Sapropterin dihydrochloride use in pregnant women with phenylketonuria: an interim report of the PKU MOMS sub-registry.

For pregnant women with phenylketonuria (PKU), maintaining blood phenylalanine (Phe)<360µmol/L is critical due to the toxicity of elevated Phe to the fetus. Sapropterin dihydrochloride (sapropterin) lowers blood Phe in tetrahydrobiopterin (BH4) responsive patients with PKU, in conjunction with a Phe-restricted diet, but clinical evidence supporting its use during pregnancy is limited. As of June 3, 2013, the Maternal Phenylketonuria Observational Program (PKU MOMS) sub-registry contained data from 21 pregnancies - in women with PKU who were treated with sapropterin either before (N=5) or during (N=16) pregnancy. Excluding data for spontaneous abortions (N=4), the data show that the mean of median blood Phe [204.7±126.6µmol/L (n=14)] for women exposed to sapropterin during pregnancy was 23% lower, and had a 58% smaller standard deviation, compared to blood Phe [267.4±300.7µmol/L (n=3)] for women exposed to sapropterin prior to pregnancy. Women on sapropterin during pregnancy experienced fewer blood Phe values above the recommended 360µmol/L threshold. When median blood Phe concentration was <360µmol/L throughout pregnancy, 75% (12/16) of pregnancy outcomes were normal compared to 40% (2/5) when median blood Phe was >360µmol/L. Severe adverse events identified by the investigators as possibly related to sapropterin use were premature labor (N=1) and spontaneous abortion (N=1) for the women and hypophagia for the offspring [premature birth (35w4d), N=1]. One congenital malformation (cleft palate) of unknown etiology was reported as unrelated to sapropterin. Although there is limited information regarding the use of sapropterin during pregnancy, these sub-registry data show that sapropterin was generally well-tolerated and its use during pregnancy was associated with lower mean blood Phe. Because the teratogenicity of elevated maternal blood Phe is without question, sapropterin should be considered as a treatment option in pregnant women with PKU who cannot achieve recommended ranges of blood Phe with dietary therapy alone.

Roundtable--the changing oncology landscape: evolution or revolution?

Complex challenges face all players in the oncology landscape, from health care policy leaders and third-party payers, to practicing physicians and nurses, to patients and their families. In these unsteady economic times, possible answers proposed by some may represent part of the problem to others. A distinguished panel assembled at the NCCN 18th Annual Conference: Advancing the Standard of Cancer Care to explore the changing oncology landscape. This article is the synopsis of that discussion, with panelists shedding light on such issues as the astronomic cost of medical care, the need for clinicians to think outside the formulary, and the therapeutic decision-making process in the new world of "big data."

Value-based benefit design: using a predictive modeling approach to improve compliance.

BACKGROUND: Increased medication compliance rates have been demonstrated to result in improved clinical outcomes and reduced overall medical expenditures. As such, managed care stakeholders should take the total value approach to benefit design and consider total medical costs beyond the cost of pharmacotherapy alone. OBJECTIVES: To describe the value-based benefit design employed by Pitney Bowes (specifically, the predictive modeling approach), to improve medication compliance, and to report the results of this intervention. SUMMARY: Despite significant skepticism surrounding value-based benefit design, there is growing evidence that these plans can be used in conjunction with careful pharmacy management. In fact, value-based design provides a different lever on pharmacy management and allows for the appropriate drug to be channeled to the appropriate person. Studies demonstrating the adverse impact of high coinsurance levels further augment the argument for value-based benefit design. Value-based benefit design was employed at Pitney Bowes, a $6.1-billion global provider of integrated mailstream solutions, with noticeable success. Patients were either placed in a disease management program or in a secondary program promoting preventive care. The company selectively cut copays to achieve that end, and this total value approach translated into significant savings. CONCLUSION: To develop a successful value-based benefit design, stakeholders cannot simply cut costs or cut copays. Action must be taken as part of a concerted program, coupled with disease management or similar interventions. "Value based" means that positive outcomes are the ultimate goal, and barriers to those positive outcomes must be addressed.

Assessing glucose monitor performance--a standardized approach.

