A cluster randomized controlled Trial to Evaluate an Ambulatory primary care Management program for patients with dyslipidemia: the TEAM study.

BACKGROUND: Few studies have reported the efficacy of collaborative care involving family physicians and community pharmacists for patients with dyslipidemia. METHODS: We randomly assigned clusters consisting of at least two physicians and at least four pharmacists to provide collaborative care or usual care. Under the collaborative care model, pharmacists counselled patients about their medications, requested laboratory tests, monitored the effectiveness and safety of medications and patients' adherence to therapy, and adjusted medication dosages. After 12 months of follow-up, we assessed changes in low-density lipoprotein (LDL) cholesterol (the primary outcome), the proportion of patients reaching their target lipid levels and changes in other risk factors. RESULTS: Fifteen clusters representing a total of 77 physicians and 108 pharmacists were initially recruited, and a total of 51 physicians and 49 pharmacists were included in the final analyses. The collaborative care teams followed a total of 108 patients, and the usual care teams followed a total of 117 patients. At baseline, mean LDL cholesterol level was higher in the collaborative care group (3.5 v. 3.2 mmol/L, p = 0.05). During the study, patients in the collaborative care group were less likely to receive high-potency statins (11% v. 40%), had more visits with health care professionals and more laboratory tests, were more likely to have their lipid-lowering treatment changed and were more likely to report lifestyle changes. At 12 months, the crude incremental mean reduction in LDL cholesterol in the collaborative care group was -0.2 mmol/L (95% confidence interval [CI] -0.3 to -0.1), and the adjusted reduction was -0.05 (95% CI -0.3 to 0.2). The crude relative risk of achieving lipid targets for patients in the collaborative care group was 1.10 (95% CI 0.95 to 1.26), and the adjusted relative risk was 1.16 (95% CI 1.01 to 1.34). INTERPRETATION: Collaborative care involving physicians and pharmacists had no significant clinical impact on lipid control in patients with dyslipidemia. International Standard Randomized Controlled Trial register no. ISRCTN66345533.

An exploratory case study of the impact of expanding cost-effectiveness analysis for second-line nivolumab for patients with squamous non-small cell lung cancer in Canada: Does it make a difference?

INTRODUCTION: Health technology appraisal agencies often rely on cost-effectiveness analyses to inform coverage decisions for new treatments. These assessments, however, frequently measure a treatment's value from the payer's perspective, and may not capture value generated from reduced caregiving costs, increased productivity, value based on patient risk preferences, option value or the insurance value to non-patients. METHODS: To examine how using a broader societal perspective of treatment value affects cost-effectiveness estimates, this case study analyzed the net monetary benefit (NMB) of second-line nivolumab treatment of patients with squamous non-small cell lung cancer (NSCLC) in Canada. The comparator was treatment with docetaxel. NMB was measured from three perspectives: (i) traditional payer, (ii) traditional societal and (iii) broad societal. RESULTS: Nivolumab was more effective (increased quality-adjusted life years by 0.66 versus docetaxel), but also increased costs by $100,168 CAD. When valuing a quality-adjusted life year at $150,000, the net monetary benefit from the payer perspective suggested that costs modestly exceed benefits (NMB: -$1031). Adopting a societal perspective, however, nivolumab's benefits outweighed its costs (NMB: +$6752 and +$91,084 from the traditional and broad societal perspectives, respectively). CONCLUSION: Broadening cost-effectiveness analysis beyond the traditional payer perspective had a significant impact on the result and should be considered in order to capture all treatment benefits and costs of societal relevance.

Economic evaluation of nivolumab for the treatment of second-line advanced squamous NSCLC in Canada: a comparison of modeling approaches to estimate and extrapolate survival outcomes.

Background Lung cancer is the most common type of cancer in the world and is associated with significant mortality. Nivolumab demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients with advanced squamous non-small cell lung cancer (NSCLC) who were previously treated. The cost-effectiveness of nivolumab has not been assessed in Canada. A contentious component of projecting long-term cost and outcomes in cancer relates to the modeling approach adopted, with the two most common approaches being partitioned survival (PS) and Markov models. The objectives of this analysis were to estimate the cost-utility of nivolumab and to compare the results using these alternative modeling approaches. Methods Both PS and Markov models were developed using docetaxel and erlotinib as comparators. A three-health state model was used consisting of progression-free, progressed disease, and death. Disease progression and time to progression were estimated by identifying best-fitting survival curves from the clinical trial data for PFS and OS. Expected costs and health outcomes were calculated by combining health-state occupancy with medical resource use and quality-of-life assigned to each of the three health states. The health outcomes included in the model were survival and quality-adjusted-life-years (QALYs). Results Nivolumab was found to have the highest expected per-patient cost, but also improved per-patient life years (LYs) and QALYs. Nivolumab cost an additional $151,560 and $140,601 per QALY gained compared to docetaxel and erlotinib, respectively, using a PS model approach. The cost-utility estimates using a Markov model were very similar ($152,229 and $141,838, respectively, per QALY gained). Conclusions Nivolumab was found to involve a trade-off between improved patient survival and QALYs, and increased cost. It was found that the use of a PS or Markov model produced very similar estimates of expected cost, outcomes, and incremental cost-utility.

