Re-examining the factor structure of the Insomnia Severity Index (ISI) and defining the meaningful within-individual change (MWIC) for subjects with insomnia disorder in two phase III clinical trials of the efficacy of lemborexant.

BACKGROUND: The Insomnia Severity Index (ISI) is a widely used measure of insomnia severity. Various ISI research findings suggest different factor solutions and meaningful within-individual change (MWIC) to detect treatment response in patients with insomnia. This study examined an ISI factor solution and psychometric indices to define MWIC in a robust patient sample from clinical trial settings. METHODS: We endeavored to improve upon previous validation of ISI by examining structural components of confirmatory factor analysis (CFA) models using two large, placebo-controlled clinical trials of lemborexant for insomnia. Using the best-fitting two-factor solution, we evaluated anchor-based, distribution-based and receiver operating characteristic (ROC) curve methods to derive an estimate of the MWIC. RESULTS: The model structure for the 7-item scale proposed in other research did not fit the observed data from our two lemborexant clinical trials (N = 1956) as well as a two-factor solution based on 6 items did. Using triangulation of anchor-based, distribution-based, and ROC methods, we determined that a 5-point reduction using 6 items best represented a clinically meaningful improvement in individuals with insomnia in our patient sample. CONCLUSIONS: A 6-item two-factor scale had better psychometric properties than the 7-item scale in this patient sample. On the 6-item scale, a reduction of 5 points in the ISI total score represented the MWIC. Generalizability of the proposed MWIC may be limited to patient populations with similar demographic and clinical characteristics.

Disease landscape of advanced HER2-breast cancer patients by treatment line in three EU countries and USA.

Aim: To report treatment patterns and quality of life (QoL) in HER2-negative advanced breast cancer patients. Methods: Data were drawn from a cross-sectional survey in Europe and USA. Results: Hormone plus targeted therapy was the most frequent first-line (1L, 62%) and second-line (2L, 45%) treatment for HR+/HER2-patients. Chemotherapy was most frequent at third-line or greater (3L+, 39%) for HR+/HER2- patients, 2L (51%) and 3L+ (48%) for triple negative breast cancer (TNBC) patients. Time to progression was 13.8 (2L) and 11.0 (3L+) months for HR+/HER2- patients. No comparisons were observed for TNBC patients. EQ-5D-5L scores were highest in patients at 1L and lowest at 3L+. Conclusion: Reduced QoL and treatment response were reported in patients at later lines of therapy.

Breast cancer is the most common cancer in women. Differences in survival are seen depending on how widespread or advanced the cancer is, how many different treatments the patient has been given, as well as whether certain receptors on the tumor are present or absent. Many new treatments are available which can target these receptors. These treatments have improved survival in patients with advanced breast cancer, but other benefits for the patient are not always clear. In addition, differences between countries are possible as official guidance can vary. This study aimed to understand these issues, by asking physicians and their patients across Europe and USA for their views on quality of life and satisfaction with their treatments. We found that, in general, physicians prescribed treatments as recommended in the treatment guidelines. As breast cancer progressed and treatment stopped working, patients were switched on to different treatments. Survival, quality of life and treatment satisfaction were all worse in patients who had switched treatments. It appears that the patients lose confidence that their new treatment will work to improve their quality of life. We also saw differences in some of these outcomes between Europe and USA, which were likely due to differences in the treatment guidelines between countries. Both quality of life and treatment satisfaction are important for the well-being of patients with advanced breast cancer as they now live longer with these new treatments. This should be considered by physicians and taken into account for future work.

Understanding the unmet needs in insomnia treatment: a systematic literature review of real-world evidence.

