Matlin OS, Kymes SM, Averbukh A, Choudhry NK, Brennan TA, Bunton A, Ducharme TA, Simmons PD, Shrank WH. Community pharmacy automatic refill program improves adherence to maintenance therapy and reduces wasted medication. American Journal of Managed Care 2015;21:785-91.Abstract

OBJECTIVES: Automatic prescription refill programs are a popular means of improving medication adherence. A concern is the potential for prescription drug wastage and unnecessary healthcare spending. We evaluated the impact of an automatic refill program on patterns of medication use. STUDY DESIGN: Retrospective propensity score matched cohort study with multivariable generalized linear modeling. METHODS: The setting of the study was a pharmacy benefit manager administering benefits for patients of retail pharmacies. Participants included patients on medication for chronic conditions; those receiving a 30-day supply (n = 153,964) and a 90-day supply (n = 100,394) were analyzed separately. The intervention was the automatic prescription refill program. Measures included medication possession ratio (MPR) and average days excess at the time of refill. The results are reported across 11 therapeutic classes. RESULTS: Overall, patients receiving 30-day supplies of medication in the automatic refill program had an MPR that was 3 points higher than those not in the refill program; among those receiving 90-day fills and in the refill program, the MPR was 1.4 points higher (P < .001 for both 30- and 90-day fills). The MPR was higher for members in the refill program across all therapeutic classes. Limiting our analysis to members receiving more than 365 days of medication, we found that patients who received 30-day fills and enrolled in the automatic refill program had 2.5 fewer days' oversupply than those in the control group, whereas automatic refill patients receiving 90-day supplies had 2.18 fewer days' oversupply than the controls (P < .001 for both 30- and 90-day fills). CONCLUSIONS: For this pharmacy provider, automatic refill programs result in improved adherence without adding to medication oversupply.

Bykov K, Franklin JM, Toscano M, Rawlins W, Spettell CM, McMahill-Walraven CN, Shrank WH, Choudhry NK. Evaluating Cardiovascular Health Disparities Using Estimated Race/Ethnicity: A Validation Study. Medical Care 2015;53:1050-1057.Abstract

Background: Methods of estimating race/ethnicity using administrative data are increasingly used to examine and target disparities; however, there has been no validation of these methods using clinically relevant outcomes. Objective: To evaluate the validity of the indirect method of race/ethnicity identification based on place of residence and surname for assessing clinically relevant outcomes. Data Sources: A total of 2387 participants in the Post-MI Free Rx Event and Economic Evaluation (MI FREEE) trial who had both self-reported and Bayesian Improved Surname Geocoding method (BISG)-estimated race/ethnicity information available. Study Design: We used tests of interaction to compare differences in the effect of providing full drug coverage for post-MI medications on adherence and rates of major vascular events or revascularization for white and nonwhite patients based upon self-reported and indirect racial/ethnic assignment. Results: The impact of full coverage on clinical events differed substantially when based upon self-identified race (HR=0.97 for whites, HR=0.65 for nonwhites; interaction P-value=0.05); however, it did not differ among race/ethnicity groups classified using indirect methods (HR=0.87 for white and nonwhites; interaction P-value=0.83). The impact on adherence was the same for self-reported and BISG-estimated race/ethnicity for 2 of the 3 medication classes studied. Conclusions: Quantitatively and qualitatively different results were obtained when indirectly estimated race/ethnicity was used, suggesting that these techniques may not accurately describe aspects of race/ethnicity related to actual health behaviors.

Lewey J, Shrank WH, Avorn J, Liu J, Choudhry NK. Medication Adherence and Healthcare Disparities: Impact of Statin Co-Payment Reduction. American Journal of Managed Care 2015;21:696 - 704.Abstract

