Strengthening pharma's contract with society: the value of trusted partnerships between pharma and healthcare facilitated by real-world data.

This White Paper is authored by 11 industry real-world evidence (RWE) experts, with support from IQVIA, as part of the 'RWE Leadership Forum': a group of industry leaders who come together as noncompetitive partners to understand and respond to internal or external RWD/E challenges and opportunities with a single expert voice. Herein we aim to clarify the rules of engagement between pharma and healthcare in order to establish trust-based partnerships, which will unlock unique value for society, including the medical community and the ultimate beneficiary, the patient.

The economic burden of treatment failure amongst patients with irritable bowel syndrome with constipation or chronic constipation: a retrospective analysis of a Medicaid population.

OBJECTIVE: To compare healthcare resource utilization (HRU) and costs between patients with irritable bowel syndrome with constipation (IBS-C) or chronic constipation (CC) with and without evidence of treatment failure. METHODS: Claims data from the Missouri Medicaid program were used to identify adults with IBS-C or CC treated for constipation. IBS-C patients were required to have ≥2 constipation therapy claims, and the index date was defined as the date of the first constipation therapy claim within 12 months after an IBS diagnosis. For CC, the index date was defined as the date of the first constipation treatment claim followed by a second claim for constipation treatment or diagnosis between 60 days and 12 months later. Indicators of treatment failure were: switch/addition of constipation therapy, IBS- or constipation-related inpatient/emergency admission, megacolon/fecal impaction, constipation-related surgery/procedure, or aggressive prescription treatments. Annual incremental HRU and costs (public payer perspective) were compared between patients with and without treatment failure. Incidence rate ratios (IRRs) and cost differences are reported. RESULTS: In total, 2830 patients with IBS-C and 8745 with CC were selected. Approximately 50% of patients had ≥1 indicator of treatment failure. After adjusting for confounding factors, patients with treatment failure experienced higher HRU, particularly in inpatient days (IRR = 1.75 for IBS-C; IRR = 1.54 for CC) and higher total healthcare costs of $4353 in IBS-C patients and $2978 in CC patients. Medical service costs were the primary driver of the incremental costs associated with treatment failure, making up 71.3% and 67.0% of the total incremental healthcare costs of the IBS-C and CC samples, respectively. LIMITATIONS: Sample was limited to Medicaid patients in Missouri. Claims data were used to infer treatment failure. CONCLUSION: Treatment failure is frequent among IBS-C and CC patients, and sub-optimal treatment response with available IBS-C and CC therapies may lead to substantial HRU and healthcare costs.

Hypoglycemia is associated with increased worry and lower quality of life among patients with type 2 diabetes treated with oral antihyperglycemic agents in the Asia-Pacific region.

AIMS: We examined the relationship of hypoglycemic symptoms with health-related quality of life and worry about hypoglycemia among type 2 diabetic patients using oral antihyperglycemic agents (AHA) in the Asia-Pacific region. METHODS: A total of 2257 type 2 diabetic patients with at least 6 months of oral AHA were enrolled in China, Korea, Malaysia, Thailand, and Taiwan. Quality of life was measured with the EuroQol Visual Analog Scale (EQ-VAS) and EuroQol-5 Dimensions questionnaire (EQ-5D), and worry about hypoglycemia with the worry subscale of the Hypoglycemic Fear Survey-II (HFS). RESULTS: The mean (SD) age was 58.7 (10.2) years and HbA(1c) was 7.5% (1.5). The proportion of patients with an HbA(1c) <6.5% and <7% was 24.9% and 41.8%, respectively. Hypoglycemic symptoms in the prior 6 months were reported by 35.8% of patients. Mean scores on the EQ-VAS and the EQ-5D were significantly lower for patients who had hypoglycemic symptoms compared to those who did not (73.6 vs. 76.9, p<0.001; 0.88 vs. 0.90, p<0.0001, respectively), whereas mean score on the HFS was significantly higher (12.5 vs. 6.3, p<0.001). In multivariate models, hypoglycemic symptoms were independently associated with scores on the EQ-5D, EQ-VAS, and HFS (all p ≤ 0.01-0.001). Symptom severity was positively associated with fear of hypoglycemia (all p ≤ 0.001). CONCLUSION: Hypoglycemic symptoms were associated with reduced quality of life and increased patient worry in patients with type 2 diabetes treated with AHA.

Cost-effectiveness analysis of roflumilast/tiotropium therapy versus tiotropium monotherapy for treating severe-to-very severe COPD.

