccination or herpes zoster vaccination, or both. METHODS: Over a 1-year period, patients with identified vaccine gaps at 246 pharmacies of 3 pharmacy chains were randomly assigned to receive either usual care or an automated telephonic prompt for pneumococcal and/or herpes zoster vaccines based on patient records contained in state immunization registries and pharmacy data. The primary outcome was the proportion with administration of at least one of the vaccines offered between March 2016 and January 2017 based on intention-to-treat principles. Subgroup analyses included vaccination rates by age and sex. An as-treated analysis was also performed. RESULTS: 21,971 patients were included in the study, 57% of whom were female, with a mean age of 63 years. Vaccine administration proportions were 0.0214 (236/11,009) in the intervention group, and 0.0205 (225/10,962) in the control group (OR = 1.05, 95% CI = 0.87-1.26). Results did not differ in subgroup analyses based on patient age, sex, or individual pharmacy chain. Among intervention patients, 3,666 (0.333) completed the call by listening to the entire prompt. In an as-treated analysis comparing individuals who completed calls versus control, the intervention increased the odds of vaccination by 26% (OR = 1.26, 95% CI = 1.00-1.61). CONCLUSIONS: The automated prompt did not significantly increase vaccination rates. Potential barriers included intervention technical flaws, low rates of connecting with patients, insufficient follow-up by the pharmacy, and patients placing a relatively low priority on being vaccinated. DISCLOSURES: This project was funded by Pfizer and Merck through a grant from the Pharmacy Quality Alliance. Stolpe was an employee of the Pharmacy Quality Alliance at the onset of this project and an employee of Scientific Technologies Corporation during the data collection phase of the project. Stolpe has also served on the advisory board for Merck. Choudhry has no conflicts of interest to declare.
Singh K, Choudhry NK, Krumme AA, McKay C, McElwee NE, Kimura J, Franklin JM. A concept-wide association study to identify potential risk factors for nonadherence among prevalent users of antihypertensives. Pharmacoepidemiology and Drug Safety 2019;:1-10.Abstract

Purpose: We sought to determine whether an association study using information contained in clinical notes could identify known and potentially novel risk factors for nonadherence to antihypertensive medications.

Methods: We conducted a retrospective concept-wide association study (CWAS) using clinical notes to identify potential risk factors for medication nonadherence, adjusting for age, sex, race, baseline blood pressure, estimated glomerular filtration rate, and a combined comorbidity score. Participants included Medicare beneficiaries 65 years and older receiving care at the Harvard Vanguard Medical Associates network from 2010-2012 and enrolled in a Medicare Advantage program. Concepts were extracted from clinical notes in the year prior to the index prescription date for each patient. We tested associations with the outcome for 5013 concepts extracted from clinical notes in a derivation cohort (4382 patients) and accounted for multiple hypothesis testing by using a false discovery rate threshold of less than 5% (q < .05). We then confirmed the associations in a validation cohort (3836 patients). Medication nonadherence was defined using a proportion of days covered (PDC) threshold less than 0.8 using pharmacy claims data.

Results: We found 415 concepts associated with nonadherence, which we organized into 11 clusters using a hierarchical clustering approach. Volume depletion and overload, assessment of needs at the point of discharge, mood disorders, neurological disorders, complex coordination of care, and documentation of noncompliance were some of the factors associated with nonadherence.

Conclusions: This approach was successful in identifying previously described and potentially new risk factors for antihypertensive nonadherence using the clinical narrative.

