Understanding and improving value frameworks with real-world patient outcomes.

OBJECTIVES: To provide recommendations that will improve approaches to measuring the value of new medical technologies to patients. STUDY DESIGN: Informed discussion by experts after literature review. METHODS: A working group was formed, and participants discussed how value frameworks should incorporate key features important to patients in evaluating new medical technologies, particularly for chronic diseases. RESULTS: The working group suggests that new value frameworks should integrate real-world evidence to complement randomized controlled trials, incorporate the ways in which real-world behavior mediates outcomes, and explicitly discuss how therapies affect real-world equity and disparities in care. CONCLUSIONS: Collective stakeholders that include key decision makers within our healthcare system need to recognize the importance of implementing real-world evidence and devote resources to further research into the chronic disease areas in which the impact of human behavior is amplified by the duration of disease and treatment.

Impact of performance improvement continuing medical education on cardiometabolic risk factor control: the COSEHC initiative.

INTRODUCTION: The Consortium for Southeastern Hypertension Control (COSEHC) implemented a study to assess benefits of a performance improvement continuing medical education (PI CME) activity focused on cardiometabolic risk factor management in primary care patients. METHODS: Using the plan-do-study-act (PDSA) model as the foundation, this PI CME activity aimed at improving practice gaps by integrating evidence-based clinical interventions, physician-patient education, processes of care, performance metrics, and patient outcomes. The PI CME intervention was implemented in a group of South Carolina physician practices, while a comparable physician practice group served as a control. Performance outcomes at 6 months included changes in patients' cardiometabolic risk factor values and control rates from baseline. We also compared changes in diabetic, African American, the elderly (> 65 years), and female patient subpopulations and in patients with uncontrolled risk factors at baseline. RESULTS: Only women receiving health care by intervention physicians showed a statistical improvement in their cardiometabolic risk factors as evidenced by a -3.0 mg/dL and a -3.5 mg/dL decrease in mean LDL cholesterol and non-HDL cholesterol, respectively, and a -7.0 mg/dL decrease in LDL cholesterol among females with uncontrolled baseline LDL cholesterol values. No other statistical differences were found. DISCUSSION: These data demonstrate that our PI CME activity is a useful strategy in assisting physicians to improve their management of cardiometabolic control rates in female patients with abnormal cholesterol control. Other studies that extend across longer PI CME PDSA periods may be needed to demonstrate statistical improvements in overall cardiometabolic treatment goals in men, women, and various subpopulations.

Antipsychotic adherence and its correlation to health outcomes for chronic comorbid conditions.

OBJECTIVE: To examine the relationship between adherence to antipsychotics and adherence to medications for cardiometabolic conditions (diabetes, hypertension, and hyperlipidemia) and subsequent health care utilization and expenditures in patients with schizophrenia and preexisting cardiometabolic conditions. METHOD: Medstat MarketScan Medicaid databases from 2004 to 2008 were used to identify a retrospective cohort of schizophrenia patients (ICD-9-CM codes 295.1-295.3, 295.6, or 295.9) with preexisting cardiometabolic medication use who had initiated antipsychotic treatments. Patients who initiated a second-generation antipsychotic between July 1, 2004, and December 31, 2006, were identified as the new user cohort. Comorbid conditions were identified if patients had at least 1 inpatient or 2 outpatient claims for hypertension, hyperlipidemia, and/or diabetes (ICD-9-CM codes 401.xx to 405.xx inclusive, 272.xx inclusive, and 250.xx inclusive, respectively) and were using medication to manage these conditions prior to antipsychotic initiation. Adherence to cardiometabolic medications was compared between adherent and nonadherent patients taking antipsychotics using the proportion of days covered over 8 quarters categorized as phases of treatment to reflect initiation (1, days 1-90), continuation (2-4, days 91-360), and maintenance (5-8, days 361-520). Proportion of days covered values ≥ 0.80 were deemed adherent. Prior period antipsychotic adherence was used to predict cardiometabolic medication adherence, health care utilization, and expenditures using generalized estimating equations and negative binomial regressions. RESULTS: The final population represented 1,006 patients. Antipsychotic adherence during continuation was a significant predictor of medication adherence for hypertension (odds ratio [OR] = 2.40, 95% CI = 1.67-3.44), diabetes (OR = 2.28, 95% CI = 1.43-3.67), and hyperlipidemia (OR = 2.16, 95% CI = 1.11-4.20) during maintenance. Antipsychotic adherence during continuation resulted in significantly lower emergency room use (OR = 0.67, 95% CI = 0.52-0.87), lower inpatient use (OR = 0.77, 95% CI = 0.56-1.06, not significant), and significantly higher outpatient ($996, 95% CI = $663-$1,330), medication ($652, 95% CI = $542-$762), and total health ($1,371, 95% CI = $490-$2,252) expenditures during maintenance. CONCLUSION: Antipsychotic adherence was associated with better adherence to cardiometabolic medications and a potential reduction in emergency room and inpatient service utilization. Clinicians should consider adherence to both antipsychotic and cardiometabolic medications when caring for patients with schizophrenia and comorbid conditions.