Objectives: Minority patients have lower rates of cardiovascularmedication adherence, which may be amenable to co-payment reductions.Our objective was to evaluate the effect of race on adherencechanges following a statin co-payment reduction intervention.Study Design: Retrospective analysis.Methods: The intervention was implemented by a large selfinsuredemployer. Eligible individuals in the intervention cohort(n = 1961) were compared with a control group of employees ofother companies without such a policy (n = 37,320). As a proxy forrace, we categorized patients into tertiles based on the proportionof black residents living in their zip code of residence. Analyseswere performed using difference-in-differences design with generalizedestimating equations.Results: Prior to the new co-payment policy, adherence rateswere higher for individuals living in areas with fewer black residents.In multivariable models adjusting for demographic factors,clinical covariates and baseline trends, the co-payment reductionincreased adherence by 2.0% (P = .14), 2.1% (P = .15) and 6% (P<.0001) for intervention patients living in areas with the bottom,middle and top tertiles of the proportion of black residents. Theseresults persisted after adjusting for income.Conclusions: Co-payment reduction for statins preferentiallyimproved adherence among patients living in communities witha higher proportion of black residents. Further research is neededon the impact of value-based insurance design programs onreducing racial disparities in cardiovascular care.

Franklin JM, Krumme AA, Tong AY, Shrank WH, Matlin OS, Brennan TA, Choudhry NK. Association between trajectories of statin adherence and subsequent cardiovascular events. Pharmacoepidemiology and Drug Safety 2015;24:1105-13.Abstract

PURPOSE: Trajectory models have been shown to (1) identify groups of patients with similar patterns of medication filling behavior and (2) summarize the trajectory, the average adherence in each group over time. However, the association between adherence trajectories and clinical outcomes remains unclear. This study investigated the association between 12-month statin trajectories and subsequent cardiovascular events. METHODS: We identified patients with insurance coverage from a large national insurer who initiated a statin during January 1, 2007 to December 31, 2010. We assessed medication adherence during the 360 days following initiation and grouped patients based on the proportion of days covered (PDC) and trajectory models. We then measured cardiovascular events during the year after adherence assessment. Cox proportional hazards models were used to evaluate the association between adherence measures and cardiovascular outcomes; strength of association was quantified by the hazard ratio, the increase in model C-statistic, and the net reclassification index (NRI). RESULTS: Among 519 842 statin initiators, 8777 (1.7%) had a cardiovascular event during follow-up. More consistent medication use was associated with a lower likelihood of clinical events, whether adherence was measured through trajectory groups or PDC. When evaluating the prediction of future cardiovascular events by including a measure of adherence in the model, the best model reclassification was observed when adherence was measured using three or four trajectory groups (NRI = 0.189; 95% confidence interval: [0.171, 0.210]). CONCLUSIONS: Statin adherence trajectory predicted future cardiovascular events better than measures categorizing PDC. Thus, adherence trajectories may be useful for targeting adherence interventions. Copyright (c) 2015 John Wiley & Sons, Ltd.

Bowry AD, Lewey J, Dugani SB, Choudhry NK. The Burden of Cardiovascular Disease in Low- and Middle-Income Countries: Epidemiology and Management. Canadian Journal of Cardiology 2015;31:1151-9.Abstract

Cardiovascular disease (CVD) is the second leading cause of mortality worldwide, accounting for 17 million deaths in 2013. More than 80% of these cases were in low- and middle-income countries (LMICs). Although the risk factors for the development of CVD are similar throughout the world, the evolving change in lifestyle and health behaviours in LMICs-including tobacco use, decreased physical activity, and obesity-are contributing to the escalating presence of CVD and mortality. Although CVD mortality is falling in high-income settings because of more effective preventive and management programs, access to evidence-based interventions for combating CVD in resource-limited settings is variable. The existing pressures on both human and financial resources impact the efforts of controlling CVD. The implementation of emerging innovative interventions to improve medication adherence, introducing m-health programs, and decentralizing the management of chronic diseases are promising methods to reduce the burden of chronic disease management on such fragile health care systems.

Gagne JJ, Kesselheim AS, Choudhry NK, Polinski JM, Hutchins D, Matlin OS, Brennan TA, Avorn J, Shrank WH. Comparative effectiveness of generic versus brand-name antiepileptic medications. Epilepsy and Behavior 2015;52:14-18.Abstract