D'Andrea E, Choudhry NK, Raby B, Weinhouse GL, Najafzadeh M. A bronchial-airway gene-expression classifier to improve the diagnosis of lung cancer: clinical outcomes and cost-effectiveness analysis. Int J Cancer 2019;Abstract
Bronchoscopy is the safest procedure for lung cancer diagnosis when an invasive evaluation is required after imaging procedures. However its sensitivity is relatively low, especially for small and peripheral lesions. We assessed benefits and costs of introducing a bronchial gene-expression classifier (BGC) to improve the performance of bronchoscopy and the overall diagnostic process for early detection of lung cancer. We used discrete-event simulation to compare clinical and economic outcomes of two different strategies with the standard practice in former and current smokers with indeterminate nodules: (i) location-based strategy - integrated the BGC to the bronchoscopy indication; (ii) simplified strategy - extended use of bronchoscopy plus BGC also on small and peripheral lesions. Outcomes modeled were rate of invasive procedures, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios. Compared with the standard practice, the location-based strategy (i) reduced absolute rate of invasive procedures by 3.3% without increasing costs at the current BGC market price. It resulted in savings when the BGC price was less than $3,000. The simplified strategy (ii) reduced absolute rate of invasive procedures by 10% and improved quality-adjusted life expectancy, producing an incremental cost-effectiveness ratio of $10,109 per QALY. In patients with indeterminate nodules, both BGC strategies reduced unnecessary invasive procedures at high risk of adverse events. Moreover, compared with the standard practice, the simplified use of BGC for central and peripheral lesions resulted in larger QALYs gains at acceptable cost. The location-based is cost-saving if the price of classifier declines. This article is protected by copyright. All rights reserved.
Lauffenburger JC, Ghazinouri R, Jan S, Makanji S, Ferro CA, Lewey J, Wittbrodt E, Lee J, Haff N, Fontanet CP, Choudhry NK. Impact of a novel pharmacist-delivered behavioral intervention for patients with poorly-controlled diabetes: The ENhancing outcomes through Goal Assessment and Generating Engagement in Diabetes Mellitus (ENGAGE-DM) pragmatic randomized trial. PLOS ONE 2019;14:e0214754.Abstract
Background Many factors contribute to suboptimal diabetes control including insufficiently-intensive treatment and non-adherence to medication and lifestyle. Determining which of these is most relevant for individual patients is challenging. Patient engagement techniques may help identify contributors to suboptimal adherence and address barriers (using motivational interviewing) and help facilitate choices among treatment augmentation options (using shared decision-making). These methods have not been used in combination to improve diabetes outcomes. Objective To evaluate the impact of a telephone-based patient-centered intervention on glycosylated hemoglobin (HbA1c) control for individuals with poorly-controlled diabetes. Design Two-arm pragmatic randomized control trial within an explanatory sequential mixed-methods design. Subjects 1,400 participants 18–64 years old with poorly-controlled type 2 diabetes. Intervention The intervention was delivered over the telephone by a clinical pharmacist and consisted of a 2-step process that integrated brief negotiated interviewing and shared decision-making to identify patient goals and options for enhancing diabetes management. Main measures The primary outcome was change in HbA1c. Secondary outcomes were medication adherence measures. Outcomes were evaluated using intention-to-treat principles; multiple imputation was used for missing values in the 12-month follow-up. We used information from pharmacist notes to elicit factors to potentially explain the intervention’s effectiveness. Key results Participants had a mean age of 54.7 years (SD:8.3) and baseline HbA1c of 9.4 (SD:1.6). Change in HbA1c from baseline was -0.79 (SD:2.01) in the control arm and -0.75 (SD:1.76) in the intervention arm (difference:+0.04, 95%CI: -0.22, 0.30). There were no significant differences in adherence. In as-treated analyses, the intervention significantly improved diabetes control (-0.48, 95%CI: -0.91, -0.05). Qualitative findings provided several potential explanations for the findings, including insufficiently addressing patient barriers. Conclusions A novel telephone-based patient-centered intervention did not improve HbA1c among individuals with poorly-controlled diabetes, though as-treated analyses suggest that the intervention was effective for those who received it. Trial registration NCT02910089
Lauffenburger JC, Lewey J, Jan S, Makanji S, Ferro CA, Krumme AA, Lee J, Ghazinouri R, Haff N, Choudhry NK. Effectiveness of Targeted Insulin-Adherence Interventions for Glycemic Control Using Predictive Analytics Among Patients With Type 2 Diabetes: A Randomized Clinical TrialTargeted Insulin-Adherence Interventions for Glycemic Control Among Patients With Dia. JAMA Network Open 2019;2(3)Abstract
