Methods for Measuring Multiple Medication Adherence: A Systematic Review-Report of the ISPOR Medication Adherence and Persistence Special Interest Group.

BACKGROUND: A broad literature base exists for measuring medication adherence to monotherapeutic regimens, but publications are less extensive for measuring adherence to multiple medications. OBJECTIVES: To identify and characterize the multiple medication adherence (MMA) methods used in the literature. METHODS: A literature search was conducted using PubMed, PsycINFO, the International Pharmaceutical Abstracts, the Cumulative Index to Nursing and Allied Health Literature and the Cochrane Library databases on methods used to measure MMA published between January 1973 and May 2015. A two-step screening process was used; all abstracts were screened by pairs of researchers independently, followed by a full-text review identifying the method for calculating MMA. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to conduct this systematic review. For studies that met the eligibility criteria, general study and adherence-specific characteristics and the number and type of MMA measurement methods were summarized. RESULTS: The 147 studies that were included originated from 32 countries, in 13 disease states. Of these studies, 26 used proportion of days covered, 23 used medication possession ratio, and 72 used self-reported questionnaires (e.g., the Morisky Scale) to assess MMA. About 50% of the studies included more than one method for measuring MMA, and different variations of medication possession ratio and proportion of days covered were used for measuring MMA. CONCLUSIONS: There appears to be no standardized method to measure MMA. With an increasing prevalence of polypharmacy, more efforts should be directed toward constructing robust measures suitable to evaluate adherence to complex regimens. Future research to understand the validity and reliability of MMA measures and their effects on objective clinical outcomes is also needed.

Hexaminolevulinate hydrochloride blue-light flexible cystoscopy in the detection and follow-up of nonmuscle-invasive bladder cancer: cost consequences during outpatient surveillance in Sweden.

AIM: This study explored the cost consequences of introducing hexaminolevulinate hydrochloride-guided blue-light flexible cystoscopy (HAL BLFC) as an adjunct to white-light flexible cystoscopy compared with white-light flexible cystoscopy alone, for the detection and management of nonmuscle invasive bladder cancer in Sweden. METHODS: The model evaluated 231 patients in the outpatient setting after successful initial transurethral resection of the bladder tumor. RESULTS: HAL BLFC introduction across all risk groups resulted in minimal budget impact (+1.6% total cost/5 years, or 189 Swedish Krona [SEK] per patient/year), and translated to cost savings in intermediate- and high-risk groups from year 2. CONCLUSION: HAL BLFC allowed more outpatient treatment with improved recurrence detection and reduced transurethral resection of the bladder tumors, cystectomies, bed days and operating room time, with minimal cost impact across all risk groups, demonstrating the economic benefits of introducing HAL.

Retrospective real-world adherence in patients with type 2 diabetes initiating once-daily liraglutide 1.8 mg or twice-daily exenatide 10 µg.

BACKGROUND: The effectiveness of a drug is significantly influenced by a patient's adherence to the required regimen. OBJECTIVE: The goal of this retrospective database analysis was to determine the factors affecting adherence over a 12-month follow-up period in adults with type 2 diabetes mellitus (DM) initiating once-daily liraglutide (1.8 mg) or twice-daily exenatide (10 µg). METHODS: A patient-centric claims database was used, covering the period January 2009 to December 2011. Patients were included if they had ≥1 claim of once-daily liraglutide 1.8 mg or twice-daily exenatide 10 µg from January to December 2010 (index date [ID]), ≥2 diagnoses of type 2 DM before ID, continuous enrollment for 12 months before and after ID, and age ≥18 years at ID. Patients were required to be glucagon-like peptide-1 receptor agonist treatment-naive in the 12 months preceding ID and have a second prescription for once-daily liraglutide 1.8 mg or twice-daily exenatide 10 µg during the 12 months after ID. The medication possession ratio (MPR) was used as a continuous variable and to categorize patients as high-adherent (MPR ≥80%) or low-adherent (MPR <80%). Regression analyses were conducted to determine the predictors for nonadherence in the type 2 DM population, with bivariate testing of the MPR categories conducted initially to determine the predictors to be included in the final regression model. RESULTS: A total of 3623 patients (once-daily liraglutide 1.8 mg, n = 2036; twice-daily exenatide 10 µg, n = 1587) were identified. Variables found to reduce adherence were younger age, female sex, Southern geographic region, twice-daily exenatide treatment, and higher percentage of copayment from the claimant. After adjusting for confounding factors, patients receiving once-daily liraglutide 1.8 mg were ∼11% more adherent than patients receiving twice-daily exenatide 10 µg (95% CI, 7-14; P < 0.0001). The odds ratio for "poor" adherence (MPR <80%) with twice-daily exenatide 10 µg therapy compared with liraglutide 1.8 mg once-daily was 1.33 (95% CI, 1.16-1.53; P < 0.0001). CONCLUSIONS: This study found that adherence to once-daily liraglutide 1.8 mg treatment was superior to twice-daily exenatide 10 µg over a 12-month follow-up period. Nonadherence has important implications to the health care system, both in terms of clinical effectiveness and economic burden (eg, hospitalization, productivity losses). Using strategies to increase adherence is vital to reduce the future clinical and economic burden of diabetes.

Impact of measures to enhance the value of observational surveys in rare diseases: the Fabry Outcome Survey (FOS).