Adherence to antipsychotics and cardiometabolic medication: association with health care utilization and costs.

OBJECTIVE: This study examined the association between adherence to antipsychotic and cardiometabolic medication and annual use of health care services and expenditures. METHODS: MarketScan Medicaid files from 2004 to 2008 were used to evaluate annual cross-sections of patients with schizophrenia and diabetes, hypertension, or hyperlipidemia. Annual adherence to antipsychotic and cardiometabolic medication was defined as a score of at least 80% on proportion of days covered. Logistic regression was used to examine the association between antipsychotic adherence and adherence to cardiometabolic medications. Count data models and generalized linear models estimated health care utilization and health care expenditures, respectively, for outpatient, emergency, inpatient, and overall health services. RESULTS: A total of 87,015 unique patients with schizophrenia received at least one antipsychotic medication. The overall prevalence of any comorbid cardiometabolic condition was 42.9% in 2004 and increased to 52.5% in 2008. Adherence to cardiometabolic medications was significantly greater among patients who were adherent to antipsychotic medications (adjusted odds ratio=6.9). Adjusted annual expenditures for emergency and inpatient care were higher for patients who were nonadherent to either antipsychotics or cardiometabolic medications than for patients who were adherent to antipsychotic and cardiometabolic medications. They were highest for patients who were nonadherent to both groups of medications. Outpatient, medication, and overall expenditures were lower for patients who were nonadherent to antipsychotic medications, regardless of cardiometabolic medication adherence. CONCLUSIONS: Among Medicaid patients with schizophrenia, cardiometabolic conditions are common, and adherence to antipsychotics and adherence to cardiometabolic medications are strongly related. Interventions that can improve medication adherence to treatment of both schizophrenia and comorbid cardiometabolic conditions may reduce emergency visits and hospitalizations.

Initial monotherapy and combination therapy and hypertension control the first year.

Initial antihypertensive therapy with single-pill combinations produced more rapid blood pressure control than initial monotherapy in clinical trials. Other studies reported better cardiovascular outcomes in patients achieving lower blood pressure during the first treatment year. We assessed the effectiveness of initial antihypertensive monotherapy, free combinations, and single-pill combinations in controlling untreated, uncontrolled hypertensives during their first treatment year. Electronic record data were obtained from 180 practice sites; 106 621 hypertensive patients seen from January 2004 to June 2009 had uncontrolled blood pressure, were untreated for ≥ 6 months before therapy, and had ≥ 1 one-year follow-up blood pressure data. Control was determined by the first follow-up visit with blood pressure <140/<90 mm Hg for patients without diabetes mellitus or chronic kidney disease and <130/<80 mm Hg for patients with either or both conditions. Multivariable hazards regression ratios (HRs) and 95% CIs for time to control were calculated, adjusting for age, sex, baseline blood pressure, body mass index, diabetes mellitus, chronic kidney disease, cardiovascular disease, initial therapy, final blood pressure medication number, and therapeutic inertia. Patients on initial single-pill combinations (N = 9194) were more likely to have stage 2 hypertension than those on free combinations (N = 18 328) or monotherapy (N = 79 099; all P<0.001). Initial therapy with single-pill combinations (HR, 1.53 [95% CI, 1.47-1.58]) provided better hypertension control in the first year than free combinations (HR, 1.34; [95% CI, 1.31-1.37]) or monotherapy (reference) with benefits in black and white patients. Greater use of single-pill combinations as initial therapy may improve hypertension control and cardiovascular outcomes in the first treatment year.