STUDY OBJECTIVE: The objective of this study was to define and characterize the unmet needs in the pharmacological management of insomnia. METHODS: A systematic literature review was conducted to identify relevant literature reporting real-world evidence in insomnia, published from January 2009 to April 2020. Pharmacological treatments - both prescription (benzodiazepines, 'Z-drugs' and suvorexant) and off-label (antidepressants, antipsychotics, and antihistamines) - were considered. RESULTS: Overall, 108 publications describing the humanistic (n = 59) and economic burden (n = 20) of insomnia, off-label treatment patterns (n = 28) and factors influencing treatment adherence or persistence (n = 8) were identified. A high prevalence of comorbid conditions was reported in patients with insomnia resulting in significantly lower health-related QoL compared to those with insomnia or a comorbidity alone. Current treatment options were associated with adverse events, including reduced sleep quality and next-day somnolence. An increased risk of accidents/injuries was also associated with insomnia and its treatment. Furthermore, safety concerns and perceived lack of efficacy for approved treatments have led to frequent off-label prescribing, despite a lack of clinical evidence of risk/benefit ratios. Safety concerns associated with benzodiazepines include risk of dependence, leading to prolonged treatment persistence and exacerbated adverse events, making them unsuitable for use in patients with chronic insomnia. Finally, the substantial economic burden of insomnia was evident, with reduced work productivity demonstrated in patients with insomnia compared to the general population. CONCLUSIONS: This review highlights a clear unmet need for insomnia therapies that improve sleep quality without resulting in next-day impairment and/or dependence.

Cyclin-dependent kinase 4/6 inhibitor treatment use in women treated for advanced breast cancer: Integrating ASCO/NCODA patient-centered standards in a community pharmacy.

BACKGROUND: Outpatients treated with oral anti-cancer drugs, including selective cyclin-dependent kinase 4/6 inhibitors (CDK4/6i), may benefit from a pharmacy practice setting adapted to support proper oral anti-cancer drug monitoring. This real-world study aimed to characterize patient-centered pharmacy practice aligned with American Society of Clinical Oncology (ASCO)/National Community Oncology Dispensing Association (NCODA) standards and to describe its impact on CDK4/6i treatment use. METHODS: This retrospective study included women with confirmed hormone receptor-positive/human epidermal growth factor 2 negative locally advanced or metastatic breast cancer treated with either palbociclib, abemaciclib or ribociclib combined with letrozole or fulvestrant. Pharmacists collected patient characteristics, clinical activities, and treatment patterns using data from the pharmacy chart. CDK4/6i treatment adherence rates were estimated based on medication claims data. Time-to-treatment discontinuation, a proxy for time-to-event, was assessed using the Kaplan-Meier estimate. RESULTS: Of the 195 patients assessed for eligibility, 65 were included in this study. The median observation duration was 13.6 months. An average of seven pharmaceutical care activities (range 2.8-21.7) per patient was documented for each treatment cycle. The mean proportion of days covered was 89.6%. The median time-to-treatment discontinuation was estimated at 44.2 months in patients treated with CDK4/6i + letrozole and 17.0 months in patients treated with CDK4/6i + fulvestrant. The average relative dose intensity was 85%, and the benefits of treatment were maintained regardless of the relative dose intensity levels. CONCLUSION: A structured patient-centered pharmacy practice model integrating the ASCO/NCODA patient-centered standards and ongoing communication with patients and healthcare providers ensure timely refills, close monitoring, and allows patients to achieve high adherence and persistence rates comparable to those reported in clinical trials.

Development of a community pharmacy-based intervention for patients with uncontrolled asthma.

Background: Achieving asthma control is often difficult, despite the availability of effective medications. Because of their expertise, regular contact with patients, and accessibility, community pharmacists can play an important role in helping patients manage uncontrolled asthma. Objective: To develop a community pharmacy-based intervention for improving asthma control in patients with uncontrolled moderate to severe asthma. Methods: A qualitative study involving two focus groups with six and five community pharmacists, respectively, five individual interviews with community pharmacists, and three individual interviews with asthma patients was conducted using semi-structured interview guides. Focus groups aimed to develop the first prototype of the intervention and the topics included criteria to identify patients with uncontrolled asthma, content of the intervention to manage uncontrolled asthma, and potential logistical issues. Interviews were subsequently conducted with individual pharmacists and asthma patients to evaluate the prototype and finalize the intervention. The interviews and focus group transcripts were analyzed thematically, using an iterative process. Results: In focus groups and interviews, the pharmacists discussed how they screen patients with uncontrolled asthma using prescriptions refills, their needs for a convenient tool to assess asthma control, the necessity to identify causes of uncontrolled asthma to guide asthma management strategies, and the importance of patient follow-up. During interviews, patients shared their interest for the commitment of pharmacists to managing asthma. The final intervention consists of structured face-to-face counselling sessions at community pharmacies, with six steps: screening of patients with potential uncontrolled moderate to severe asthma, assessment of asthma control, identification of the causes of uncontrolled asthma, strategies for controlling asthma, an optional follow-up at the next prescription refill, and a follow-up 3 months after the initial intervention. Conclusions: The patients and community pharmacists reached consensus on the intervention's key elements and provided support for implementing the intervention in community pharmacies.

