A path to improve colorectal cancer screening outcomes: faculty roundtable evaluation of cost-effectiveness and utility.

The American Journal of Managed Care® and Exact Sciences Corporation hosted a roundtable meeting to discuss the impact of colorectal cancer (CRC) screening modalities on improving patient outcomes. The roundtable participants were a diverse panel of experts, including primary care, gastroenterology, and oncology providers; experts in health outcomes research and health policy; and managed care executives with commercial and public payer experience. Participants discussed CRC prevention and treatment strategies, screening modalities and adherence, molecular diagnostics, patient navigation, evaluation of large data sets, managed care, outcomes research, quality improvement, and reimbursement policies. They focused on developing better value-based medical policies and payment procedures, identifying knowledge, practice, and access deficits related to CRC screening. Participants also provided suggestions on how to improve care quality and patient outcomes through effective evidence-based approaches. They also discussed costeffectiveness modeling for CRC screening, specifically the advantages and the real-world limitations of these models.

Value-Based Benefit Design to Improve Medication Adherence for Employees with Anxiety or Depression.

BACKGROUND: Through reduced out-of-pocket costs and wellness offerings, value-based benefit design (VBBD) is a promising strategy to improve medication adherence and other health-related outcomes across populations. There is limited evidence, however, of the effectiveness of these policy-level changes among individuals with anxiety or depression. OBJECTIVES: To assess the impact of a multifaceted VBBD policy that incorporates waived copayments, wellness offerings, and on-site services on medication adherence among plan members with anxiety or depression, and to explore how this intervention and its resulting improved adherence affects other health-related outcomes. METHODS: A retrospective longitudinal pre/post design was utilized to measure outcomes before and after the VBBD policy change. Repeated measures statistical regression models with correlated error terms were utilized to evaluate outcomes among employees of a self-insured global health company and their spouses (N = 529) who had anxiety or depression after the VBBD policy change. A multivariable linear regression model was chosen as the best fit to evaluate a change in medication possession ratio (MPR) after comparing parameters for several distributions. The repeated measures multivariable regression models were adjusted for baseline MPR and potential confounders, including continuous age, sex, continuous modified Charlson Comorbidity Index, and the continuous number of prescriptions filled that year. The outcomes were assessed for the 1 year before the policy change (January 1, 2011, through December 31, 2011) and for 2 years after the change (January 1, 2012, through December 31, 2013). The primary outcome was a change in MPR. The secondary outcomes included healthcare utilization, medical or pharmacy costs, the initiation of medication, generic medication use, and employee absenteeism (the total number of sick days). RESULTS: The implementation of the VBBD strategy was associated with a significant increase in average MPR (0.65 vs 0.61 in the pre-VBBD period; P = .004), the initiation of new medications for anxiety or depression (31.4% vs 29.5%, respectively; P = .033), and the filling of generic medications for anxiety or depression (85.1% vs 80.5%, respectively; P <.001). A multivariable adjusted analysis revealed a 0.05 increase in MPR after the benefit enhancement (P = .002). Healthcare utilization, costs, and absenteeism were not statistically different before and after the VBBD policy change. CONCLUSION: The VBBD strategy was associated with improved medication adherence and cost-conscious medication use. Future analyses should explore whether these trends persist over time, and if they can further impact healthcare utilization, cost, and absenteeism.

Impact of Employer-Sponsored Onsite Pharmacy and Condition Management Programs on Medication Adherence.