Indirect costs associated with nonadherence to treatment for bipolar disorder.

OBJECTIVE: To examine the association between treatment adherence and indirect productivity costs within a cohort of commercially insured employees with bipolar disorder in the United States. METHODS: Adults diagnosed with bipolar disorder who had at least one prescription claim for a mood stabilizer or atypical antipsychotic, with 6 months prior and 12 months subsequent continuous medical and prescription coverage, were identified in the MarketScan research databases (2000-2005). Two-part multiple regression models estimated the association between adherence (medication possession ratio > or =0.80) and costs of absence, short-term disability, and workers' compensation. RESULTS: Of 1258 eligible employees, only 35.3% were adherent. Relative to adherent employees, nonadherent employees had higher adjusted indirect costs due to absence (+$771.41), short-term disability (+$284.72), and workers' compensation (+$360.63). CONCLUSIONS: Employers incur greater indirect costs when employees are not adherent to bipolar treatment.

Evidence that value-based insurance can be effective.

Value-based insurance design reduces patient copayments to encourage the use of health care services of high clinical value. As employers face constant pressure to control health care costs, this type of coverage has received much attention as a cost-savings device. This paper's examination of one value-based insurance design program found that the program led to reduced use of nondrug health care services, offsetting the costs associated with additional use of drugs encouraged by the program. The findings suggest that value-based insurance design programs do not increase total systemwide medical spending.

A framework for planning and critiquing medication compliance and persistence research using prospective study designs.

BACKGROUND: Medication compliance and persistence are important determinants of clinical outcomes. With the application of evidence-based therapy, it is increasingly important to ensure that studies that use compliance or persistence as a primary or secondary outcome are designed suitably and employ appropriate analyses to support the inferences made. OBJECTIVE: The aim of this work was to describe the designs of medication compliance/persistence studies and provide guidance on appropriate analyses, with the ultimate goal of helping health providers and payers of health care understand the impact of compliance and persistence on health outcomes. METHODS: MEDLINE, CINAHL, EMBASE, and all EBM Reviews databases were searched to locate key research articles about prospective medication compliance and persistence studies. Articles published between 1978 and 2008 were included in the search. Inclusion criteria included a focus on medication compliance and persistence, and prospective research designs. Articles that largely focused on retrospective study designs or were based on opinion rather than evidence were excluded. RESULTS: A systematic framework was developed that comprised a prospective checklist and a quantitative tool to assess the quality of studies. The key elements of the checklist included the following: title and abstract, introduction or background, objectives, methods and study design, statistical analysis and results, discussion, conclusions, and disclosure of conflicts of interest. For each element, examples are provided to help readers make an informed decision about the design, value, and quality of a particular prospective study. CONCLUSIONS: The checklist and quantitative tool can be used to provide objective validation of the rigor of prospective research designs. It is anticipated that future research will follow a uniform approach to presentation and evaluation of data, thereby facilitating a clear understanding of the impact of compliance and persistence on health outcomes.

Further testing of the reliability and validity of the ASK-20 adherence barrier questionnaire in a medical center outpatient population .