A Pre-Phase III Efficacy Trial of the Spermicide/Contraceptive Effect of the Invisible Condom, a Non-Hormonal Vaginal Gel, in Women from Canada.

OBJECTIVES: To evaluate the spermicidal efficacy of non-hormonal vaginal gel in vitro and in a post-coital test, and to evaluate its contraceptive efficacy in Canadian women of childbearing age. METHODS: We conducted single-centre trial to assess spermicidal and contraceptive efficacy of vaginal gel. Participants were healthy, sexually active women aged 18-49 years and their regular male sexual partners (30 couples). Measured outcomes included effect of vaginal gel on sperm motility in vitro, its effect on sperm in a post-coital test, and its effect on pregnancy prevention over 3 months. RESULTS: For in vitro spermicidal effect, 98% and 67% of sperm were immotile in the presence of the gel with sodium lauryl sulfate (gel-SLS) and gel alone, respectively. For the post-coital test, 99% and 93% of sperm were immotile in the presence of gel-SLS and gel alone, respectively. In the second part of trial, a total of 410 instances of vaginal intercourse in 95 menstrual cycles were protected (during 3-month period of gel-SLS use before each sexual intercourse with probability of 24 conceptions prevented according to Wilcox's table). Four women became pregnant during the study period; 2 during unprotected vaginal intercourse around the time of ovulation, and 2 attributed to user failure. CONCLUSION: Based on our results, the vaginal gel demonstrated important spermicidal and contraceptive effect. A larger phase III contraceptive efficacy trial is warranted. The vaginal gel may represent a non-hormonal spermicide/contraceptive option for women.

Network meta-analysis of eribulin versus other chemotherapies used as second- or later-line treatment in locally advanced or metastatic breast cancer.

BACKGROUND: Eribulin mesylate (ERI; Halaven®) is a microtubule inhibitor approved in the United States for metastatic breast cancer patients with at least two prior chemotherapy regimens for metastatic breast cancer, and in the European Union in locally advanced breast cancer or metastatic breast cancer patients who progressed after at least one chemotherapy for advanced disease. This network meta-analysis compared the efficacy and safety of ERI versus other chemotherapies in this setting. METHODS: Systematic searches conducted in MEDLINE, Embase, and the Cochrane Central Register of Clinical Trials identified randomized controlled trials of locally advanced breast cancer/metastatic breast cancer chemotherapies in second- or later-line settings. Efficacy assessment included pre-specified subgroup analysis of breast cancer subtypes. Included studies were assessed for quality using the Centre for Reviews and Dissemination tool. Bayesian network meta-analysis estimated primary outcomes of overall survival and progression-free survival using fixed-effect models. Comparators included: capecitabine (CAP), gemcitabine (GEM), ixabepilone (IXA), utidelone (UTI), treatment by physician's choice (TPC), and vinorelbine (VIN). RESULTS: The network meta-analysis included seven trials. Results showed that second- or later-line patients treated with ERI had statistically longer overall survival versus TPC (hazard ratio [HR]: 0.81; credible interval [CrI]: 0.66-0.99) or GEM+VIN (0.62; 0.42-0.90) and statistically longer progression-free survival versus TPC (0.76; 0.64-0.90), but statistically shorter progression-free survival versus CAP+IXA (1.40; 1.17-1.67) and CAP+UTI (1.61; 1.23-2.12). In triple negative breast cancer, ERI had statistically longer overall survival versus CAP (0.70; 0.54-0.90); no statistical differences in progression-free survival were observed in triple negative breast cancer. CONCLUSIONS: This network meta-analysis suggests that ERI may provide an overall survival benefit in the overall locally advanced breast cancer/metastatic breast cancer populations and triple negative breast cancer subgroup compared to standard treatments. These findings support the use of ERI in second- or later-line treatment of patients with locally advanced breast cancer/metastatic breast cancer.