BACKGROUND: Poor medication adherence is associated with worsened health outcomes and higher health care expenditures. An increasing number of employers are sponsoring wellness initiatives designed to support healthy lifestyles, improve productivity, and offer a return on investment. Onsite pharmacies may facilitate higher medication adherence rates by providing employees a convenient, low-cost option for filling prescriptions that is integrated with other onsite health services. OBJECTIVES: To (a) assess the impact of an employer's onsite pharmacy on health plan members' medication adherence using multiple measures of medication adherence and persistence, including medication possession ratio (MPR), average number of days until discontinuation (60-day gap in coverage), and percentage of members without a 30-day gap in coverage, and (b) evaluate these outcomes between those members who participated in condition management programs and those who did not. METHODS: A retrospective analysis of a self-insured employer's claims data was undertaken. Medication adherence was assessed among the self-insured employer's health plan members, which included subscribers and their dependents who filled an asthma, depression, diabetes, hypertension, or hyperlipidemia medication at an onsite pharmacy, compared with those who used a community pharmacy. Multiple standard measures of medication adherence were considered. These measures included MPR, which was assessed for 1- and 2-year time periods. MPR was chosen because it is one of the most commonly referenced formulas in the literature and represents adherence over a fixed period of time. In addition, medication persistence was estimated by 30-day gaps in coverage and discontinuation of treatment. To assess the impact of onsite pharmacy use and account for covariate effects, the linear mixed model approach was applied with the logit transformed MPR as the response variable. An analysis of MPR among condition management participants was also performed. RESULTS: In total, 2,498 subscribers and their dependents were included in the analysis. The average MPR at 365 days was significantly higher (P < 0.0001) among onsite pharmacy users for all medication types, ranging from 13% higher for depression medications to 20% higher for hypertension medications. This trend persisted at 730 days (P < 0.001), with average MPRs ranging from 6% higher for hyperlipidemia medications to 11% higher for hypertension medications. A mixed model analysis indicated that members who used the onsite pharmacy were 3.44 times more likely to demonstrate medication adherence (95% CI = 2.84-4.16; P < 0.0001) at 365 days. Likewise, at 180 and 365 days, onsite pharmacy users were less likely to have 30-day gaps in treatment. The average number of days until discontinuation (defined as a 60-day gap) was also significantly longer (P < 0.0001) among onsite pharmacy users, ranging from an average of 56 additional days for depression medications to 105 additional days for hypertension medications. While the average MPR tended to be higher among those subscribers and their dependents who participated in condition management programs, this trend was not statistically significant for all medication types. CONCLUSIONS: Based on multiple measures, onsite pharmacy use was associated with higher medication adherence, while the results were inconclusive for condition management participation.

Impact of chiropractic services at an on-site health center.

OBJECTIVE: To compare the influence of employer-sponsored, on-site chiropractic care against community-obtained care on health care utilization. METHODS: This was a retrospective claims analysis of members of a single employee health plan receiving chiropractic care on-site or off-site from 2010 to 2012. Utilization differences were evaluated by having 1 health care event or more, including radiology or clinical visits. RESULTS: There were 876 on-site and 759 off-site participants. The off-site group received more radiology services overall (55.5% vs 38.2%; P < 0.001) including magnetic resonance imaging, ultrasound, and radiograph (all P < 0.0001); had higher outpatient (P < 0.0001) and emergency department (P = 0.022) utilization; and demonstrated greater use of chiropractic care and physical therapy (both P < 0.0001). CONCLUSIONS: Compared with off-site care, on-site chiropractic services are associated with lower health care utilization. These results support the value of chiropractic services offered at on-site health centers.

Implementation of a pharmacy-based adult vaccine benefit: recommendations for a commercial health plan benefit.

BACKGROUND: Although vaccination rates in children exceed 90% in the United States, adults are vaccinated at far lower rates. In order to address this issue, additional community immunizers are needed, and pharmacists are in an ideal position to fill this void. OBJECTIVES: To explore issues and barriers related to implementation of a pharmacy-based adult vaccine benefit and develop recommendations supporting a pathway for benefit expansion. METHODS: A literature review on the current environment surrounding pharmacy-based adult vaccinations and structured interviews were conducted to inform an expert panel meeting using a modified Delphi process (pre/post survey). The goal was to develop recommendations on how to improve access to adult vaccines. RESULTS: Findings suggest employers play a key role in requesting changes in benefit design to include pharmacy-based vaccinations. However, the lack of consistent communication between pharmacists and primary care providers remains a significant barrier. CONCLUSIONS: Pharmacy-based access to vaccinations improves patient access and benefits individuals and employers. In order to take advantage of this opportunity, pharmacists must be viewed within the broader context of preventative care, including pharmacy-based vaccinations.

The spectral properties of (-)-epigallocatechin 3-O-gallate (EGCG) fluorescence in different solvents: dependence on solvent polarity.

