BACKGROUND: The need to identify how best to structure health insurance and to deliver health care services is a central priority for comparative effectiveness research. Studies designed to evaluate these issues are frequently conducted in large insurance systems. We sought to describe the challenges faced when conducting trials in this context. METHODS: Using the Post-Myocardial Infarction Free Rx Event and Economic Evaluation (MI FREEE) trial as an example, we describe the methodological and practical challenges of conducting trials in large insurance systems. RESULTS: We encountered six key challenges while conducting MI FREEE trial, namely the need to obtain plan sponsor permission to experiment, the desire of plan sponsors to have all of their beneficiaries receive the same intervention, the inaccuracy of claims-based identification methods and the impact of claims lag on the timely enrollment of potentially eligible patients, the reluctance of patients to participate in insurance-based interventions and the potential need for informed consent, the frequent introduction of new cointerventions in real-world delivery systems, and the high rates of loss to follow-up because of insurance "churn." We describe the approaches we used to overcome these challenges. CONCLUSIONS: Studies in insurance settings are a powerful and necessary design for evaluating comparative effectiveness interventions. There are numerous strategies to address the potential logistical and methodological challenges that this research environment uniquely creates.
OBJECTIVES: To ascertain predictors of initiation of brand-name versus generic narrow therapeutic index (NTI) drugs. DESIGN: Retrospective cohort study. SETTING: Data from CVS Caremark were linked to Medicare claims and to U.S. census data. PARTICIPANTS: Individuals aged 65 and older who initiated an NTI drug in 2006 and 2007 (N = 36,832). MEASUREMENTS: Demographic, health service utilization, and geographic predictors of whether participants initiated a generic or brand-name version of their NTI drug were identified using logistic regression. RESULTS: Overall, 30,014 (81.5%) participants started on a generic version of their NTI drug. The most commonly initiated NTI drugs were warfarin (n = 17,790; 48%), levothyroxine (n = 10,779; 29%), and digoxin (n = 6,414; 17%). Older age (odds ratio (OR) = 1.12, 95% confidence interval (CI) = 1.02-1.22 comparing aged >/=85 with 65-74), higher burden of comorbidity (OR = 1.05, 95% CI = 1.04-1.07 for each 1-point increase in comorbidity score), and prior use of any generic drug (OR = 1.55, 95% CI = 1.29-1.87) were positively associated with generic drug initiation. Independent of other predictors, residing in the census block group with the highest generic use was positively associated with greater odds of generic NTI drug initiation (OR = 1.24, 95% CI = 1.14-1.35 compared with the lowest quintile). CONCLUSION: Demographic, health service utilization, and geographic characteristics are important determinants of whether individuals initiate treatment with a brand-name or generic NTI drug. These factors may contribute to disparities in care and highlight potential targets for educational campaigns.
OBJECTIVES: To better understand the impact of retail clinic use on a patient's annual total cost of care. STUDY DESIGN: A propensity score matched-pair, cohort design was used to analyze healthcare spending patterns among CVS Caremark employees in the year following a visit to a MinuteClinic, the retail clinics inside CVS pharmacies. METHODS: De-identified medical and pharmacy claims for CVS Caremark employees and their dependents who received care at a retail clinic between June 1, 2009, and May 31, 2010, were matched to those of subjects who received care elsewhere. High-dimensional propensity score and greedy matching techniques were used to create a 1-to-1 matched cohort that was analyzed using generalized linear regression models. RESULTS: Individuals using a retail clinic had a lower total cost of care (-$262; 95% confidence interval, -$510 to -$31; P = .025) in the year following their clinic visit than individuals who received care in other settings. This savings was primarily due to lower medical expenses at physicians' offices ($77 savings, P = .008) and hospital inpatient care ($121 savings, P = .049). The 6022 retail clinic users also had 142 (12%) fewer emergency department visits (P = .01), though this was not related to significant cost savings. CONCLUSIONS: This study found that retail clinic use was associated with lower overall total cost of care compared with that at alternative sites. Savings may extend beyond the retail clinic visit itself to other types of medical utilization.
