Joanne LaFleur

A Review of Diabetes Treatment Adherence and the Association with Clinical and Economic Outcomes

BACKGROUND The benefits of drug therapy to diabetic patients in terms of glycemic control, microvascular complications, cardiovascular event risk, mortality, and quality of life have been well established by clinical trial data. However, it has been a challenge to quantify the relationship between adherence and outcomes such as glycemic control, disease-related events, hospitalizations, cost, and quality of life. OBJECTIVE This article provides a comprehensive summary of empirical studies that examine the associations between adherence and glycemic control, health care utilization, quality of life, and mortality in patients with diabetes. It is intended to provide a framework for researchers interested in conducting studies to improve their understanding of the value of medication adherence for patients with diabetes. METHODS Relevant published articles were identified through searches of the National Center for Biotechnology PubMed database. Medical subject heading (MESH) terms diabetes mellitus, hypoglycemic agents, and insulin, were each combined with the MESH term medication adherence and with the subheadings economics, prevention and control, psychology, statistics and numerical data, therapy, adverse effects, therapeutic use, and administration and dosage, where available. Studies were included if they met the following criteria: (1) analyzed empirical data on some measure of patient adherence to diabetes pharmacotherapy; (2) described methods for measuring patient adherence; (3) evaluated economic, clinical, or humanistic outcomes related to diabetes; and (4) had as a goal of the research to evaluate the link between patient adherence and outcomes (as a primary or secondary objective). The data from the articles meeting these criteria were then abstracted, including mention of the specific interventions being compared, specific methods for measuring adherence, outcomes compared between adherent and nonadherent patients and how these outcomes were measured, and information on variables that were adjusted for in predictive and causal multivariable models. RESULTS A total of 37 articles that met all 4 criteria in this review underwent data extraction. Of these studies, 22 (59%) used objective measures to assess adherence, with 1 study using pill counts to assess adherence and 21 using either pharmacy claims or similar refill records to assess refill behavior. The remaining 15 (41%) studies used a wide variety of subjective patient-reported adherence assessments. The majority (13/23 [57%]) of the glycemic control studies reported that improved adherence was associated with better glycemic control. The ability to draw a distinction between adherence and glycemic control tended to occur more frequently [7/9 (78%)] among studies that characterized adherence in terms of prescription refills compared with studies that used various constructs for patient-reported adherence measures. CONCLUSIONS Based on the literature, better adherence was found to be associated with improved glycemic control and decreased health care resource utilization. There was no consistent association between improved adherence and decreased health care costs. Little data were available on the association between adherence and quality of life.

The clinical epidemiology of male osteoporosis: a review of the recent literature

Osteoporosis, a musculoskeletal disease characterized by decreased bone mineral density (BMD) and an increased risk of fragility fractures, is now recognized as an important public health problem in men. Osteoporotic fractures, particularly of the hip, result in significant morbidity and mortality in men and lead to considerable societal costs. Many national and international organizations now address screening and treatment for men in their osteoporosis clinical guidelines. However, male osteoporosis remains largely underdiagnosed and undertreated. The objective of this paper is to provide an overview of recent findings in male osteoporosis, including pathophysiology, epidemiology, and incidence and burden of fracture, and discuss current knowledge about the evaluation and treatment of osteoporosis in males. In particular, clinical practice guidelines, fracture risk assessment, and evidence of treatment effectiveness in men are addressed.

Clinical Risk Factors for Fracture in Postmenopausal Osteoporotic Women: A Review of the Recent Literature

Objective: To review recent literature regarding relationships among age, weight or body mass index (BMI), bone mineral density (BMD), maternal history of fracture, or personal prior history of fracture and fragility fractures in women with postmenopausal osteoporosis (PMO). Data Sources: A MEDLINE database search (1995–June 30, 2007) was conducted to identify literature related to risk factors of interest for PMO-related fractures. Study Selection and Data Extraction: Cohort studies, case—control studies, and meta-analyses that reported fracture outcomes were included if they provided an estimate of relative risk for at least 1 of the 5 selected clinical risk factors (CRFs) and studied women with PMO or stratified risk estimates by age and sex. Of 313 identified studies that evaluated fractures as an endpoint, 245 did not report risk estimates for a CRF of interest and/or did not report data for a PMO population. Data Synthesis: In the 68 included articles, the risks associated with the evaluated CRFs were high and significant. Prior fracture was a strong predictor of fracture and increased risk up to 18 times. Each standard deviation below the referent mean for BMD was associated with an increased fracture risk of up to 4.0 times; maternal fracture history increased risk 1.3–2.9 times. Age (per 5 year increment) increased risk by 1.2–5.0 times; low weight or BMI inconsistently showed a 0.5–3.0 times greater risk. Conclusions: Low BMD is widely used as a diagnostic indicator for osteoporosis; however, other CRFs play an important role in determining fracture risk among women with PMO.

Absolute and relative contraindications to pegylated-interferon or ribavirin in the US general patient population with chronic hepatitis C: Results from a US database of over 45 000 HCV-infected, evaluated patients

Chronic hepatitis C (HCV) treatment with pegylated‐interferon (PEG‐IFN)/ribavirin (RBV) is often limited by preexisting medical, psychiatric and psychosocial contraindications. However, limited data exist in general patient populations.

