Shrank WH, Choudhry NK, Liberman JN, Brennan TA. The use of generic drugs in prevention of chronic disease is far more cost-effective than thought, and may save money [Internet]. Health Affairs (Millwood) 2011;30:1351-7. Publisher's VersionAbstract

In this article we highlight the important role that medication therapy can play in preventing disease and controlling costs. Focusing on coronary artery disease, we demonstrate that prevention, with the appropriate use of generic medications, appears far more cost-effective than previously documented, and it may even save on costs. For example, an earlier study estimated that reducing blood pressure to widely established clinical guidelines in nondiabetic patients cost an estimated $52,983 per quality-adjusted life-year if a brand-name drug was used. However, we estimate that the cost is just $7,753 per quality-adjusted life-year at generic medication prices. As the nation attempts to find strategies to improve population health without adding to the unsustainably high cost of care, policy makers should focus on ensuring that patients have access to essential generic medications.

Shrank WH, Liberman JN, Fischer MA, Kilabuk E, Girdish C, Cutrona S, Brennan T, Choudhry NK. Are caregivers adherent to their own medications? [Internet]. Journal of the American Pharmacists Association (2003) 2011;:e53-e59. Publisher's VersionAbstract

Objective: To explore caregiver adherence to chronic medications and predictors of appropriate medication use.Design: Descriptive, nonexperimental, cross-sectional study.Setting: United States in May 2009.Participants: 2,000 adults randomly selected from a large national consumer panel.Intervention: Web-based survey of community pharmacy patients.Main outcome measure: Self-reported medication adherence.Results: 21% of those invited (3,775) responded to the survey invitation. Of the 2,000 individuals who were eligible to participate, 38% described themselves as caregivers. Among caregivers, 45% agreed that they were more likely to forget their own medications than medications for their caregivees. Caregivers were 10% more likely to forget to take their medications, 11% more likely to stop taking medications if they felt well, and 13% more likely to forget to refill their medications than noncaregivers (P < 0.001 for all). In fully adjusted models, caregivers had 36% greater odds (95% CI 0.52-0.79) of reporting that they were nonadherent compared with noncaregivers and increased medication use among caregivees was associated with worse adherence among caregivers (P < 0.05).Conclusion: Medication nonadherence was common in this population, and caregivers were more likely to report poor medication adherence than noncaregivers. Considering that caregivers often engage health professionals, physicians and pharmacists may choose to screen for caregiving status. Pharmacists are uniquely positioned to intervene to enhance appropriate medication adherence.

Margulis AV, Choudhry NK, Dormuth CR, Schneeweiss S. Variation in initiating secondary prevention after myocardial infarction by hospitals and physicians, 1997 through 2004 [Internet]. Pharmacoepidemiology and Drug Saftey 2011;20:1088-97. Publisher's VersionAbstract

PURPOSE: Myocardial infarction (MI) survivors benefit from receiving secondary prevention, including beta-blockers, angiotensin-blocking agents, and statins, as recommended by guidelines. Compliance with these guidelines is suboptimal. We sought to describe the initiation of secondary prevention in MI survivors, and to describe the variation in initiation by discharging the hospital, the physician, and the physician "responsible" for secondary prevention prescribing decisions in British Columbia in 1997-2004. METHODS: We assembled a cohort of 28 613 patients discharged alive from the hospital after their first MI and were not readmitted within 30 days. Physicians responsible for prescribing post-MI secondary prevention medications were identified as the physicians prescribing the greatest number of cardiac medications (post-discharge cardiac prescribers). We used multilevel logistic regression to assess the variation in drug initiation at discharging hospital, discharging physician, and post-discharge cardiac prescriber levels, which were adjusted for patient and provider characteristics during the study period. RESULTS: Beta-blockers initiation increased from 56 to 71% over the 8-year study period; angiotensin-converting enzyme/angiotensin II receptor blocker initiation increased from 37 to 70%, and statin initiation increased from 22 to 66% (0-28% for high-potency statins). The probability for initiating an average patient with the study drugs varied widely in age-sex-adjusted models at the hospital and physician levels. Further adjustment did not meaningfully change findings. The variation was largest for statins. The maximum between-provider variance was found for high-potency statins in 2003-2004 at the post-discharge cardiac prescriber level. CONCLUSIONS: Study-drug initiation is increasing among MI survivors, but the variation in initiation is wide between discharging hospitals and physicians. Copyright (c) 2011 John Wiley & Sons, Ltd.