Value-based insurance design (VBID) is an approach that attempts to improve the quality of care by selectively encouraging or discouraging the use of specific health care services, based on their potential benefit to patients' health, relative to their cost. Lowering beneficiary cost sharing or out-of-pocket spending to increase medication adherence is one common element of value-based insurance design. We conducted a systematic review of the peer-reviewed literature to evaluate the evidence of the effects of VBID policies on medication adherence and medical expenditures. We identified thirteen studies assessing the effects of VBID programs and found that the programs were consistently associated with improved adherence (average change of 3.0 percent over one year), as well as with lower out-of-pocket spending for drugs. In the studies we reviewed, providing more generous coverage did not lead to significant changes in overall medical spending for patients and insurers. Further research is needed to understand how best to structure VBID programs to both improve quality and reduce spending.
BACKGROUND: Given the huge burden of coronary artery disease and the effectiveness of medication therapy, understanding and quantifying known impacts of poor medication adherence for primary and secondary prevention is crucial. We sought to systematically review the literature on this topic area with a focus on quantified cost and clinical outcomes related to adherence. METHODS: We conducted a systematic review of the literature between 1966 and November 2011 using a fixed search strategy, multiple reviewers, and a quality rating scale. We found 2636 articles using this strategy, eventually weaning them down to 25 studies that met our inclusion criteria. Three reviewers independently reviewed the studies and scored them for quality using the Newcastle Ottawa Scoring Scale. RESULTS: We found 5 studies (4 of which focused on statins) that measured the impact of medication adherence on primary prevention of coronary artery disease and 20 articles that focused on the relationship between medication adherence to costs and outcomes related to secondary prevention of coronary artery disease. Most of these latter studies focused on antihypertensive medications and aspirin. All controlled for confounding comorbidities and sociodemographic characteristics, but few controlled for likelihood of adherent patients to have healthier behaviors ("healthy adherer effect"). Three studies found that high adherence significantly improves health outcomes and reduces annual costs for secondary prevention of coronary artery disease (between $294 and $868 per patient, equating to 10.1%-17.8% cost reductions between high- and low-adherence groups). The studies were all of generally of high quality on the Newcastle Ottawa Scale (median score 8 of 9). CONCLUSIONS: Increased medication adherence is associated with improved outcomes and reduced costs, but most studies do not control for a "healthy adherer" effect.
BACKGROUND: Generic prescription drugs are bioequivalent to brand-name versions but may not have consistent color or shape, which can cause confusion and lead to interruptions in medication use. We sought to determine whether switching among different-appearing antiepileptic drugs (AEDs) is associated with increased rates of medication nonpersistence, which can have serious medical, financial, and social consequences. METHODS: We designed a nested case-control study of commercially insured patients in the United States who initiated an AED. Cases were patients who became nonpersistent, defined as failure to fill a prescription within 5 days of the elapsed days supplied. Controls had no delay in refilling and were matched by sex, age, number of refills, and the presence of a seizure disorder diagnosis. We evaluated the 2 refills preceding nonpersistence and determined whether pill color and/or shape matched (“concordant”) or did not match (“discordant”). We compared the odds of discordance among cases and controls using multivariate conditional logistic regression, adjusting for baseline characteristics, and drug type. We repeated our analysis among patients with a seizure diagnosis. RESULTS: The AEDs dispensed had 37 colors and 4 shapes. A total of 11 472 patients with nonpersistence were linked to 50 050 controls. Color discordance preceded 136 cases (1.20%) but only 480 controls (0.97%) (adjusted odds ratio [OR], 1.27 [95% CI, 1.04-1.55]). Shape discordance preceded 18 cases (0.16%) and 54 controls (0.11%) (OR, 1.47 [95% CI, 0.85-2.54]). Within the seizure disorder diagnosis subgroup, the risk of nonpersistence after changes in pill color was also significantly elevated (OR, 1.53 [95%, CI 1.07-2.18]). CONCLUSIONS: Changes in pill color significantly increase the odds of nonpersistence; this may have important clinical implications. Our study supports a reconsideration of current regulatory policy that permits wide variation in the appearance of bioequivalent drugs.