OBJECTIVE: The objective of this study was to compare treatment persistence and rates of seizure-related events in patients who initiate antiepileptic drug (AED) therapy with a generic versus a brand-name product. METHODS: We used linked electronic medical and pharmacy claims data to identify Medicare beneficiaries who initiated one of five AEDs (clonazepam, gabapentin, oxcarbazepine, phenytoin, zonisamide). We matched initiators of generic versus brand-name versions of these drugs using a propensity score that accounted for demographic, clinical, and health service utilization variables. We used a Cox proportional hazards model to compare rates of seizure-related emergency room (ER) visit or hospitalization (primary outcome) and ER visit for bone fracture or head injury (secondary outcome) between the matched generic and brand-name initiators. We also compared treatment persistence, measured as time to first 14-day treatment gap, between generic and brand-name initiators. RESULTS: We identified 19,760 AED initiators who met study eligibility criteria; 18,306 (93%) initiated a generic AED. In the matched cohort, we observed 47 seizure-related hospitalizations and ER visits among brand-name initiators and 31 events among generic initiators, corresponding to a hazard ratio of 0.53 (95% confidence interval, 0.30 to 0.96). Similar results were observed for the secondary clinical endpoint and across sensitivity analyses. Mean time to first treatment gap was 124.2days (standard deviation [sd], 125.8) for brand-name initiators and 137.9 (sd, 148.6) for generic initiators. SIGNIFICANCE: Patients who initiated generic AEDs had fewer adverse seizure-related clinical outcomes and longer continuous treatment periods before experiencing a gap than those who initiated brand-name versions.

Kim SC, Schneeweiss S, Choudhry N, Liu J, Glynn RJ, Solomon DH. Effects of xanthine oxidase inhibitors on cardiovascular disease in patients with gout: a cohort study. American Journal of Medicine 2015;128:653 e7-653 e16.Abstract

BACKGROUND: Hyperuricemia and gout are associated with an increased risk of cardiovascular disease (CVD). It is unknown whether treating hyperuricemia with xanthine oxidase inhibitors (XOIs), including allopurinol and febuxostat, modifies cardiovascular risks. METHODS: We used US insurance claims data to conduct a cohort study among gout patients, comparing XOI initiators with non-users with hyperuricemia defined as serum uric acid level >/=6.8 mg/dL. We calculated incidence rates of a composite nonfatal cardiovascular outcome that included myocardial infarction, coronary revascularization, stroke, and heart failure. Propensity score (PS)-matched Cox proportional hazards regression compared the risk of composite cardiovascular endpoint in XOI initiators vs those with untreated hyperuricemia, controlling for baseline confounders. In a subgroup of patients with uric acid levels available, PS-matched Cox regression further adjusted for baseline uric acid levels. RESULTS: There were 24,108 PS-matched pairs with a mean age of 51 years and 88% male. The incidence rate per 1000 person-years for composite CVD was 24.1 (95% confidence interval [CI] 22.6-26.0) in XOI initiators and 21.4 (95% CI, 19.8-23.2) in the untreated hyperuricemia group. The PS-matched hazard ratio for composite CVD was 1.16 (95% CI, 0.99-1.34) in XOI initiators vs those with untreated hyperuricemia. In subgroup analyses, the PS-matched hazard ratio for composite CVD adjusted for serum uric acid levels was 1.10 (95% CI, 0.74-1.64) among XOI initiators. CONCLUSIONS: Among patients with gout, initiation of XOI was not associated with an increased or decreased cardiovascular risk compared with those with untreated hyperuricemia. Subgroup analyses adjusting for baseline uric acid levels also showed no association between XOI and cardiovascular risk.

Ito K, Avorn J, Shrank WH, Toscano M, Spettel C, Brennan T, Choudhry NK. Long-term cost-effectiveness of providing full coverage for preventive medications after myocardial infarction. Circulation Cardiovascular Quality and Outcomes 2015;8:252-9.Abstract