OBJECTIVE: To conduct a cost-effectiveness analysis comparing roflumilast/tiotropium therapy vs tiotropium monotherapy in patients with severe-to-very severe COPD. METHODS: The economic evaluation applied a disease-based Markov cohort model with five health states: (1) severe COPD, (2) severe COPD with a history of severe exacerbation, (3) very severe COPD, (4) very severe COPD with a history of severe exacerbation, and (5) death. Within a given health state, a patient may have a mild/moderate or severe exacerbation or die. Data from roflumilast clinical trials and published literature were used to populate model parameters. The model calculated health outcomes and costs for roflumilast/tiotropium therapy vs tiotropium monotherapy over a 5-year horizon. Incremental cost and benefits were then calculated as cost-effectiveness ratios, including cost per exacerbation avoided and cost per quality adjusted life year ($/QALY). RESULTS: Over a 5-year horizon, the estimated incremental costs per exacerbation and per severe exacerbation avoided were $589 and $5869, respectively, and the incremental cost per QALY was $15,815. One-way sensitivity analyses varying key parameters produced an incremental cost per QALY ranging from $1963-$32,773. LIMITATIONS: A number of key parameters used in the model were obtained from studies in the literature that were conducted under different contexts. Specifically, the relative risk estimate for severe COPD patients originates from a small trial not designed to demonstrate the impact of roflumilast on frequency of exacerbations. In addition, the model extrapolates the relative risk estimates over periods of 5-30 years, even though the estimates were only observed in trials that spanned less than a year. CONCLUSIONS: The addition of roflumilast to tiotropium is cost-effective for the treatment of severe to very severe COPD patients.

Association of hypoglycemic symptoms with patients' rating of their health-related quality of life state: a cross sectional study.

BACKGROUND: To evaluate the association between patient-reported hypoglycemic symptoms with ratings of their health-related quality of life state and patient-reported adverse events in patients with type 2 diabetes mellitus (T2DM). METHODS: This observational, multicenter, cross sectional study was based on a sample of patients with T2DM from seven European countries who added sulfonylurea or thiazolidinedione to metformin monotherapy between January 2001 and January 2006. Included patients were required to have at least one hemoglobin A1c (HbA1c) measurement in the 12 months before enrollment and to not be receiving insulin. Demographic and clinical data from medical records were collected using case report forms. Questionnaires measured patient-reported hypoglycemic symptoms, health-related quality of life (EuroQol visual analogue scale, EQ-5D VAS), and treatment-related adverse events. RESULTS: A total of 1,709 patients were included in the study. Mean patient age was 63 years, 45% were female, mean HbA1c was 7.06%, and 28% were at HbA1c goal (HbA1c < 6.5%). Hypoglycemic symptoms during the 12 months before enrollment were reported by 38% of patients; among whom 68% reported their most severe symptoms were mild, 27% moderate, and 5% severe. Adjusted linear regression analyses revealed that patients reporting hypoglycemic symptoms had significantly lower EQ-5D VAS scores indicating worse patient-reported quality of life (mean difference -4.33, p < 0.0001). Relative to those not reporting symptoms, the adjusted decrement to quality of life increased with greater hypoglycemic symptom severity (mild: -2.68, p = 0.0039; moderate: -6.42, p < 0.0001; severe: -16.09, p < 0.0001). Patients with hypoglycemia reported significantly higher rates of shakiness, sweating, excessive fatigue, drowsiness, inability to concentrate, dizziness, hunger, asthenia, and headache (p < 0.0001 for each comparison). CONCLUSIONS: Hypoglycemic symptoms and symptom severity have an adverse effect on patients' rating of their health related quality of life state. Hypoglycemic symptoms are correlated with treatment-related adverse effects. Minimizing the risk and severity of hypoglycemia may improve patients' quality of life and clinical outcomes. Results are subject to limitations associated with observational studies including the potential biases due to unobserved patient heterogeneity and the use of a convenience sample of patients.

Differences in baseline characteristics between patients prescribed sitagliptin versus exenatide based on a US electronic medical record database.