Non-adherence to evidence-based medications is a major public health problem. Less than 50 % of patients with coronary artery disease adhere to their prescribed therapies and this has important implications for morbidity, mortality, and health care spending. Like most complex behaviors, medication non-adherence is not solely the result of poor patient choices. Rather, there are myriad potential contributors attributable to patients, health care providers, and, more broadly, the health care system. Interventions including patient education and behavioral modification, improving patient-physician communication, and eliminating copayments for preventive pharmacotherapy have all been studied. Clinicians play a critical role in helping improve adherence and assessment of adherence must become a standard component of each clinical encounter. Ultimately, given the various etiologies that contribute to non-adherence, achieving meaningful gains will undoubtedly require payors, providers, and policymakers to develop, rigorously evaluate, and systematically deploy strategies that address key patient, clinician, and health system factors.
PURPOSE: Treatment guidelines recommend insulin progression (switching from basal to a premixed insulin regimen, adding bolus doses, and/or increasing dosing frequency) to achieve A1C targets as type 2 diabetes progresses, but fewer patients are being progressed than would be indicated based on their disease status. This systematic review proposes 2 questions regarding insulin progression among patients with type 2 diabetes: (1) What are the patient, provider, and health system barriers to insulin progression? (2) Do insulin progression barriers differ between insulin-naive and insulin-experienced patients? METHODS: We conducted a systematic review in the MEDLINE, EMBASE, Science Citation Index, PsycINFO, CINAHL, and Cochrane Library databases through July 2011.RESULTS: Of 745 potentially relevant articles, 10 met inclusion criteria: 7 evaluated patient and 2 evaluated provider barriers, and 1 was an intervention to reduce barriers among physicians. Patients with prior insulin experience had fewer barriers arising from injection-related concerns and worries about the burden of insulin progression than did insulin-naive patients. Physician barriers included concerns about patients' ability to follow more complicated regimens as well as physicians' own inexperience with insulin and progression algorithms. The cross- sectional nature, narrow scope, and failure of all studies to examine patient, provider, and health systems barriers concurrently limited both barrier identification and an assessment of their impact on progression.CONCLUSIONS: Patient and physician experience with insulin and diabetes/insulin education were associated with fewer perceived barriers to insulin progression. Future studies should use multilevel longitudinal designs to quantify the relative impact of potential patient, provider, and health system factors on progression and health outcomes.
HMG-CoA reductase inhibitors, commonly known as statins, are some of the most widely prescribed medications worldwide and have been shown to be effective at lowering cholesterol in numerous long-term prospective trials, yet there are significant limitations to their use. First, patients receiving statin therapy have relatively low levels of medication adherence compared with other drug classes. Next, numerous statin formulations are available, each with its own unique safety and efficacy profile, and it may be unclear to prescribers which treatment is optimal for their patients. Finally, statins have class-wide side effects of myopathy and rhabdomyolysis that have resulted in a product recall and dosage limitations. Recent evidence suggests that two genomic markers, KIF6 and SLCO1B1, may inform the therapy choice of patients initiating statins. Given the prevalence of statin usage, their potential health advantages and their overall cost to the healthcare system, there could be significant clinical benefit from creating personalized treatment regimens. Ultimately, if this approach is effective it may encourage higher adoption of generic statins when appropriate, promote adherence, lower rates of myopathy, and overall achieve higher value cardiovascular care. This paper will review the evidence for personalized prescribing of statins via KIF6 and SLCO1B1 and consider some of the implications for testing these markers as part of routine clinical care.