Health-related quality of life in pediatric patients with partial onset seizures or primary generalized tonic-clonic seizures receiving adjunctive perampanel.

RATIONALE: Study 311 (E2007-G000-311; NCT02849626) was a Phase 3, multicenter, open-label single-arm study of adjunctive perampanel oral suspension in pediatric patients (aged 4 to <12 years) with partial-onset seizures (POS) (with/without secondarily generalized tonic-clonic seizures [SGTCS]) or primary generalized tonic-clonic seizures (PGTCS). Health-related quality of life (HRQoL) was an exploratory endpoint initially analyzed through simple descriptive summaries. The aim of this post hoc analysis was to provide a more thorough assessment of HRQoL. METHODS: This analysis focused on EQ-5D-Y data collected at Baseline, Week 23, and Week 52. Individual dimensions, visual analog scale (VAS) and summed misery index (MI) were evaluated at all visits and compared by seizure type (POS versus SGTCS versus PGTCS), age (4 to <7 versus 7 to <12), and use of concomitant enzyme-inducing antiepileptic drugs (EIAEDs) (yes versus no). Paretian Classification of Health Change (PCHC) analysis summarized the proportion of patients who showed improvement or deterioration in HRQoL. Waterfall plots assessed changes in EQ-5D-Y scores by treatment-emergent adverse events (TEAEs) and by reduction in seizure frequency. Health state utility values associated with differing seizure frequency states were estimated using a linear mixed model. RESULTS: One hundred and fifteen patients completed EQ-5D-Y at relevant study visits (Seizure type: POS n = 84 [of which 21 had SGTCS], PGTCS n = 31; Age: 4 to <7 years n = 30, 7 to <12 years n = 85; Concomitant EIAEDs: Yes n = 35, No n = 80). Completion rates out of those expected to complete EQ-5D-Y were high at both timepoints (84.4% at Week 23 and 97.2% at Week 52). Overall, VAS/MI remained stable over time (did not exceed minimal important difference); this was similar according to seizure type, age, and EIAED usage. In patients with 'no problems' on any EQ-5D-Y dimension at Baseline, nearly all retained their full health at Week 23 (94.7%), and all retained it at Week 52 (100.0%). PCHC analysis showed fewer patients with POS experienced deterioration in EQ-5D-Y than patients with PGTCS at Week 23 (24.1% versus 42.1%). Not experiencing a TEAE, or remaining seizure-free, was associated with improvements in VAS score at Week 23 compared to those experiencing TEAEs or seizures, respectively. Health state utility values (HSUVs) were estimated as follows: seizure free (LS Mean 0.914 [95% CIs 0.587, 1.240]), ≥1 seizure per year (0.620 [0.506, 0.734]), ≥1 seizure per month (0.596 [0.338, 0.855]), ≥1 seizure per week (0.284 [-0.014, 0.582]). CONCLUSIONS: An in-depth analysis of EQ-5D-Y data allowed for a more nuanced exploration of HRQoL than previous descriptive summaries. Our findings provide evidence that perampanel as adjunctive therapy did not result in deterioration of patient HRQoL. The association between TEAEs or remaining seizure-free and HRQoL warrants further exploration. Increasing seizure frequency was associated with decreasing HSUVs; these can inform cost-effectiveness modeling of perampanel and other therapies aiming to reduce seizure frequency in pediatric patients.

Systematic review of Real-World effectiveness of eribulin for locally advanced or metastatic breast cancer.

BACKGROUND: Eribulin mesylate (eribulin) is indicated for patients with metastatic breast cancer (MBC) who have previously received at least two chemotherapies in the US and for patients with locally advanced breast cancer (LABC) or MBC who have progressed after at least one chemotherapy in the European Union (EU). In both indications, prior therapy should include an anthracycline and a taxane in adjuvant or metastatic setting. Numerous studies evaluated eribulin in real-world (RW) breast cancer populations to reinforce its consistent effectiveness beyond registration randomized controlled trials (RCTs) that reported median overall survival (OS) of 13.1 and 15.9 months. In this systematic literature review (SLR), we summarize the cumulative evidence on eribulin's RW effectiveness in LABC/MBC. METHODS: We searched through Medline/PubMed and Embase databases between 2012 and 2019 for articles reporting RW eribulin use in the second- or third-line or later LABC/MBC setting. Because eribulin showed greatest OS benefits in triple negative breast cancer (TNBC) in RCTs, we also reviewed this tumor subtype. OS and progression-free survival (PFS) were the effectiveness outcomes of interest. RESULTS: Overall, 34 journal articles or abstracts met the selection criteria. Median OS ranged between 6.9 and 28.0 months; median PFS varied from 2.3 to 14.7 months. Eight studies reported OS outcomes for TNBC patients, and median OS ranged between 3.0 and 23.0 months. CONCLUSION: The SLR showed high variability in OS and to a lesser extent in PFS associated with eribulin use in RW setting. Despite heterogeneity in line of use and patient subtypes, this SLR supports effectiveness of eribulin for LABC/MBC in clinical practice.