INTRODUCTION: Sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, and exenatide, an injectable glucagon-like peptide-1 receptor agonist, are incretin-based therapies for the treatment of type 2 diabetes. This study examined differences in baseline characteristics between patients with type 2 diabetes initiating sitagliptin vs. exenatide treatment in clinical practice settings in the US. METHODS: The General Electric Healthcare's Clinical Data Services electronic medical records database, covering 12 million US patients of all ages from 49 states, was used to identify patients with type 2 diabetes, aged > or =30 years, who received their first sitagliptin or exenatide prescription between October 1, 2006 and June 30, 2008 (index period). Patient's medical records, including demographics, diagnoses, procedures, prescriptions, and laboratory results were extracted for the 12-month period (baseline) prior to the date of the first prescription of sitagliptin or exenatide (ie, the index date). Patient baseline profiles were stratified by mono-, dual, or triple therapy and compared between regimens with sitagliptin or exenatide. RESULTS: A total of 9543 patients initiated therapy with sitagliptin (n=5589) or exenatide (n=3954) during the index period. For those initiating monotherapy, 876 patients initiated sitagliptin and 476 initiated exenatide. Compared with patients initiating exenatide at baseline, patients on sitagliptin were older (64 vs. 55 years), more likely to be men (45% vs. 35%), and less likely to be obese (60% vs. 87%), and had higher hemoglobin A(1c) (HbA(1c); 7.1% vs. 6.9%), a higher serum creatinine (1.2 mg/dL vs. 1.0 mg/dL), and a higher prevalence of pre-existing cardiovascular complications or microvascular conditions (all P<0.01 for sitagliptin vs. exenatide). For dual therapy, 1885 were prescribed sitagliptin and 1392 were prescribed exenatide. For triple therapy, 2828 were prescribed sitagliptin and 2086 were prescribed exenatide. The observed patient profile differences with dual and triple therapy were generally consistent with those observed with monotherapy. CONCLUSION: In a clinical practice setting, there are differences in the baseline characteristics of patients with type 2 diabetes who are prescribed sitagliptin relative to those prescribed exenatide. These findings have important implications for conclusions drawn from observational studies using medical record or claim databases, as estimated clinical and health outcomes measures may be biased due to channeling of patients to different therapies based on different baseline characteristics.

Baseline characteristic differences between patients prescribed sitagliptin vs. other oral antihyperglycemic agents: analysis of a US electronic medical record database.

AIMS: This study examined the relationship of baseline characteristics and medication use in patients with type 2 diabetes who were prescribed sitagliptin versus other oral antihyperglycemic agents in clinical practice settings in the United States. METHODS: The General Electric Healthcare's Clinical Data Services electronic medical record (EMR) database, covering 12 million US patients of all ages from 49 states, was used to identify patients with type 2 diabetes, aged >or=30 years, who received their first sitagliptin, metformin, sulfonylurea, or thiazolidinedione prescription between October 2006 and June 2008 (index period) as part of new mono-, dual, or triple therapy regimens. Patient demographics, diagnoses, prescriptions, and laboratory results were extracted for the 12-month period (baseline) prior to the index date (i.e., date of first prescription). Data were stratified by mono-, dual, or triple therapy and compared between sitagliptin regimens and non-sitagliptin regimens with other oral agents (metformin, sulfonylureas, or thiazolidinediones). Adjusted logistic regression analyses were used to estimate odds ratios (OR) associated with prescribing sitagliptin versus other oral monotherapy in relation to patient baseline characteristics. RESULTS: Among 41,836 patients new to oral monotherapy, 876 (2.1%) received sitagliptin. Compared to patients initiating non-sitagliptin monotherapy, patients on sitagliptin monotherapy were older (64 vs. 60 years) and had lower body mass index (33 kg/m(2) vs. 34 kg/m(2)), higher serum creatinine (1.2 vs. 1.0 mg/dL), higher prevalence of chronic renal disease (7.2% vs. 1.9%), greater use of lipid-lowering agents (42% vs. 38%), and higher prevalence of cardiovascular conditions (CVD: 12.7% vs. 8.3%) and microvascular complications (MVD: 13.4% vs. 5.8%) (all p < 0.05). Of 22,683 patients new to dual therapy, 1885 (8.3%) were on sitagliptin regimens. Relative to patients on non-sitagliptin dual therapy regimens, patients prescribed sitagliptin as part of dual therapy regimens were older and had higher serum creatinine, higher prevalence of CVD, MVD, or chronic renal disease, and greater use of lipid-lowering and antihypertensive agents (all p < 0.05). Among 9967 patients new to triple therapy, 2828 (28.4%) were on triple therapy regimens with sitagliptin. Relative to patients on non-sitagliptin triple therapy regimens, patients on sitagliptin as part of triple therapy regimens were older, and had higher serum creatinine and greater use of antihypertensive or lipid-lowering agents (all p < 0.05). Adjusted logistic regression showed that significant predictors of being prescribed sitagliptin monotherapy were older age (OR 1.01, 95% CI 1.00, 1.02), higher HbA(1c) level (OR 1.10, 95% CI 1.04, 1.17), higher serum creatinine level (OR 1.22, 95% CI 1.08, 1.39), presence of MVD (OR 1.50, 95% CI 1.08, 2.09), and presence of chronic renal disease (OR 2.22, 95% CI 1.41, 3.49). LIMITATIONS: Diabetes care delivered by non-participating physicians is not captured in the GE CDS EMR database and, therefore, the prevalence of the diseases identified based on ICD-9 diagnosis/procedure and CPT codes provided in the Appendix may be underestimated. Duration of diabetes was not consistently recorded and some measures were not available. CONCLUSION: Patients with type 2 diabetes who were prescribed sitagliptin regimens in clinical practice were older and more likely to have pre-existing co-morbid conditions compared to patients receiving non-sitagliptin regimens with other common oral antihyperglycemic agents. These findings have important implications for observational studies in that estimated clinical and health outcome measures may be biased due to channeling of patients to different therapies based on different baseline characteristics.

