Publications

2018
Najafzadeh M, Schneeweiss SS, Choudhry NK, Wang SV, Gagne JJ. Simulation for predicting effectiveness and safety of new cardiovascular drugs in routine care populations. Clin Pharmacol TherClin Pharmacol Ther 2018;Abstract
In the presence of heterogeneity of treatment effect (HTE), the average treatment effect from a randomized controlled trial (RCT) may not be applicable to different patients, such as those in observational settings. Our objective was to develop a novel approach that uses individual-level simulation to expand RCT results to target patient populations in the presence of HTE. For this purpose, we compared the results of the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial, and two observational studies that compared benefits and risks of dabigatran to warfarin in patients with atrial fibrillation. We developed a simulation model that replicates the rates of ischemic stroke and major bleeding observed in RE-LY using published outcome risk models and participants' baseline characteristics. We used our validated simulation model to predict what the results of the RCT would have been had it been conducted in populations similar to those in the observational studies. This article is protected by copyright. All rights reserved.
Franklin JM, Gopalakrishnan C, Krumme AA, Singh K, Rogers JR, Kimura J, McKay C, McElwee NE, Choudhry NK. The relative benefits of claims and electronic health record data for predicting medication adherence trajectory. American Heart Journal 2018;197:153-162.Abstract
Background Healthcare providers are increasingly encouraged to improve their patients' adherence to chronic disease medications. Prediction of adherence can identify patients in need of intervention, but most prediction efforts have focused on claims data, which may be unavailable to providers. Electronic health records (EHR) are readily available and may provide richer information with which to predict adherence than is currently available through claims. Methods In a linked database of complete Medicare Advantage claims and comprehensive EHR from a multi-specialty outpatient practice, we identified patients who filled a prescription for a statin, antihypertensive, or oral antidiabetic during 2011 to 2012. We followed patients to identify subsequent medication filling patterns and used group-based trajectory models to assign patients to adherence trajectories. We then identified potential predictors from both claims and EHR data and fit a series of models to evaluate the accuracy of each data source in predicting medication adherence. Results Claims were highly predictive of patients in the worst adherence trajectory (C=0.78), but EHR data also provided good predictions (C=0.72). Among claims predictors, presence of a prior gap in filling of at least 6 days was by far the most influential predictor. In contrast, good predictions from EHR data required complex models with many variables. Conclusion EHR data can provide good predictions of adherence trajectory and therefore may be useful for providers seeking to deploy resource-intensive interventions. However, prior adherence information derived from claims is most predictive, and can supplement EHR data when it is available.
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Krumme AA, Pawar A, Schneeweiss S, Glynn RJ, Choudhry NK, Kulldorff M, Ortiz AS, Avorn J, Gagne JJ. Study protocol for the dabigatran, apixaban, rivaroxaban, edoxaban, warfarin comparative effectiveness research study. J Comp Eff Res 2018;7:57-66.Abstract
Since 2010, four oral anticoagulants have been approved for marketing in addition to warfarin for treatment of thromboembolic disease. Limited head-to-head data exist comparing these treatments, leaving patients and clinicians with little guidance for selecting a strategy that balances recurrence reduction with bleeding risk. In the dabigatran, apixaban, rivaroxban, edoxaban and warfarin comparative effectiveness research study, we compare all five currently available oral anticoagulant agents for the extended treatment of deep venous thrombosis and pulmonary embolism, as well as no extended treatment, and evaluate whether results differ in specific sub-populations. As our population includes Medicare novel anticoagulant users and large numbers of commercially insured and Medicaid patients, our results will likely be transportable to the majority of US patients experiencing a DVT or pulmonary embolism. CLINICAL TRIALS REGISTRATION: NCT03271450.
