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.
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.
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.
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.
OBJECTIVE: Despite the proliferation of databases with increasingly rich patient data, prediction of medication adherence remains poor. We proposed and evaluated approaches for improved adherence prediction. DATA SOURCES: We identified Medicare beneficiaries who received prescription drug coverage through CVS Caremark and initiated a statin. STUDY DESIGN: A total of 643 variables were identified at baseline from prior claims and linked Census data. In addition, we identified three postbaseline predictors, indicators of adherence to statins during each of the first 3 months of follow-up. We estimated 10 models predicting subsequent adherence, using logistic regression and boosted logistic regression, a nonparametric data-mining technique. Models were also estimated within strata defined by the index days supply. RESULTS: In 77,703 statin initiators, prediction using baseline variables only was poor with maximum cross-validated C-statistics of 0.606 and 0.577 among patients with index supply
30 days, respectively. Using only indicators of initial statin adherence improved prediction accuracy substantially among patients with shorter initial dispensings (C = 0.827/0.518), and, when combined with investigator-specified variables, prediction accuracy was further improved (C = 0.842/0.596). CONCLUSIONS: Observed adherence immediately after initiation predicted future adherence for patients whose initial dispensings were relatively short.
. Annals of Internal Medicine 2014;161:400-7.Abstract
BACKGROUND: Statins are effective in preventing cardiovascular events, but patients do not fully adhere to them. OBJECTIVE: To determine whether patients are more adherent to generic statins versus brand-name statins (lovastatin, pravastatin, or simvastatin) and whether greater adherence improves health outcomes. DESIGN: Observational, propensity score-matched, new-user cohort study. SETTING: Linked electronic data from medical and pharmacy claims. PARTICIPANTS: Medicare beneficiaries aged 65 years or older with prescription drug coverage between 2006 and 2008. INTERVENTION: Initiation of a generic or brand-name statin. MEASUREMENTS: Adherence to statin therapy (measured as the proportion of days covered [PDC] up to 1 year) and a composite outcome comprising hospitalization for an acute coronary syndrome or stroke and all-cause mortality. Hazard ratios (HRs) and absolute rate differences were estimated. RESULTS: A total of 90 111 patients who initiated a statin during the study was identified; 83 731 (93%) initiated a generic drug, and 6380 (7%) initiated a brand-name drug. The mean age of patients was 75.6 years, and most (61%) were female. The average PDC was 77% for patients in the generic group and 71% for those in the brand-name group (P < 0.001). An 8% reduction in the rate of the clinical outcome was observed among patients in the generic group versus those in the brand-name group (HR, 0.92 [95% CI, 0.86 to 0.99]). The absolute difference was -1.53 events per 100 person-years (CI, -2.69 to -0.19 events per 100 person-years). LIMITATION: Results may not be generalizable to other populations with different incomes or drug benefit structures. CONCLUSION: Compared with those initiating brand-name statins, patients initiating generic statins were more likely to adhere and had a lower rate of a composite clinical outcome. PRIMARY FUNDING SOURCE: Teva Pharmaceuticals.
