Overcoming Barriers to Development of Novel Therapies for Cardiovascular Disease: Insights From the Oncology Drug Development Experience.

Despite the fact that cardiovascular disease (CVD) is the number 1 cause of death globally, investment in drug development and new drug approvals for CVD are precipitously declining. In contrast, the trajectory of both investment in development as well as new drug approvals for oncology have been increasing steadily over the same time frame. The factors that have spurred drug development in oncology may be applicable to new efforts to overcome barriers to drug development for CVD. Greater investment in basic research and application of expedited regulatory pathways have contributed to a lowering of development barriers in oncology. Barriers in implementation are also critical. More rapid adoption of guideline-based therapies and lower access barriers by payers have contributed to fewer implementation barriers for oncology therapeutics. There is substantially greater advocacy among patients and physicians for new oncology therapeutics, and such advocacy efforts are likely to have had a meaningful impact on lowering barriers to develop new oncology therapeutics. Broad support of patient and physician advocacy efforts directed towards CVD may help overcome existing development and implementation barriers to new drug development, thereby spurring more rapid progress in the fight to eradicate cardiovascular disease.

Real-world cardiovascular disease burden in patients with atherosclerotic cardiovascular disease: a comprehensive systematic literature review.

OBJECTIVE: Based on randomized controlled trials (RCTs), non-fatal myocardial infarction (MI) rates range between 9 and 15 events per 1000 person-years, ischemic stroke between 4 and 6 per 1000 person-years, CHD death rates between 5 and 7 events per 1000 person-years, and any major vascular event between 28 and 53 per 1000 person-years in patients with atherosclerotic cardiovascular disease (ASCVD). We reviewed global literature on the topic to determine whether the real-world burden of secondary major adverse cardiovascular events (MACEs) is higher among ASCVD patients. METHODS: We searched PubMed and Embase using MeSH/keywords including cardiovascular disease, secondary prevention and observational studies. Studies published in the last 5 years, in English, with ≥50 subjects with elevated low-density lipoprotein cholesterol (LDL-C) or on statins, and reporting secondary MACEs were included. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of each included study. RESULTS: Of 4663 identified articles, 14 studies that reported MACE incidence rates per 1000 person-years were included in the review (NOS grades ranged from 8 to 9; 2 were prospective and 12 were retrospective studies). Reported incidence rates per 1000 person-years had a range (median) of 12.01-39.9 (26.8) for MI, 13.8-57.2 (41.5) for ischemic stroke, 1.0-94.5 (21.1) for CV-related mortality and 9.7-486 (52.6) for all-cause mortality. Rates were 25.8-211 (81.1) for composite of MACEs. Multiple event rates had a range (median) of 60-391 (183) events per 1000 person-years. CONCLUSIONS: Our review indicates that MACE rates observed in real-world studies are substantially higher than those reported in RCTs, suggesting that the secondary MACE burden and potential benefits of effective CVD management in ASCVD patients may be underestimated if real-world data are not taken into consideration.

Corrigendum to "Prevalence of Fracture Risk Factors in Postmenopausal Women Enrolled in the POSSIBLE US Treatment Cohort".

[This corrects the article DOI: 10.1155/2013/715025.].

Cost-Effectiveness of Ivabradine for Heart Failure in the United States.

BACKGROUND: Ivabradine is a heart rate-lowering agent approved to reduce the risk of hospitalization for worsening heart failure. This study assessed the cost-effectiveness of adding ivabradine to background therapy in the United States from the perspective of a commercial or Medicare Advantage payer. METHODS AND RESULTS: A cost-effectiveness, cohort-based Markov model using a state transition approach tracked a cohort of heart failure patients with heart rate ≥70 beats per minute in sinus rhythm who were treated with ivabradine+background therapy or background therapy alone. Model inputs, including adjusted hazard ratios, rates of hospitalization and mortality, adverse events, and utility-regression equations, were derived from a large US claims database and SHIFT (Systolic Heart failure treatment with the If inhibitor ivabradine Trial). In the commercial population, ivabradine+background therapy was associated with a cost savings of $8594 versus the cost of background therapy alone over a 10-year time horizon, primarily because of reduced hospitalization. Ivabradine was associated with an incremental benefit of 0.24 quality-adjusted life years over a 10-year time horizon. In the Medicare Advantage population, the incremental cost-effectiveness ratio for ivabradine was estimated to be $24 920/quality-adjusted life years. CONCLUSIONS: The cost-effectiveness model suggests that for a commercial population, the addition of ivabradine to background therapy was associated with cost savings and improved clinical outcomes. For a Medicare Advantage population, the analysis indicates that the clinical benefit of ivabradine can be achieved at a reasonable cost.