The initial state of the human gut microbiome determines its reshaping by antibiotics.

Microbiome studies have demonstrated the high inter-individual diversity of the gut microbiota. However, how the initial composition of the microbiome affects the impact of antibiotics on microbial communities is relatively unexplored. To specifically address this question, we administered a second-generation cephalosporin, cefprozil, to healthy volunteers. Stool samples gathered before antibiotic exposure, at the end of the treatment and 3 months later were analysed using shotgun metagenomic sequencing. On average, 15 billion nucleotides were sequenced for each sample. We show that standard antibiotic treatment can alter the gut microbiome in a specific, reproducible and predictable manner. The most consistent effect of the antibiotic was the increase of Lachnoclostridium bolteae in 16 out of the 18 cefprozil-exposed participants. Strikingly, we identified a subgroup of participants who were enriched in the opportunistic pathogen Enterobacter cloacae after exposure to the antibiotic, an effect linked to lower initial microbiome diversity and to a Bacteroides enterotype. Although the resistance gene content of participants' microbiomes was altered by the antibiotic, the impact of cefprozil remained specific to individual participants. Resistance genes that were not detectable prior to treatment were observed after a 7-day course of antibiotic administration. Specifically, point mutations in beta-lactamase blaCfxA-6 were enriched after antibiotic treatment in several participants. This suggests that monitoring the initial composition of the microbiome before treatment could assist in the prevention of some of the adverse effects associated with antibiotics or other treatments.

Evolution of health technology assessment: best practices of the pan-Canadian Oncology Drug Review.

BACKGROUND: In 2007, Canada chose to develop a separate and distinct path for oncology drug health technology assessment (HTA). In 2013, the decision was made to transfer the pan-Canadian Oncology Drug Review (pCODR) to the Canadian Agency for Drugs and Technologies in Health (CADTH), to align the pCODR and CADTH Common Drug Review processes while building on the best practices of both. The objective of this research was to conduct an examination of the best practices established by the pCODR. METHODS: A qualitative research approach was taken to assess the policies, processes, and practices of the pCODR, based on internationally accepted best practice "principles" in HTA, with a particular focus on stakeholder engagement. Publicly available information regarding the approach of the pCODR was used to gauge the agency's performance against these principles. In addition, stakeholder observations and real-world experiences were gathered through key informant interviews to be inclusive of perspectives from patient advocacy groups, provincial and/or cancer agency decision-makers, community and academic oncologists, industry, expert committee members, and health economists. RESULTS: This analysis indicated that, through the pCODR, oncology stakeholders have had a voice in and have come to trust the quality and relevance of oncology HTA as a vital tool to ensure the best decisions for Canadians with cancer and their health care system. It could be expected that adoption of the principles and processes of the pCODR would bring a similar level of engagement and trust to other HTA organizations in Canada and elsewhere. CONCLUSION: The results of this research led to recommendations for improvement and potential extrapolation of these best practices to other HTA organizations worldwide, along with suggestions for continued evolution of the pCODR in conjunction with its integration into the CADTH. It is clear that the transition of the pCODR to CADTH provides an opportunity for practices initiated by the pCODR to become the standard for these newly amalgamated HTA agencies in Canada.

Oncology drug health technology assessment recommendations: Canadian versus UK experiences.