Choudhry NK. Promoting Persistence: Improving Adherence Through Choice of Drug Class [Internet]. Circulation 2011; Publisher's Version PDF
Hayward RM, Upadhyay GA, Mela T, Ellinor PT, Barrett CD, Heist EK, Verma A, Choudhry NK, Singh JP. Pulmonary Vein Isolation with Complex Fractionated Atrial Electrogram Ablation for Paroxysmal and Nonparoxysmal Atrial Fibrillation: A Meta-Analysis [Internet]. Heart Rhythm 2011;8:994-1000. WebsiteAbstract

BACKGROUND:: Pulmonary vein isolation (PVI) is recognized as a potentially curative treatment for atrial fibrillation (AF). Ablation of complex fractionated atrial electrograms (CFAEs) in addition to PVI has been advocated as a means to improve procedural outcomes, but the benefit remains unclear. OBJECTIVE:: To synthesize the available data testing the incremental benefit of adding CFAE ablation to PVI. METHODS:: We performed a meta-analysis of controlled studies comparing the effect of PVI with CFAE ablation versus PVI alone in patients with paroxysmal and nonparoxysmal AF. RESULTS:: Of the 481 reports identified, 8 studies met our inclusion criteria. There was a statistically significant increase in freedom from atrial tachyarrhythmia (AT) with the addition of CFAE ablation (RR 1.15, p=0.03). In the 5 reports of nonparoxsymal AF (3 randomized controlled trials, one controlled clinical trial, and one trial using matched historical controls), addition of CFAE ablation resulted in a statistically significant increase in freedom from AT (n=112/181 [62%] for PVI+CFAE versus n=84/179 [47%] for PVI alone; RR 1.32, p=0.02). In trials of paroxysmal AF (3 randomized controlled trials and one trial using matched historical controls), addition of CFAE ablation did not result in a statistically significant increase in freedom from AT (n=131/166 [79%] for PVI+CFAE versus n=122/164 [74%] for PVI alone; RR 1.04, p=0.52). CONCLUSIONS:: In these studies of patients with nonparoxysmal AF, addition of CFAE ablation to PVI results in greater improvement in freedom from AF. No additional benefit of this combined approach was observed in patients with paroxysmal AF.

Kulik A, Shrank WH, Levin R, Choudhry NK. Adherence to Statin Therapy in Elderly Patients After Hospitalization for Coronary Revascularization [Internet]. American Journal of Cardiology 2011;107:1409-14. Publisher's VersionAbstract

Low levels of statin adherence have been documented in patients with coronary artery disease (CAD), but whether coronary revascularization is associated with improved adherence rates has yet to be evaluated. We identified all Medicare beneficiaries enrolled in 2 statewide pharmacy assistance programs who were >/=65 years old, who had been hospitalized for CAD from 1995 through 2004, and who had been prescribed statin therapy within 90 days of discharge (n = 13,130). Statin adherence was measured based on the proportion of days covered with statin therapy after hospital discharge, and full adherence was defined as proportion of days covered >/=80%. Statin adherence was compared in patients with CAD treated with medical therapy (n = 3,714), percutaneous coronary intervention (n = 6,309), or coronary artery bypass graft surgery (n = 3,107). Statin adherence significantly increased over the period of the study from 70.5% to 75.4% (p <0.0001). After hospitalization for CAD, patients treated with percutaneous coronary intervention and coronary artery bypass graft surgery had full adherence rates of 70.6% and 70.2%, respectively. Full adherence rates were significantly lower for patients treated with coronary revascularization compared to patients treated with medical therapy (79.4%, p <0.0001). Independent predictors of higher statin adherence included treatment with medical therapy, later year of hospital admission, white race, previous statin use, and use of other cardiac medications after CAD hospitalization (p <0.01 for all comparisons). In conclusion, in patients receiving invasive coronary treatment, statin adherence remains suboptimal, despite strong evidence supporting their use. Given the health and economic consequences of nonadherence, these findings highlight the need for developing cost-effective strategies to improve medication adherence after coronary revascularization.

