Publications by Year: 2019

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