BACKGROUND: CANADA HAS TWO HEALTH TECHNOLOGY ASSESSMENT (HTA) AGENCIES RESPONSIBLE FOR ONCOLOGY DRUG FUNDING RECOMMENDATIONS: the Institut National d'Excellence en Santé et Services Sociaux (INESSS) for the province of Québec and the pan-Canadian Oncology Drug Review for the rest of Canada. The objective of the research was to review and compare the recommendations of these two agencies alongside an international comparator - the National Institute for Health and Care Excellence (NICE) in the United Kingdom - with respect to their recommendations records and the influence of clinical and cost-effectiveness evidence on the recommendations. METHODS: Recommendations were identified from the three agencies from January 1, 2002 to June 1, 2013. Recommendations were limited to five cancer sites (lung, breast, colon, kidney, blood) and to metastatic/advanced settings. Descriptive analyses examined the frequency of positive recommendations and factors related to a positive recommendation. For each recommendation, only publicly available information posted on the agency website was used to abstract data. RESULTS: There was a wide variation in the rate of positive recommendations, ranging from 48% for NICE to 95% for Canada's national process (among the 74% of its recommendations that were publicly posted). Interagency agreement was low, with full agreement for only six of the 14 drugs commonly reviewed by all three agencies. Evidence of a survival gain was not necessary for a positive recommendation; progression-free survival was acceptable. Different approaches were taken when addressing unacceptable cost-effectiveness. NICE was most likely to yield a negative recommendation on these grounds, whereas Canada's national process was most likely to yield a positive recommendation with a required pricing arrangement. CONCLUSION: In this analysis, the primary reason for the observed divergence between agency recommendations appeared to be the availability of mechanisms in each jurisdiction to address cost-effectiveness subsequent to the HTA assessment process. Furthermore, caution is needed when interpreting cross-agency comparisons between HTA agencies, as recommendations may not correspond directly to subsequent funding decisions and actual patient access. This may be a concern, given the high international profile of assessments conducted by the reviewed HTA agencies.

How do cost-effectiveness analyses inform reimbursement decisions for oncology medicines in Canada? The example of sunitinib for first-line treatment of metastatic renal cell carcinoma.

BACKGROUND: Canadian oncology decision-makers have reimbursed cancer drugs at incremental cost-effectiveness ratios (ICER) higher than those considered acceptable in other therapeutic areas. Sunitinib is a multitargeted receptor tyrosine kinase inhibitor, indicated for metastatic renal-cell carcinoma (MRCC) of clear cell histology. Canadian decision-makers evaluated sunitinib funding in the presence of important data limitations (including interim analysis of a surrogate outcome) and in the context of a high ICER. METHODS: First, a description was presented of the cost-effectiveness analysis submitted for sunitinib reimbursement decision-making in Canada before conclusive survival evidence had been available. Second, sunitinib access decisions and the oncology drug reimbursement literature were reviewed to explore the interpretation of sunitinib perceived value in the context of the decision-making framework in Canada. RESULTS: The economic evaluation yielded an ICER of $144K/quality-adjusted life-year gained for sunitinib compared with interferon-alfa. This high ratio was not an insurmountable barrier to access in Canada because all provinces now reimburse sunitinib for first-line treatment of MRCC. In this particular instance, payers were receptive to immature survival data but substantial progression-free gains, for patients with a relatively rare cancer and few treatment options. CONCLUSION: This demonstrates that the cost-effectiveness ratio is only one of many factors that affect an access decision in oncology.

The challenge of conducting pharmacoeconomic evaluations in oncology using crossover trials: the example of sunitinib for gastrointestinal stromal tumour.

This paper examines the challenge of conducting economic evaluations to support patient access to cancer therapies when the cost-effectiveness estimation is hampered by crossover trial design. To demonstrate these limitations, we present the submission to the Canadian Drug Review (CDR) of a cost-effectiveness evaluation of sunitinib versus best supportive care (BSC) for the treatment of gastrointestinal stromal tumour in patients intolerant or resistant to imatinib. The economic model generated an incremental cost-effectiveness ratio for sunitinib versus BSC of dollars 79,884/quality-adjusted life-year gained. Eight months after initial submission, CDR granted a final recommendation to fund sunitinib following the manufacturer's appeal against their first recommendation. Although cost-effectiveness is an important consideration in reimbursement decisions, there is a need for improved decision-making processes for cancer drugs, as well as a better understanding of the limitations of clinical trial design.