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Krumme AA, Glynn RJ, Schneeweiss S, Gagne JJ, Dougherty JS, Brill G, Choudhry NK. Medication Synchronization Programs Improve Adherence To Cardiovascular Medications And Health Care Use. Health Aff (Millwood) 2018;37:125-133.Abstract
Medication synchronization programs based in pharmacies simplify the refill process by enabling patients to pick up all of their medications on a single visit. This can be especially important for improving medication adherence in patients with complex chronic diseases. We evaluated the impact of two synchronization programs on adherence, cardiovascular events, and resource use among Medicare beneficiaries treated between 2011 and 2014 for two or more chronic conditions-at least one of which was hypertension, hyperlipidemia, or diabetes. Among nearly 23,000 patients matched by propensity score, the mean proportion of days covered (a measure of medication adherence) for the control group of patients without a synchronization program was 0.84 compared to 0.87 for synchronized patients-a gain of 3 percentage points. Adherence improvement in synchronized versus control patients was three times greater in patients with low baseline adherence, compared to those with higher baseline adherence. Rates of hospitalization and emergency department visits and rates of outpatient visits were 9 percent and 3 percent lower in the synchronized group compared to the control group, respectively, while cardiovascular event rates were similar. Synchronization programs were associated with improved adherence for patients with cardiovascular disease, especially those with low baseline adherence.
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2017
Simon M, Choudhry NK, Frankfort J, Margolius D, Murphy J, Paita L, Wang T, Milstein A. Exploring Attributes of High-Value Primary Care. Ann Fam Med 2017;15:529-534.Abstract
PURPOSE: Medicare's merit-based incentive payment system and narrowing of physician networks by health insurers will stoke clinicians' and policy makers' interest in care delivery attributes associated with value as defined by payers. METHODS: To help define these attributes, we analyzed 2009 to 2011 commercial health insurance claims data for more than 40 million preferred provider organization patients attributed to over 53,000 primary care practice sites. We identified sites ranking favorably on both quality and low total annual per capita health care spending ("high-value") and sites ranking near the median ("average-value"). Sites were selected for qualitative assessment from 64 high-value sites and 102 average-value sites with more than 1 primary care physician who delivered adult primary care and provided services to enough enrollees to permit meaningful spending and quality ranking. Purposeful sampling ensured regional diversity. Physicians experienced in primary care assessment and blinded to site rankings visited 12 high-value sites and 4 average-value sites to identify tangible attributes of care delivery that could plausibly explain a high ranking on value. RESULTS: Thirteen attributes of care delivery distinguished sites in the high-value cohort. Six attributes attained statistical significance: decision support for evidence-based medicine, risk-stratified care management, careful selection of specialists, coordination of care, standing orders and protocols, and balanced physician compensation. CONCLUSIONS: Awareness of care delivery attributes that distinguish their high-value peers may help physicians respond successfully to incentives from Medicare and private payers to lower annual health care spending and improve quality of care.
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Lewey J, Wei W, Lauffenburger JC, Makanji S, Chant A, DiGeronimo J, Nanchanatt G, Jan S, Choudhry NK. Targeted Adherence Intervention to Reach Glycemic Control with Insulin Therapy for patients with Diabetes (TARGIT-Diabetes): rationale and design of a pragmatic randomised clinical trial. BMJ Open 2017;7:e016551.Abstract
Introduction Adherence to and persistence of medications for chronic diseases remains poor and many interventions to improve medication use have only been modestly effective. Targeting interventions to patients who are most likely to benefit should improve their efficiency and clinical impact. This study aims to test the impact of three cost-equivalent pharmacist-led interventions on insulin persistence and glycaemic control among patients with diabetes.Methods and analysis TARGIT-Diabetes (Targeted Adherence Intervention to Reach Glycemic Control with Insulin Therapy for patients with Diabetes) is a randomised controlled trial that will evaluate three different multifaceted pharmacist-outreach strategies for improving long-term insulin use among individuals with diabetes. We will randomise 6000 patients in a large insurer to one of three arms. The arms are designed to deliver an increasingly intensive intervention to a progressively