A systematic review of osteoporosis medication adherence and osteoporosis-related fracture costs in men.

BACKGROUND AND OBJECTIVE: Male osteoporosis is an increasingly important public health concern. Although several medications are approved for the treatment of osteoporosis, medication non-adherence and the associated consequences are not well documented in male populations. Our objective was to identify and summarize the current knowledge related to osteoporotic medication adherence, the potential implications of non-adherence to the medication, and the cost of osteoporosis-related fractures and health-resource utilization in men. METHODS: Two separate systematic searches were conducted concurrently: one to identify literature reporting male-specific adherence to anti-osteoporotic medication and the clinical consequence of non-adherence in men, and the other to identify literature reporting the cost and resource burden of osteoporosis-related fractures in men. The PubMed, MEDLINE, EMBASE, and Cochrane databases were searched using a date range of 1 January 1998 to 30 June 2012, and citations were screened based on pre-defined criteria. RESULTS: The percentage of males adherent to bisphosphonates [medication possession ratio (MPR) >0.8] over a 1-year period ranged from 32% to 64%. The data imply worse clinical outcomes with treatment non-adherence. Costs and resource use associated with osteoporosis-related fractures in men are high, with hip fractures generating the most cost. CONCLUSIONS: One-third to two-thirds of men are not adherent to bisphosphonates. Non-adherence is associated with increased fracture risk. Estimates of direct and indirect osteoporosis-related fracture costs are also substantial in men, and may even be more costly than in women. More robust data would better inform disease management initiatives that could improve adherence to medication and outcomes in men with osteoporosis.

Development and preliminary validation of a Function IndeX for Trauma (FIX-IT).

BACKGROUND: Assessing fracture healing in clinical trials is subjective. The new Function IndeX for Trauma (FIX-IT) score provides a simple, standardized approach to assess weight-bearing and pain in patients with lower extremity fractures. We conducted an initial validation of the FIX-IT score. METHODS: We conducted a cross-sectional study involving 50 patients with lower extremity fractures across different stages of healing to evaluate the reliability and preliminary validity of the FIX-IT score. Patients were independently examined by 2 orthopedic surgeons, 1 orthopedic fellow, 2 orthopedic residents and 2 research coordinators. Patients also completed the Short Form-36 version 2 (SF-36v2) questionnaire, and convergent validity was tested with the SF-36v2. RESULTS: For interrater reliability, the intraclass correlation coefficients ranged from 0.637 to 0.915. The overall interrater reliability for the total FIX-IT score was 0.879 (95% confidence interval 0.828-0.921). The correlations between the FIX-IT score and the SF-36 ranged from 0.682 to 0.770 for the physical component summary score, from 0.681 to 0.758 for the physical function subscale, and from 0.677 to 0.786 for the role-physical subscale. CONCLUSION: The FIX-IT score had high interrater agreement across multiple examiners. Moreover, FIX-IT scores correlate with the physical scores of the SF-36. Although additional research is needed to fully validate FIX-IT, our results suggest the potential for FIX-IT to be a reliable adjunctive clinician measure to evaluate healing in lower extremity fractures. LEVEL OF EVIDENCE: Diagnostic Study Level I.