Pre-existing cardiovascular diseases and glycemic control in patients with type 2 diabetes mellitus in Europe: a matched cohort study.

BACKGROUND: Although there is a growing body of evidence showing that patients with type 2 diabetes mellitus (T2DM) have poor glycemic control in general, it is not clear whether T2DM patients with pre-existing cardiovascular diseases (CVD) are more or less likely to have good glycemic control than patients without pre-existing CVD. Our aim was to examine the degree of glycemic control among T2DM patients in Europe with and without pre-existing CVD. METHODS: This is a matched cohort study based on a multi-center, observational study with retrospective medical chart reviews of T2DM patients in Spain, France, United Kingdom, Norway, Finland, Germany, and Poland. Included patients were aged >= 30 years at time of diagnosis of T2DM, had added a SU or a PPARgamma agonist to failing metformin monotherapy (index date) and had pre-existing CVD (cases). A control cohort with T2DM without pre-existing CVD was identified using 1:1 propensity score matching. With difference-in-difference approach, logistic and linear regression analyses were applied to identify differences in glycemic control by CVD during the follow up period, after controlling for baseline demographics, clinical information, and concurrent anti-hyperglycemic medication use. RESULTS: The percentage of case patients with adequate glycemic control relative to control patients during the 1st, 2nd, 3rd, and 4th years after the index date was 19.9 vs. 26.5, 16.8 vs. 26.5, 18.8 vs. 28.3, and 16.8 vs. 23.5 respectively. Cases were significantly less likely to have adequate glycemic control (odds ratio: 0.62; 95% confidence interval: 0.46-0.82) than controls after adjusting for baseline differences, secular trend, and other potential confounding covariates. CONCLUSIONS: T2DM patients with pre-existing CVD tended to have poorer glycemic control than those without pre-existing CVD, all other factors being equal. It suggests that clinicians may need to pay more attention to glycemic control among T2DM patients with CVD.

The impact of acute myocardial infarction and stroke on health care costs in patients with type 2 diabetes in Sweden.

BACKGROUND: Estimates of the economic impact of cardiovascular events in patients with type 2 diabetes are scarce. The aim of this study was to determine the health care costs associated with acute myocardial infarction (AMI) and stroke in patients with type 2 diabetes in Sweden. DESIGN: Population-based open cohort study of 9941 patients with type 2 diabetes retrospectively identified in primary care records at 26 centres in Uppsala County. METHODS: Episodes of AMI and stroke suffered by study patients were tracked in the Swedish National Inpatient Register. Annual per patient costs of health care were computed for the years 2000-2004 using register data covering inpatient care, outpatient hospital care, primary care and drugs. Panel data regression was applied to determine the impact of suffering a first or repeat AMI or stroke on health care costs during the year of the event and in subsequent years. RESULTS: Total health care costs of patients suffering a first AMI/stroke increased by 4.1/6.5 during the year of the event [95% confidence interval (CI): 3.1-5.4/4.9-8.5] and by 1.1/1.4 during subsequent years (95% CI: 1.0-1.3/1.2-1.6), controlling for age, sex, the event of amputation and presence of renal failure, heart failure and diabetic eye disease. Total health care costs of patients suffering a first or repeat AMI/stroke increased by 4.1/6.4 during the year of an event (95% CI: 3.2-5.2/5.0-8.1) but were not significantly higher during subsequent years. CONCLUSION: Estimates of the costs related to major cardiovascular complications of type 2 diabetes are critical input to economic evaluations.

Cholesterol reduction yields clinical benefits: meta-analysis including recent trials.