targeted population, identified using predictive analytics. The central component of the intervention in all arms is a tailored telephone consultation with a pharmacist which varies across arms based on the: (A) proportion of patients offered the intervention and (B) intervention intensity, including follow-up frequency and cointerventions such as text reminders and interactions with patients’ providers. The primary outcome is insulin persistence, assessed using pharmacy claims data, and the secondary outcomes are glycaemic control as measured by glycosylated haemoglobin values, healthcare utilisation and healthcare spending.Ethics and dissemination This protocol has been approved by the Institutional Review Board of Brigham and Women’s Hospital and the Privacy Board of Horizon Blue Cross Blue Shield of New Jersey. We plan to present the results of this trial at national meetings and in manuscripts submitted to peer-reviewed journals.Trial registration number NCT 02846779.%U http://bmjopen.bmj.com/content/bmjopen/7/10/e016551.full.pdf
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Sarpatwari A, Choudhry NK. Recalibrating Privacy Protections to Promote Patient Engagement. New England Journal of Medicine 2017;377:1509-1511. PDF
Mundkur ML, Rough K, Huybrechts KF, Levin R, Gagne JJ, Desai RJ, Patorno E, Choudhry NK, Bateman BT. Patterns of opioid initiation at first visits for pain in United States primary care settings. Pharmacoepidemiology and Drug Safety 2017;Abstract
Purpose: The primary objective of this study was to characterize variation in patterns of opioid prescribing within primary care settings at first visits for pain, and to describe variation by condition, geography, and patient characteristics. Methods: 2014 healthcare utilization data from Optum's Clinformatics™ DataMart were used to evaluate individuals 18 years or older with an initial presentation to primary care for 1 of 10 common pain conditions. The main outcomes assessed were (1) the proportion of first visits for pain associated with an opioid prescription fill and (2) the proportion of opioid prescriptions with >7 days' supply. Results: We identified 205 560 individuals who met inclusion criteria; 9.1% of all visits were associated with an opioid fill, ranging from 4.1% (headache) to 28.2% (dental pain). Approximately half (46%) of all opioid prescriptions supplied more than 7 days, and 10% of prescriptions supplied ≥30 days. We observed a 4-fold variation in rates of opioid initiation by state, with highest rates of prescribing in Alabama (16.6%) and lowest rates in New York (3.7%). Conclusions: In 2014, nearly half of all patients filling opioid prescriptions received more than 7 days' of opioids in an initial prescription. Policies limiting initial supplies have the potential to substantially impact opioid prescribing in the primary care setting.
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Choudhry NK. Randomized, Controlled Trials in Health Insurance Systems. New England Journal of Medicine 2017;377:957-964. PDF
Girdish C, Shrank W, Freytag S, Chen D, Gebhard D, Bunton A, Choudhry N, Polinski J. The impact of a retail prescription synchronization program on medication adherence. J Am Pharm Assoc (2003) 2017;57:579-584.e1.Abstract
OBJECTIVES: To understand the impact of prescription synchronization, offered through the ScriptSync(R) program at CVS pharmacies nationwide, on adherence and reducing visits to the pharmacy. DESIGN: Cohort study, conducted between March 26, 2015, and December 18, 2015. Program enrollment occurred in August 2015, with a 120-day baseline period preceding enrollment and a 120-day follow-up period. SETTING AND PARTICIPANTS: CVS retail community pharmacies across the United States. CVS Pharmacy patients voluntarily enrolling in the prescription synchronization program at CVS retail community pharmacies across the United States who filled 3 or more eligible prescriptions before program enrollment. The study included 126,597 patients who enrolled in the program and 81,355 patients who enrolled after the study enrollment period. OUTCOME MEASURES: Adherence was defined as the medication possession ratio. The average number of pharmacy visits per month was a second outcome measure. RESULTS: Exposed patients had a 7.5 percentage point adherence improvement (from 79.6% to 87.1%), compared with a 2.8 percentage point improvement among the unexposed (from 78.1% to 80.9%) for a benefit of 4.7 percentage points (P < 0.0001). Among patients with adherence opportunities, the net impact on adherence was 10.6% (P < 0.0001). The program resulted in 0.17 fewer visits per month (P < 0.0001). CONCLUSION: Offering prescription refill synchronization at a large national retail pharmacy chain resulted in improved adherence and fewer visits to the pharmacy in the 4 months following ScriptSync enrollment. Prescription refill synchronization programs should be considered in the care of patients with multiple comorbidities.