(-)-Epigallocatechin 3-O-gallate (EGCG) a molecule found in green tea and known for a plethora of bioactive properties is an inhibitor of heat shock protein 90 (HSP90), a protein of interest as a target for cancer and neuroprotection. Determination of the spectral properties of EGCG fluorescence in environments similar to those of binding sites found in proteins provides an important tool to directly study protein-EGCG interactions. The goal of this study is to examine the spectral properties of EGCG fluorescence in an aqueous buffer (AB) at pH=7.0, acetonitrile (AN) (a polar aprotic solvent), dimethylsulfoxide (DMSO) (a polar aprotic solvent), and ethanol (EtOH) (a polar protic solvent). We demonstrate that EGCG is a highly fluorescent molecule when excited at approximately 275 nm with emission maxima between 350 and 400 nm depending on solvent. Another smaller excitation peak was found when EGCG is excited at approximately 235 nm with maximum emission between 340 and 400 nm. We found that the fluorescence intensity (FI) of EGCG in AB at pH=7.0 is significantly quenched, and that it is about 85 times higher in an aprotic solvent DMSO. The Stokes shifts of EGCG fluorescence were determined by solvent polarity. In addition, while the emission maxima of EGCG fluorescence in AB, DMSO, and EtOH follow the Lippert-Mataga equation, its fluorescence in AN points to non-specific solvent effects on EGCG fluorescence. We conclude that significant solvent-dependent changes in both fluorescence intensity and fluorescence emission shifts can be effectively used to distinguish EGCG in aqueous solutions from EGCG in environments of different polarity, and, thus, can be used to study specific EGCG binding to protein binding sites where the environment is often different from aqueous in terms of polarity.

Is there an association between elevated or low serum levels of phosphorus, parathyroid hormone, and calcium and mortality in patients with end stage renal disease? A meta-analysis.

BACKGROUND: Biochemical markers of altered mineral metabolism have been associated with increased mortality in end stage renal disease patients. Several studies have demonstrated non-linear (U-shaped or J-shaped) associations between these minerals and mortality, though many researchers have assumed linear relationships in their statistical modeling. This analysis synthesizes the non-linear relationships across studies. METHODS: We updated a prior systematic review through 2010. Studies included adults receiving dialysis and reported categorical data for calcium, phosphorus, and/or parathyroid hormone (PTH) together with all-cause mortality. We performed 2 separate meta-analyses to compare higher-than-referent levels vs referent and lower-than-referent levels vs referent levels. RESULTS: A literature review showed that when a linear relationship between the minerals and mortality was assumed, the estimated associations were more likely to be smaller or non-significant compared to non-linear models. In the meta-analyses, higher-than-referent levels of phosphorus (4 studies, RR = 1.20, 95% CI = 1.15-1.25), calcium (3 studies, RR = 1.10, 95% CI = 1.05-1.14), and PTH (5 studies, RR = 1.11, 95% CI = 1.07-1.16) were significantly associated with increased mortality. Although no significant associations between relatively low phosphorus or PTH and mortality were observed, a protective effect was observed for lower-than-referent calcium (RR = 0.86, 95% CI = 0.83-0.89). CONCLUSIONS: Higher-than-referent levels of PTH, calcium, and phosphorus in dialysis patients were associated with increased mortality risk in a selection of observational studies suitable for meta-analysis of non-linear relationships. Findings were less consistent for lower-than-referent values. Future analyses should incorporate the non-linear relationships between the minerals and mortality to obtain accurate effect estimates.

Systematic review of employer-sponsored wellness strategies and their economic and health-related outcomes.

This review determines the characteristics and health-related and economic outcomes of employer-sponsored wellness programs and identifies possible reasons for their success. PubMed, ABI/Inform, and Business Source Premier databases, and Corporate Wellness Magazine were searched. English-language articles published from 2005 to 2011 that reported characteristics of employer-sponsored wellness programs and their impact on health-related and economic outcomes among US employees were accepted. Data were abstracted, synthesized, and interpreted. Twenty references were accepted. Wellness interventions were classified into health assessments, lifestyle management, and behavioral health. Improved economic outcomes were reported (health care costs, return on investment, absenteeism, productivity, workers' compensation, utilization) as well as decreased health risks. Programs associated with favorable outcomes had several characteristics in common. First, the corporate culture encouraged wellness to improve employees' lives, not only to reduce costs. Second, employees and leadership were strongly motivated to support the wellness programs and to improve their health in general. Third, employees were motivated by a participation-friendly corporate policy and physical environment. Fourth, successful programs adapted to the changing needs of the employees. Fifth, community health organizations provided support, education, and treatment. Sixth, successful wellness programs utilized technology to facilitate health risk assessments and wellness education. Improved health-related and economic outcomes were associated with employer-sponsored wellness programs. Companies with successful programs tended to include wellness as part of their corporate culture and supported employee participation in several key ways.

Value of chiropractic services at an on-site health center.

