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.
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.
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
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.
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;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.
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:, NCT02770612.
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: NCT02783287; (Archived by WebCite at
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;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.
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.
Mamiya H, Tahara RK, Tolaney SM, Choudhry N, Najafzadeh M. Cost-Effectiveness of Palbociclib in Hormone Receptor-Positive Advanced Breast Cancer. Ann Oncol 2017;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.

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.

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.

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 Identifier: NCT02015806

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.

Morawski K, Ghazinouri R, Krumme A, McDonough J, Durfee E, Oley L, Mohta N, Juusola J, Choudhry NK. Rationale and design of the Medication adherence Improvement Support App For Engagement—Blood Pressure (MedISAFE-BP) trial. American Heart Journal 2017;186:40-47.Abstract

BackgroundHypertension is a major contributor to the health and economic burden imposed by stroke, heart disease, and renal insufficiency. Antihypertensives can prevent many of the harmful effects of elevated blood pressure, but medication nonadherence is a known barrier to the effectiveness of these treatments. Smartphone-based applications that remind patients to take their medications, provide education, and allow for social interactions between individuals with similar health concerns have been widely advocated as a strategy to improve adherence but have not been subject to rigorous testing.

Dong YH, Bykov K, Choudhry NK, Donneyong MM, Huybrechts KF, Levin R, Schneeweiss S, Gagne JJ. Clinical Outcomes of Concomitant Use of Warfarin and Selective Serotonin Reuptake Inhibitors: A Multidatabase Observational Cohort Study. J Clin Psychopharmacol 2017;37:200-209.Abstract

BACKGROUND: Patients treated with warfarin are often coprescribed selective serotonin reuptake inhibitors (SSRIs) for coexisting depression. Some SSRIs are potent CYP2C9 inhibitors that may increase warfarin plasma concentrations and the risk of bleeding. We aimed to examine the effect of the putative CYP2C9-mediated warfarin-SSRI interaction on clinical outcomes. METHODS: We conducted an observational cohort study among warfarin initiators who had a subsequent SSRI prescription in 5 US claims databases. Patients were followed for up to 180 days as long as they were exposed to both warfarin and their index SSRI groups. Cox regression models were used to estimate hazard ratios and 95% confidence intervals for bleeding events, ischemic or thromboembolic events, and mortality comparing patients treated with SSRIs that are potent CYP2C9 inhibitors (fluoxetine, fluvoxamine) with those treated with other SSRIs after propensity score matching. FINDINGS: The eligible cohort comprised 52,129 patients. Hazard ratios were 1.14 (95% confidence interval [CI], 0.94-1.38) for bleeding events, 1.03 (95% CI, 0.87-1.21) for ischemic or thromboembolic events, and 0.90 (95% CI, 0.72-1.14) for mortality. Results were consistent across individual component outcomes, different warfarin stabilization periods, and subgroup analyses. CONCLUSIONS: Patients concomitantly treated with warfarin and SSRIs that are potent CYP2C9 inhibitors had comparable rates of bleeding events, ischemic or thromboembolic events, and mortality as did patients cotreated with warfarin and other SSRIs, although small but potentially meaningful effects on bleeding cannot be completely excluded. SSRI inhibition of CYP2C9 does not appear to affect major safety or effectiveness outcomes of warfarin treatment in clinical practice, where patients may be closely monitored.

Lauffenburger JC, Franklin JM, Krumme AA, Shrank WH, Brennan TA, Matlin OS, Spettell CM, Brill G, Choudhry NK. Longitudinal Patterns of Spending Enhance the Ability to Predict Costly Patients: A Novel Approach to Identify Patients for Cost Containment. Med Care 2017;55:64-73.Abstract

BACKGROUND: With rising health spending, predicting costs is essential to identify patients for interventions. Many of the existing approaches have moderate predictive ability, which may result, in part, from not considering potentially meaningful changes in spending over time. Group-based trajectory modeling could be used to classify patients into dynamic long-term spending patterns. OBJECTIVES: To classify patients by their spending patterns over a 1-year period and to assess the ability of models to predict patients in the highest spending trajectory and the top 5% of annual spending using prior-year predictors. SUBJECTS: We identified all fully insured adult members enrolled in a large US nationwide insurer and used medical and prescription data from 2009 to 2011. RESEARCH DESIGN: Group-based trajectory modeling was used to classify patients by their spending patterns over a 1-year period. We assessed the predictive ability of models that categorized patients in the top fifth percentile of annual spending and in the highest spending trajectory, using logistic regression and split-sample validation. Models were estimated using investigator-specified variables and a proprietary risk-adjustment method. RESULTS: Among 998,651 patients, in the best-performing model, prediction was strong for patients in the highest trajectory group (C-statistic: 0.86; R: 0.47). The C-statistic of being in the top fifth percentile of spending in the best-performing model was 0.82 (R: 0.26). Approaches using nonproprietary investigator-specified methods performed almost as well as other risk-adjustment methods (C-statistic: 0.81 vs. 0.82). CONCLUSIONS: Trajectory modeling may be a useful way to predict costly patients that could be implementable by payers to improve cost-containment efforts.