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Prabhu M, McQuaid-Hanson E, Hopp S, Burns SM, Leffert LR, Landau R, Lauffenburger JC, Choudhry NK, Kaimal A, Bateman BT. A Shared Decision-Making Intervention to Guide Opioid Prescribing After Cesarean Delivery. Obstet Gynecol 2017;130:42-46.Abstract
OBJECTIVE: To assess whether a shared decision-making intervention decreases the quantity of oxycodone tablets prescribed after cesarean delivery. TECHNIQUE: A tablet computer-based decision aid formed the basis of a shared decision-making session to guide opioid prescribing after cesarean delivery. Women first received information on typical trajectories of pain resolution and expected opioid use after cesarean delivery and then chose the number of tablets of 5 mg oxycodone they would be prescribed up to the institutional standard prescription of 40 tablets. EXPERIENCE: From April 11, 2016, to June 10, 2016, 105 women were screened, 75 were eligible, and 51 consented to participate; one patient was excluded after enrollment as a result of prolonged hospitalization. The median number of tablets (5 mg oxycodone) women chose for their prescription was 20.0 (interquartile range 15.0-25.0), which was less than the standard 40-tablet prescription (P<.001). CONCLUSION: A shared decision-making approach to opioid prescribing after cesarean delivery was associated with approximately a 50% decrease in the number of opioids prescribed postoperatively in this cohort compared with our institutional standard prescription. This approach is a promising strategy to reduce the amount of leftover opioid medication after treatment of acute postcesarean pain. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02770612.
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Pandey A, Krumme A, Patel T, Choudhry N. The Impact of Text Messaging on Medication Adherence and Exercise Among Postmyocardial Infarction Patients: Randomized Controlled Pilot Trial. JMIR Mhealth Uhealth 2017;5:e110.Abstract
BACKGROUND: Adherence to evidence-based therapies such as medications and exercise remains poor among patients after a myocardial infarction (MI). Text message reminders have been shown to improve rates of adherence to medication and exercise, but the existing studies have been of short duration. OBJECTIVE: Two single-center randomized controlled pilot trials were conducted to evaluate the impact of text message reminders over 12 months on adherence to cardiac medications and exercise among patients receiving cardiac rehabilitation after hospitalization for MI. METHODS: In the medication adherence trial, 34 patients were randomized to receive usual care alone or usual care plus daily text message reminders delivered at the time of day at which medications were to be taken. In the exercise adherence trial, 50 patients were randomized to receive usual care alone or usual care plus 4 daily text messages reminding them to exercise as directed. RESULTS: The text message reminders led to a mean 14.2 percentage point improvement in self-reported medication adherence over usual care (P<.001, 95% CI 7-21). In the exercise trial, text message reminders resulted in an additional 4.2 days (P=.001, 95% CI 1.9-6.4) and 4.0 hours (P<.001, 95% CI 2.4-5.6) of exercise per month over usual care and a nonsignificant increase of 1.2 metabolic equivalents (METS; P=.06) in exercise capacity as assessed by a BRUCE protocol at 12 months. CONCLUSIONS: Text message reminders significantly increased adherence to medication and exercise among post-MI patients receiving care in a structured cardiac rehabilitation program. This technology represents a simple and scalable method to ensure consistent use of evidence-based cardiovascular therapies. TRIAL REGISTRATION: Clinicaltrials.gov NCT02783287; https://clinicaltrials.gov/ct2/show/NCT02783287 (Archived by WebCite at http://www.webcitation.org/6sBnvNb05).