OBJECTIVE: Chiropractic care offered at an on-site health center could reduce the economic and clinical burden of musculoskeletal conditions. METHODS: A retrospective claims analysis and clinical evaluation were performed to assess the influence of on-site chiropractic services on health care utilization and outcomes. RESULTS: Patients treated off-site were significantly more likely to have physical therapy (P < 0.0001) and outpatient visits (P < 0.0001). In addition, the average total number of health care visits, radiology procedures, and musculoskeletal medication use per patient with each event were significantly higher for the off-site group (all P < 0.0001). Last, headache, neck pain, and low back pain-functional status improved significantly (all P < 0.0001). CONCLUSIONS: These results suggest that chiropractic services offered at on-site health centers may promote lower utilization of certain health care services, while improving musculoskeletal function.

Approaches to the management of agents used for the treatment of multiple sclerosis: consensus statements from a panel of U.S. managed care pharmacists and physicians.

BACKGROUND: Multiple sclerosis (MS) is a chronic, disabling, and costly disease with several treatment options available; however, there is variability in evidence-based clinical guidelines. Therefore, payers are at a disadvantage when making management decisions without the benefit of definitive guidance from treatment guidelines. OBJECTIVE: To outline approaches for the management of agents used to treat MS, as determined from a group of U.S. managed care pharmacists and physicians. METHODS: A modified Delphi process was used to develop consensus statements regarding MS management approaches. The panel was composed of experts in managed care and included 8 pharmacy directors and 6 medical directors presently or previously involved in formulary decision making from 12 health plans, 1 specialty pharmacy, and 1 consulting company. These decision makers, who have experience designing health care benefits that include MS treatments, provided anonymous feedback through 2 rounds of web-based surveys and participated in 1 live panel meeting held in December 2010. Consensus was defined as a mean response of at least 3.3 or 100% of responses either "agree" or "strongly agree" (i.e., no panelist answered "disagree" or "strongly disagree") on a 4-item Likert scale (1=strongly disagree, 2=disagree, 3=agree, 4=strongly agree). RESULTS: After 3 phases, these managed care representatives reached consensus on 25 statements for management of patients with MS. Consistent with managed care principles, this group of managed care experts found that health plans should consider efficacy, effectiveness, and safety, as well as patient preference, when evaluating MS therapies for formulary placement. Cost and contracting should be considered if efficacy and safety are judged to be comparable between agents. CONCLUSION: The consensus statements developed by a panel of managed care representatives provide some insight into decision making in formulary and utilization management of MS therapies.

Systematic review of efficacy of dose-dense versus non-dose-dense chemotherapy in breast cancer, non-Hodgkin lymphoma, and non-small cell lung cancer.

Randomized controlled trials (RCTs) have suggested a potential advantage of dose-dense chemotherapy in improving disease-free and overall survival in patients with certain malignancies. This systematic review summarizes the literature on the efficacy of dose-dense chemotherapy across various cancers (breast cancer, non-Hodgkin lymphoma [NHL], and non-small cell lung cancer) and chemotherapy regimens. Among the 17 trials identified, few reported statistically significant differences between dose-dense and standard chemotherapy, and most were small with limited statistical power. Statistically significant differences in overall survival favoring dose-dense schedules were apparent among large RCTs in potentially curative settings such as early-stage breast cancer and NHL. Clinical and treatment heterogeneity demonstrated the flexibility of the dose-dense paradigm but also precluded quantitative meta-analysis of results. Further study of dose-dense schedules based on large RCTs is needed to demonstrate the consistency and generalizability of these findings.

Managing the risks of on-site health centers.

This review sought to assess compliance concerns, determine risk management strategies, and identify opportunities for future research to contribute to employers' understanding of the laws and regulations that apply to on-site care. A comprehensive review of databases, professional organizations' websites, and journals resulted in 22 publications reporting on the consequences of noncompliance among on-site health centers accepted for inclusion. None of those studies reported a study design or quantifiable outcome data. Two noncompliance themes were repeated among the publications. First, direct penalties included fines, civil actions, loss of licensure, and, potentially, criminal charges. Second, noncompliance also resulted in indirect costs such as employee mistrust and lowered standards of care, which jeopardize on-site health centers' ability to demonstrate a return on investment. Further research with rigorous methodology is needed to inform employer decisions about on-site health services and associated risk management.

Cost-effectiveness of natalizumab versus fingolimod for the treatment of relapsing multiple sclerosis.