Patient adherence to antidiabetic medications, especially insulin, remains poor, leading to adverse outcomes and increased costs. Most adherence interventions have only been modestly effective, partly because they are not targeted to patients who could benefit most.To evaluate whether delivering more intensive insulin-adherence interventions only to individuals with type 2 diabetes predicted to benefit most was more effective than delivering a lower-intensity intervention to a larger group of unselected individuals.This 3-arm pragmatic randomized clinical trial used data from Horizon, the largest health insurer in New Jersey, on 6000 participants 18 years or older with type 2 diabetes who were receiving basal insulin. Patients were excluded if they were insured by Medicaid or Medicare or had fewer than 3 months of continuous enrollment. The study was conducted from July 7, 2016, through October 5, 2017. Analyses were conducted from February 5 to September 24, 2018.Eligible patients were randomized to 3 arms in a 1:1:1 ratio. Randomization was stratified based on baseline availability of 1 or more glycated hemoglobin A1c (HbA1c) test values. All arms were designed to cost the same, and each cohort received a tailored pharmacist telephone consultation varying based on (1) proportion receiving the intervention and (2) intensity, including follow-up frequency and cointerventions. Arm 1 offered a low-intensity intervention to all patients. Arm 2 offered a moderate-intensity intervention to 60% of patients based on their predicted risk of insulin nonadherence. Arm 3 offered a high-intensity intervention to 40% of patients based on glycemic control and predicted risk of insulin nonadherence.The primary outcome was insulin persistence. Secondary outcomes were changes in HbA1c level and health care utilization. Outcomes were evaluated in arms 2 and 3 vs arm 1 using claims data, intention-to-treat principles, and multiple imputation for missing values in the 12-month follow-up.Among 6000 participants, mean (SD) age was 55.9 (11.0) years and 3344 (59.8%) were male. Compared with arm 1, insulin nonpersistence did not differ in arm 2 (relative risk, 0.88; 95% CI, 0.75-1.03) or arm 3 (relative risk, 0.91; 95% CI, 0.77-1.06). Glycemic control was similar in arm 2 and arm 1 (absolute HbA1c level difference, –0.15%; 95% CI, –0.34% to 0.05%) but was better in arm 3 (absolute HbA1c level difference, –0.25%; 95% CI, –0.43% to –0.06%). Total spending and office visits did not differ, but arm 2 (moderate intensity intervention) had more hospitalizations (odds ratio, 1.22; 95% CI, 1.06-1.41) and emergency department visits (odds ratio, 1.38; 95% CI, 1.24-1.53) than did arm 1 (low intensity intervention).Compared with an untargeted low-intensity intervention, delivering a highly targeted high-intensity intervention did not improve insulin persistence but modestly improved mean glycemic control. A partially targeted moderate-intensity intervention did not change insulin persistence or HbA1c level but was associated with a small increase in Identifier: NCT02846779
Desai RJ, Mahesri M, Gagne JJ, Hurley E, Tong A, Chitnis T, Minden S, Spettell CM, Matlin OS, Shrank WH, Choudhry NK. Utilization Patterns of Oral Disease-Modifying Drugs in Commercially Insured Patients with Multiple Sclerosis. Journal of Managed Care & Specialty Pharmacy 2019;25:113-121.Abstract
ABSTRACT BACKGROUND: The approval of new oral disease-modifying drugs (DMDs), such as fingolimod, dimethyl fumarate (DMF), and teriflunamide, has considerably expanded treatment options for relapsing forms of multiple sclerosis (MS). However, data describing the use of these agents in routine clinical practice are limited. OBJECTIVE: To describe time trends and identify factors associated with oral DMD treatment initiation and switching among individuals with MS. METHODS: Using data from a large sample of commercially insured patients, we evaluated changes over time in the proportion of MS patients who initiated treatment with an oral DMD and who switched from an injectable DMD to an oral DMD between 2009 and 2014 in the United States. We evaluated predictors of oral DMD use using conditional logistic regression in 2 groups matched on calendar time: oral DMD initiators matched to injectable DMDs initiators and oral DMD switchers matched to those who switched to a second injectable DMD. RESULTS: Our cohort included 7,576 individuals who initiated a DMD and 1,342 who switched DMDs, of which oral DMDs accounted for 6% and 39%, respectively. Oral DMD initiation and switching steadily increased from 5% to 16% and 35% to 84%, respectively, between 2011 and 2014, with DMF being the most commonly used agent. Of the potential predictors with clinical significance, a recent neurologist consultation (OR = 1.60; 95% CI = 1.20-2.15) and emergency department visit (OR = 1.43; 95% CI = 1.01-2.01) were significantly associated with oral DMD initiation. History of depression was noted to be a potential predictor of oral DMD initiation; however, the estimate for this predictor did not