BACKGROUND: Previous meta-analyses reported by Gould et al found significant decreases of 15% in the risk for coronary heart disease (CHD)-related mortality and 11 % in risk for all-cause mortality per decrease of 10% in total cholesterol (TC) level. OBJECTIVE: To evaluate the effects of reducing cholesterol on clinical events after including data from recent clinical trials. METHODS: Using a literature search (MeSH key terms, including: bezafibrate, coronary disease, efficacy, gemfibrozil, hydroxymethylglutaryl-CoA reductase inhibitors, hypercholesterolemia, niacin [nicotinic acids], randomized controlled trials, and treatment outcome; years: 1999-2005), we identified trials published in English that assessed the effects of lipid-modifying therapies on CHD end points, including CHD-related death, myocardial infarction, and angina pectoris. We also included all studies from the previously published meta-analysis. Using the same analytic approach as previously, we determined the effects of net absolute reductions (1 mmol/L [38.7 mg/dL]) in TC and low-density lipoprotein cholesterol (LDL-C) on the relative risks (RRs) for all-cause mortality, CHD-related mortality, any CHD event (mortality or nonfatal myocardial infarction), and non-CHD-related mortality. RESULTS: We included 62 studies involving 216,616 patients, including 126,474 from 24 randomized controlled trials the findings of which were published since the previous meta-analysis (1998). Among all patients, for every 1-mmol/L decrease in TC, there was a 17.5 reduction in RR for all-cause mortality; 24.5 %, for CHD-related mortality; and 29.5% for any CHD event. Corresponding reductions for every 1-mmol/L decrease in LDL-C were 15.6%, 28.0%, and 26.6%, respectively. Similar relationships were observed in patients without CHD. No significant relationship was found between lipid reduction and non-CHD-related mortality risk. CONCLUSIONS: The results from the present analysis support conclusions from previous meta-analyses that cholesterol lowering is clinically beneficial in patients with CHD or at elevated CHD risk. These results also support the previous finding that non-CHD-related mortality is unrelated to lipid reductions.

Development and validation of stroke risk equation for Hong Kong Chinese patients with type 2 diabetes: the Hong Kong Diabetes Registry.

OBJECTIVE: We sought to develop stroke risk equations for Chinese patients with type 2 diabetes in Hong Kong. RESEARCH DESIGN AND METHODS: A total of 7,209 Hong Kong Chinese type 2 diabetic patients without a history of stroke at baseline were analyzed. The data were randomly and evenly divided into the training subsample and the test subsample. In the training subsample, stepwise Cox models were used to develop the risk equation. Validation of the U.K. Prospective Diabetes Study (UKPDS) stroke risk engine and the current stroke equation was performed in the test dataset. The life-table method was used to check calibration, and the area under the receiver operating characteristic curve (aROC) was used to check discrimination. RESULTS: A total of 372 patients developed incident stroke during a median of 5.37 years (interquartile range 2.88-7.78) of follow-up. Age, A1C, spot urine albumin-to-creatinine ratio (ACR), and history of coronary heart disease (CHD) were independent predictors. The performance of the UKPDS stroke engine was suboptimal in our cohort. The newly developed risk equation defined by these four predictors had adequate performance in the test subsample. The predicted stroke-free probability by the current equation was within the 95% CI of the observed probability. The aROC was 0.77 for predicting stroke within 5 years. The risk score was computed as follows: 0.0634 x age (years) + 0.0897 x A1C + 0.5314 x log(10) (ACR) (mg/mmol) + 0.5636 x history of CHD (1 if yes). The 5-year stroke probability can be calculated by: 1 - 0.9707(EXP (Risk Score - 4.5674)). CONCLUSIONS: Although the risk equation performed reasonably well in Chinese type 2 diabetic patients, external validation is required in other populations.

Asthma and allergy medication use and costs among pediatric primary care patients on asthma controller therapy.

As observational studies in children initiating GINA-Step 3 therapies are scarce, we evaluated outcomes and costs in a primary care cohort. Two-yr retrospective cohort study included French children (age: 6-14) continuously followed in BKL-Thalès database who received > or =2 consecutive prescriptions for GINA-Step 3 therapy (=addition of montelukast or other controllers ('other'), such as increasing inhaled-corticosteroid dose (hICS), adding long-acting beta agonist (LABA), or ICS + LABA). After matching on gender and propensity score, medication use [rescue (short-acting beta agonists), acute (antibiotics (AB), oral corticosteroids (OCS)), allergy (antihistamines, nasal steroids) and other respiratory] was estimated via mean number of prescriptions and mean cost (per child/per month), and cost trends. During 12-month follow-up, children adding montelukast (n = 71) vs. 'other' (n = 213) had similar asthma rescue/acute and allergy medication use. Subgroup with asthma and allergic rhinitis (A + AR) adding montelukast used less OCS and AB (p = 0.014). Two-yr cost trends suggest stable asthma/allergy medication use in montelukast group (0.83 euro) compared with increase in 'other' (5.39 euro), which was driven by nasal steroid use [0.32 euro ('other') vs. -0.04 euro (montelukast), p = 0.0013]. In subgroup with A + AR decline in asthma/allergy medication use in montelukast group (-0.47 euro) vs. increase in 'other' (11.05 euro), p = 0.015, was driven by differences in AB and OCS (p = 0.04) and nasal steroid use (p = 0.001). Concomitant asthma/allergy medication use was similar in children adding montelukast or 'other' controllers (hICS, LABA, ICS + LABA), while children with allergic rhinitis on montelukast used less AB. Concomitant medication costs after addition of montelukast remained stable, while 'other' group experienced increase, especially in children with concomitant allergic rhinitis.