Shrank WH, Liberman JN, Fischer MA, Avorn J, Kilabuk E, Chang A, Kesselheim AS, Brennan TA, Choudhry NK. The consequences of requesting "dispense as written" [Internet]. The American Journal of Medicine 2011;124:309-17. Publisher's VersionAbstract

BACKGROUND: All US states have adopted generic substitution laws to reduce medication costs. However, physicians may override these regulations by prescribing branded drugs and requesting that they are dispensed as written. Patients also can make these requests. Little is known about the frequency and correlates of dispense as written requests or their association with medication filling. METHODS: We identified beneficiaries of a large pharmacy benefits manager who submitted a prescription claim from any pharmacy in January 2009. We categorized claims as a physician-assigned dispense as written, patient-assigned dispense as written, or no dispense as written. We described rates of these requests and used generalized estimating equations to evaluate physician, patient, treatment, and pharmacy characteristics associated with dispense as written requests. We also used generalized estimating equations to assess the relationship between dispense as written designation and rates prescriptions are not filled by patients. RESULTS: Our sample included 5.6 million prescriptions for more than 2 million patients. More than 2.7% were designated as dispense as written by physicians, and 2.0% were designated as dispense as written by patients. Substantial variation in dispense as written requests were seen by medication class, patient and physician age, and geographic region. The odds of requesting dispense as written was 78.5% greater for specialists than generalists (P<;.001). When chronic prescriptions were initiated, physician dispense as written (odds ratio 1.50, P<;.001) and patient dispense as written (odds ratio 1.60, P<;.001) were associated with greater odds that patients did not fill the prescription. CONCLUSION: Dispense as written requests were common and associated with decreased rates of prescription filling. Options to reduce rates of dispense as written requests may reduce costs and improve medication adherence.

Greene JA, Choudhry NK, Kilabuk E, Shrank WH. Online social networking by patients with diabetes: a qualitative evaluation of communication with Facebook [Internet]. Journal of General Internal Medicine 2011;26:287-92. Publisher's VersionAbstract

BACKGROUND: Several disease-specific information exchanges now exist on Facebook and other online social networking sites. These new sources of knowledge, support, and engagement have become important for patients living with chronic disease, yet the quality and content of the information provided in these digital arenas are poorly understood. OBJECTIVE: To qualitatively evaluate the content of communication in Facebook communities dedicated to diabetes. DESIGN: We identified the 15 largest Facebook groups focused on diabetes management. For each group, we downloaded the 15 most recent "wall posts" and the 15 most recent discussion topics from the 10 largest groups. PATIENTS: Four hundred eighty unique users were identified in a series of 690 comments from wall posts and discussion topics. MAIN MEASURES: Posts were abstracted and aggregated into a database. Two investigators evaluated the posts, developed a thematic coding scheme, and applied codes to the data. KEY RESULTS: Patients with diabetes, family members, and their friends use Facebook to share personal clinical information, to request disease-specific guidance and feedback, and to receive emotional support. Approximately two-thirds of posts included unsolicited sharing of diabetes management strategies, over 13% of posts provided specific feedback to information requested by other users, and almost 29% of posts featured an effort by the poster to provide emotional support to others as members of a community. Approximately 27% of posts featured some type of promotional activity, generally presented as testimonials advertising non-FDA approved, "natural" products. Clinically inaccurate recommendations were infrequent, but were usually associated with promotion of a specific product or service. Thirteen percent of posts contained requests for personal information from Facebook participants. CONCLUSIONS: Facebook provides a forum for reporting personal experiences, asking questions, and receiving direct feedback for people living with diabetes. However, promotional activity and personal data collection are also common, with no accountability or checks for authenticity.