Adherence and Persistence with Single-Dosage Form Extended-Release Niacin/Lovastatin Compared with Statins Alone or in Combination with Extended-Release Niacin:

Background: Lipid-lowering therapies have been shown to reduce cardiovascular events and mortality; patient cooperation with therapy varies. A fixed-dose combination product, extended-release niacin/lovastatin (ERNL), has been shown to be beneficial in lipid management; however, little is known regarding patient behavior with ERNL therapy. Objective: To evaluate patient adherence and persistence with ERNL, statin monotherapy (SM), extended-release niacin (ERN) monotherapy, and ERN plus a statin (ERN-S). Methods: Prescription claims for lipid-lowering therapies were obtained from a pharmacy benefits manager between 2002 and 2003. Claims for a total of 2389 patients were analyzed for adherence and persistence, using medication possession ratios (MPRs) and proportions of days covered (PDCs). Adherence and persistence were defined, respectively, as an MPR or PDC greater than or equal to 0.80. Logistic regression was conducted to detect differences among groups. Covariates included age, gender, copay, and number of lipid-lowering therapies, a surrogate for disease severity. Results: Average MPR scores were relatively high in all groups at 0.88, 0.81, 0.89, and 0.90 for ERNL, SM, ERN, and ERN-S, respectively. The adjusted odds ratio for adherence was lowest for SM (0.69), which was statistically significant compared with ERN-S (1.43), but not ERNL (1.00) or ERN (0.74). Persistence outcomes were poor in all groups. By the fourth quarter, patients receiving ERN-S (OR 1.31) had significantly greater persistence than those receiving ERN (OR 0.41) and SM (0.61), but not those receiving ERNL (OR 1.00). Conclusions: Managed care patients tended to be adherent to chronic lipid-lowering therapies, based on a mean MPR greater than 0.8. However, most patients failed to persist for at least 6 months.

Cost-effectiveness analysis of fecal microbiota transplantation for recurrent Clostridium difficile infection.

OBJECTIVE Clostridium difficile infection (CDI) places a high burden on the US healthcare system. Recurrent CDI (RCDI) occurs frequently. Recently proposed guidelines from the American College of Gastroenterology (ACG) and the American Gastroenterology Association (AGA) include fecal microbiota transplantation (FMT) as a therapeutic option for RCDI. The purpose of this study was to estimate the cost-effectiveness of FMT compared with vancomycin for the treatment of RCDI in adults, specifically following guidelines proposed by the ACG and AGA. DESIGN We constructed a decision-analytic computer simulation using inputs from the published literature to compare the standard approach using tapered vancomycin to FMT for RCDI from the third-party payer perspective. Our effectiveness measure was quality-adjusted life years (QALYs). Because simulated patients were followed for 90 days, discounting was not necessary. One-way and probabilistic sensitivity analyses were performed. RESULTS Base-case analysis showed that FMT was less costly (

Overestimation of the effects of adherence on outcomes: a case study in healthy user bias and hypertension

1,669 vs

Factors associated with screening or treatment initiation among male United States veterans at risk for osteoporosis fracture.

3,788) and more effective (0.242 QALYs vs 0.235 QALYs) than vancomycin for RCDI. One-way sensitivity analyses showed that FMT was the dominant strategy (both less expensive and more effective) if cure rates for FMT and vancomycin were ≥70% and <91%, respectively, and if the cost of FMT was <

The Treatment Outcomes of Pain Survey (TOPS): A Clinical Monitoring and Outcomes Instrument for Chronic Pain Practice and Research

3,206. Probabilistic sensitivity analysis, varying all parameters simultaneously, showed that FMT was the dominant strategy over 10, 000 second-order Monte Carlo simulations. CONCLUSIONS Our results suggest that FMT may be a cost-saving intervention in managing RCDI. Implementation of FMT for RCDI may help decrease the economic burden to the healthcare system.

Healthcare costs and resource utilization of patients with binge‐eating disorder and eating disorder not otherwise specified in the Department of Veterans Affairs

Background The healthy user bias is usually overlooked as an explanation in studies in which a strong association is found between poor patient medication adherence and worse disease outcomes. Such studies are increasing in frequency across disease states and influence clinical practice. Adherence to antihypertensive medications was studied to illustrate confounding in such studies. Methods Using data from veterans with hypertension starting antihypertensive treatment, causal models were developed that predicted the risks of hospitalisation, myocardial infarction (MI) and death associated with poor adherence (<80%) while adjusting for patient demographics, baseline disease severity and disease comorbidity. In a second set of otherwise identical models, adjustment was made for time-varying blood pressure (BP), thus controlling for adherence effects that were mediated through the main pharmacological effects of the drugs. It was hypothesised that the second set of models would reveal a positive association between poor adherence and adverse disease outcomes that is largely explained by unmeasured confounders, including health-related behaviours. Results The models that did not adjust for time-varying BP levels showed that patients with poor adherence had statistically significantly increased risks of 3.7% for hospitalisation, 28.1% for MI and 23.3% for death. These estimates exceed the benefits of these drugs demonstrated by clinical trials. When controlling for time-varying BP, the increased risks were similar (3.4% for hospitalisation, 27.7% for MI and 23.4% for death). The findings were consistent across a range of adherence thresholds (50–90%) and when allowing disease status variables to vary. Conclusions The associations between poor adherence and outcomes are largely independent of the pharmacological effects of the drugs on BP control as well as commonly measured patient covariates. This finding suggests that even carefully designed observational adherence studies using rich clinical data are impossibly confounded and probably overestimate the true magnitude of the effect. Clinical practice guidelines based on reported adherence effects should be reconsidered.