BACKGROUND: With the addition of new agents for the treatment of multiple sclerosis (MS) (e.g., fingolimod), there is a need to evaluate the relative value of newer therapies in terms of cost and effectiveness, given healthcare resource constraints in the United States. OBJECTIVE: To assess the cost-effectiveness of natalizumab vs fingolimod in patients with relapsing MS. METHODS: A decision analytic model was developed to estimate the incremental cost per relapse avoided of natalizumab and fingolimod from a US managed care payer perspective. Two-year costs of treating patients with MS included drug acquisition costs, administration and monitoring costs, and costs of treating MS relapses. Effectiveness was measured in terms of MS relapses avoided (data from AFFIRM and FREEDOMS trials). One-way and probabilistic sensitivity analyses were conducted to assess uncertainty. RESULTS: Mean 2-year estimated treatment costs were $86,461 (natalizumab) and $98,748 (fingolimod). Patients receiving natalizumab had a mean of 0.74 relapses avoided per 2 years vs 0.59 for fingolimod. Natalizumab dominated fingolimod in the incremental cost-effectiveness analysis, as it was less costly and more effective in reducing relapses. One-way sensitivity analysis showed the results of the model were robust to changes in drug acquisition costs, administration costs, and costs of treating MS relapses. Probabilistic sensitivity analysis showed natalizumab was cost-effective 95.1% of the time, at a willingness-to-pay (WTP) threshold of $0 per relapse avoided, increasing to 96.3% of the time at a WTP threshold of $50,000 per relapse avoided. LIMITATIONS: Absence of data from direct head-to-head studies comparing natalizumab and fingolimod, use of relapse rate reduction rather than sustained disability progression as primary model outcome, assumption of 100% adherence to MS treatment, and not capturing adverse event costs in the model. CONCLUSIONS: Natalizumab dominates fingolimod in terms of incremental cost per relapse avoided, as it is less costly and more effective.

Systematic review and meta-analysis of real-world adherence to drug therapy for osteoporosis.

OBJECTIVE: To quantify the adherence of patients to drug therapy for osteoporosis in real-world settings via a systematic review and meta-analysis of observational studies. METHODS: The PubMed and Cochrane databases were searched for English-language observational studies published from January 1, 1990, to February 15, 2006, that assessed patient adherence to drug therapy for osteoporosis using the following medical subject headings and keywords: drug therapy, medication adherence, medication persistence, medication possession ratio, patient compliance, and osteoporosis. Studies were stratified into 3 groups: persistence (how long a patient continues therapy), compliance (how correctly, in terms of dose and frequency, a patient takes the medication), and adherence (a combination of persistence and compliance). A random-effects model was used to pool results from the selected studies. RESULTS: Twenty-four studies were included in the meta-analysis. The pooled database-derived persistence rate was 52% (95% confidence interval [CI], 44%-59%) for treatment lasting 1 to 6 months, 50% (95% CI, 37%-63%) for treatment lasting 7 to 12 months, 42% (95% CI, 20%-68%) for treatment lasting 13 to 24 months, returning to 52% (95% CI, 45%-58%) for treatment lasting more than 24 months. Pooled adherence rates decreased from 53% (95% CI, 52%-54%) for treatment lasting 1 to 6 months to 43% for treatment lasting 7 to 12 months (95% CI, 38%-49%) or 13 to 24 months (43%; 95% CI, 32%-54%). The pooled refill compliance estimate was 68% (95% CI, 63%-72%) for treatment lasting 7 to 12 months and 68% (95% CI, 67%-69%) for treatment lasting 13 to 24 months. The pooled self-reported compliance rate was 62% (95% CI, 48%-75%) for treatment lasting 1 to 6 months and 66% (95% CI, 45%-81%) for treatment lasting 7 to 12 months. CONCLUSION: One-third to half of patients do not take their medication as directed. Nonadherence occurs shortly after treatment initiation. Terms and definitions need to be standardized to permit comparability of technologies designed to improve patient adherence. Prospective trials are needed to assess the relationship between adherence and patient outcomes.

Improving the management of chronic obstructive pulmonary disease.

As the fourth leading cause of death in the United States, chronic obstructive pulmonary disease (COPD) represents a major burden to the healthcare system and society at large. Underdiagnosis and undertreatment lead to an increased economic burden, with exacerbations being a key driver of costs. COPD symptoms compromise quality of life (QOL), which affects both patients and caregivers. Appropriate management decreases healthcare utiization and improves QOL. This article provides an overview of COPD and promotes understanding of opportunities to optimize patient health and outcomes for those with the disease. Specific interventions that have been demonstrated to improve clinical and economic outcomes for COPD include improved implementation of guidelines, optimized pharmacologic treatment, and risk-factor reduction.