CONTEXTE: Évaluer la guérison d'une fracture dans le cadre d'essais cliniques est un processus subjectif. Le nouveau score FIX-IT (pour Function IndeX for Trauma) constitue une approche simple et standardisée pour évaluer la mise en charge et la douleur chez les patients ayant subi une fracture d'un membre inférieur. Nous avons procédé à une validation initiale du score FIX-IT. MÉTHODES: Nous avons réalisé une étude transversale regroupant 50 patients qui ont subi une fracture d'un membre inférieur, à différents stades de la guérison, pour évaluer la fiabilité et la validité préliminaire du score FIX-IT. Les patients ont été examinés indépendamment par 2 chirurgiens orthopédistes, 1 chargé de cours en orthopédie, 2 médecins résidents en orthopédie et 2 coordonnateurs de recherche. Les patients ont aussi répondu au questionnaire SF-36v2 (Short Form-36 version 2) et la validité convergente a été vérifiée au moyen du SF-36v2. RÉSULTATS: En ce qui concerne la fiabilité interexaminateur, les coefficients de corrélation intraclasse ont varié de 0,637 à 0,915. La fiabilité interexaminateur pour le score FIX-IT total a été de 0,879 (intervalle de confiance de 95 % 0,828­0,921). Les corrélations entre le score FIX-IT et le SF-36 ont varié de 0,682 à 0,770 pour le score sommaire de la composante physique, de 0,681 à 0,758 pour la sous-échelle du fonctionnement physique et de 0,677 à 0,786 pour la sous-échelle du rôle physique. CONCLUSION: Le score FIX-IT a offert une concordance interexaminateur élevée entre les multiples examinateurs. De plus, les scores FIX-IT sont en corrélation avec les scores physiques obtenus au SF-36. Même s'il faudra approfondir la recherche pour valider complètement le score FIX-IT, nos résultats donnent à penser que cet indice pourrait être une mesure clinique d'appoint fiable pour évaluer la guérison des fractures de membres inférieurs. NIVEAU DE PREUVE: Étude diagnostique de niveau I.

Cost effectiveness of denosumab versus oral bisphosphonates for postmenopausal osteoporosis in the US.

BACKGROUND: In the US, 26 % of women aged ≥65 years, and over 50 % of women aged ≥85 years are affected with postmenopausal osteoporosis (PMO). Each year, the total direct health care costs are estimated to be $US12-18 billion. OBJECTIVE: The cost effectiveness of denosumab versus oral bisphosphonates in postmenopausal osteoporotic women from a US third-party payer perspective was evaluated. METHODS: A lifetime cohort Markov model was developed with seven health states: 'well', hip fracture, vertebral fracture, 'other' osteoporotic fracture, post-hip fracture, post-vertebral fracture, and dead. During each cycle, patients could have a fracture, remain healthy, remain in a post-fracture state or die. Relative fracture risk reductions, background fracture risks, mortality rates, treatment-specific persistence rate, utilities, and medical and drug costs were derived using published sources. Expected costs and quality-adjusted life years (QALYs) were estimated for generic alendronate, denosumab, branded risedronate, and branded ibandronate in the overall PMO population and high-risk subgroups: (a) ≥2 of the following risks: >70 years of age, bone mineral density (BMD) T score less than or equal to -3.0, and prevalent vertebral fracture; and (b) ≥75 years of age. Costs and QALYs were discounted at 3 % annually, and all costs were inflated to 2012 US dollars. Sensitivity analyses were conducted by varying parameters e.g., efficacies of interventions, costs, utilities, and the medication persistence ratio. RESULTS: In the overall PMO population, total lifetime costs for alendronate, denosumab, risedronate, and ibandronate were $US64,400, $US67,400, $US67,600 and $US69,200, respectively. Total QALYs were 8.2804, 8.3155, 8.2735 and 8.2691, respectively. The incremental cost-effectiveness ratio (ICER) for denosumab versus generic alendronate was $US85,100/QALY. Risedronate and ibandronate were dominated by denosumab. In the high-risk subgroup (a), total costs for alendronate, denosumab, risedronate and ibandronate were $US70,400, $US70,800, $US74,000 and $US76,900, respectively. Total QALYs were 7.2006, 7.2497, 7.1969 and 7.1841, respectively. Denosumab had an ICER of $US7,900/QALY versus generic alendronate and dominated all other strategies. Denosumab dominated all strategies in women aged ≥75 years. Base-case results between denosumab and generic alendronate were most sensitive to the relative risk of hip fracture for both drugs and the cost of denosumab. CONCLUSION: In each PMO population examined, denosumab represented good value for money compared with branded bisphosphonates. Furthermore, denosumab was either cost effective or dominant compared with generic alendronate in the high-risk subgroups.