BACKGROUND: Adherence to drugs that are prescribed after myocardial infarction remains suboptimal. Although eliminating patient cost sharing for secondary prevention increases adherence and reduces rates of major cardiovascular events, the long-term clinical and economic implications of this approach have not been adequately evaluated. METHODS AND RESULTS: We developed a Markov model simulating a hypothetical cohort of commercially insured patients who were discharged from the hospital after myocardial infarction. Patients received beta-blockers, renin-angiotensin system antagonists, and statins without cost sharing (full coverage) or at the current level of insurance coverage (usual coverage). Model inputs were extracted from the Post Myocardial Infarction Free Rx Event and Economic Evaluation trial and other published literature. The main outcome was an incremental cost-effectiveness ratio as measured by cost per quality-adjusted life year gained. Patients receiving usual coverage lived an average of 9.46 quality-adjusted life years after their event and incurred costs of $171,412. Patients receiving full coverage lived an average of 9.60 quality-adjusted life years and incurred costs of $167,401. Compared with usual coverage, full coverage would result in greater quality-adjusted survival (0.14 quality-adjusted life years) and less resource use ($4011) per patient. Our results were sensitive to alterations in the risk reduction for post-myocardial infarction events from full coverage. CONCLUSIONS: Providing full prescription drug coverage for evidence-based pharmacotherapy to commercially insured post-myocardial infarction patients has the potential to improve health outcomes and save money from the societal perspective over the long-term. CLINICAL TRIAL REGISTRATION INFORMATION: Unique identifier: NCT00566774.

Kulik A, Bykov K, Choudhry NK, Bateman BT. Non-steroidal anti-inflammatory drug administration after coronary artery bypass surgery: utilization persists despite the boxed warning. Pharmacoepidemiology and Drug Safety 2015;24:647-53.Abstract

PURPOSE: In 2005, the US Food and Drug Administration (FDA) issued a boxed warning against the administration of non-steroidal anti-inflammatory drugs (NSAIDs) after coronary artery bypass graft (CABG) surgery because of cardiovascular safety concerns. We assessed utilization rates before and after the advisory and evaluated predictors of NSAID administration following CABG. METHODS: We assembled a cohort of 277,576 patients who underwent CABG from 2004 to 2010. Temporal trends in NSAID exposure were evaluated, and predictors of postoperative NSAID use were identified using generalized estimating equations. RESULTS: Over the study period, 92,938 CABG patients (33.5%) received NSAIDs following surgery. The frequency of NSAID administration declined steadily over time, from a peak of 38.9% in 2004 to a low of 29.0% in 2010 (p < 0.0007). Ketorolac was the most frequent NSAID prescribed, commonly on the first postoperative day. Surgery performed after the boxed warning was independently associated with a 20% lower odds of NSAID administration [odds ratio (OR): 0.80; p = 0.0003]. Other factors that predicted a lower odds of NSAID use following surgery included a history of renal disease (OR: 0.33; p < 0.0001) and liver disease (OR: 0.66; p < 0.0001), and the need for concurrent valve surgery (OR: 0.78; p < 0.0001). A mammary graft at the time of surgery increased the odds of NSAID administration (OR: 1.23; p < 0.0001). CONCLUSIONS: The frequency of NSAID administration after CABG has declined since the FDA advisory, yet many patients continue to receive them in recent years. Our data highlight the need for future research initiatives to further define the risks associated with NSAID use in this population.

Gagne JJ, Polinski JM, Rassen JA, Fischer MA, Seeger JD, Franklin JM, Liu J, Schneeweiss S, Choudhry NK. Selective Serotonin Reuptake Inhibitor Use and Perioperative Bleeding and Mortality in Patients Undergoing Coronary Artery Bypass Grafting: A Cohort Study. Drug Safety 2015;Abstract

INTRODUCTION: Several small studies have reported inconsistent findings about the safety of selective serotonin reuptake inhibitors (SSRIs) among patients undergoing coronary artery bypass grafting (CABG). We sought to investigate post-CABG bleeding and mortality outcomes related to antidepressant exposure. METHODS: We identified patients who underwent CABG between 2004 and 2008 in the Premier Perspective Comparative Database. We determined whether they received SSRIs, other antidepressants, or no antidepressants on any pre-CABG hospital day and used Cox proportional hazards models to compare bleeding and mortality rates among the exposure groups while adjusting for potential confounders based on administrative data, pre-CABG charge codes, and discharge diagnosis codes. RESULTS: We identified 132,686 eligible patients: 7112 exposed to SSRIs, 1905 exposed to other antidepressants, and 123,668 unexposed. As compared with no exposure, neither SSRIs (hazard ratio [HR] 0.98; 95 % confidence interval [CI] 0.90-1.07) nor other antidepressants (HR 1.11; 95 % CI 0.96-1.28) increased major bleeds, and neither SSRIs (HR 0.93; 95 % CI 0.80-1.07) nor other antidepressants (HR 0.84; 95 % CI 0.62-1.14) increased mortality. Both SSRIs (HR 1.14; 95 % CI 1.10-1.18) and other antidepressants (HR 1.11; 95 % CI 1.03-1.19) were associated with a slight increase in receipt of one or more packed red blood cell (pRBC) units, but neither were associated with substantial increases in receipt of three or more pRBC units (HR 1.06; 95 % CI 0.96-1.17 for SSRIs; HR 1.09; 95 % CI 0.91-1.31 for other antidepressants). CONCLUSION: In this large cohort study, neither SSRIs nor other antidepressants were associated with elevated rates of major bleed, or in-hospital mortality.