BACKGROUND: Glucose monitor evaluations must be carefully designed and executed in order to control protocol-specific bias and random patient interferences. Although published guidelines and recommendations exist, investigators rarely incorporate consensus standards or quality guidelines into glucose monitor evaluation studies. METHODS: We performed a literature search for "best practice" quality guidelines for conducting and reporting glucose monitor evaluation studies. These guidelines included: Standards for Reporting Diagnostic Accuracy (STARD); Clinical and Laboratory Standards Institute (CLSI) C30-A2 and EP9-A2; U.S. Food and Drug Administration (FDA); International Federation of Clinical Chemistry (IFCC); Netherlands Organization for Applied Scientific Research (TNO); U.K. Medicines and Healthcare products Regulatory Agency (MHRA); Scandinavian evaluation of laboratory equipment for primary health care (SKUP); National Standard of the People's Republic of China (China GB/T 19634); and International Standards Organization (ISO 15197). RESULTS: We constructed a checklist that outlines a standardized approach to glucose monitor evaluations, along with associated references applicable to international standards and consensus recommendations. We expect that the checklist could be used as the basis for a protocol that is (1) evidence-based, (2) scientifically defensible, and (3) sufficiently descriptive to allow for test and result reproducibility. CONCLUSIONS: We propose a standardized 14-step checklist that facilitates the incorporation of international consensus standards, quality guidelines, and acceptance criteria into the design and reporting of glucose monitor evaluation protocols.

Reducing patient drug acquisition costs can lower diabetes health claims.

Concerned about rising prevalence and costs of diabetes among its employees, Pitney Bowes Inc recently revamped its drug benefit design to synergize with ongoing efforts in its disease management and patient education programs. Specifically, based on a predictive model showing that low medication adherence was linked to subsequent increases in healthcare costs in patients with diabetes, the company shifted all diabetes drugs and devices from tier 2 or 3 formulary status to tier 1. The rationale was that reducing patient out-of-pocket costs would eliminate financial barriers to preventive care, and thereby increase adherence, reduce costly complications, and slow the overall rate of rising healthcare costs. This single change in pharmaceutical benefit design immediately made critical brand-name drugs available to most Pitney Bowes employees and their covered dependents for 10% coinsurance, the same coinsurance level as for generic drugs, versus the previous cost share of 25% to 50%. After 2 to 3 years, preliminary results in plan participants with diabetes indicate that medication possession rates have increased significantly, use of fixed-combination drugs has increased (possibly related to easier adherence), average total pharmacy costs have decreased by 7%, and emergency department visits have decreased by 26%. Hospital admission rates, although increasing slightly, remain below the demographically adjusted Medstat benchmark. Overall direct healthcare costs per plan participant with diabetes decreased by 6%. In addition, the rate of increase in overall per-plan-participant health costs at Pitney Bowes has slowed markedly, with net per-plan-participant costs in 2003 at about 4000 dollars per year versus 6500 dollars for the industry benchmark. This recent moderation in overall corporate health costs may be related to these strategic changes in drug benefit design for diabetes, asthma, and hypertension and also to ongoing enhancements in the company's disease management and wellness programs.

Sapropterin Dihydrochloride Mixed With Common Foods and Beverages.

Sapropterin dihydrochloride is used to lower blood phenylalanine levels in tetrahydrobiopterin-responsive phenylketonuria in conjunction with a phenylalanine-restricted diet. This study investigated the solubility and stability of sapropterin tablets and a sapropterin powder formulation when mixed in selected beverages and foods. Solubility was partial for the tablets and complete for the powder. The stability testing showed that 93% or more of active sapropterin dihydrochloride is present at 1 hour after either tablets or powders are mixed with certain foods and beverages. Mixing sapropterin powder with foods and beverages might facilitate its administration in patients who have difficulty swallowing the drug according to prescribing information.

Diabetes wellness care: a successful employer-endorsed program for employees.

OBJECTIVE: A 12-month wellness program was provided for employees of a major employer in the Orlando area. METHODS: The program involved screening and measurement of baseline indices, educational sessions, telephonic support, quarterly laboratory monitoring, and provision of glucometers and test strips. RESULTS: For the 73 enrolled employees with prediabetes, serum hemoglobin A1c levels-mean (standard deviation)-decreased from 6.10% (0.53%) to 5.42% (0.51%) (P < 0.0001). For the 151 enrolled employees with diabetes, mean serum hemoglobin A1c levels-mean (standard deviation)-decreased from 8.03% (1.91%) to 7.48% (1.52%) (P < 0.0001). In the 12 months before, during, and after the program, 27, 15, and 27 diabetic employees required hospitalization, respectively. Health insurance per member per month claims costs for employees with diabetes rose only 1.2% over the prior 12 months, and self-reported presenteeism increased (P < 0.0001). CONCLUSIONS: This employer-endorsed program achieved favorable outcomes for employees with prediabetes and diabetes.