Importance: Although many classes of oral glucose-lowering medications have been approved for use, little comparative effectiveness evidence exists to guide initial selection of therapy for diabetes mellitus. Objective: To determine the effect of initial oral glucose-lowering agent class on subsequent need for treatment intensification and 4 short-term adverse clinical events. Design, Setting, and Participants: This study was a retrospective cohort study of patients who were fully insured members of Aetna (a large national health insurer) who had been prescribed an oral glucose-lowering medication from July 1, 2009, through June 30, 2013. Individuals newly prescribed an oral glucose-lowering agent who filled a second prescription for a medication in the same class and with a dosage at or above the World Health Organization's defined daily dose within 90 days of the end-of-day's supply of the first prescription were studied. Individuals with interim prescriptions for other oral glucose-lowering medications were excluded. Exposures: Initiation of treatment with metformin, a sulfonylurea, a thiazolidinedione, or a dipeptidyl peptidase 4 inhibitor. Main Outcomes and Measures: Time to addition of a second oral agent or insulin, each component separately, hypoglycemia, other diabetes-related emergency department visits, and cardiovascular events. Results: A total of 15 516 patients met the inclusion criteria, of whom 8964 (57.8%) started therapy with metformin. In unadjusted analyses, use of medications other than metformin was significantly associated with an increased risk of adding a second oral agent only, insulin only, and a second agent or insulin (P < .001 for all). In propensity score and multivariable-adjusted Cox proportional hazards models, initiation of therapy with sulfonylureas (hazard ratio [HR], 1.68; 95% CI, 1.57-1.79), thiazolidinediones (HR, 1.61; 95% CI, 1.43-1.80), and dipeptidyl peptidase 4 inhibitors (HR, 1.62; 95% CI, 1.47-1.79) was associated with an increased hazard of intensification. Alternatives to metformin were not associated with a reduced risk of hypoglycemia, emergency department visits, or cardiovascular events. Conclusions and Relevance: Despite guidelines, only 57.8% of individuals began diabetes treatment with metformin. Beginning treatment with metformin was associated with reduced subsequent treatment intensification, without differences in rates of hypoglycemia or other adverse clinical events. These findings have significant implications for quality of life and medication costs.
. 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.
Significant racial/ethnic disparities have been documented in cardiovascular care. Although health care quality is improving for many Americans, differences in clinical outcomes have persisted between racial/ethnic minority patients and non-minorities, even when income, education level, and site of care are taken into consideration. Potential causes of disparities are complex and are related to differences in risk factor prevalence and control, use of evidence-based procedures and medications, and social and environmental factors. Minority patients are more likely to receive care from lower-quality health care providers and institutions and experience more barriers to accessing care. Factors such as stereotyping and bias in medicine are hard to quantify, but likely contribute to differences in treatment. Recent trends suggest that some disparities are decreasing. Opportunities for change and improvement exist for patients, providers, and health care systems. Promising interventions, such as health policy changes, quality improvement programs, and culturally targeted community and clinic-based interventions offer hope that high-quality health care in the USA can be provided to all patients.
. 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.
BACKGROUND: Dabigatran, rivaroxaban, and apixaban have been approved for use in patients with atrial fibrillation based upon randomized trials demonstrating their comparable or superior efficacy and safety relative to warfarin. Little is known about their adoption into clinical practice, whether utilization is consistent with the controlled-trials on which their approval was based, and how their use has affected health spending for patients and insurers. STUDY DESIGN: We used medical and prescription claims data from a large insurer to identify patients with non-valvular atrial fibrillation who were prescribed an oral anticoagulant in 2010-2013. We plotted trends in medication initiation over time, assessed corresponding insurer and patient out-of-pocket spending, and evaluated the cumulative number and cost of anticoagulants. We identified predictors of novel anticoagulant initiation using multivariable logistic models. Finally, we estimated the difference in total drug expenditures over 6 months for patients initiating warfarin vs. a novel anticoagulant. RESULTS: 6,893 patients with atrial fibrillation initiated an oral anticoagulant during the study period. By the end of the study period, novel anticoagulants accounted for 62% of new prescriptions and 98% of anticoagulant-related drug costs. Female sex, lower household income and higher CHADS2, CHA2DS2-VASC, and HAS-BLED scores were significantly associated with lower odds of receiving a novel anticoagulant (p<0.001 for each). Average combined patient and insurer anticoagulant spending in the first 6 months after initiation was more than $900 greater for patients initiating a novel anticoagulant. CONCLUSIONS: This study demonstrates rapid adoption of novel anticoagulants into clinical practice, particularly among patients with lower CHADS2 and HAS-BLED scores, and high health care cost consequences. These findings provide important directions for future comparative and cost-effectiveness research.