reach statistical significance (OR = 1.35; 95% CI = 0.99-1.84). No clinically relevant factors measured in our data were associated with switching to an oral DMD. CONCLUSIONS: Oral DMDs were found to be routinely used as second-line treatment. However, we identified few factors predictive of oral DMD initiation or switching, which implies that their selection is driven by patient and/or physician preferences. DISCLOSURES: This study was funded by CVS Caremark through an unrestricted research grant to Brigham and Women?s Hospital. Shrank and Matlin were employees of, and shareholders in, CVS Health at the time of the study; they report no financial interests in products or services that are related to the subject of this study. Spettell is an employee of, and shareholder in, Aetna. Chitnis serves on clinical trial advisory boards for Novartis and Genzyme-Sanofi; has consulted for Bayer, Biogen Idec, Celgene, Novartis, Merck-Serono, and Genentech-Roche; and has received research support from NIH, National Multiple Sclerosis Society, Peabody Foundation, Consortium for MS Centers, Guthy Jackson Charitable Foundation, EMD-Serono, Novartis Biogen, and Verily. Desai reports receiving a research grant from Merck for unrelated work. Gagne is principal investigator of a research grant from Novartis Pharmaceuticals Corporation to the Brigham and Women?s Hospital and has received grant support from Eli Lilly, all for unrelated work. He is also a consultant to Aetion and Optum. Minden reports grants from Biogen and other fees from Genentech, EMD Serano, Avanir, and Novartis, unrelated to this study. The other authors have no conflicts to report. This study was presented as a poster at the International Society for Pharmacoepidemiology 32nd Annual Meeting; August 25-28, 2016; Dublin, Ireland.
Wang TY, Kaltenbach LA, Cannon CP, Fonarow GC, Choudhry NK, et al. Effect of medication co-payment vouchers on P2Y12 inhibitor use and major adverse cardiovascular events among patients with myocardial infarction: The ARTEMIS randomized clinical trial. JAMA 2019;321:44-55.Abstract
Importance  Despite guideline recommendations, many patients discontinue P2Y12 inhibitor therapy earlier than the recommended 1 year after myocardial infarction (MI), and higher-potency P2Y12 inhibitors are underutilized. Cost is frequently cited as an explanation for both of these observations.Objective  To determine whether removing co-payment barriers increases P2Y12 inhibitor persistence and lowers risk of major adverse cardiovascular events (MACE).Design, Setting, and Participants  Cluster randomized clinical trial among 301 hospitals enrolling adult patients with acute MI (June 5, 2015, through September 30, 2016); patients were followed up for 1 year after discharge (final date of follow-up was October 23, 2017), with blinded adjudication of MACE; choice of P2Y12 inhibitor was per clinician discretion.Interventions  Hospitals randomized to the intervention (n = 131 [6436 patients]) provided patients with co-payment vouchers for clopidogrel or ticagrelor for 1 year (median voucher value for a 30-day supply, $137 [25th-75th percentile, $20-$339]). Hospitals randomized to usual care (n = 156 [4565 patients]) did not provide study vouchers.Main Outcomes and Measures  Independent coprimary outcomes were patient-reported persistence with P2Y12 inhibitor (defined as continued treatment without gap in use ≥30 days) and MACE (death, recurrent MI, or stroke) at 1 year among patients discharged with a prescription for clopidogrel or ticagrelor.Results  Among 11 001 enrolled patients (median age, 62 years; 3459 [31%] women), 10 102 patients were discharged with prescriptions for clopidogrel or ticagrelor (clopidogrel prescribed to 2317 [36.0%] in the intervention group and 2497 [54.7%] in the usual care group), 4393 of 6135 patients (72%) in the intervention group used the voucher, and follow-up data at 1 year were available for 10 802 patients (98.2%). Patient-reported persistence with P2Y12 inhibitors at 1 year was higher in the intervention group than in the control group (unadjusted rates, 5340/6135 [87.0%] vs 3324/3967 [83.8%], respectively; P < .001; adjusted difference, 2.3% [95% CI, 0.4% to 4.1%]; adjusted odds ratio, 1.19 [95% CI, 1.02 to 1.40]). There was no significant difference in MACE at 1 year between intervention and usual care groups (unadjusted cumulative incidence, 10.2% vs 10.6%; P = .65; adjusted difference, 0.66% [95% CI, −0.73% to 2.06%]; adjusted hazard ratio, 1.07 [95% CI, 0.93 to 1.25]).Conclusions and Relevance  Among patients with MI, provision of vouchers to offset medication co-payments for P2Y12 inhibitors, compared with no vouchers, resulted in a 3.3% absolute increase in patient-reported persistence with P2Y12 inhibitors and no significant reduction in 1-year MACE outcomes.Trial Registration Identifier: NCT02406677
Lauffenburger JC, Khan NF, Brill G, Choudhry NK. Quantifying Social Reinforcement Among Family Members on Adherence to Medications for Chronic Conditions: a US-Based Retrospective Cohort Study. Journal of General Internal Medicine 2018;Abstract