Factors associated with the effect-size of thiazolidinedione (TZD) therapy on HbA(1c): a meta-analysis of published randomized clinical trials.

OBJECTIVE: To examine factors affecting the size of the HbA(1c) response to thiazolidinedione (TZD) therapy. RESEARCH DESIGN AND METHODS: Meta-analysis of randomized TZD controlled trials which were identified using PubMed, EBSCO and Sci-lit databases and were published in English. Sociodemographic and clinical data were extracted from each trial. HbA(1c) effect size was defined as either a placebo-subtracted change in HbA(1c) or a change in HbA(1c) from baseline. Weighted multivariable regression was used to examine factors associated with changes in HbA(1c). Bootstrapped smearing estimates were computed to obtain reliable estimates of HbA(1c) effect size. RESULTS: Forty-two trials yielded 60 trial arms which represented 8322 patients treated with thiazolidinediones. Weighted placebo-subtracted change in HbA(1c) was -0.99% +/- 0.02% with an average baseline HbA(1c) of 9.1% +/- 1.0%. Weighted bootstrapped smearing estimate of the placebo-subtracted change in HbA(1c) was -1.02% +/- 0.004%. After controlling for other variables, the baseline HbA(1c) level had a significant negative association with placebo-subtracted HbA(1c) change (p = 0.004) and also with change in HbA(1c) from baseline (p = 0.002). Longer trial duration was associated with greater placebo-subtracted HbA(1c) change (p = 0.01) but not with the change in HbA(1c) from baseline. The multivariable models explained 72% of the variation in placebo-subtracted HbA(1c) change. It was not possible to estimate effects of the run-in period and obesity on TZD effect size. CONCLUSION: Baseline HbA(1c) and trial duration significantly impacted the effect size of TZD therapy on HbA(1c). Age, gender, duration of diabetes and prior use of anti-diabetic therapy were not associated with the TZD effect size.

Cost effectiveness of adding ezetimibe to atorvastatin therapy in patients not at cholesterol treatment goal in Canada.

INTRODUCTION: This analysis compared the cost effectiveness of adding ezetimibe to atorvastatin therapy versus atorvastatin titration or adding cholestyramine (a resin) for patients at high risk of a coronary artery disease (CAD) event who did not reach target cholesterol levels on their current atorvastatin dosage. The primary analysis focused on 65-year-old patients with low-density lipoprotein cholesterol (LDL-C) levels of 3.1 or 3.6 mmol/L with a treatment goal of <2.5 mmol/L, classified as very high risk according to the 2000 Canadian Guidelines for Management and Treatment of Hyperlipidaemia. METHODS: A previously developed Markov model was utilised to capture the cost and clinical consequences of lipid-lowering therapy in primary and secondary prevention of CAD. Comparisons between treatment strategies were made using ICERs (cost per QALY) from a Canadian Ministry of Health perspective. The effects of lipid-lowering therapies were based on clinical trial data. The risks of CAD events were estimated using Framingham Heart Study risk equations. Treatment costs and the costs of acute and long-term care for CAD events were included in the analysis. Costs (Canadian dollar, 2002 values) and outcomes were discounted at 5% per annum. RESULTS: Ezetimibe added to atorvastatin therapy compared with treatment with the most common fixed atorvastatin daily dosage (10 mg) or with common atorvastatin titration strategies (up to 20 mg daily; up to 40 mg daily) resulted in cost per QALY estimates ranging from 25,344 to 44,332 Canadian dollars. The addition of ezetimibe to atorvastatin therapy was less costly and more effective than the addition of cholestyramine (dominant). CONCLUSION: Our analysis suggests that adding ezetimibe to atorvastatin for patients not achieving treatment goals with their current atorvastatin dose produces greater clinical benefits than treatment with a fixed-dose atorvastatin or atorvastatin titration at an increased overall cost. The cost-effectiveness ratios provide strong evidence for the adoption of ezetimibe within the Canadian healthcare system.

Association between achieving treatment goals for lipid-lowering and cardiovascular events in real clinical practice.