Substantial racial and ethnic disparities in cardiovascular care persist in the United States. For example, African Americans and Hispanics with cardiovascular disease are 10–40 percent less likely than whites to receive secondary prevention therapies, such as aspirin and beta-blockers. Lowering copayments for these therapies improves outcomes among all patients who have had a myocardial infarction, but the impact of lower copayments on health disparities is unknown. Using self-reported race and ethnicity for participants in the Post-Myocardial Infarction Free Rx Event and Economic Evaluation (MI FREEE) trial, we found that rates of medication adherence were significantly lower and rates of adverse clinical outcomes were significantly higher for nonwhite patients than for white patients. Providing full drug coverage increased medication adherence in both groups. Among nonwhite patients, it also reduced the rates of major vascular events or revascularization by 35 percent and reduced total health care spending by 70 percent. Providing full coverage had no effect on clinical outcomes and costs for white patients. We conclude that lowering copayments for medications after myocardial infarctions may reduce racial and ethnic disparities for cardiovascular disease.
BACKGROUND: Methods for near-real-time monitoring of new drugs in electronic healthcare data are needed. OBJECTIVE: In a novel application, we prospectively monitored ischemic, bleeding, and mortality outcomes among patients initiating prasugrel versus clopidogrel in routine care during the first 2 years following the approval of prasugrel. METHODS: Using the HealthCore Integrated Research Database, we conducted a prospective cohort study comparing prasugrel and clopidogrel initiators in the 6 months following the introduction of prasugrel and every 2 months thereafter. We identified patients who initiated antiplatelets within 14 days following discharge from hospitalizations for myocardial infarction (MI) or acute coronary syndrome. We matched patients using high-dimensional propensity scores (hd-PSs) and followed them for ischemic (i.e., MI and ischemic stroke) events, bleed (i.e., hemorrhagic stroke and gastrointestinal bleed) events, and all-cause mortality. For each outcome, we applied sequential alerting algorithms. RESULTS: We identified 1,282 eligible new users of prasugrel and 8,263 eligible new users of clopidogrel between September 2009 and August 2011. In hd-PS matched cohorts, the overall MI rate difference (RD) comparing prasugrel with clopidogrel was -23.1 (95 % confidence interval [CI] -62.8-16.7) events per 1,000 person-years and RDs were -0.5 (-12.9-11.9) and -2.8 (-13.2-7.6) for a composite bleed event outcome and death from any cause, respectively. No algorithms generated alerts for any outcomes. CONCLUSIONS: Near-real-time monitoring was feasible and, in contrast to the key pre-marketing trial that demonstrated the efficacy of prasugrel, did not suggest that prasugrel compared with clopidogrel was associated with an increased risk of gastrointestinal and intracranial bleeding.
Value-based insurance design (VBID) plans selectively lower cost sharing to increase medication adherence. Existing plans have been structured in a variety of ways, and these variations could influence the effectiveness of VBID plans. We evaluated seventy-six plans introduced by a large pharmacy benefit manager during 2007-10. We found that after we adjusted for the other features and baseline trends, VBID plans that were more generous, targeted high-risk patients, offered wellness programs, did not offer disease management programs, and made the benefit available only for medication ordered by mail had a significantly greater impact on adherence than plans without these features. The effects were as large as 4-5 percentage points. These findings can provide guidance for the structure of future VBID plans.
OBJECTIVE: To determine the impact of FDA safety communications regarding the weight loss medications sibutramine and orlistat. METHODS: The 2008 to 2011 pharmacy claims data from CVS Caremark were used to determine the effect of the relevant FDA warnings on (1) use of sibutramine and orlistat, (2) their rates of discontinuation, and (3) substitution to an alternate weight loss medication in the 3-month period following discontinuation. RESULTS: The use of sibutramine, orlistat, or phentermine declined from 45 users per 100,000 Caremark enrollees in May 2008 to 24 users per 100,000 enrollees in December 2010. In the time series analyses of overall use of medications, a very small decline in the trend of use of sibutramine after the FDA communication (0.000002% per month decline after the communication; P < 0.001) was found. However, rates of discontinuation of sibutramine and orlistat were similar before and after relevant FDA communications (all P values >0.1 for both level and trend changes post-warning). Patients discontinuing sibutramine post-communication increased use of phentermine at a rate of 0.004% per month after discontinuation (P = 0.01). CONCLUSION: From 2008 to 2010, use of prescription weight loss medications was low and declined over time. FDA communications regarding the safety of these medications had limited effect on use.