OBJECTIVES: To evaluate the association between social support and medication adherence. STUDY DESIGN: A search of articles published before November 2010 in peer-reviewed, healthcarerelated journals was conducted using PubMed, EMBASE, and Web of Science, and search terms related to social support (social support OR friend OR family OR agency) and adherence (patient compliance OR medication adherence), yielding 5331 articles. METHODS: Articles were included if they directly measured the relationship between medication adherence and some form of social support. Excluded were case studies, studies with participants < 18 years of age, and non-English language studies. Four social support categories were reported: structural, practical, emotional, and combination. Medication adherence was reported in the manner in which it was described in each study. RESULTS: Fifty studies were included in the final analysis. A greater degree of practical support was most consistently associated with greater adherence to medication; evidence for structural or emotional support was less compelling. However, most studies were limited in size and design, and substantial variability in designs and outcome measurement prohibited pooling of results, necessitating qualitative evaluation of the studies. CONCLUSIONS: This qualitative analysis found that practical social support was most consistently associated with greater medication adherence. Interventions that use existing contacts (friends or family) to engage patients in the mundane and practical aspects of medication purchasing and administration may be an effective approach to promoting better medication adherence.
BACKGROUND: Little is known about the use of warfarin in hemodialysis (HD) patients with atrial fibrillation (AF). We studied temporal trends of AF among older HD patients, and of warfarin use among those with AF. METHODS: We linked US Medicare and prescription claims from older patients undergoing HD in 2 Eastern US states. We established annual cohorts of prevalent HD patients; AF was ascertained from >2 claims (>7 days apart) in the same year, with a diagnosis code indicating AF. Among those with AF, we defined current and past warfarin use. Demographic and clinical characteristics were also ascertained for each cohort. We used repeated-measures logistic regression to define the odds of AF and of current or past versus absence of warfarin use. RESULTS: Of 6,563 unique patients, 2,185 were determined to have AF. The prevalence of AF increased from 26% in 1998 to 32% in 2005. In 2005, current warfarin use was present in 24% of AF patients and past use in 25%; 51% had no evidence of any warfarin use. No significant trends in utilization were observed from 1998 through 2005. Patients aged =85 years and nonwhites were less likely to have received warfarin; most comorbidities were not associated with warfarin use except for patients with past pulmonary embolism or deep venous thrombosis who were more likely than those without such history. CONCLUSION: While the prevalence of AF has been increasing among older HD patients, warfarin use was low and unchanged over time, perhaps reflecting the lack of evidence supporting its use.
BACKGROUND: Although consensus guidelines recommend insulin progression among patients with type 2 diabetes (T2DM) who fail to meet glycemic targets over time, many fewer patients are progressed than may benefit. We describe the rationale and design of the MOSAIc (Multinational Observational Study Assessing Insulin use) study, a multinational observational cohort study to identify patient-, physician, and health care environment-based factors associated with insulin progression for patients with T2DM in real-world practice. Methods/design We will enroll 4,500 patients with T2DM taking initial insulin therapy for [greater than or equal to]3 months across 175 physician practice sites in 18 countries. Extensive demographic, clinical, and psychosocial data at the patient and physician level and practice site characteristics will be collected at baseline and regular intervals during a 24-month follow-up period. We will use a multivariable logistic regression model to identify predictors of insulin progression and highlight potential opportunities for health behavior intervention to improve insulin progression rates. Secondary outcomes include evaluating factors associated with glycemic control, hypoglycemia, and treatment adherence among patients who do and do not progress beyond their initial insulin therapy and exploring geographic heterogeneity in treatment. DISCUSSION: Practice site and patient recruitment began in 2011 and baseline data will be available in late 2012. The MOSAIC study's longitudinal observational design as well as the breadth and depth of data will be used to explore and quantify predictors of insulin progression and to identify potential opportunities for health behavior intervention in order to improve T2DM treatment and clinical outcomes.
Given rising pharmaceutical expenditures and the widespread use of reference pricing as a costcontainment instrument abroad, we systematically reviewed the evidence evaluating reference pricing policies. We performed a structured electronic search of peer-reviewed journals for studies published before that reported on the effects of reference pricing policies on medication use, payer and patient spending, and resource consumption. Our search yielded 16 studies describing 9 reference-pricing policies from 6 countries. Reference-pricing policies led to decreases in drug prices and increases in utilization of targeted medications, while also reducing payer and patient expenditures. In addition, these policies did not lead to increased use of medical services, such as physician office visits and hospitalization. These results suggest that reference pricing may be an attractive policy strategy for the US healthcare system.