Najafzadeh M, Schneeweiss S, Choudhry N, Bykov K, Kahler KH, Martin DP, Gagne JJ. A unified framework for classification of methods for benefit-risk assessment. Value in Health 2015;18:250-9.Abstract

BACKGROUND: Patients, physicians, and other decision makers make implicit but inevitable trade-offs among risks and benefits of treatments. Many methods have been proposed to promote transparent and rigorous benefit-risk analysis (BRA). OBJECTIVE: To propose a framework for classifying BRA methods on the basis of key factors that matter most for patients by using a common mathematical notation and compare their results using a hypothetical example. METHODS: We classified the available BRA methods into three categories: 1) unweighted metrics, which use only probabilities of benefits and risks; 2) metrics that incorporate preference weights and that account for the impact and duration of benefits and risks; and 3) metrics that incorporate weights based on decision makers' opinions. We used two hypothetical antiplatelet drugs (a and b) to compare the BRA methods within our proposed framework. RESULTS: Unweighted metrics include the number needed to treat and the number needed to harm. Metrics that incorporate preference weights include those that use maximum acceptable risk, those that use relative-value-adjusted life-years, and those that use quality-adjusted life-years. Metrics that use decision makers' weights include the multicriteria decision analysis, the benefit-less-risk analysis, Boers' 3 by 3 table, the Gail/NCI method, and the transparent uniform risk benefit overview. Most BRA methods can be derived as a special case of a generalized formula in which some are mathematically identical. Numerical comparison of methods highlights potential differences in BRA results and their interpretation. CONCLUSIONS: The proposed framework provides a unified, patient-centered approach to BRA methods classification based on the types of weights that are used across existing methods, a key differentiating feature.

Choudhry NK, Krumme AA, Ercole PM, Girdish C, Isaman DL, Matlin OS, Brennan TA, Shrank WH, Franklin JM. Rationale and design of the Randomized Evaluation to Measure Improvements in Non-adherence from Low-Cost Devices (REMIND) trial. Contemporary Clinical Trials 2015;43:53-59.Abstract

AbstractBackground Long-term adherence to prescription medications for the treatment of chronic disease remains low. While there are many contributors to suboptimal medication use, simple forgetfulness is widely believed to be central. Relatively simple devices may be a particularly cost-efficient and scalable way to promote adherence, however limited data exists about their ability to improve adherence in real-world settings. Methods/design The REMIND trial is a prospective, intent-to-treat randomized control trial to evaluate the impact on medication adherence of three simple, low-cost devices (Take-N-Slide™, the RxTimerCap™, and a standard pillbox). In March 2014, we enrolled 53,480 individuals 18 to 64 years old taking one to three medications to treat chronic disease whose prescription drug benefits were administered by CVS Caremark. The study's primary outcome is optimal adherence over the 12-month period after randomization. Using a randomization ratio of 1:2 between control and each intervention arm, the study has more than 80% power with an alpha of 5% to detect a 1% difference in the rate of optimal adherence between intervention and control groups and across intervention arms. Discussion The REMIND trial is the first randomized study to rigorously evaluate the impact of simple, low-cost reminder devices on medication adherence. The results will inform comparative cost effectiveness studies of reminder systems in improving medication adherence and clinical outcomes.

