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
Chan DC, Shrank WH, Cutler D, Jan S, Fischer MA, Liu J, Avorn J, Solomon D, Brookhart MA, Choudhry NK. Patient, physician, and payment predictors of statin adherence [Internet]. Medical Care 2010;48:196-202. Publisher's VersionAbstract

BACKGROUND:: Although many patient, physician, and payment predictors of adherence have been described, knowledge of their relative strength and overall ability to explain adherence is limited. OBJECTIVES:: To measure the contributions of patient, physician, and payment predictors in explaining adherence to statins. RESEARCH DESIGN:: Retrospective cohort study using administrative data. SUBJECTS:: A total of 14,257 patients insured by Horizon Blue Cross Blue Shield of New Jersey who were newly prescribed a statin cholesterol-lowering medication. MEASURES:: Adherence to statin medication was measured during the year after the initial prescription, based on proportion of days covered. The impact of patient, physician, and payment predictors of adherence were evaluated using multivariate logistic regression. The explanatory power of these models was evaluated with C statistics, a measure of the goodness of fit. RESULTS:: Overall, 36.4% of patients were fully adherent. Older patient age, male gender, lower neighborhood percent black composition, higher median income, and fewer number of emergency department visits were significant patient predictors of adherence. Having a statin prescribed by a cardiologist, a patient's primary care physician, or a US medical graduate were significant physician predictors of adherence. Lower copayments also predicted adherence. All of our models had low explanatory power. Multivariate models including patient covariates only had greater explanatory power (C = 0.613) than models with physician variables only (C = 0.566) or copayments only (C = 0.543). A fully specified model had only slightly more explanatory power (C = 0.633) than the model with patient characteristics alone. CONCLUSIONS:: Despite relatively comprehensive claims data on patients, physicians, and out-of-pocket costs, our overall ability to explain adherence remains poor. Administrative data likely do not capture many complex mechanisms underlying adherence.

Cutrona SL, Choudhry NK, Stedman M, Servi A, Liberman JN, Brennan T, Fischer MA, Brookhart MA, Shrank WH. Physician effectiveness in interventions to improve cardiovascular medication adherence: a systematic review [Internet]. Journal of General Internal Medicine 2010;25:1090-6. Publisher's VersionAbstract

BACKGROUND: Medications for the prevention and treatment of cardiovascular disease save lives but adherence is often inadequate. The optimal role for physicians in improving adherence remains unclear. OBJECTIVE: Using existing evidence, we set the goal of evaluating the physician's role in improving medication adherence. DESIGN: We conducted systematic searches of English-language peer-reviewed publications in MEDLINE and EMBASE from 1966 through 12/31/2008. SUBJECTS AND INTERVENTIONS: We selected randomized controlled trials of interventions to improve adherence to medications used for preventing or treating cardiovascular disease or diabetes. MAIN MEASURES: Articles were classified as either (1) physician "active"-a physician participated in designing or implementing the intervention; (2) physician "passive"-physicians treating intervention group patients received patient adherence information while physicians treating controls did not; or (3) physicians noninvolved. We also identified studies in which healthcare professionals helped deliver the intervention. We did a meta-analysis of the studies involving healthcare professionals to determine aggregate Cohen's D effect sizes (ES). KEY RESULTS: We identified 6,550 articles; 168 were reviewed in full, 82 met inclusion criteria. The majority of all studies (88.9%) showed improved adherence. Physician noninvolved studies were more likely (35.0% of studies) to show a medium or large effect on adherence compared to physician-involved studies (31.3%). Among interventions requiring a healthcare professional, physician-noninvolved interventions were more effective (ES 0.47; 95% CI 0.38-0.56) than physician-involved interventions (ES 0.25; 95% CI 0.21-0.29; p < 0.001). Among physician-involved interventions, physician-passive interventions were marginally more effective (ES 0.29; 95% CI 0.22-0.36) than physician-active interventions (ES 0.23; 95% CI 0.17-0.28; p = 0.2). CONCLUSIONS: Adherence interventions utilizing non-physician healthcare professionals are effective in improving cardiovascular medication adherence, but further study is needed to identify the optimal role for physicians.

Choudhry NK. Relationship between high cost sharing and adverse outcomes: a truism that's tough to prove [Internet]. American Journal of Managed Care 2010;16:287-9. Publisher's Version PDF
Shrank WH, Choudhry NK, Agnew-Blais J, Federman AD, Liberman JN, Liu J, Kesselheim AS, Brookhart MA, Fischer MA. State generic substitution laws can lower drug outlays under medicaid [Internet]. Health Affairs (Millwood) 2010;29:1383-90. Publisher's VersionAbstract

To stem the rising costs of medications provided to patients enrolled in Medicaid, states have implemented varying policies about generic substitution. These policies differ in the extent to which pharmacists or patients can influence which medications they choose. Using national Medicaid data, we evaluated the relationship between different generic substitution policies and the use of generic simvastatin, a cholesterol-lowering drug, after the patent for the brand-name equivalent, Zocor, expired. States that implemented policies requiring patients' consent prior to generic substitution experienced rates of substitution that were 25 percent lower than those of states that did not require patient consent. By eliminating patient consent requirements, state Medicaid programs could expect to save more than $100 million in coverage for three top-selling medications that are nearing patent expiration. Although these consent requirements are probably intended to increase patient autonomy, policy makers should consider the sizable opportunity costs.