BACKGROUND: Controversy exists regarding the optimal preventative therapy for venous thromboembolism (VTE) after coronary artery bypass graft (CABG) surgery. We sought to compare the effectiveness and safety of the most commonly used regimens. METHODS AND RESULTS: We assembled a cohort of 92 699 patients who underwent CABG between 2004 and 2008, using the Premier database. Patients were categorized by method of VTE prevention initiated within 48 hours of surgery, including no preventative therapy (n=55 400), mechanical preventative therapy (n=21 162), subcutaneous unfractio--nated or low-molecular-weight heparin (n=10 718), subcutaneous fondaparinux (n=88), and concurrent mechanical-chemical therapy (n=5331). The incidence of VTE and major bleeding events within 6 weeks of CABG were compared, using multivariable and propensity score adjustment. The overall incidence of VTE for the entire cohort was 0.74%, and the incidence of major bleeding was 1.43%. VTE and bleeding events occurred with similar incidence in each of the patient categories (VTE: 0.70%, 0.79%, 0.81%, 1.14%, and 0.73%; major bleeding: 1.36%, 1.45%, 1.69%, 3.41%, 1.50%; no prevention, mechanical prevention, subcutaneous heparin, subcutaneous fondaparinux, concurrent mechanical-chemical prevention, respectively). Compared with receiving no prevention, the use of mechanical prevention or subcutaneous heparin did not significantly reduce the risk of VTE or change the risk of major bleeding (P=NS). CONCLUSION: Venous thromboembolism occurs infrequently after CABG. Compared with the use of no prevention, the administration of chemical or mechanical preventative therapies to CABG patients does not appreciably lower the risk of VTE. These data provide support for the common practice of administering no VTE preventative therapy after CABG, used for nearly 60% of patients within this cohort.
BACKGROUND: Dabigatran, an oral thrombin inhibitor, and rivaroxaban and apixaban, oral factor Xa inhibitors, have been found to be safe and effective in reducing stroke risk in patients with atrial fibrillation. We sought to compare the efficacy and safety of the 3 new agents based on data from their published warfarin-controlled randomized trials, using the method of adjusted indirect comparisons. METHODS AND RESULTS: We included findings from 44 535 patients enrolled in 3 trials of the efficacy of dabigatran (Randomized Evaluation of Long-Term Anticoagulation Therapy [RELY]), apixaban (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]), and rivaroxaban (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation [ROCKET-AF]), each compared with warfarin. The primary efficacy end point was stroke or systemic embolism; the safety end point we studied was major hemorrhage. To address a lack of comparability between trial populations caused by the restriction of ROCKET-AF to high-risk patients, we conducted a subgroup analysis in patients with a CHADS(2) score >/=3. We found no statistically significant efficacy differences among the 3 drugs, although apixaban and dabigatran were numerically superior to rivaroxaban. Apixaban produced significantly fewer major hemorrhages than dabigatran and rivaroxaban. CONCLUSIONS: An indirect comparison of new anticoagulants based on existing trial data indicates that in patients with a CHADS(2) score >/=3 dabigatran 150 mg, apixaban 5 mg, and rivaroxaban 20 mg resulted in statistically similar rates of stroke and systemic embolism, but apixaban had a lower risk of major hemorrhage compared with dabigatran and rivaroxaban. Until head-to-head trials or large-scale observational studies that reflect routine use of these agents are available, such adjusted indirect comparisons based on trial data are one tool to guide initial therapeutic choices.