Prevalence of Fracture Risk Factors in Postmenopausal Women Enrolled in the POSSIBLE US Treatment Cohort.

Subject- and physician-reported data from 4,429 postmenopausal women receiving osteoporosis treatment in the Prospective Observational Scientific Study Investigating Bone Loss Experience (POSSIBLE US) were used to assess the prevalence of risk factors (RFs) and on-study fracture. RFs assessed at study entry were age >70 years; fracture since age 50; minimum T-score (hip/spine) ≤-2.5 at diagnosis; body mass index <18.5 kg/m(2); rheumatoid arthritis; parental history of hip fracture; current smoking; and recent oral glucocorticoid use. Data were collected with semiannual self-administered questionnaires. Results were stratified by physician-reported osteoporosis/osteopenia diagnosis. Low T-score and age >70 years were the most common RFs in the osteoporosis group, and age >70 years and prior fracture were the most common risk factors in the osteopenia group. Multiple RFs were more common than a single RF in osteoporotic women (54.2% versus 34.6%; P < 0.0001) but not osteopenic women (13.8% versus 33.6%; P < 0.0001). Women with multiple RFs had more on-study osteoporosis-related fractures than women with a single RF (osteoporosis group: 9.9% versus 6.2%; P = 0.0092; osteopenia group: 11.2% versus 4.7%; P < 0.0001). In postmenopausal women receiving osteoporosis treatment, multiple RFs increased fracture risk. RFs, in addition to bone mineral density, can help identify candidates for osteoporosis treatment.

The impact of body weight on patient utilities with or without type 2 diabetes: a review of the medical literature.

BACKGROUND: Weight gain is a common side effect of many therapies for type 2 diabetes (T2DM). Selecting utility values for incorporation into cost-utility analyses (CUAs) of T2DM therapies is difficult because of variations in methodologies to elicit utilities and other study limitations. METHODS: A review of the medical literature was conducted to identify studies assessing the impact of body weight on patient utility. RESULTS: Eighteen articles presented either: 1) utility values by body-mass index (BMI) or body weight, or 2) the change in utility scores or quality-adjusted life-years based on unit changes in BMI or body weight. Regardless of the study population or methodology used to elicit utility scores, all studies reviewed found that as body weight increased, patient utility decreased. Utility scores obtained using standard gamble were generally higher than those using time trade-off(TTO) or the EQ-5D. Most studies reported utility scores stratified by BMI and used regression analyses to attribute the difference in utility scores to differences in weight while controlling for other factors. Studies generally assumed a constant change in utility occurs with a one unit change in BMI. Recent studies, however, demonstrate the magnitude of changes in utility may vary depending on 1) valuing weight loss versus weight gain; 2) valuing a small or large change in body weight; and 3) baseline BMI. CONCLUSIONS: Various utility values associated with body weight using different methodologies have been published. Careful consideration should be given to determine the most appropriate utility values to use in CUAs of T2DM therapies.

Prevalence and antihyperglycemic prescribing trends for patients with type 2 diabetes in Italy: a 4-year retrospective study from national primary care data.