BACKGROUND: There is substantial evidence that treatment with lipid-lowering agents can decrease cardiovascular morbidity and total mortality in patients with elevated serum lipid values and/or prior ischaemic heart disease. However, only a minority of these high-risk patients are believed to receive treatment, and among those who do receive pharmaceutical treatment the majority do not reach the therapeutic goal. Our goal was to investigate if this translates to a higher risk of cardiovascular events in real clinical practice. DESIGN: A retrospective cohort study using linkage of electronic medical records, the Swedish national inpatient registry and cause of death registry was performed, enrolling a total of 4976 patients who received treatment with a lipid-lowering agent at any time between 1 January 1993 and 1 December 2001. METHODS: Cox proportional hazards regression was used to evaluate the impact of goal attainment along with potential confounding factors. RESULTS: Patients who reached treatment goals were 24% less likely to suffer a cardiovascular event (relative risk: 0.76, 95% confidence interval: 0.60-0.96) than patients who did not reach treatment goals. A substantial proportion of patients treated with lipid-lowering agents do not achieve the treatment goals. CONCLUSIONS: Failure to reach treatment goals translates into a higher risk of cardiovascular events, and it is thus of importance to ensure that patients reach goals.

Asthma rescue and allergy medication use among asthmatic children with prior allergy prescriptions who initiated asthma controller therapy.

BACKGROUND: Asthma and allergic rhinitis are frequently comorbid conditions. Montelukast is effective in treating both diseases and may reduce total medication use among children with asthma and allergic rhinitis. OBJECTIVE: To determine the differences in respiratory and allergy medication use and costs, as proxies for control, in pediatric patients with asthma and allergy who initiated asthma controller therapy. METHODS: A 24-month, retrospective, pre-post cohort study using a pharmacy claims database of children (age < 16 years) with 2 or more consecutive asthma controller prescriptions and 1 or more allergy prescription (within 12 months before initial controller prescription). Children taking inhaled corticosteroids (ICSs) and montelukast were matched one to one based on age, days of prior allergic rhinitis therapy supply, duration of controller therapy, and propensity score. Differences in costs of rescue or acute asthma medications, prescription allergy medications, other respiratory medications, and the number of days of rescue or acute asthma medication use and allergy medication use were calculated. RESULTS: A total of 1,236 children were matched into ICS and montelukast groups (n = 618 each). Montelukast patients had a smaller cost increase overall compared with ICS patients (combined cost for rescue or acute asthma medications, allergy medications, and other respiratory medications: $5.55 vs $12.08, P < .001). Cost increase for rescue or acute asthma medications was significantly lower in the montelukast group ($0.94 vs $3.82, P = .003). The cost increase for allergy medications ($5.29 vs $10.06, P < .001) was also significantly lower in the montelukast group. Patients taking montelukast also had fewer days of therapy with asthma rescue medication and allergy medication compared with patients taking ICSs. CONCLUSIONS: Initiating therapy with montelukast was associated with better asthma and allergy control demonstrated via lower increase in use and costs of asthma rescue and allergy medications compared with initiating ICS therapy.

Real-world effectiveness of lipid-lowering therapy in male and female outpatients with coronary heart disease: relation to pre-treatment low-density lipoprotein-cholesterol, pre-treatment coronary heart disease risk, and other factors.

BACKGROUND: Determinants of the real-world effectiveness of lipid-lowering therapy have been rarely assessed in an unselected observational coronary heart disease (CHD) community cohort over time. DESIGN: Randomly drawn patients (n=605) from randomly drawn practices (n=62) were retrospectively followed for a median of 3.6 years (1998-2002) on lipid-lowering therapy (98% statins). METHODS: Coronary heart disease population-averaged estimates and variances accounting for repeated measurements within patients were obtained using generalized estimating equations. RESULTS: Post-treatment low-density lipoprotein-cholesterol (LDL-C) was 124 mg/dl in men and 141 mg/dl in women and was independently associated (all P<0.05) with pre-treatment LDL-C (+3.7 mg/dl per 10 mg/dl increment), female sex (+14.0 mg/dl), coronary bypass (-9.5 mg/dl), drug-treated diabetes mellitus (-6.8 mg/dl), and era 2002/2001 versus 1999/2000 (-6.4 mg/dl) in age-adjusted multivariate analyses. Holding pre-treatment LDL-C constant post-treatment LDL-C was associated with pre-treatment Framingham CHD risk in men (-13.9 mg/dl per doubling of risk), whereas LDL-C control in women resembled that in low-risk men. The likelihood of attaining LDL-C <100 mg/dl was 0.28 in men and 0.17 in women and was likewise associated with the above factors. CONCLUSION: Low-density lipoprotein-cholesterol control remained low despite lipid-lowering therapy across a wide range of pre-treatment LDL-C and pre-treatment CHD risk. Low-density lipoprotein-cholesterol control in women was inferior to that in men, a finding that warrants attention and clarification.

Quality of life during pollen season in patients with seasonal allergic rhinitis with or without asthma.