OBJECTIVE: This study examined the psychometric properties of the ASK-20 questionnaire, which was developed to assess barriers to medication adherence. RESEARCH DESIGN AND METHODS: Patients with asthma, diabetes, and congestive heart failure were recruited from a university medical center. Participants in this convenience sample completed the ASK-20 questionnaire and other questionnaires. Approximately one-third of participants were randomized to a 2-week retest administration. Analyses examined the reliability and validity of the ASK-20. RESULTS: A total of 112 patients participated (75.9% female; mean age = 46.7 years). The ASK-20 had good internal consistency reliability (Cronbach's alpha = 0.76) and test-retest reliability (0.80). Concurrent validity was demonstrated through significant correlations with the Morisky Medication Adherence Scale (r = -0.61, p < 0.001), condition-specific measures, and the SF-12 Mental Component Summary score (r = -0.40, p < 0.001). The correlation of the ASK-20 with proportion of days covered by filled medication prescriptions in the past 6 months (based on pharmacy claims) was relatively weak (r = -0.13), but in the expected direction. The ASK-20 total score significantly discriminated among groups of patients who differed in self-reported indicators including the Morisky score; missing a medication dose in the past week; number of days medication was not taken as directed; and treatment satisfaction. CONCLUSION: The ASK-20 demonstrated adequate reliability and validity, and it may be a useful measure of barriers to treatment adherence across a spectrum of chronic diseases. Limitations related to scale construction, lack of longitudinal data, and item characteristics are discussed.

Development of the ASK-20 adherence barrier survey.

OBJECTIVE: Poor medication adherence is widespread among patients with chronic conditions requiring long-term drug therapy. Medication adherence is determined by multiple patient-, context-, and therapy-dependent factors. This paper describes the development and initial validation of the ASK-20 survey, created to identify actionable risk factors for medication nonadherence and to improve communication about adherence. METHODS: A pool of 30 items was generated through comprehensive literature review. Items were refined and the item pool was expanded through an expert panel review and patient focus groups to yield 47 candidate items, each with five response options ranging from either Strongly Agree to Strongly Disagree or from In the Last Week to Never. The pool of 47 candidate items was administered to a web-based sample of 605 patients taking medications and reporting a diagnosis of asthma, diabetes, or depression for psychometric testing and item reduction. RESULTS: Eleven multi-item factor groupings with two additional unique items were identified on the basis of principal components analysis and interpretability. Twenty (20) items representing ten factor groupings were selected for the final instrument. Each of the final items was dichotomized as positive - indicating a barrier, or negative. Two summary scores - the sum of all positive barriers or Total Barrier Count (TBC) and the sum of raw item scores, the ASK-20 score - were calculated. Concurrent validity of the dichotomously scored individual items, the TBC and ASK-20 scores in relation to self-reported adherence was generally good. Cronbach's alpha coefficient was 0.77 for the TBC and 0.85 for the ASK-20 score. CONCLUSIONS: ASK-20 consists of 20 clinically actionable items representing multiple factors that affect medication adherence. The ASK-20 survey demonstrated satisfactory validity and internal consistency and may be used to identify actionable barriers to adherence across a spectrum of chronic diseases. Future research using more objective measures of adherence is warranted to confirm the exploratory validity and reliability of ASK-20 reported in this study.

The effects of health plan copayments on adherence to oral diabetes medication and health resource utilization.

OBJECTIVE: To assess the effects of copayments on oral diabetes medication adherence, health resource utilization, and expenditure. METHODS: Retrospective, observational analysis of medical and pharmacy claims data from PPG Industries employees, retirees, and dependents (2003-2005). Average monthly copayments were stratified low (US$0-9), medium (US$10-19), or high (US$20+). RESULTS: In 2052 individuals, adherence to oral diabetes medication was highest for the low copayment group for both age groups >or=65 years; 84% low, 77% medium, 64% high (P < 0.0001) and <65 years; 74% low, 71% medium, 55% high (P < 0.0001). For patients <65 years, total health care expenditure was 22% lower in the low versus high copayment group (P = 0.024), resulting in average savings of US $3116 per patient per year. Risk of hospitalization was significantly lower in the low versus the high copayment group for patients >or=65 years of age. CONCLUSIONS: High copayments were associated with lower adherence to oral diabetes medications for all patients and higher total health care costs for patients less than 65.