Effect of drug utilization reviews on the quality of in-hospital prescribing: a quasi-experimental study.

BACKGROUND: Drug utilization review (DUR) programs are being conducted in Canadian hospitals with the aim of improving the appropriateness of prescriptions. However, there is little evidence of their effectiveness. The objective of this study was to assess the impact of both a retrospective and a concurrent DUR programs on the quality of in-hospital prescribing. METHODS: We conducted an interrupted time series quasi-experimental study. Using explicit criteria for quality of prescribing, the natural history of cisapride prescription was established retrospectively in three university-affiliated hospitals. A retrospective DUR was implemented in one of the hospitals, a concurrent DUR in another, whereas the third hospital served as a control. An archivist abstracted records of all patients who were prescribed cisapride during the observation period. The effect of DURs relative to the control hospital was determined by comparing estimated regression coefficients from the time series models and by testing the statistical significance using a 2-tailed Student's t test. RESULTS: The concurrent DUR program significantly improved the appropriateness of prescriptions for the indication for use whereas the retrospective DUR brought about no significant effect on the quality of prescribing. CONCLUSION: Results suggest a retrospective DUR approach may not be sufficient to improve the quality of prescribing. However, a concurrent DUR strategy, with direct feedback to prescribers seems effective and should be tested in other settings with other drugs.

Retrospective analysis of utilization patterns and cost implications of coxibs among seniors in Quebec, Canada: what is the potential impact of the withdrawal of rofecoxib?

OBJECTIVE: In September 2004, the manufacturer of rofecoxib announced a voluntary worldwide withdrawal of the drug. The impact of this withdrawal on drug budgets is unclear. This study evaluated average daily doses and costs of rofecoxib and celecoxib and concomitant use of gastroprotective agents (GPAs) in elderly patients with osteoarthritis (OA) or rheumatoid arthritis (RA) in Quebec, prior to the rofecoxib withdrawal. METHODS: This retrospective cohort study used prescription drug and medical service data from the Quebec government health agency administrative database and included coxib users > or =66 years of age with OA or RA who filled > or =3 consecutive rofecoxib or celecoxib prescriptions in 2001-2002. Results were adjusted for gastrointestinal risk factors and other patient baseline characteristics. RESULTS: Data were analyzed for 11,975 rofecoxib and 12,480 celecoxib users. Mean daily dosages were 20.7 mg for rofecoxib and 231.3 mg for celecoxib. Rofecoxib users consumed a mean +/- SD of 0.95 +/- 0.43 pills per day, and celecoxib users took 1.34 +/- 0.65 pills per day. Mean +/- SD unadjusted daily acquisition costs were $1.18 +/- $0.53 (Canadian) for rofecoxib and $1.45 +/- $0.74 for celecoxib. After adjusting for patient baseline characteristics, the mean daily acquisition cost for rofecoxib was $0.25 lower than for celecoxib. Rofecoxib users were less likely than celecoxib users to fill a GPA coprescription (odds ratio 0.88; 95% confidence interval 0.81, 0.95). Subgroup analyses yielded comparable results. CONCLUSION: Celecoxib appears to be a more expensive therapeutic option than rofecoxib due to a relatively higher daily dose and tablet consumption.

Treatment persistence with leukotriene receptor antagonists and inhaled corticosteroids.

BACKGROUND: Leukotriene receptor antagonists (LTRAs) and inhaled corticosteroids (ICSs) must be taken continuously to control persistent asthma. We compared the use of LTRAs and ICSs in patients with similar level of asthma control at treatment initiation with particular attention to treatment persistence. METHODS: Two cohorts of 15 to 45 year old patients with asthma were selected from the Quebec Health Insurance Plan Database between January 1, 1998, and December 31, 2000. We first identified new users of LTRAs and from the remaining patients, we selected new users of ICSs. The ICS patients were then one-to-one matched to LTRA patients on the use of short-acting beta2-agonists and oral corticosteroids in the year prior to the date of the first LTRA or ICS dispensation (index date). We compared compliance to initial therapies using Cox proportional hazards models. RESULTS: Each of the LTRA and ICS cohorts included 2200 patients. Multivariate model showed that compliance was significantly better for LTRAs than for ICSs [adjusted rate ratio of treatment discontinuation (aRR), 0.46; 95% confidence interval (CI), 0.42-0.49]. If in both groups all medications filled were taken at the prescribed dose, the annual percent of days on therapy for LTRA users would have been twice that for ICS users (38% vs. 19%; p<0.0001). CONCLUSION: The findings of this observational study indicate a far from optimal persistence to LTRAs and ICSs in asthmatic patients. The superior persistence to LTRAs might result in better effectiveness.