To estimate the prevalence of type 2 diabetes in Italy and to investigate patient-related variables associated with the use of different antihyperglycemic therapies. This study was conducted between the years 2000-2003 from a source population comprising a cumulative sample of 394,719 patients from 320 General Practitioners across Italy, who provide information to the Health Search/Thales Database (HSD). A total sample of 23,729 of patients with type 2 diabetes age 15 years or older was selected from the source population. During the study years, the prevalence of type 2 diabetes increased from 4.7 to 6.0%. A significant increase in the use of antihyperglycemic therapy was also observed between 2000 and 2003. In particular, the use of biguanides increased. During the same period, the use of sulfonylurea monotherapy, oral combination therapy and insulin with oral combination therapy decreased. The results from the multivariate analysis revealed that healthier patients were more likely to be prescribed biguanide and sulfonylurea monotherapy, whereas patients with more diabetes complications and poorer glycemic control were more likely to be prescribed oral combination therapy or insulin (monotherapy or combination therapy). In conclusion, the study results appear to suggest that the prescribing patterns of Italian GPs and the predictors of different antihyperglycemic drug use are consistent with recent scientific evidence.

Obesity and the use of insulin: a study of patients with type 2 diabetes in the UK.

OBJECTIVE: This analysis examines how obesity affects the prescribing of insulin for individuals with type 2 diabetes and poor glycemic control. METHODS: Data were obtained from the UK General Practice Research Database for the years 2000-2004. Patients were eligible if they had been identified as having type 2 diabetes and had undergone at least two valid glycosylated hemoglobin (HbA(1c)) tests. Additionally, patients had to have poor glycemic control on the index date (HbA(1c)>7.4), no use of insulin 6 months prior to the index date, and at least 30 months of data after the index date (N=6468). Descriptive statistics were used to examine unadjusted differences between obese and nonobese patients. A Cox proportional hazards model was applied to examine the relationship between obesity and the relative likelihood of initiation of insulin while controlling for differences in patient characteristics, medication use, and HbA(1c) levels. RESULTS: Obese individuals were significantly younger (P<.01), significantly more likely to be treated with two oral antidiabetic agents (P=.02), and significantly less likely to be treated with oral monotherapy (P=.02). Controlling for a wide range of factors that may impact receipt of insulin, results revealed that obese individuals had a "hazard" of initiation of insulin significantly lower than that of nonobese patients (hazard ratio=0.814, P=.01). CONCLUSIONS: Patient age, severity of illness, and prior medication use all affect whether the individual will be initially prescribed insulin. Moreover, the results of this study demonstrate that obesity is an additional critical factor in physicians' decision to begin treatment with insulin.

Physician and patient management of type 2 diabetes and factors related to glycemic control in Spain.

The objective of this study was to assess current treatment patterns, blood glucose test strip usage, and treatment compliance in patients with type 2 diabetes mellitus (T2DM) in primary care centers in Spain, and to assess factors related to glycemic control. We conducted a retrospective chart review of patients with T2DM and measured treatment compliance using the Morisky-Green questionnaire. 294 patients were included in the study from a population of patients attending 30 primary care centers throughout Spain. Results showed that the majority of patients were treated with oral monotherapy (36%) and oral combination therapy (35%). Less than half of the patients had good glycemic control (HbA(1c)

Trends in the prescription of antidiabetic medications in France: evidence from primary care physicians.

This study examined prescribing patterns for antidiabetic medications in France and explored the relationships between those patterns and changes in patient characteristics. Data were obtained from the IMS Disease Analyzer-Mediplus France Database (IMS Health Incorporated, London, United Kingdom). Patients were included in the study if they were identified as having type 2 diabetes during the calendar years 2001 to 2003. Univariate analyses examined changes in patient characteristics and trends in prescribing over time. In addition, multivariate logistic regression analysis examined the impact of the year on the likelihood of a patient's receiving prescriptions for a specific therapy. A total of 14,281 unique diabetic patients were studied during the years 2001 through 2003. An average of 1.28 drug therapy episodes per calendar year was reported among individual users of antidiabetic agents. Univariate analysis revealed that between 2001 and 2003, monotherapy with sulfonylurea decreased from 34.98% to 29.47% (P<.0001), monotherapy with metformin increased from 17.38% to 21.31% (P<.0001), and monotherapy with insulin increased from 1.71% to 2.27% of the population (P=.0437). Multivariate logistic regression analyses that compared prescription therapy episodes in 2003 with those in 2001 revealed that the influence of the year on the likelihood of metformin or insulin use (alone or in combination with other medications) was positive and significant (P<.05). In contrast, the influence of the year on the likelihood of sulfonylurea monotherapy use was negative and significant (P<.05). In France, antidiabetic medication prescribing patterns changed from 2001 to 2003. In general, the trend has been away from sulfonylurea monotherapy and toward metformin monotherapy, insulin monotherapy, or combination therapy.