BACKGROUND: Disease registries are an important source of information on the natural history of rare diseases and the response to new therapies in a real-world setting. The value of the information, however, is directly related to the completeness of the data entered for each patient over the course of time. The Fabry Outcome Survey (FOS) is a Shire Human Genetic Therapies-sponsored, physician-directed registry of patients with Fabry disease, a rare, multisystem, lysosomal storage disorder, established in 2001. OBJECTIVE AND METHODS: In 2005, measures were introduced to improve the completeness of data capture, including a focus on centers with 20 or more patients enrolled in the FOS, concentration on a limited number of core variables (i.e., serum creatinine, urinary protein, left ventricular mass [echocardiography], blood pressure [systolic and diastolic], pain, quality of life, and other Fabry disease-related signs and symptoms, as well as height and weight) and the introduction of Clinical Project Associates (CPAs) to facilitate data management by participating treatment centers. RESULTS: An analysis of random samples of approximately 25% of patients in the registry in 2008 showed significant increases in data capture for most of the core variables examined. CONCLUSIONS: We conclude that the measures introduced in 2005 significantly improved the value of the information in the registry, which has contributed greatly to our understanding of patients' real-world experience with enzyme replacement therapy for Fabry disease.

Renal effects of the cyclooxygenase-inhibiting nitric oxide donator AZD3582 compared with rofecoxib and naproxen during normal and low sodium intake.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) and can thereby reduce renal function, especially with respect to solute excretion and renal perfusion. AZD3582 [4-(nitrooxy)butyl-(2S)-2-(6-methoxy-2-naphthyl)propanoate] is a COX-inhibiting nitric oxide donator. Donation of nitric oxide by AZD3582 could preserve blood flow and thereby counteract the deleterious effects of COX inhibition in the gastrointestinal tract and possibly in other organ systems, including the kidney. The aim of this single-dose study was to assess the hypothesis that AZD3582 would not adversely affect renal function compared with NSAIDs. METHODS: In a parallel, randomized, double-blind fashion, a total of 60 healthy subjects (age range, 20-44 years) received 2 single doses of 750 mg AZD3582, 1500 mg AZD3582, 50 mg rofecoxib, 500 mg naproxen, or placebo (n = 12 per group). The first dose was given after a 5-day normal-sodium diet (150 mmol/d), and the second was given after a consecutive 3-day low-sodium diet (10 mmol/d). Urinary sodium excretion during normal sodium intake and glomerular filtration rate (GFR) (assessed by iohexol clearance) during sodium depletion were the primary variables measured. RESULTS: Urinary sodium excretion was reduced in all active treatment groups (maximal reduction of approximately 11 mmol/h during normal sodium intake, P < .05 versus placebo for all groups). GFR was also reduced in all active treatment groups. In sodium-depleted subjects, the mean (SD) maximal reduction in GFR during 0 to 6 hours for 750 mg AZD3582, 1500 mg AZD3582, 50 mg rofecoxib, and 500 mg naproxen was 28.1 mL/min (13.5 mL/min), 33.7 mL/min (23.3 mL/min), 25.2 mL/min (29.2 mL/min), and 41.7 mL/min (30.7 mL/min), respectively, with a statistically significant difference between 500 mg naproxen and placebo. Relative changes in sodium excretion and GFR were similar during normal sodium intake and sodium depletion during active treatment. CONCLUSION: The renal effects of 750 mg and 1500 mg AZD3582 were similar to those of 500 mg naproxen and 50 mg rofecoxib. Thus the potential for nitric oxide donation to create a renal-sparing agent was not found for AZD3582.

Patient evaluation of a novel non-injectable anesthetic gel: a multicenter crossover study comparing the gel to infiltration anesthesia during scaling and root planing.

BACKGROUND: Periodontal scaling procedures commonly require some kind of anesthesia. From the patient's perspective, the choice of anesthetic method is a trade-off between the degree of anesthesia and accepting the side effects. The present study evaluates the preferences for a novel non-injection anesthetic product (a gel, containing lidocaine 25 mg/g plus prilocaine 25 mg/g and thermosetting agents) versus injection anesthesia (lidocaine 2% adrenaline) in conjunction with scaling and/or root planing (SRP). METHODS: In a multicenter, crossover, randomized, open study patients were asked, after they had experienced both products, if they preferred anesthetic gel or injection anesthesia. In addition, the adequacy of anesthesia and occurrence of post-procedure problems were assessed. The patients were also asked about their willingness to return if they were offered anesthetic gel at their next visit and their maximum willingness to pay (WTP) for this option. RESULTS: One-hundred seventy (170) patients at eight centers in Belgium were included in the study. There were 157 per protocol (PP) patients. A vast majority of the PP patients (70%) preferred the anesthetic gel to injection anesthesia (22%). The most common reason was less post-procedure numbness. Eighty percent (80%) of the patients expressed satisfactory anesthesia with the gel and 96% with injection anesthesia (P <0.001). Post-procedure problems were significantly less with the gel than with injection (P <0.001): numbness 15% versus 66%, unpleasant sensations such as soreness and pain 44% versus 63%, and problems connected with daily activities 19% versus 69%. The majority of patients (60%) who preferred gel were also willing to pay for it. A conservative estimate of the median WTP was $10.00. Furthermore, anesthetic gel would make almost every second patient (45%) more or much more willing to return for the next treatment. CONCLUSIONS: The data suggest that a somewhat less profound anesthesia with gel is clearly preferred by the patients because of the low incidence of post-procedure problems as compared to conventional injection anesthesia. The median WTP is likely in excess of the acquisition cost of the product, which indicates a favorable cost-benefit ratio for the individual patient.