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Kim SC, Choudhry N, Franklin JM, Bykov K, Eikermann M, Lii J, Fischer MA, Bateman BT. Patterns and predictors of persistent opioid use following hip or knee arthroplasty. Osteoarthritis Cartilage 2017;25:1399-1406.Abstract
OBJECTIVE: The relationship between arthroplasty and long-term opioid use in patients with knee or hip osteoarthritis is not well studied. We examined the prevalence, patterns and predictors of persistent opioid use after hip or knee arthroplasty. METHOD: Using claims data (2004-2013) from a US commercial health plan, we identified adults who underwent hip or knee arthroplasty and filled >/=1 opioid prescription within 30 days after the surgery. We defined persistent opioid users as patients who filled >/=1 opioid prescription every month during the 1-year postoperative period based on group-based trajectory models. Multivariable logistic regression was used to determine preoperative predictors of persistent opioid use after surgery. RESULTS: We identified 57,545 patients who underwent hip or knee arthroplasty. The mean +/- SD age was 61.5 +/- 7.8 years and 87.1% had any opioid use preoperatively. Overall, 7.6% persistently used opioids after the surgery. Among patients who used opioids in 80% of the time for >/=4 months preoperatively (n = 3023), 72.1% became persistent users. In multivariable analysis, knee arthroplasty vs hip, a longer hospitalization stay, discharge to a rehabilitation facility, preoperative opioid use (e.g., a longer duration and greater dosage and frequency), a higher comorbidity score, back pain, rheumatoid arthritis, fibromyalgia, migraine and smoking, and benzodiazepine use at baseline were strong predictors for persistent opioid use (C-statistic = 0.917). CONCLUSION: Over 7% of patients persistently used opioids in the year after hip or knee arthroplasty. Given the adverse health effects of persistent opioid use, strategies need to be developed to prevent persistent opioid use after this common surgery.
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Picon RV, Dias-da-Costa JS, Fuchs FD, Olinto MTA, Choudhry NK, Fuchs SC. Hypertension Management in Brazil: Usual Practice in Primary Care—A Meta-Analysis. International Journal of Hypertension 2017;2017 PDF
Lauffenburger JC, Lewey J, Jan S, Nanchanatt G, Makanji S, Ferro CA, Sheehan J, Wittbrodt E, Morawski K, Lee J, Ghazinouri R, Choudhry NK. Rationale and design of the ENhancing outcomes through Goal Assessment and Generating Engagement in Diabetes Mellitus (ENGAGE-DM) pragmatic trial. Contemporary Clinical Trials 2017;59:57-63.Abstract
Abstract Background Poor glycemic control among patients with diabetes may stem from poor medication and lifestyle adherence or a failure to appropriately intensify therapy. A patient-centered approach could discern the most likely possibility and would then, as appropriate, address patient barriers to non-adherence (using behavioral interviewing methods such as motivational interviewing) or help facilitate choices among treatment augmentation options (using methods such as shared decision-making). Objective To test the impact of a novel telephone-based patient-centered intervention on glycemic control for patients with poorly-controlled diabetes. Methods/design ENGAGE-DM (ENhancing outcomes through Goal Assessment and Generating Engagement in Diabetes Mellitus) is a pragmatic trial of patients with poorly-controlled diabetes receiving treatment with an oral hypoglycemic agent. We randomized 1400 patients in a large health insurer to intervention or usual care. The intervention is delivered over the telephone by a pharmacist and consists of a 2-step process that integrates brief negotiated interviewing and shared decision-making to identify patient-concordant goals and options for enhancing patients' diabetes management. The trial's primary outcome is disease control, assessed using glycosylated hemoglobin values. Secondary outcomes include medication adherence measures, assessed using pharmacy claims data. Conclusions This trial will determine whether a novel highly-scalable patient engagement strategy improves disease control and adherence to medications among individuals with poorly-controlled diabetes.