Validation of two generic patient-reported outcome measures in patients with type 2 diabetes.

BACKGROUND: Prior to using a generic patient-reported outcome measure (PRO), the measure should be validated within the target population. The purpose of the current study was to validate two generic measures in patients with type 2 diabetes. METHODS: Patients with type 2 diabetes in Scotland and England completed two generic measures: EQ-5D and Psychological General Well-Being Index (PGWB). Two diabetes-specific measures were administered: ADS and DSC-R. Analyses assessed reliability and validity. RESULTS: There were 130 participants (53 Scotland; 77 England; 64% male; mean age = 55.7 years). Responses on the EQ-5D and PGWB reflected moderate impairment consistent with previous diabetes samples: mean EQ-5D Index score, 0.75; EQ-5D VAS, 68.8; PGWB global score, 67.9. All scales of the PGWB demonstrated good internal consistency reliability (Cronbach's alpha = 0.77 to 0.97). The EQ-5D and PGWB demonstrated convergent validity through significant correlations with the ADS (r = 0.48 to 0.61), DSC-R scales (r = 0.33 to 0.81 except ophthalmology subscale), and Body Mass Index (r = 0.15 to 0.38). The EQ-5D and PGWB discriminated between groups of patients known to differ in diabetes-related characteristics (e.g., history of hypoglycemia). CONCLUSION: Results support the use of the EQ-5D and PGWB among patients with type 2 diabetes, possibly in combination with condition-specific measures.

Obese versus non-obese patients with type 2 diabetes: patient-reported outcomes and utility of weight change.

INTRODUCTION: This study (1) used patient-reported outcome measures to assess and compare the health status of type 2 diabetes patients with and without obesity and (2) assessed the value of weight change among obese and non-obese subgroups, using standard gamble (SG) utility methodology. METHODS: Among a sample with type 2 diabetes in the United Kingdom, individuals with obesity (BMI > or = 30 kg/m2) were identified and compared to non-obese patients. Patients completed the EQ-5D, Psychological General Well-Being Index, Appraisal of Diabetes Symptoms, and Diabetes Symptom Checklist-Revised (DSC-R). SG interviews assessed the utility of the 'basic' type 2 diabetes health state anchored to respondents' body weight, as well as health states with altered weight. RESULTS: A total of 129 patients (74 obese; 55 non-obese) completed interviews (mean age 55.9 years; 64.3% male). Obese patients reported lower health status (EQ-5D VAS; between-group difference: p < 0.001) and greater symptom impact (several DSC-R scales, p < 0.05). Utilities of the basic health state were 0.86 (obese) and 0.91 (non-obese; p = 0.02). Hypothetical health states with higher weight received lower utilities, whereas reduced weight was associated with increased utility. There was a between-group difference in the disutility associated with 5% higher weight (obese 0.068; non-obese 0.051; p = 0.03). DISCUSSION: Compared with non-obese patients, the obese group reported lower health status and greater symptom impact. SG interviews found an inverse relationship between weight and utility. Furthermore, obese patients with type 2 diabetes may value weight change differently than non-obese patients. Study limitations include the sample size and the use of a patient sample, rather than a sample selected from the general population. Overall, the results demonstrate that utilities can differ by patient subgroups, even among patients with the same diagnosis.

Utilities and disutilities for type 2 diabetes treatment-related attributes.