BACKGROUND: Acute kidney injury is a frequent postoperative complication that confers increased mortality, morbidity, and costs. The purpose of this study was to evaluate whether preoperative statin use is associated with a decreased risk of postoperative acute kidney injury. METHODS: We assembled a retrospective cohort of 98,939 patients who underwent a major open abdominal, cardiac, thoracic, or vascular procedure between 2000 and 2010. Statin users were pair-matched to nonusers on the basis of surgery type, baseline kidney function, days from admission until surgery, and propensity score based on demographics, comorbid conditions, and concomitant medications. Acute kidney injury was defined based on changes in serum creatinine measurements applying Acute Kidney Injury Network and Risk-Injury-Failure staging systems, and on the need for renal replacement therapy. Associations between statin use and acute kidney injury were estimated by conditional logistic regression. RESULTS: Across various acute kidney injury definitions, statin use was consistently associated with a decreased risk: adjusted odds ratios (95% confidence intervals) varied from 0.74 (0.58-0.95) to 0.80 (0.71-0.90). Associations were similar among diabetics and nondiabetics, and across strata of baseline kidney function. The protective association of statins was most pronounced among patients undergoing vascular surgery and least among patients undergoing cardiac surgery. CONCLUSIONS: Preoperative statin use is associated with a decreased risk of postoperative acute kidney injury. Future randomized clinical trials are needed to determine causality.
OBJECTIVES: The aim of this study was to evaluate the impact of reductions in statin and clopidogrel copayments on cardiovascular resource utilization, major coronary events, and insurer spending. BACKGROUND: Copayments are widely used to contain health spending but cause patients to reduce their use of essential cardiovascular medications. Reducing copayments for post-myocardial infarction secondary prevention has beneficial effects, but the impact of this strategy for lower risk patients and other drugs remains unclear. METHODS: An evaluation was conducted of health care spending and resource use by a large self-insured employer that reduced statin copayments for patients with diabetes or vascular disease and reduced clopidogrel copayments for all patients prescribed this drug. Eligible individuals in the intervention company (n = 3,513) were compared with a control group from other companies without such a policy (n = 49,803). Analyses were performed using segmented regression models with generalized estimating equations. RESULTS: Lowering copayments was associated with significant reductions in rates of physician visits (relative change: statin users 0.80; 95% confidence interval [CI]: 0.57 to 0.98; clopidogrel users: 0.87; 95% CI: 0.59 to 0.96) and hospitalizations and emergency department admissions (relative change: statin users 0.90; 95% CI: 0.80 to 0.92; clopidogrel users: 0.89; 95% CI: 0.74 to 0.90) although not major coronary events. Patient out-of-pocket spending for drugs and other medical services decreased (relative change: statin users 0.79; 95% CI: 0.75 to 0.83; clopidogrel users 0.74; 95% CI: 0.66 to 0.82). Providing more generous coverage did not increase overall spending (relative change: statin users 1.03; 95% CI: 0.97 to 1.09; clopidogrel users 0.94; 95% CI: 0.87 to 1.03). CONCLUSIONS: Lowering copayments for statins and clopidogrel was associated with reductions in health care resource use and patient out-of-pocket spending. The policy appeared cost neutral with respect to overall health spending.
To the Editor: Direct-to-consumer advertising (DTCA) can influence the use of prescription drugs.1,2 The US Food and Drug Administration (FDA) regulates prescription drug advertising, including requirements to provide consumers with a ‚"fair balance"‚ of risks and benefits. When prescription drugs switch to over-the-counter (OTC) status, regulatory oversight of their advertising shifts to the Federal Trade Commission (FTC). Unlike the FDA, the FTC holds drug advertisements to the same standards as any consumer product: it applies a ‚"reasonable consumer"‚ standard of truthfulness and nondeception that does not require any balancing of potential benefits and harms. Such a shift may be associated with changes in content.
On January 31, 2012, Pfizer recalled nearly 1 million packs of birth control pills because of concerns that inert and active pills were miscounted and incorrectly ordered in their blister packs.1 This and other recent recalls highlight concerns about the potential clinical impact of defective and otherwise compromised drug products. However, little is known about the public health burden of drug recalls and whether health care providers are properly notified about clinically important recalls. We sought to quantify the frequency, cause, and extent of distribution of drug recalls in the United States and to evaluate the processes by which the US Food and Drug Administration (FDA) communicates clinically important recall information to health care providers.