Shrank WH, Liberman JN, Fischer MA, Girdish C, Brennan TA, Choudhry NK. Physician perceptions about generic drugs [Internet]. Annals of Pharmacotherapy 2011;45:31-8. Publisher's VersionAbstract

BACKGROUND: With constrained health-care resources, there is a need to understand barriers to cost-effective medication use. OBJECTIVE: To study physician perceptions about generic medications. METHODS: Physicians used 5-point Likert scales to report perceptions about cost-related medication nonadherence, the efficacy and quality of generic medications, preferences for generic use, and the implications of dispensing medication samples. Descriptive statistics were used to assess physician perceptions and logistic regression models were used to evaluate predictors of physician perceptions. RESULTS: Among the invited sample, 839 (30.4%) responded and 506 (18.3%) were eligible and included in the final study population. Over 23% of physicians surveyed expressed negative perceptions about efficacy of generic drugs, almost 50% reported negative perceptions about quality of generic medications, and more than one quarter do not prefer to use generics as first-line medications for themselves or for their family. Physicians over the age of 55 years were 3.3 times more likely to report negative perceptions about generic quality, 5.8 times more likely to report that they would not use generics themselves, and 7.5 times more likely to state that they would not recommend generics for family members (p < 0.05 for all). Physicians reported that pharmaceutical company representatives are the most common (75%) source of information about market entry of a generic medication. Almost half of the respondents expressed concern that free samples may adversely affect subsequent affordability, yet two thirds of respondents provide free samples. CONCLUSIONS: A meaningful proportion of physicians expressed negative perceptions about generic medications, representing a potential barrier to generic use. Payors and policymakers trying to encourage generic use may consider educational campaigns targeting older physicians.

Choudhry NK, Rosenthal MB, Milstein A. Assessing the evidence for value-based insurance design [Internet]. Health Affairs (Millwood) 2010;29:1988-94. Publisher's VersionAbstract

High copayments for medical services can cause patients to underuse essential therapies. Value-based health insurance design attempts to address this problem by explicitly linking cost sharing and value. Copayments are set at low levels for high-value services. The Mercer National Survey of Employer-Sponsored Health Plans demonstrates that value-based insurance design use is increasing and that 81 percent of large employers plan to offer it in the near future. Despite this increase, few studies have adequately evaluated its ability to improve quality and reduce health spending. Maximizing the benefits of value-based insurance design will require mechanisms to target appropriate copayment reductions, offset short-run cost outlays, and expand its use to other health services.

Choudhry NK, Fischer MA, Avorn J, Schneeweiss S, Solomon DH, Berman C, Jan S, Liu J, Lii J, Brookhart MA, Mahoney JJ, Shrank WH. At Pitney Bowes, value-based insurance design cut copayments and increased drug adherence [Internet]. Health Affairs (Millwood) 2010;29:1995-2001. Publisher's VersionAbstract

To date, there has been little empirical evidence to support the broader use of value-based insurance design, which lowers copayments for services with high value relative to their costs. To address this lack of data, we evaluated the impact of the value-based insurance program of a US corporation, Pitney Bowes. The program eliminated copayments for cholesterol-lowering statins and reduced them for clopidogrel, a blood clot inhibitor. We found that the policy was associated with an immediate 2.8 percent increase in adherence to statins relative to controls, which was maintained for the subsequent year. For clopidogrel, the policy was associated with an immediate stabilizing of the adherence rate and a four-percentage-point difference between intervention and control subjects a year later. Our study thus provides an empirical basis for the use of this approach to improve the quality of health care.