INTRODUCTION: Although cost-utility analyses are frequently used to estimate treatment outcomes for type 2 diabetes, utilities are not available for key medication-related attributes. The purpose of this study was to identify the utility or disutility of diabetes medication-related attributes (weight change, gastrointestinal side effects, fear of hypoglycemia) that may influence patient preference. METHODS: Patients with type 2 diabetes in Scotland and England completed standard gamble (SG) interviews to assess utility of hypothetical health states and their own current health state. The EQ-5D, PGWB, and Appraisal of Diabetes Symptoms were administered. Construct validity and differences among health states were examined with correlations, t-tests, and ANOVAs. RESULTS: A total of 129 patients (51 Scotland; 78 England) completed interviews. Mean utility of diabetes without complications was 0.89. Greater body weight was associated with disutility, and lower body weight with added utility (e.g., 3% higher = -0.04; 3% lower = +0.02). Gastrointestinal side effects and fear of hypoglycemia were associated with significant disutility (p < 0.001). SG utility of current health (mean = 0.87) demonstrated construct validity through correlations with patient-reported outcome measures (r = 0.08-0.31). DISCUSSION: The vignette-based approach was feasible and useful for assessing added utility or disutility of medication-related attributes.

Patterns of blood glucose monitoring in relation to glycemic control among patients with type 2 diabetes in the UK.

AIMS: The objectives of this study were to compare patterns of blood glucose monitoring among patients with type 2 diabetes initiating therapy with insulin or oral medication and to examine the relationship between the quantity of prescribed monitoring strips and glycemic control. METHODS: Data were obtained from the UK General Practice Research Database. Patients were eligible if they were identified as having type 2 diabetes, initiated therapy with insulin or an oral agent, and had 12-month postinitiation data. Differences in patient characteristics and number of test strips prescribed between the insulin (n=347) and oral cohorts (n=2436) were examined. Multivariate regressions examined the relationship between quantity of monitoring and glycemic control for a subset of patients (insulin, n=245; oral, n=1795) with available glycosylated hemoglobin (HbA1c) data. RESULTS: During the 12-month postinitiation period, patients using insulin were prescribed approximately twice as many test strips compared with those patients using oral medication (149 vs. 78, P<.0001). Multivariate regressions revealed that individuals who initiated insulin therapy and were prescribed enough test strips to test at least once per day in the 6 months prior to the HbA1c test date had, on average, a 0.65% lower HbA1c value (P=.02) compared with individuals who were prescribed fewer test strips. CONCLUSIONS: Results indicate significant differences in the prescription of blood glucose monitoring strips, with patients initiated on insulin prescribed almost twice as many test strips compared with patients initiated on orals. The greater number of blood glucose test strips prescribed was associated with lower HbA1c values for insulin patients.

Antidiabetic prescriptions and glycemic control in German patients with type 2 diabetes mellitus: a retrospective database study.