Parikh S, Shrank WH, Mogun H, Choudhry NK. Statin Utilization in Nursing Home Patients after Cardiac Hospitalization [Internet]. Journal of General Internal Medicine 2010; Publisher's VersionAbstract

BACKGROUND: Coronary artery disease (CAD) is highly prevalent in nursing home residents and is associated with a substantial clinical and economic burden. Statins reduce mortality and hospitalization rates in older patients with CAD. OBJECTIVES: To assess rates and predictors of statin use among high-risk patients with symptomatic coronary artery disease (CAD) admitted to nursing homes after acute cardiac hospitalization. DESIGN: Cohort study. PARTICIPANTS: Medicare beneficiaries enrolled in either a state-run drug assistance program or Medicaid in nursing homes in New Jersey from 1994 through 2005. MEASUREMENTS: Statin utilization within 60 days of nursing home admission was determined for patients recently hospitalized with symptomatic CAD in whom statins are indicated consisting of those with: acute coronary syndrome (ACS) without revascularization, ACS with revascularization and congestive heart failure (CHF) with revascularization. Predictors of statin use were evaluated with multivariate logistic regression models. RESULTS: While statin use over the 11-year period increased from 1.2% to 31.8%, overall utilization was very low. Predictors of greater statin use included prior cardiac hospitalization [odds ratio (OR) 1.32, 95% confidence interval (95% CI) 1.13 to 1.57], prior statin use (OR 6.92, 95% CI 5.86 to 8.82) and receipt of a concurrent cardiac medication (range of odds ratios, 2.36-3.40). Older patients admitted for ACS with or without revascularization were less likely to receive a statin. Patients who had received anti-platelets or angiotensin-modifying agents prior to their hospitalization were less likely to receive statins after discharge. Renal disease, prior stroke, diabetes, hypertension and hyperlipidemia did not influence statin utilization. Predictors of treatment did not change when the cohort was dichotomized according to length of stay. CONCLUSIONS: Patients are infrequently treated with statins when discharged to nursing homes following hospitalization for a symptomatic cardiovascular event. Barriers to statin treatment in this setting require closer examination.

Setoguchi S, Choudhry NK, Levin R, Shrank WH, Winkelmayer WC. Temporal trends in adherence to cardiovascular medications in elderly patients after hospitalization for heart failure [Internet]. Clinical Pharmacology and Therapeutics 2010;88:548-54. Publisher's VersionAbstract

Although the complexity of treatment regimens for patients with heart failure (HF) has increased over time because of the increased availability of efficacious medications, little is known about temporal trends in adherence to treatment regimens in these patients. We assessed trends in adherence to angiotensin-system blockers (ABs), beta-blockers (BBs), and spironolactone (SL) for HF in Medicare beneficiaries enrolled in two statewide pharmacy benefit programs from 1995 to 2004. The proportion of days covered (PDC) (%) was assessed after the first dispensing among users of an AB, BB, or SL. Proportions of full adherence (PDC >80%) did not change over time for ABs (54% in both 1996 and 2003) but increased slightly for BBs (from 47% in 1996 to 57% in 2003) and SL (from 31% in 1996 to 42% in 2003). Black race and dialysis treatment predicted poor adherence to any medications. Adherence to BBs and SL increased modestly over time, but overall nonadherence remained high.

Choudhry NK, Schneeweiss S, Fischer MA, Liu J, Lii J, Solomon DH, Brookhart MA, Avorn J, Shrank WH. Reducing Co-Payments of Essential Cardiovascular Medications. Pharmacoepidemiology and Drug Safety 2009;18:S128. PDF
Dhalla IA, Smith MA, Choudhry NK, Denburg AE. Costs and benefits of free medications after myocardial infarction [Internet]. Healthcare Policy 2009;5:68-86. Publisher's VersionAbstract

BACKGROUND: Although combination pharmacotherapy after myocardial infarction dramatically reduces morbidity and mortality, the full benefits of secondary prevention medications remain unrealized owing to medication non-adherence. Because financial barriers are a major determinant of non-adherence, we examined the costs and benefits of providing free medications to myocardial infarction patients who do not have private insurance and are ineligible for substantial public coverage. METHODS: An economic evaluation combining decision analysis and Markov modelling was conducted to compare full public coverage of secondary prevention medications with the status quo. Costs and benefits were estimated using Canadian data wherever possible. The main outcome was the incremental cost-effectiveness ratio measured in cost per quality-adjusted life-year (QALY) gained. RESULTS: From the perspective of the publicly funded healthcare system, full coverage resulted in greater quality-adjusted survival than the status quo (7.02 vs. 6.13 QALYs) but at increased cost ($20,423 vs. $17,173). The incremental cost-effectiveness ratio (ICER) for full coverage compared to the status quo was $3,663/QALY. This result was robust to a wide range of sensitivity analyses. In a secondary analysis from the perspective of government, the ICER for full coverage compared to the status quo was $12,350/QALY. In this analysis, the ICER was sensitive to changes in price elasticity, but remained below $50,000/QALY as long as the elasticity remained below -0.035. INTERPRETATION: Public payers in Canada should consider providing secondary prevention medications to myocardial infarction patients without private insurance free of charge. Full public coverage is cost-effective compared to the status quo.

Choudhry NK. Copayment levels and medication adherence: less is more [Internet]. Circulation 2009;119:365-7. Publisher's Version PDF