Effects of increased patient cost sharing on socioeconomic disparities in health care.

BACKGROUND: Increasing patient cost sharing is a commonly employed mechanism to contain health care expenditures. OBJECTIVE: To explore whether the impact of increases in prescription drug copayments differs between high- and low-income areas. DESIGN: Using a database of 6 million enrollees with employer-sponsored health insurance, econometric models were used to examine the relationship between changes in drug copayments and adherence with medications for the treatment of diabetes mellitus (DM) and congestive heart failure (CHF). SUBJECTS: Individuals 18 years of age and older meeting prespecified diagnostic criteria for DM or CHF were included. MEASUREMENTS: Median household income in the patient's ZIP code of residence from the 2000 Census was used as the measure of income. Adherence was measured by medication possession ratio: the proportion of days on which a patient had a medication available. RESULTS: Patients in low-income areas were more sensitive to copayment changes than patients in high- or middle-income areas. The relationship between income and price sensitivity was particularly strong for CHF patients. Above the lowest income category, price responsiveness to copayment rates was not consistently related to income. CONCLUSIONS: The relationship between medication adherence and income may account for a portion of the observed disparities in health across socioeconomic groups. Rising copayments may worsen disparities and adversely affect health, particularly among patients living in low-income areas.

In chronic disease, nationwide data show poor adherence by patients to medication and by physicians to guidelines.

PURPOSE: It is widely acknowledged in small studies that provider variation from evidence-based care guidelines and patient medication nonadherence lead to less than optimal health outcomes, increasing costs, and higher utilization. The research presented here aims to determine the prevalence of patient adherence to a medication regimen and provider adherence to guidelines for a variety of chronic conditions, using nationally representative data. DESIGN: A retrospective analysis of administrative claims data from a large national insurer was conducted. METHODOLOGY: The study examined multiple quality indicators exemplifying evidence-based medicine and medication adherence for several chronic conditions. Medication possession ratio (MPR) determined patient adherence. Using EBM Connect software created by Ingenix, we measured adherence to guidelines by applying a series of clinical rules and algorithms. PRINCIPAL FINDINGS: Adherence to the evidence-based practice guidelines examined in this study averaged approximately 59 percent, while patient medication nonadherence rates for all the conditions studied averaged 26.2 percent, with a range of 11 percent to 42 percent. Physician adherence to guidelines was highest in the prescribing of inhaled corticosteroids for persistent asthma. Ironically, medication adherence rates for inhaled corticosteroids were the worst identified. The best medication adherence rate was observed in patients with hypertension. CONCLUSION: Like earlier studies, this analysis finds that poor adherence is common across the nation and across common chronic conditions.

Impact of decreasing copayments on medication adherence within a disease management environment.

This paper estimates the effects of a large employer's value-based insurance initiative designed to improve adherence to recommended treatment regimens. The intervention reduced copayments for five chronic medication classes in the context of a disease management (DM) program. Compared to a control employer that used the same DM program, adherence to medications in the value-based intervention increased for four of five medication classes, reducing nonadherence by 7-14 percent. The results demonstrate the potential for copayment reductions for highly valued services to increase medication adherence above the effects of existing DM programs.

Comparison of costs and utilization between users of insulin lispro versus users of regular insulin in a managed care setting.