Choudhry NK, Shrank WH. Four-dollar generics--increased accessibility, impaired quality assurance [Internet]. New England Journal of Medicine 2010;363:1885-7. Publisher's Version PDF
Shrank WH, Choudhry NK. Comparative effectiveness research: is "synchronicity" a valid outcome?. American Journal of Pharmacy Benefits 2010;2:195-196. PDF
Avorn J, Choudhry NK. Funding for medical education: maintaining a healthy separation from industry [Internet]. Circulation 2010;121:2228-34. Publisher's Version PDF
Shrank WH, Choudhry NK, Fischer MA, Avorn J, Powell M, Schneeweiss S, Liberman JN, Dollear T, Brennan TA, Brookhart MA. The epidemiology of prescriptions abandoned at the pharmacy [Internet]. Annals of Internal Medicine 2010;153:633-40. Publisher's VersionAbstract

BACKGROUND: Picking up prescriptions is an essential but previously unstudied component of adherence for patients who use retail pharmacies. Understanding the epidemiology and correlates of prescription abandonment may have an important effect on health care quality. OBJECTIVE: To evaluate the rates and correlates of prescription abandonment. DESIGN: Cross-sectional cohort study. SETTING: One large retail pharmacy chain and one large pharmacy benefits manager (PBM) in the United States. MEASUREMENTS: Prescriptions bottled at the retail pharmacy chain between 1 July 2008 and 30 September 2008 by patients insured by the PBM were identified. Pharmacy data were used to identify medications that were bottled and either dispensed or returned to stock (RTS) or abandoned. Data from the PBM were used to identify previous or subsequent dispensing at any pharmacy. The first (index) prescription in a class for each patient was assigned to 1 of 3 mutually exclusive outcomes: filled, RTS, or RTS with fill (in the 30 days after abandonment, the patient purchased a prescription for a medication in the same medication class at any pharmacy). Outcome rates were assessed by drug class, and generalized estimating equations were used to assess patient, neighborhood, insurance, and prescription characteristics associated with abandonment. RESULTS: 10 349 139 index prescriptions were filled by 5 249 380 patients. Overall, 3.27% of index prescriptions were abandoned; 1.77% were RTS and 1.50% were RTS with fill. Patients were least likely to abandon opiate prescriptions. Prescriptions with copayments of $40 to $50 and prescriptions costing more than $50 were 3.40 times and 4.68 times more likely, respectively, to be abandoned than prescriptions with no copayment (P < 0.001 for both comparisons). New users of medications had a 2.74 times greater probability of abandonment than prevalent users (P < 0.001), and prescriptions delivered electronically were 1.64 times more likely to be abandoned than those that were not electronic (P < 0.001). LIMITATION: The study included mainly insured patients and analyzed data collected during the summer months only. CONCLUSION: Although prescription abandonment represents a small component of medication nonadherence, the correlates to abandonment highlight important opportunities to intervene and thereby improve medication taking. PRIMARY FUNDING SOURCE: CVS Caremark.

Misono AS, Cutrona SL, Choudhry NK, Fischer MA, Stedman MR, Liberman JN, Brennan TA, Jain SH, Shrank WH. Healthcare information technology interventions to improve cardiovascular and diabetes medication adherence [Internet]. American Journal of Managed Care 2010;16:SP82-92. Publisher's VersionAbstract

OBJECTIVE: To determine the efficacy of healthcare information technology (HIT) interventions in improving adherence. STUDY DESIGN: Systematic search of randomized controlled trials of HIT interventions to improve medication adherence in cardiovascular disease or diabetes. METHODS: Interventions were classified as 1-way patient reminder systems, 2-way interactive systems, and systems to enhance patient-provider interaction. Studies were subclassified into those with and without real-time provider feedback. Cohen's d effect sizes were calculated to assess each intervention's magnitude of effectiveness. RESULTS: We identified 7190 articles, only 13 of which met inclusion criteria. The majority of included studies (54%, 7 studies) showed a very small ES. The effect size was small in 15%, large in 8%, and was not amenable to calculation in the remainder. Reminder systems were consistently effective, showing the largest effect sizes in this review. Education/counseling HIT systems were less successful, as was the addition of realtime adherence feedback to healthcare providers. Interactive systems were rudimentary and not integrated into electronic health records; they exhibited very small effect sizes. Studies aiming to improve patient-provider communication also had very small effect sizes. CONCLUSIONS: There is a paucity of data about HIT's efficacy in improving adherence to medications for cardiovascular disease and diabetes, although simple patient reminder systems appear effective. Future studies should focus on more sophisticated interactive interventions that expand the functionality and capabilities of HIT and better engage patients in care.