Development of an atherogenic metabolic risk factor profile associated with the use of atypical antipsychotics.

BACKGROUND: It is important to assess cardiovascular risk factors to properly verify the potential consequences of atypical antipsychotic-related weight gain. The objective of the present study was to evaluate whether 2 atypical antipsychotics differ regarding their impact on the cardiovascular disease risk profile compared with a reference group. METHOD: We conducted a cross-sectional, multicenter study to assess anthropometric indices of obesity and to obtain a comprehensive fasting metabolic risk profile. Either risperidone or olanzapine had to be prescribed as the first and only antipsychotic for a minimum of 6 months. Patients were compared with a reference group of nondiabetic men. Data were collected from August 1999 to August 2001. RESULTS: Eighty-seven patients treated with olanzapine (N = 42) or risperidone (N = 45) were evaluated. Olanzapine-treated patients had significantly higher plasma triglyceride concentrations (2.01 +/-1.05 vs. 1.34 +/-0.65 mmol/L, p < or =.05), lower high-density lipoprotein (HDL)-cholesterol levels (0.92 +/-0.17 vs. 1.04 +/- 0.21 mmol/L, p < or =.05), higher cholesterol/HDL-cholesterol ratios (5.62 +/-1.70 vs. 4.50 +/- 1.44, p < or =.05), higher apolipoprotein B levels (1.07 +/- 0.35 vs. 0.92 +/- 0.27 g/L, p < or =.05), smaller low-density lipoprotein peak particle diameters (252.6 +/-4.1 vs. 255.2 +/-4.3 A, p <.01), and higher fasting insulin concentrations (103.9 +/- 67.6 vs. 87.5 +/- 56.1 pmol/L, p < or =.05) than risperidone-treated patients. Moreover, 33% of olanzapine-treated patients were carriers of 3 atherogenic features of the metabolic syndrome as opposed to a prevalence of only 11% of risperidone-treated patients. CONCLUSION: These results suggest that olanzapine-treated patients are characterized by a more deteriorated metabolic risk factor profile compared with risperidone-treated patients. These observations raise concerns about the potential differential long-term deleterious effects of some antipsychotics, such as olanzapine, on cardiovascular health.

Hypoglycemia-related emergency department visits and hypoglycemia-related hospitalizations among new users of antidiabetes treatments.

OBJECTIVE: To describe the burden of severe hypoglycemia among new users of insulin and oral antidiabetes drugs (OAD) in terms of 2 hypoglycemia-related outcomes: emergency department (ED) visit and hospitalization. METHODS: We conducted an inception cohort study using the databases of the Quebec health insurance board and the Quebec registry of hospitalizations. The source population was made of individuals 18 years of age or older who were newly dispensed an antidiabetes treatment made of either insulin or OAD between January 1, 2000 and December 31, 2008. Individuals were followed from initiation of antidiabetes treatment to December 31, 2008, occurrence of hypoglycemia-related outcome, loss of eligibility to the drug plan or death, whichever came first. Individuals' characteristics at antidiabetes treatment initiation were described using frequency distributions. The incidence rate for the occurrence of hypoglycemia-related ED visit and hypoglycemia-related hospitalization were calculated using the Kaplan-Meier method. RESULTS: A total of 188 659 new users of antidiabetes treatment were included in the cohort. A total of 3575 (1.9%) individuals had at least 1 hypoglycemia-related ED visit whereas 194 (0.1%) had at least 1 hypoglycemia-related hospitalization. Incidence rates for the occurrence of hypoglycemia-related ED visits and hypoglycemia-related hospitalizations were 5.2 and 0.3 cases per 1000 patient years, respectively. CONCLUSION: Although the incidence of ED visit or hospitalization due to hypoglycemia seems low, severe hypoglycemia episodes could be associated with a high economic burden.

Modeling the lifetime costs of insulin glargine and insulin detemir in type 1 and type 2 diabetes patients in Canada: a meta-analysis and a cost-minimization analysis.