Wang B, Choudhry NK, Gagne JJ, Landon J, Kesselheim AS. Availability and utilization of cardiovascular fixed-dose combination drugs in the United States. American Heart Journal 2015;169:379-386 e1.Abstract

BACKGROUND: Solid clinical evidence supports the effectiveness and safety of multiple drugs in treating diabetes, dyslipidemia, and hypertension, and numerous fixed-dose combination products (FDCs) containing such drugs have been developed for patients with more severe forms of these diseases. We sought to evaluate the extent to which utilization of treatment combinations for these conditions corresponded to the availability of FDCs. METHODS: Using claims data from a large national commercial insurer, we identified 2 cohorts of patients: those who filled multiple single-agent drugs to treat diabetes, dyslipidemia, and hypertension in 2012, and those who used FDCs containing these products during the same period. We determined the fill rate of single-agent pairs and FDCs, availability of FDCs for the most frequently filled single-agent and drug class pairs, and the number of conditions treated by frequently filled single-agent pairs and FDCs. RESULTS: During our study period, 848,082 patients filled prescriptions for 3,248 unique single-agent pairs (mean 4.7 per patient, standard deviation [SD] 5.0); and 568,923 patients received prescriptions for 43 unique FDCs (mean 1.1 per patient, SD 0.3). Three (15%) of the 20 most frequently filled single-agent pairs were available as FDCs, whereas 9 (45%) of the 20 most frequently filled drug class pairs were available as FDCs. Nearly all of the frequently filled FDCs had lower fill rates than the most frequently filled single-agent pairs. CONCLUSIONS: Utilization of drug combinations to treat cardiovascular conditions does not correspond well with availability of FDCs containing these agents. A concerted set of strategies should be implemented to streamline the development of useful combination products, including expedited approval pathways and increased investment in formulation studies.

Najafzadeh M, Andersson K, Shrank WH, Krumme AA, Matlin OS, Brennan T, Avorn J, Choudhry NK. Cost-effectiveness of novel regimens for the treatment of hepatitis C virus. Annals of Internal Medicine 2015;162:407-19.Abstract

BACKGROUND: New regimens for hepatitis C virus (HCV) have shorter treatment durations and increased rates of sustained virologic response compared with existing therapies but are extremely expensive. OBJECTIVE: To evaluate the cost-effectiveness of these treatments under different assumptions about their price and efficacy. DESIGN: Discrete-event simulation. DATA SOURCES: Published literature. TARGET POPULATION: Treatment-naive patients infected with chronic HCV genotype 1, 2, or 3. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Usual care (boceprevir-ribavirin-pegylated interferon [PEG]) was compared with sofosbuvir-ribavirin-PEG and 3 PEG-free regimens: sofosbuvir-simeprevir, sofosbuvir-daclatasvir, and sofosbuvir-ledipasvir. For genotypes 2 and 3, usual care (ribavirin-PEG) was compared with sofosbuvir-ribavirin, sofosbuvir-daclatasvir, and sofosbuvir-ledipasvir-ribavirin (genotype 3 only). OUTCOME MEASURES: Discounted costs (in 2014 U.S. dollars), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. RESULTS OF BASE-CASE ANALYSIS: Assuming sofosbuvir, simeprevir, daclatasvir, and ledipasvir cost $7000, $5500, $5500, and $875 per week, respectively, sofosbuvir-ledipasvir was cost-effective for genotype 1 and cost $12 825 more per QALY than usual care. For genotype 2, sofosbuvir-ribavirin and sofosbuvir-daclatasvir cost $110 000 and $691 000 per QALY, respectively. For genotype 3, sofosbuvir-ledipasvir-ribavirin cost $73 000 per QALY, sofosbuvir-ribavirin was more costly and less effective than usual care, and sofosbuvir-daclatasvir cost more than $396 000 per QALY at assumed prices. RESULTS OF SENSITIVITY ANALYSIS: Sofosbuvir-ledipasvir was the optimal strategy in most simulations for genotype 1 and would be cost-saving if sofosbuvir cost less than $5500. For genotype 2, sofosbuvir-ribavirin-PEG would be cost-saving if sofosbuvir cost less than $2250 per week. For genotype 3, sofosbuvir-ledipasvir-ribavirin would be cost-saving if sofosbuvir cost less than $1500 per week. LIMITATION: Data are lacking on real-world effectiveness of new treatments and some prices. CONCLUSION: From a societal perspective, novel treatments for HCV are cost-effective compared with usual care for genotype 1 and probably genotype 3 but not for genotype 2. PRIMARY FUNDING SOURCE: CVS Health.