OBJECTIVE: To compare medical and pharmacy costs and utilization between patients with diabetes who received insulin lispro versus regular human insulin. METHODS: A retrospective analysis of medical and pharmacy claims was conducted among continuously enrolled users of insulin lispro or regular insulin during the identification period, March 1, 2000, through February 28, 2001, within a large managed care organization. This study improved upon the methodology used in previous studies by (a) stratifying (rather than 1:1 matching) individuals by their likelihood to use insulin lispro using the propensity score binning technique, and (b) refining the study inclusion criteria to include only patients with 3 or more fills of the insulin under study (lispro or regular) to exclude individuals who may have been on either product for a short time. Because the propensity score binning technique groups patients with similar baseline characteristics within strata (bins) and not among individual patients, almost the entire available sample is retained in the analysis, unlike propensity score matching, where large numbers of patients can be excluded depending on the matching scheme. Therefore, the propensity score binning technique, because it uses more complete information, is less likely to produce biased results. Patients were grouped into 5 bins (quintiles) based on their estimated likelihood to receive insulin lispro rather than regular insulin. The propensity score model used baseline characteristics of age, gender, comorbidities, use of oral antidiabetic medications, prescription copayment, and diabetes-related costs and utilization. Overall cost and utilization differences (lispro minus regular insulin) during the 12-month follow-up period were calculated using weights inversely proportional to variances of within-bin differences. RESULTS: Of 6,436 patients, 1,972 (30.6%) received insulin lispro and 4,464 (69.4%) received regular insulin. The propensity score estimation produced 5 bins, each containing between 1,287 and 1,288 patients, utilizing all patients in the analysis. Patients in the lower-numbered propensity score quintiles were older, more likely to use oral antidiabetic medications, and had more comorbidities than those in the higher-numbered quintiles. As quintile number increased, the percentage of insulin lispro users also increased. The weighted mean annual cost difference (lispro minus regular insulin) per patient was + USD 79 (P < 0.001) for diabetes-related pharmacy cost, + USD 212 (P < 0.001) for total pharmacy cost, USD 75 (P < 0.857) for diabetes-related medical cost, USD 2,286 (P <0.011) for nondiabetes medical cost, and USD 2,327 (P = 0.072) for total medical cost. CONCLUSIONS: Compared with regular insulin users, insulin lispro users incurred higher diabetes-related and total pharmacy costs but lower nondiabetes medical costs and similar total medical costs. Fewer hospitalizations among insulin lispro as compared with regular insulin users contributed to lower nondiabetes medical costs and similar total medical costs.

Acute and continuation treatment adequacy with venlafaxine extended release compared with fluoxetine.

STUDY OBJECTIVE: To compare treatment adequacy in the management of depression during the acute and continuation phases between patients newly treated with venlafaxine extended release (XR) and those newly treated with fluoxetine. DESIGN: Retrospective observational analysis of pharmacy claims data. SETTING: Large California-based managed care organization. PATIENTS: A total of 11,298 patients newly prescribed venlafaxine XR or fluoxetine between January 1, 2000, and February 28, 2001, and continuously enrolled throughout the study, as well as a subset of 7430 patients who continued taking venlafaxine XR or fluoxetine during the follow-up period. MEASUREMENTS AND MAIN RESULTS: The Health Plan Employer Data and Information Set definition was used for continuous antidepressant treatment during the acute and continuation phases. Treatment adequacy was determined for those deemed continuous. Patients receiving within +/- 10% of the target dose for each drug (venlafaxine XR 75-150 mg, fluoxetine 20 mg) were defined as receiving an adequate dose. Logistic regression was used to evaluate venlafaxine XR versus fluoxetine on treatment adequacy, controlling for age, sex, physician specialty, and pharmacy benefit. The unadjusted adequacy rate for the venlafaxine XR-only group was 79% versus 57% for the fluoxetine-only group for 84 continuous days (p<0.0001) and 77% versus 52%, respectively, for 180 continuous days (p<0.0001). The adjusted odds ratios of achieving treatment adequacy with venlafaxine XR only versus that with fluoxetine only were 3.05 (95% confidence interval [CI] 2.65-3.52) for 84 continuous days and 3.57 (95% CI 3.00-4.24) for 180 continuous days. CONCLUSION: Patients newly prescribed venlafaxine XR were at least 3 times more likely to achieve treatment adequacy for 84 and 180 days compared with those newly prescribed fluoxetine. Treatment adequacy as a proxy for optimal treatment may be an important factor to consider when selecting an antidepressant drug.