Cutrona SL, Choudhry NK, Fischer MA, Servi A, Liberman JN, Brennan TA, Shrank WH. Modes of delivery for interventions to improve cardiovascular medication adherence [Internet]. American Journal of Managed Care 2010;16:929-42. Publisher's VersionAbstract

OBJECTIVE: To determine the optimal modes of delivery for interventions to improve adherence to cardiovascular medications. STUDY DESIGN: Systematic review. METHODS: We conducted systematic searches of English-language, peer-reviewed publications in MEDLINE and EMBASE, 1966 through December 31, 2008. We selected randomized controlled trials of interventions to improve adherence to medications for preventing or treating cardiovascular disease or diabetes. Articles were classified based on mode of delivery of the main intervention as (1) person-independent interventions (mailed, faxed, or hand distributed; or delivered via electronic interface) or (2) person-dependent interventions (nonautomated phone calls, in-person interventions). RESULTS: We identified 6550 articles. Of these, 168 were reviewed in full and 51 met inclusion criteria. Among person-independent interventions (56% successful), electronic interventions were most successful (67%). Among person-dependent interventions (52% successful), phone calls showed low success rates (38%). In-person interventions at hospital discharge were more effective (67%) than clinic interventions (47%). In-person pharmacist interventions were effective when held in a pharmacy (83% successful), but were less effective in clinics (38%). CONCLUSIONS: Future medication adherence studies should explore new electronic approaches and in-person interventions at the site of medication distribution. Identifying times of increased patient receptivity to the adherence message such as hospital discharge also will be important.

Choudhry NK, Cox E, Fischer MA, Mehta J, Shrank WH. Setting prices for generic medications: a survey of patient perceptions. American Journal of Pharmacy Benefits 2010;2:33-38. PDF
Kulik A, Singh JP, Levin R, Avorn J, Choudhry NK. Association between statin use and the incidence of atrial fibrillation following hospitalization for coronary artery disease [Internet]. American Journal of Cardiology 2010;105:1655-60. Publisher's VersionAbstract

Mounting evidence suggests that statins possess antiarrhythmic properties and inhibit atrial fibrillation (AF). The goal of this study was to evaluate the relation between statin use and new-onset AF in a large cohort of patients with coronary artery disease. We identified all Medicare beneficiaries > or =65 years old who had been hospitalized for acute myocardial infarction or coronary revascularization from 1995 to 2004 and participated in 1 of 2 government-sponsored medication benefit programs. Patients with a history of AF before and during hospitalization were excluded. This yielded a cohort of 29,088. The incidence of new AF was compared between patients who were (n = 8,450) and were not (n = 20,638) prescribed statins within 1 month of hospital discharge after their cardiac event. New-onset AFs within 5 and 10 years were 32.6% and 51.2%, respectively, in patients who received statins compared to 38.3% and 58.0% in patients who did not receive statins (unadjusted hazard ratio 0.82, 95% confidence interval 0.78 to 0.86). Multivariable analysis controlling for demographic and clinical confounders indicated that statin use independently decreased the risk of developing new-onset AF compared to nonusers (adjusted hazard ratio 0.90, 95% confidence interval 0.85 to 0.94). Adjustment for propensity-score and health-seeking behaviors yielded nearly identical results. In conclusion, statin therapy initiated within 1 month after hospital discharge is independently associated with a decrease in the risk of new-onset AF after myocardial infarction or coronary revascularization. These findings lend support to the antiarrhythmic effects of statins and suggest another benefit for their use in patients with coronary artery disease.

Choudhry NK. Improving the Pathway From Cardiovascular Medication Prescribing to Longer-Term Adherence: New Results About Old Issues [Internet]. Circulation. Cardiovascular and Quality Outcomes 2010;3:223-225. Publisher's Version PDF