Polinski JM, Kesselheim AS, Seeger JD, Connolly JG, Choudhry NK, Shrank WH. A cross-national comparison of 17 countries' insulin glargine drug labels. Pharmacoepidemiology and Drug Safety 2015;24:159-65.Abstract

PURPOSE: Type 2 diabetes mellitus has reached epidemic proportions worldwide. Many patients with type 2 diabetes mellitus will require insulin, and the evidence-based use of insulin is described in the prescription drug label. Product labels in different countries may provide inconsistent information. We evaluated the variability in drug label content for one brand of basal insulin across diverse settings. METHODS: We examined the drug label content pertinent to effective and safe use of insulin glargine across 17 countries: Abu Dhabi (United Arab Emirates), Argentina, Brazil, Canada, China, Germany, Israel, Italy, Japan, Mexico, Russia, Saudi Arabia, South Korea, Spain, Turkey, UK, and the USA. We compared label characteristics in settings where drug labels were governed by a local regulatory authority versus countries where labels were administered by a regional body or adopted from another locale. RESULTS: All 17 labels cautioned that providers should consider age, illness, diet, and exercise when prescribing. Only two (12%) described care of the fasting patient. Caution was urged for patients with renal or hepatic impairment in 16 (94%) labels. Four (24%) did not describe responses to missed doses, and five (29%) failed to recommend patient counseling about the risk of hypoglycemia. Labels emerging from regional or adopted regulatory bodies reported fewer patients in efficacy studies than did labels from settings with their own drug regulatory agencies (365 +/- 0 patients vs. 3560 +/- 2938, p = 0.04). CONCLUSIONS: There is substantial variation in the content of drug labels for glargine, which may lead to international inconsistency in quality of care for diabetic patients.

Sarpatwari A, Choudhry NK, Avorn J, Kesselheim AS. Paying physicians to prescribe generic drugs and follow-on biologics in the United States. PLoS Medicine 2015;12:e1001802.Abstract

Aaron Kesselheim and colleagues examine potential strategies to promote greater prescribing of generic drugs and follow-on biologics.

Kesselheim AS, Huybrechts KF, Choudhry NK, Fulchino LA, Isaman DL, Kowal MK, Brennan TA. Prescription drug insurance coverage and patient health outcomes: a systematic review. American Journal of Public Health 2015;105:e17-30.Abstract

Previous reviews have shown that changes in prescription drug insurance benefits can affect medication use and adherence. We conducted a systematic review of the literature to identify studies addressing the association between prescription drug coverage and health outcomes. Studies were included if they collected empirical data on expansions or restrictions of prescription drug coverage and if they reported clinical outcomes. We found 23 studies demonstrating that broader prescription drug insurance reduces use of other health care services and has a positive impact on patient outcomes. Coverage gaps or caps on drug insurance generally led to worse outcomes. States should consider implementing the Affordable Care Act expansions in drug coverage to improve the health of low-income patients receiving state-based health insurance.

Fischer MA, Choudhry NK, Bykov K, Brill G, Bopp G, Wurst AM, Shrank WH. Pharmacy-based interventions to reduce primary medication nonadherence to cardiovascular medications. Medical Care 2014;52:1050-4.Abstract

BACKGROUND: Primary medication nonadherence (PMN) occurs when patients do not fill new prescriptions. Interventions to reduce PMN have not been well described. OBJECTIVES: To determine whether 2 pharmacy-based interventions could decrease PMN. DESIGN: Two sequential interventions with a control group were evaluated after completion. The automated intervention began in 2007 and consisted of phone calls to patients on the third and seventh days after a prescription was processed but remained unpurchased. The live intervention began in 2009 and used calls from a pharmacist or technician to patients who still had not picked up their prescriptions after 8 days. SUBJECTS: Patients with newly prescribed cardiovascular medications received at CVS community pharmacies. Patients with randomly selected birthdays served as the control population. MEASURES: Patient abandonment of new prescription, defined as not picking up medications within 30 days of initial processing at the pharmacy. RESULTS: The automated intervention included 852,612 patients and 1.2 million prescriptions, with a control group of 9282 patients and 13,178 prescriptions. The live intervention included 121,155 patients and 139,502 prescriptions with a control group of 2976 patients and 3407 prescriptions. The groups were balanced by age, sex, and patterns of prior prescription use. For the automated intervention, 4.2% of prescriptions were abandoned in the intervention group and 4.5% in the control group (P>0.1), with no significant differences for any individual classes of medications. The live intervention was used in a group that had not purchased prescriptions after 8 days and thus had much higher PMN. In this setting 36.9% of prescriptions were abandoned in the intervention group and 41.7% in the control group, a difference of 4.8% (P<0.0001). The difference in abandoned prescriptions for antihypertensives was 6.9% (P<0.0001) but for antihyperlipidemics was only 1.4% (P>0.1). CONCLUSIONS: Automated reminder calls had no effect on PMN. Live calls from pharmacists decreased antihypertensive PMN significantly, although many patients still abandoned their prescriptions.