OBJECTIVES: We studied the evolution of generic and rhinoconjunctivitis-specific quality of life (QOL) during pollen season in patients with isolated seasonal allergic rhinitis (SAR) and those with asthma and concomitant SAR (AS+SAR). Generic QOL between groups was also compared at pollen peak. METHODS: A prospective cohort study was conducted in Southern France in 2002. Outpatients aged 18-60, regularly visiting respiratory physicians for SAR, were recruited before the grass (grass cohort) or ragweed pollination period (ragweed cohort). Before the pollination period (baseline) and at peak pollination, patients completed French versions of the Mini Rhinoconjuctivitis Quality of Life Questionnaire (Mini-RQLQ) and physical and mental Short Form-12 (SF-12) scores (PCS and MCS) to determine rhinoconjunctivitis and generic QOL. RESULTS: Totals of 83 and 52 patients were included in the SAR and AS+SAR groups, respectively (mean age=35.4; 56.4% females). Mini-RQLQ scores indicated slightly worse QOL in the A+SAR group at inclusion, which significantly deteriorated at the time of pollen peak, both in the SAR (p<0.0001) and AS+SAR groups (p=0.003). In univariate analysis, significantly higher SF-12 PCS (meaning better QOL) were observed at pollen peak in the SAR compared with the AS+SAR group (p=0.0008), while the difference for SF-12 MCS was more limited (p=0.05). Results were confirmed in multivariable analyses adjusting for gender, allergy medication use at pollen peak, cohort of inclusion (grass/ragweed) and comorbid conditions. CONCLUSIONS: Significant deterioration in rhinoconjunctivitis-specific QOL was observed through the pollination period in patients with SAR and AS+SAR. At pollen peak, AS+SAR patients experienced significantly worse physical functioning than patients with SAR alone.

Asthma-related health care resource use among asthmatic children with and without concomitant allergic rhinitis.

OBJECTIVE: To determine the incremental effect of allergic rhinitis on health care resource use in children with asthma. DESIGN: Population-based historical cohort study. SETTING: Data in a general practice database in the United Kingdom during 1998 to 2001. PATIENTS: Children 6 to 15 years old with asthma and with >or=1 asthma-related visits to a general practitioner (GP) during a 12-month follow-up period. MAIN OUTCOME MEASURES: Asthma-related hospitalizations, GP visits, and prescription drug costs during the 12-month follow-up period for patients with and without comorbid allergic rhinitis. RESULTS: Of 9522 children with asthma, 1879 (19.7%) had allergic rhinitis recorded in the GP medical records. Compared with children with asthma alone, children with comorbid allergic rhinitis experienced more GP visits (4.4 vs 3.4) and more of them were hospitalized for asthma (1.4% vs 0.5%) during the 12-month follow-up period. In multivariable regression analyses, comorbid allergic rhinitis was an independent predictor of hospitalization for asthma (odds ratio: 2.34; 95% confidence interval [CI]: 1.41-3.91) and was associated with increases in the number of asthma-related GP visits (mean increase: 0.53; 95% CI: 0.52-0.54) and asthma drug costs (mean increase pound: 6.7; 95% CI: 6.5-7.0). The association between allergic rhinitis and higher costs of prescriptions for asthma drugs was independent of asthma severity, measured indirectly by the intensity of use of asthma drugs. CONCLUSIONS: Children with comorbid allergic rhinitis incurred greater prescription drug costs and experienced more GP visits and hospitalizations for asthma than did children with asthma alone. A unified treatment strategy for asthma and allergic rhinitis, as recommended by the Allergic Rhinitis and Its Impact on Asthma initiative, might reduce the costs of treating these conditions.

[Cholesterol goal attainment with lipid lowering drugs. The COMETA Mexico Trial]. / Cumplimiento de las metas con reductores del colesterol en pacientes mexicanos. El estudio COMETA México.

In a retrospective study to determine rate of patients attaining therapeutic LDL-C goal values with lipid-lowering drugs, 20 specialists and general practitioners were selected who enrolled 120 patients whose lipids were measured after at least 12 weeks of treatment. They were grouped in three categories: group A (absolute risk of CHD in 10 years <10%); group B, with 10-20% risk, and group C, with >20% risk. Goal LDL-C values were <160 mg/dL for group A, <130 for group B, and <100 for group C. Mean age was 57 +/- 12 years, 59% were males, and 51% were in group C; 83% took statins, 12% fibrates alone, and 5%, combinations. Atorvastatin and simvastatin were the most used drugs, at medium doses (mean 12 and 27 mg/day). LDL-C was reduced 25%; overall, 22% of patient doses were adjusted. Therapeutic goals were attained in 29% with initial doses and 42% at the end of study. Goal values were better attained in groups with lower risk. No differences were noticed among distinct physician categories. Data show poor compliance with international guidelines and insufficient attainment of therapeutic goals.