OBJECTIVES: This study examined patterns of antidiabetic treatment among individuals with type 2 diabetes in Germany and investigated potential differences in attainment of glycemic control associated with the use of specific antidiabetic regimens. METHODS: This was a retrospective database study. Data were obtained from the German IMS Disease Analyzer-MediPlus database. Patients aged >or=20 years who were identified as having type 2 diabetes and who underwent glycosylated hemoglobin (HbA(1c)) testing at least once between April 1, 2004, and December 31, 2004, were included in the analyses. Potential associations between age, sex, and diabetic complications and the use of specific antidiabetic medications were examined. Also examined were potential associations between attainment of the HbA(1c) target for glycemic control (56.5%), particular patient characteristics, and the use of specific antidiabetic medications. RESULTS: The study included data from 5135 patients with type 2 diabetes (mean age, 67 years; 2702 men, 2433 women; mean [SD] HbA(1c), 6.9% [1.2%]). The most commonly diagnosed comorbidities were hypertension (66.5%) and obesity (18.7%). There were no significant differences in mean age, sex, or comorbidities between patients categorized by HbA(1c) values 6.5%. The most commonly prescribed antidiabetic medications were metformin (20.4%), a sulfonylurea (11.7%), and oral combination therapy (10.9%). In the assessment of potential associations between selected patient characteristics and the receipt of specific antidiabetic medications, individuals were less likely to receive metformin monotherapy if they were aged >or=75 years (12.0%, compared with 21.4% of those aged 65-74 years and 24.7% of those aged <65 years; P < 0.001) or had a diagnosis of a diabetic complication (15.9%, compared with 21.2% in those without complications; P < 0.001). Among those who were more likely to receive insulin monotherapy were women (11.5%, compared with 9.6% of men; P = 0.025) and patients with diabetic complications (13.9%, compared with 9.8% of those without complications; P < 0.001). More than half (52.7%) of patients did not attain the HbA(1c) target. There were significant differences between patients attaining the HbA(1c) target and receipt of specific antidiabetic medications (P < 0.001). Patients treated with insulin monotherapy or oral plus insulin combination therapy were least likely to reach the HbA(1c) target (26.4% and 22.9%, respectively, attained glycemic control; both, P < 0.001). Only 179 (31.9%) of 562 patients treated with oral combination therapy achieved the HbA(1c) target (P < 0.001). CONCLUSIONS: Over half of these German patients with type 2 diabetes failed to attain the HbA(1c) target for glycemic control. Patients who were prescribed insulin monotherapy or combination therapy were least likely to achieve the target.

Exenatide versus insulin glargine in patients with type 2 diabetes in the UK: a model of long-term clinical and cost outcomes.

OBJECTIVES: The aim of this study was to evaluate the long-term clinical and economic outcomes associated with exenatide or insulin glargine, added to oral therapy in individuals with type 2 diabetes inadequately controlled with combination oral agents in the UK setting. METHODS: A published and validated computer simulation model of diabetes was used to project long-term complications, life expectancy, quality-adjusted life expectancy and direct medical costs. Probabilities of diabetes-related complications were derived from published sources. Treatment effects and patient characteristics were extracted from a recent randomised controlled trial comparing exenatide with insulin glargine. Simulations incorporated published quality of life utilities and UK-specific costs from 2004. Pharmacy costs for exenatide were based on 20, 40, 60, 80 and 100% of the US value (as no price for the UK was available at the time of analysis). Future costs and clinical benefits were discounted at 3.5% annually. Sensitivity analyses were performed. RESULTS: In the base-case analysis exenatide was associated with improvements in life expectancy of 0.057 years and in quality-adjusted life expectancy of 0.442 quality-adjusted life years (QALYs) versus insulin glargine. Long-term projections demonstrated that exenatide was associated with a lower cumulative incidence of most cardiovascular disease (CVD) complications and CVD-related death than insulin glargine. Using the range of cost values, evaluation results showed that exenatide is likely to fall in a range between dominant (cost and life saving) at 20% of the US price and cost-effective (with an ICER of 22,420 pounds per QALY gained) at 100% of the US price, versus insulin glargine. CONCLUSIONS: Based on the findings of a recent clinical trial, long-term projections indicated that exenatide is likely to be associated with improvement in life expectancy and quality-adjusted life expectancy compared to insulin glargine. The results from this modelling analysis suggest that that exenatide is likely to represent good value for money by generally accepted standards in the UK setting in individuals with type 2 diabetes inadequately controlled on oral therapy.

Impact of dose frequency on compliance and health outcomes: a literature review (1966-2006).

In order for treatments to be effective, patients must be compliant with their medication regimens. Currently, patient compliance is seen as one of the most challenging issues in treating patients with chronic diseases. Studies in which dose frequency has been changed have been reviewed across several different diseases to examine the impact of a change in dose frequency on compliance and health outcomes, as well as efficacy and tolerability. In general, reducing dose frequency may improve medication compliance and effectiveness, and reduce adverse events, while possibly reducing healthcare costs. Suggestions for future research have been presented, including a need to measure compliance with injectable formulations and a standardized definition of compliance.