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Mamiya H, Tahara RK, Tolaney SM, Choudhry N, Najafzadeh M. Cost-Effectiveness of Palbociclib in Hormone Receptor-Positive Advanced Breast Cancer. Ann Oncol 2017;28:1825-1831.Abstract

BACKGROUND: Palbociclib, a novel small-molecule inhibitor of cyclin-dependent kinases 4 and 6 for the treatment of advanced breast cancer, has demonstrated significant efficacy in prolonging progression-free survival when added to existing therapies. Considering the high cost of palbociclib, we assessed cost-effectiveness of adding palbociclib to usual care in treatment of advanced breast cancer. METHODS: We developed a discrete event simulation model to simulate time to cancer progression and to compare life time clinical benefit and cost of alternative treatment strategies for patients with metastatic disease from societal perspective. Per approved indication, endocrine treatment naive patients were assigned to palbociclib plus letrozole (PAL+LET) or letrozole alone (LET). Patients with prior endocrine therapy were assigned to palbociclib plus fulvestrant (PAL+FUL) or fulvestrant alone (FUL). The model assumptions were informed based on published clinical trial data and other peer reviewed studies. We performed one-way and probabilistic sensitivity analyses to assess the robustness of our results to the changes in model assumptions. RESULTS: In treatment-naive patients, the addition of palbociclib to letrozole cost an estimated $768,498 per additional quality-adjusted life-year (QALY) gained. The addition of palbociclib to fulvestrant in patients with prior endocrine therapy cost an estimated $918,166 per QALY gained. Sensitivity analyses demonstrated adding palbociclib has a 0% chance of being cost-effectiveness in either patient groups at a willingness-to-pay threshold of $100,000 per QALY. CONCLUSION: From a societal perspective, palbociclib treatment for both patient groups (with and without prior endocrine therapy) is highly unlikely to be cost-effective compared with the usual care in the United States.

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Dong YH, Choudhry NK, Krumme A, Lee MP, Wu LC, Lai MS, Gagne JJ. Impact of hospitalization on medication adherence estimation in claims data. J Clin Pharm Ther 2017;43:318-328.Abstract

WHAT IS KNOWN AND OBJECTIVE: Pharmacy claims are commonly used to assess medication adherence. It is unclear how different approaches to handling hospitalizations compare to the gold standard of using outpatient and inpatient drug data. This study aimed to compare the impact of different approaches to handling hospitalizations on medication adherence estimation in administrative claims data. METHODS: We identified beta-blocker initiators after myocardial infarction (MI) and statin initiators regardless of hospitalization histories in the population-based, Taiwan database, which includes outpatient and inpatient drug claims data. Adherence to beta-blockers or to statins during a 365-day follow-up period was estimated in outpatient pharmacy claims using the proportion of days covered (PDC) in three ways: ignoring hospitalizations (PDC1); subtracting hospitalized days from the denominator (PDC2); and assuming drug use on all hospitalized days (PDC3). We compared these to an approach that incorporated inpatient drug use (PDC4). We also used a hypothetical example to examine variations across approaches in several scenarios, such as increasing hospitalized days. RESULTS AND DISCUSSION: Mean 365-day PDC was 74% among 1729 post-MI beta-blocker initiators (range: 73.1%-74.9%) and 44% among 69 435 statins initiators (range: 43.5%-44.0%), which varied little across approaches. Differences across approaches increased with increasing number of hospitalized days. For patients hospitalized for >28 days, mean difference across approaches was >15%. PDC3 consistently yielded the highest value and PDC1 the lowest. WHAT IS NEW AND CONCLUSIONS: On average, different approaches to handling hospitalizations lead to similar adherence estimates to the gold standard of incorporating inpatient drug use. When patients have many hospitalization days during follow-up, the choice of approach should be tailored to the specific setting.