Najafzadeh M, Gagne JJ, Choudhry NK, Polinski JM, Avorn J, Schneeweiss SS. Patients’ Preferences in Anticoagulant Therapy: Discrete Choice Experiment. Circulation: Cardiovascular Quality and Outcomes 2014;Abstract

Background—With proliferating treatment options for anticoagulant therapy, physicians and patients must choose among them based on their benefits and risks. Using a Discrete Choice Experiment, we elicited patients’ relative preferences for specific benefits and risks of anticoagulant therapy.Methods and Results—We selected a sample of US patients with cardiovascular disease from an online panel and elicited their preferences for benefits and risks of anticoagulant therapy: nonfatal stroke, nonfatal myocardial infarction, cardiovascular death, minor bleeding, major bleeding, bleeding death, and need for monitoring. These attributes were used to design scenarios describing hypothetical treatments that were labeled as new drug, old drug, or no drug. Latent class analysis was used to identify groups of patients with similar preferences. A total of 341 patients completed all Discrete Choice Experiment questions. On average, patients valued a 1% increased risk of a fatal bleeding event the same as a 2% increase in nonfatal myocardial infarction, a 3% increase in nonfatal stroke, a 3% increase in cardiovascular death, a 6% increase in major bleeding, and a 16% increase in minor bleeding. The odds of choosing no drug or old drug versus new drug were 0.72 (95% confidence interval, 0.61–0.84) and 0.86 (95% confidence interval, 0.81–0.93), respectively. Previous stroke or myocardial infarction was associated with membership in the class with larger negative preferences for these outcomes.Conclusions—Patients’ preferences for various outcomes of anticoagulant therapy vary and depend on their previous experiences with myocardial infarction or stroke. Incorporating these preferences into benefit risk calculation and treatment decisions can enhance patient-centered care.

Shrank WH, Krumme AA, Tong AY, Spettell CM, Matlin OS, Sussman A, Brennan TA, Choudhry NK. Quality of care at retail clinics for 3 common conditions. American Journal of Managed Care 2014;20:794-801.Abstract

Objectives Evaluation of quality of care across retail clinics in a geographically diverse population has not been undertaken to date. We sought to evaluate and compare the quality of care for otitis media, pharyngitis, and urinary tract infection received in retail medical clinics in CVS pharmacies ("MinuteClinics" [MCs]), ambulatory care facilities (ACFs), and emergency departments (EDs). Methods We used 14 measures constructed from RAND Corporation's Quality Assurance Tools and guidelines from the American Academy of Pediatrics, the American Academy of Family Physicians, and the Infectious Diseases Society of America. Our cohort was drawn from Aetna medical and prescription claims, 2009-2012. Members were matched on visit date, condition, and propensity score. Generalized estimating equations were used to compare quality across clinic type, overall, and by index condition. Results We matched 75,886 episodes of care, of which 20,153 were eligible for at least 1 quality measure. MCs performed better than EDs and ACFs in 7 measures. In a multivariable model, MCs performed better than ACFs and EDs across all quality measures ([OR 0.42; 95% CI, 0.40-0.45; P < .0001; ACF vs MC] [OR 0.29; 95% CI, 0.27-0.31; P < .0001; ED vs MC]). Results for each condition were significant at P < .0001. Conclusions Quality of care for these conditions based on widely accepted objective measures was superior in MinuteClinics compared with ACFs and EDs.