Quality of life in hypertension: the SF-12 compared to the SF-36.

BACKGROUND: The SF-36 has frequently been used to measure health related quality of life (HRQOL) in hypertension. Recently, the SF-12, a shorter form of the SF-36, has been proposed. However, the validity of the SF-12 in hypertension has not yet been assessed. OBJECTIVES: To determine the extent to which the SF-12 provides similar measurements of HRQOL to those of the SF-36 in hypertensive individuals. METHODS: A study assessing the impact of a pharmacy-based intervention program on hypertensive individuals served as background for this study. One hundred and twelve individuals participated in this study. We compared the SF-36 with the SF-12 on item scores and summary measures using intraclass correlation coefficients (ICC), Pearson correlation coefficients and linear regression. RESULTS: The concordance between the SF-12 and the SF-36 on both physical (ICC=0.88) and mental (ICC=0.92) component summary scores (PCS and MCS respectively) is high and the relationship is linear and positive. Most of the variance in the SF-36 PCS (R2=0.78) and MCS (R2=0.85) can be explained by their SF-12 counterparts. The SF-12 PCS and MCS are the only significant predictor variables for the corresponding measure of the SF-36. CONCLUSIONS: The SF-12 appears to be a valid alternative to the SF-36 for clinical practice or research purposes when studying hypertensive individuals and their treatment.

Losartan reduces the costs associated with nephropathy and end-stage renal disease from type 2 diabetes: Economic evaluation of the RENAAL study from a Canadian perspective.

BACKGROUND: The Reduction of Endpoints in NIDDM [non-insulin-dependent diabetes mellitus] with the Angiotensin II Antagonist Losartan (RENAAL) study demonstrated the renoprotective effects of losartan in patients with nephropathy from type 2 diabetes. OBJECTIVE: To perform an economic evaluation of the costs associated with end-stage renal disease (ESRD) from a Canadian public health perspective, based on the clinical outcomes reported in the RENAAL study. METHODS: ESRD-related costs were determined by estimating the mean number of days with ESRD multiplied by the daily cost of ESRD (140 dollars); mean days with ESRD were calculated by subtracting the area under the Kaplan-Meier survival curve for time to the first event of ESRD or all-cause mortality from the area under the curve for all-cause mortality. Daily ESRD cost was determined using Canadian specific data sources. ESRD-related cost savings with losartan were obtained by subtracting the ESRD-related costs of the losartan group from those of the placebo group. Net cost savings were ESRD-related cost savings with losartan minus the drug cost of losartan. RESULTS: Losartan reduced the number of ESRD days by 33.6 per patient over 3.5 years (95% CI 10.9 to 56.3) compared with placebo. Losartan reduced ESRD-related costs by 4,695 dollars per randomized patient over 3.5 years (95% CI 1,523 dollars to 7,868 dollars). After accounting for the drug cost of losartan, net cost savings with losartan were 3,675 dollars per randomized patient over 3.5 years. CONCLUSION: Losartan therapy for patients with nephropathy from type 2 diabetes reduces the clinical incidence of ESRD and can result in considerable cost savings for the Canadian public health system.

The societal value of universal childhood vaccination.

Availability of new vaccines preventing infectious diseases in healthy children populations is increasing worldwide. In Canada, despite the current recommendation of the National Advisory Committee on Immunization to include recent vaccines in routine schedule, only a few provinces have incorporated some of the newer vaccines in routine vaccination programs. A review was undertaken of economic evaluations of childhood vaccination strategies performed from the societal point of view in industrialized countries, to gain perspective on their global benefits. The general trend supports most universal vaccination programs as cost-saving or cost-effective for society. Comparison of vaccination programs with other health care interventions indicates that vaccines are often one of society's best healthcare investments. Current data suggest that the Canadian society would benefit from a more complete immunization program.