BACKGROUND: Two basal insulin analogues, insulin glargine once daily and insulin detemir once or twice daily, are marketed in Canada. OBJECTIVE: To estimate the long-term costs of insulin glargine once daily (QD) versus insulin detemir once or twice daily (QD or BID) for type 1 (T1DM) and type 2 (T2DM) diabetes mellitus from a Canadian provincial government's perspective. METHODS: A cost-minimization analysis comparing insulin glargine (IGlarg) to insulin detemir (IDet) was conducted using a validated computer simulation model, the CORE Diabetes Model. Lifetime direct medical costs including costs of insulin treatment and diabetes complications were projected. T1DM and T2DM patients' daily insulin dose (T1DM: IGlarg QD 26.2 IU; IDet BID 33.6 IU; T2DM: IGlarg QD 47.2 IU; IDet QD 65.7 IU or IDet BID 80.4 IU) was derived from a meta-analysis of randomized trials. All patients were assumed to stay on the same treatment for life. Costs were discounted at 5% per annum and reported in 2010 Canadian Dollars. RESULTS: The meta-analysis showed T1DM and T2DM patients had similar HbA(1c) change from baseline when receiving IGlarg compared to IDet (T1DM: 0.002%-points; p = 0.97; T2DM: -0.05%-points; p = 0.28). Treatment of T1DM patients with IGlarg versus IDet BID resulted in lifetime cost savings of $4231 per patient. Treatment of T2DM patients with IGlarg resulted in lifetime cost savings of $4659 per patient versus IDet QD and cost savings of $8709 per patient versus IDet BID. CONCLUSIONS: Similar HbA(1c) change from baseline can be achieved with a lower IGlarg than IDet dose. From the perspective of a Canadian provincial government, treatment of T1DM and T2DM patients with IGlarg instead of IDet can generate long-term cost savings. Main limitations include trial data were derived from multi-country studies rather than the Canadian population and self-monitoring blood glucose costs were not included.

Physician-pharmacist collaborative care in dyslipidemia management: the perception of clinicians and patients.

BACKGROUND: Collaborative practices allow physicians and pharmacists to comanage pharmacotherapy to maximize the benefits of medication regimens. The Trial to Evaluate an Ambulatory primary care Management program for patients with dyslipidemia (TEAM) study compared the efficacy of a physician-pharmacist collaborative primary care (PPCC) intervention, where pharmacists requested laboratory tests and adjusted medication dosage, to the usual care (UC) for patients under treatment with lipid-lowering medication. OBJECTIVE: In a qualitative study nested within the TEAM study, the perceptions of physicians, pharmacists, and patients regarding the PPCC model, interprofessional collaboration, and the clinicians' willingness to implement the model in their practice were explored. METHODS: In the area of Montreal (Quebec, Canada), TEAM study participants assigned to the PPCC group were invited to participate. Individual semistructured interviews with physicians (n=7) and 2 six-member focus groups with pharmacists (n=12) and patients (n=12) were analyzed using a phenomenological approach. RESULTS: The vast majority of participants reported PPCC was more structured and systematic than the UC they had received previously, wherein physicians prescribe and adjust pharmacotherapy and pharmacists provide the counseling and dispense medications. Many patients felt they received better follow-up and reported being reassured and well informed, making them more inclined to care for themselves better. These feelings were attributed largely to the pharmacists' accessibility and ability to communicate with them easily. Given the physician shortage, physicians perceived interprofessional collaboration as almost inevitable. They considered PPCC to be safe and effective. However, obstacles were also identified. Physicians were concerned that it might alter their special relationship with patients and threaten their overall medical follow-up. Pharmacists felt enthusiastic about their new role, but found PPCC time consuming and thought it might not be applicable to all the patients. CONCLUSIONS: PPCC model was highly appreciated by patients, and clinicians saw it as beneficial to patients. However, several obstacles still have to be overcome before the model can be implemented in the current health care context.

Physician-pharmacist collaborative care for dyslipidemia patients: knowledge and skills of community pharmacists.

INTRODUCTION: In a physician-pharmacist collaborative-care (PPCC) intervention, community pharmacists were responsible for initiating lipid-lowering pharmacotherapy and adjusting the medication dosage. They attended a 1-day interactive workshop supported by a treatment protocol and clinical and communication tools. Afterwards, changes in pharmacists' knowledge, their skills, and their satisfaction with the workshop were evaluated. METHODS: In a descriptive study nested in a clinical trial, pharmacists assigned to the PPCC intervention (n = 58) completed a knowledge questionnaire before and after the workshop. Their theoretical skills were evaluated with the use of a vignette approach (n = 58) after the workshop and their practical skills were assessed by direct observation with study patients (n = 28). RESULTS: The mean (SD) overall knowledge score was 45.8% (12.1%) before the workshop; it increased significantly to 89.3% (8.3%) afterwards (mean difference: 43.5%; 95% CI: 40.3%-46.7%). All the pharmacists had an overall theoretical-skill score of at least 80%, the minimum required to apply the PPCC in the trial. From 92.9% to 100% of the pharmacists' interventions with study patients complied with the treatment protocol. DISCUSSION: In primary care, a short continuing-education program based on a specific treatment protocol and clinical tools is necessary and probably sufficient to prepare pharmacists to provide advanced pharmaceutical care.