Performance of a new meter designed for assisted monitoring of blood glucose and point-of-care testing.

BACKGROUND: Blood glucose (BG) meters used for assisted monitoring of blood glucose (AMBG) require different attributes compared with meters designed for home use. These include safety considerations (i.e., minimized risk of blood-borne pathogen transmission), capability for testing multiple blood sample types, and enhanced performance specifications. The OneTouch® Verio™Pro+ BG meter is designed to incorporate all of these attributes. METHODS: Meter accuracy was assessed in clinical studies with arterial, venous, and capillary blood samples with a hematocrit range of 22.9-59.8%. The effect of interferents, including anticoagulants, on accuracy was evaluated. The meter disinfection protocol was validated, and instructions for use and user acceptance of the system were assessed. RESULTS: A total of 97% (549/566) of BG measures from all blood sample types and 95.5% (191/200) of arterial blood samples were within ±12 mg/dl or 12.5% of reference measurements. The system was unaffected by 4 anticoagulants and 57 of 59 endogenous and exogenous compounds; it was affected by 2 compounds: pralidoxime iodide and xylose. Bleach wipes were sufficient to disinfect the meter. Users felt that the meter's quality control (QC) prompts would help them to comply with regulatory requirements. CONCLUSION: The meter provided accurate measurements of different blood samples over a wide hematocrit range and was not affected by 57 physiologic and therapeutic compounds. The QC prompts and specific infection-mitigating design further aid to make this meter system practical for AMBG in care facilities.

Automated glycemic pattern analysis can improve health care professional efficiency and accuracy.

BACKGROUND: Health care professionals (HCPs) routinely review handwritten blood glucose (BG) logbooks during office visits of patients with diabetes. METHOD: In this study, 64 HCPs were asked to assess glycemic patterns and estimate BG averages in six simulated handwritten logbooks. The HCPs then reviewed the pattern logs and averages in six OneTouch® Verio™IQ meters containing corresponding data sets. RESULTS: The average time needed for pattern review was 7.3 min for handwritten logbooks versus 0.9 min using the meter. The total error rate for logbook pattern identification was 43.0% compared with the meter. The mean percentage deviation between HCP estimates of 30-day BG averages and actual values was 14.5%. CONCLUSIONS: The meter is associated with faster and more accurate pattern analysis compared with handwritten logbooks.

Effect of disinfectants on glucose monitors.

BACKGROUND: Monitoring blood glucose levels is an integral part of routine diabetes management. To minimize the risk of transmission of bloodborne pathogens during monitoring, the Centers for Disease Control and Prevention (CDC) recommends that glucose meters be disinfected after each use whenever they are used to test multiple patients. The objective of this study is to assess the compatibility of some common disinfectants with certain blood glucose meter systems. METHODS: We tested six disinfectants for adverse impact on meter performance or the exterior meter surfaces. The disinfectants tested were 0.525% sodium hypochlorite, 20% 2-propanol and 10% ethanol, 17.2% isopropanol, 55% isopropanol, 70% isopropanol, and hydrogen peroxide. To assess meter performance, we tested OneTouch® Ultra® blood glucose monitoring systems with control solution before and after application of either water or disinfectant. To assess the effect on exterior meter surfaces, we performed a soaking test to simulate long-term exposure to disinfectant. RESULTS: Paired t-test results showed that the control solution data associated with disinfectant and with water application were not significantly different for each meter type. However, most of the meter types were adversely affected by hydrogen peroxide and/or by the higher concentrations of alcohol-based disinfectants. CONCLUSIONS: Although none of the six disinfectants affected meter performance, hydrogen peroxide and isopropanol >20% adversely affected the exterior surfaces of the tested meters. When complying with CDC instructions for meter disinfection, users should use caution and choose disinfectants that have been validated by the meter manufacturer.

Importance of blood glucose meter and carbohydrate estimation accuracy.