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Krumme AA, Franklin JM, Isaman DL, Matlin OS, Tong AY, Spettell CM, Brennan TA, Shrank WH, Choudhry NK. Predicting 1-Year Statin Adherence Among Prevalent Users: A Retrospective Cohort Study. J Manag Care Spec Pharm 2017;23:494-502.Abstract

BACKGROUND: Attempts to predict who is at risk of future nonadherence have largely focused on predictions at the time of therapy initiation; however, these users are only a small proportion of all patients on therapy at any point in time. Methods to predict nonadherence for established medication users, which have not been previously described in the literature, would be helpful to guide efforts to enhance the use of evidence-based therapies. OBJECTIVE: To test approaches for adherence prediction among prevalent statin users, namely the use of short-term filling behavior, investigator-specified predictors from medical and pharmacy administrative claims, and the empirical selection of potential predictors using the high-dimensional propensity score variable selection algorithm. METHODS: Medical and prescription claims data from a large national health insurer were used to create a cohort of patients who filled statin medication prescriptions in January 2012. We defined 6 groups of adherence predictors and estimated 10 main models to predict medication adherence in the full cohort. The same was done for the population stratified based on the days supply of the index statin prescription ( 30 days). RESULTS: The study cohort consisted of 93,777 individuals, 58.4% of which were adherent to statins during follow-up. The use of 3 pre-index adherence predictors alone achieved a c-statistic of 0.70. Investigator-specified and empirically selected pharmacy, medical, and demographic variables did substantially worse (0.57-0.60). The use of 3 indicators of post-index adherence achieved a higher c-statistic than the best-performing model using pre-index information (0.74 vs. 0.72). The addition of 3 pre-index adherence predictors further improved discrimination (0.78). CONCLUSIONS: This analysis demonstrated the ability to predict adherence among medication users using filling behavior before and immediately after an index prescription fill. DISCLOSURES: This work was supported by an unrestricted grant from CVS Health to Brigham and Women's Hospital. Shrank, Brennan, and Matlin were employees and shareholders at CVS Health at the time of this manuscript preparation; they report no financial interests in products or services that are related to the subject of the manuscript. Franklin has received consulting fees from Aetion. Chourdry has received grants from the National Heart, Lung, and Blood Institute, PhRMA Foundation, Merck, Sanofi, AstraZeneca, and MediSafe. Spettell is an employee of, and shareholder in, Aetna. The other authors have nothing to disclose. Krumme, Choudhry, Tong, and Franklin contributed to the study design, interpretation of results, and manuscript drafting. Tong prepared and analyzed the data. Isaman, Spettell, Shrank, Brennan, and Matlin provided interpretation of results and critical manuscript revisions.

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Choudhry NK, Krumme AA, Ercole PM, Girdish C, Tong AY, Khan NF, Brennan TA, Matlin OS, Shrank WH, Franklin JM. Effect of Reminder Devices on Medication Adherence: The REMIND Randomized Clinical Trial. JAMA Internal Medicine 2017;177:624-631.Abstract

Importance  Forgetfulness is a major contributor to nonadherence to chronic disease medications and could be addressed with medication reminder devices.Objective  To compare the effect of 3 low-cost reminder devices on medication adherence.Design, Setting, and Participants  This 4-arm, block-randomized clinical trial involved 53 480 enrollees of CVS Caremark, a pharmacy benefit manager, across the United States. Eligible participants were aged 18 to 64 years and taking 1 to 3 oral medications for long-term use. Participants had to be suboptimally adherent to all of their prescribed therapies (with a medication possession ratio of 30% to 80%) in the 12 months before randomization. Participants were stratified on the basis of the medications they were using at randomization: medications for cardiovascular or other nondepression chronic conditions (the chronic disease stratum) and antidepressants (the antidepressant stratum). In each stratum, randomization occurred within blocks defined by whether all of the patient’s targeted medications were