More than 50% of patients are non-adherent to medications, often without an easily identifiable reason to clinicians. No study has quantified the extent to which health behaviors like medication-taking are correlated within families using national or routinely collected data for a range of conditions.


To examine how an individual’s health behaviors are influenced by those of their family members, particularly in adherence to medications for chronic conditions.


Retrospective cohort study.


Using claims from a large nationwide insurer, we identified patients initiating medications for one of five chronic conditions with a family member who also recently filled one of these medications.

Main Measures

The primary exposure was whether family members were fully adherent (defined as a proportion of days covered ≥ 80%) before the patient’s date of initiation. The outcome of interest was whether patients were fully adherent in the 12 months after initiation. Baseline demographic and clinical characteristics were also measured before initiation. We used multivariable modified Poisson regression to examine the association between prior family adherence and subsequent patient adherence.

Key Results

Among 254,144 patients, rates of full adherence among patients whose family members were and were not fully adherent were 37.3% and 26.9%, respectively (adjusted relative risk [aRR] 1.29, 95%CI 1.28–1.31). The association was stronger when both used cardiometabolic medications (aRR 1.35, 95%CI 1.32–1.37). Similarly, patients were also 38% more likely to be adherent if they and their family members used a medication for the same condition (aRR 1.38, 95%CI 1.35–1.40).


Adherence among family members appeared to be highly correlated, suggesting positive reinforcement by family or the sharing of unmeasured behaviors or characteristics associated with better adherence. Regardless, information about prior adherence among family members from routinely collected data could potentially inform adherence prediction or intervention efforts.