BACKGROUND: The clinical significance of blood glucose meter (BGM) error in the presence of increasing carbohydrate errors in diabetes patients who use both the BGM result and the carbohydrate estimation to dose insulin is unknown. METHODS: This Monte Carlo simulation modeled diabetes patients who calculate insulin dosages based on BGM results and carbohydrate estimations. It evaluated the likelihood of on-target insulin dosing and clinically significant insulin dose errors based on data from five BGMs with different levels of performance (expressed as bias and imprecision [coefficient of variation (%CV)]) and increasing levels of carbohydrate estimation errors. The study was performed across three separate preprandial glucose (PPG) ranges (90-150, 150-270, and 270-450 mg/dl). RESULTS: When carbohydrate estimation is accurate (%CV = 0%), the likelihood for on-target insulin doses ranged 50.1-98.5%. The likelihood depended on BGM performance and PPG range. In the presence of carbohydrate estimation errors (%CV = 5-20%), the likelihood of on-target insulin dosages markedly decreased (range, 27.2-80.1%) for all BGMs, the likelihood of insulin underdosing (range, 0-12.8%) and overdosing (range, 0-32.3%) increased, and the influence of BGM error on insulin dosing accuracy was blunted. Even in the presence of carbohydrate error, the BGM with the best performance (bias 1.35% and %CV = 4.84) had the highest probability for on-target insulin dosages. CONCLUSIONS: Both BGM and carbohydrate estimation error contribute to insulin dosing inaccuracies. The BGM with the best performance was associated with the most on-target insulin dosages.

The impact of reducing cardiovascular medication copayments on health spending and resource utilization.

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.

The effect of an instant hand sanitizer on blood glucose monitoring results.

BACKGROUND: People with diabetes mellitus are instructed to clean their skin prior to self-monitoring of blood glucose to remove any dirt or food residue that might affect the reading. Alcohol-based hand sanitizers have become popular when soap and water are not available. The aim of this study was to determine whether a hand sanitizer is compatible with glucose meter testing and effective for the removal of exogenous glucose. METHODS: We enrolled 34 nonfasting subjects [14 male/20 female, mean ages 45 (standard deviation, 9.4)] years, 2 with diagnosed diabetes/32 without known diabetes]. Laboratory personnel prepared four separate fingers on one hand of each subject by (1) cleaning the second finger with soap and water and towel drying (i.e., control finger), (2) cleaning the third finger with an alcohol-based hand sanitizer, (3) coating the fourth finger with cola and allowing it to air dry, and (4) coating the fifth finger with cola and then cleaning it with the instant hand sanitizer after the cola had dried. Finger sticks were performed on each prepared finger and blood glucose was measured. Several in vitro studies were also performed to investigate the effectiveness of the hand sanitizer for removal of exogenous glucose.z RESULTS: Mean blood glucose values from fingers cleaned with instant hand sanitizer did not differ significantly from the control finger (p = .07 and .08, respectively) and resulted in 100% accurate results. Blood glucose data from the fourth (cola-coated) finger were substantially higher on average compared with the other finger conditions, but glucose data from the fifth finger (cola-coated then cleaned with hand sanitizer) was similar to the control finger. The data from in vitro experiments showed that the hand sanitizer did not adversely affect glucose meter results, but when an exogenous glucose interference was present, the effectiveness of the hand sanitizer on glucose bias (range: 6% to 212%) depended on the surface area and degree of dilution. CONCLUSIONS: In our study, use of an instant hand sanitizer was compatible with the results of a blood glucose monitor and did not affect finger stick blood glucose results. However, depending on surface area, hand sanitizers may not be adequate for cleaning the skin prior to glucose meter testing.

At Pitney Bowes, value-based insurance design cut copayments and increased drug adherence.

To date, there has been little empirical evidence to support the broader use of value-based insurance design, which lowers copayments for services with high value relative to their costs. To address this lack of data, we evaluated the impact of the value-based insurance program of a US corporation, Pitney Bowes. The program eliminated copayments for cholesterol-lowering statins and reduced them for clopidogrel, a blood clot inhibitor. We found that the policy was associated with an immediate 2.8 percent increase in adherence to statins relative to controls, which was maintained for the subsequent year. For clopidogrel, the policy was associated with an immediate stabilizing of the adherence rate and a four-percentage-point difference between intervention and control subjects a year later. Our study thus provides an empirical basis for the use of this approach to improve the quality of health care.