dosed once daily. Patients were randomized to receive in the mail a pill bottle strip with toggles, digital timer cap, or standard pillbox. The control group received neither notification nor a device. Data were collected from February 12, 2013, through March 21, 2015, and data analyses were on the intention-to-treat population. Main Outcomes and Measures  The primary outcome was optimal adherence (medication possession ratio ≥80%) to all eligible medications among patients in the chronic disease stratum during 12 months of follow-up, ascertained using pharmacy claims data. Secondary outcomes included optimal adherence to cardiovascular medications among patients in the chronic disease stratum as well as optimal adherence to antidepressants.Results  Of the 53 480 participants, mean (SD) age was 45 (12) years and 56% were female. In the primary analysis, 15.5% of patients in the chronic disease stratum assigned to the standard pillbox, 15.1% assigned to the digital timer cap, 16.3% assigned to the pill bottle strip with toggles, and 15.1% assigned to the control arm were optimally adherent to their prescribed treatments during follow-up. There was no statistically significant difference in the odds of optimal adherence between the control and any of the devices (standard pillbox: odds ratio [OR], 1.03 [95% CI, 0.95-1.13]; digital timer cap: OR, 1.00 [95% CI, 0.92-1.09]; and pill bottle strip with toggles: OR, 0.94 [95% CI, 0.85-1.04]). In direct comparisons, the odds of optimal adherence were higher with a standard pillbox than with the pill bottle strip (OR, 1.10 [95% CI, 1.00-1.21]). Secondary analyses yielded similar results.Conclusions and Relevance  Low-cost reminder devices did not improve adherence among nonadherent patients who were taking up to 3 medications to treat common chronic conditions. The devices may have been more effective if coupled with interventions to ensure consistent use or if targeted to individuals with an even higher risk of nonadherence.Trial Registration  clinicaltrials.gov Identifier: NCT02015806

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Lauffenburger JC, Shrank WH, Bitton A, Franklin JM, Glynn RJ, Krumme AA, Matlin OS, Pezalla EJ, Spettell CM, Brill G, Choudhry NK. Association Between Patient-Centered Medical Homes and Adherence to Chronic Disease Medications: A Cohort Study. Ann Intern Med 2017;166:81-88.Abstract

Background: Despite the widespread adoption of patient-centered medical homes into primary care practice, the evidence supporting their effect on health care outcomes has come primarily from geographically localized and well-integrated health systems. Objective: To assess the association between medication adherence and medical homes in a national patient and provider population, given the strong ties between adherence to chronic disease medications and health care quality and spending. Design: Retrospective cohort study. Setting: Claims from a large national health insurer. Patients: Patients initiating therapy with common medications for chronic diseases (diabetes, hypertension, and hyperlipidemia) between 2011 and 2013. Measurements: Medication adherence in the 12 months after treatment initiation was compared among patients cared for by providers practicing in National Committee for Quality Assurance-recognized patient-centered medical homes and propensity score-matched control practices in the same Primary Care Service Areas. Linear mixed models were used to examine the association between medical homes and adherence. Results: Of 313 765 patients meeting study criteria, 18 611 (5.9%) received care in patient-centered medical homes. Mean rates of adherence were 64% among medical home patients and 59% among control patients. Among 4660 matched control and medical home practices, medication adherence was significantly higher in medical homes (2.2% [95% CI, 1.5% to 2.9%]). The association between medical homes and better adherence did not differ significantly by disease state (diabetes, 3.0% [CI, 1.5% to 4.6%]; hypertension, 3.2% [CI, 2.2% to 4.2%]; hyperlipidemia, 1.5% [CI, 0.6% to 2.5%]). Limitation: Clinical outcomes related to medication adherence were not assessed. Conclusion: Receipt of care in a patient-centered medical home is associated with better adherence, a vital measure of health care quality, among patients initiating treatment with medications for common high-cost chronic diseases. Primary Funding Source: CVS Health.

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