. American Journal of Gastroenterology 2014;Abstract
OBJECTIVES:Poor adherence to mesalamine is common and driven by a combination of lifestyle and behavioral factors, as well as health beliefs. We sought to develop a valid tool to identify barriers to patient adherence and predict those at risk for future nonadherence.METHODS:A 10-item survey was developed from patient-reported barriers to adherence. The survey was administered to 106 patients with ulcerative colitis who were prescribed mesalamine, and correlated with prospectively collected 12-month pharmacy refills (medication possession ratio (MPR)), urine levels of salicylates, and self-reported adherence (Morisky Medication Adherence Scale (MMAS)-8).RESULTS:From the initial 10-item survey, 8 items correlated highly with the MMAS-8 score at enrollment. Computer-generated randomization produced a derivation cohort of 60 subjects and a validation cohort of 46 subjects to assess the survey items in their ability to predict future adherence. Two items from the patient survey correlated with objective measures of long-term adherence: their belief in the importance of maintenance mesalamine even when in remission and their concerns about side effects. The additive score based on these two items correlated with 12-month MPR in both the derivation and validation cohorts (P<0.05). Scores on these two items were associated with a higher risk of being nonadherent over the subsequent 12 months (relative risk (RR) =2.2, 95% confidence interval=1.5-3.5, P=0.04). The area under the curve for the performance of this 2-item tool was greater than that of the 10-item MMAS-8 score for predicting MPR scores over 12 months (area under the curve 0.7 vs. 0.5).CONCLUSIONS:Patients' beliefs about the need for maintenance mesalamine and their concerns about side effects influence their adherence to mesalamine over time. These concerns could easily be raised in practice to identify patients at risk of nonadherence (Clinical Trial number NCT01349504).Am J Gastroenterol advance online publication, 10 June 2014; doi:10.1038/ajg.2014.158.
. American Journal of Public Health 2014;104:1052-8.Abstract
OBJECTIVES: We assessed the relationship between individual characteristics and receipt of oseltamivir (Tamiflu) in the United States during the H1N1 pandemic and other flu seasons. METHODS: In a cohort of individuals enrolled in pharmacy benefit plans, we used a multivariate logistic regression model to measure associations between subscriber characteristics and filling a prescription for oseltamivir during 3 flu seasons (October 2006-May 2007, October 2007-May 2008, and October 2008-May 2010). In 19 states with county-level influenza rates reported, we controlled for disease burden. RESULTS: Approximately 56 million subscribers throughout the United States were included in 1 or more study periods. During pandemic flu, beneficiaries in the highest income category had 97% greater odds of receiving oseltamivir than those in the lowest category (P < .001). After we controlled for disease burden, subscribers in the 2 highest income categories had 2.18 and 1.72 times the odds of receiving oseltamivir compared with those in the lowest category (P < .001 for both). CONCLUSIONS: Income was a stronger predictor of oseltamivir receipt than prevalence of influenza. These findings corroborate concerns about equity of treatment in pandemics, and they call for improved approaches to distributing potentially life-saving treatments.
Statin use has increased substantially in North America and Europe, with resultant reductions in cardiovascular mortality. However, little is known about statin use in lower-income countries. India is of interest because of its burden of cardiovascular disease, the unique nature of its prescription drug market, and the growing globalization of drug sales. We conducted an observational study using IMS Health data for the period February 2006–January 2010. During the period, monthly statin prescriptions increased from 45.8 to 84.1 per 1,000 patients with coronary heart disease—an increase of 0.80 prescriptions per month. The proportion of the Indian population receiving a defined daily statin dose increased from 3.35 percent to 7.78 percent. Nevertheless, only a fraction of those eligible for a statin appeared to receive the therapy, even though there were 259 distinct statin products available to Indian consumers in January 2010. Low rates of statin use in India may reflect problems with access to health care, affordability, underdiagnosis, and cultural beliefs. Because of the growing burden of cardiovascular disease in lower-income countries such as India, there is an urgent need to increase statin use and ensure access to safe products whose use is based on evidence. Policies are needed to expand insurance, increase medications’ affordability, educate physicians and patients, and improve regulatory oversight.