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Cost containment in pharmaceutical benefits plans is often controversial because of its potential for unintended effects on health and overall expenditures. Thorough evaluations are needed to support benefits plans in developing evidence-based policies. Evaluations of income-based deductibles for prescription drugs using non-experimental data are challenging because the time until patients' expenses exceed their annual deductible varies with the number of drugs used, which depends on their health status and income. We sought to clarify conceptual and methodological issues in longitudinal designs to evaluate income-based deductibles for prescription drugs, and provide a framework for the evaluation of such policies using longitudinal claims data. One of the main challenges is the violation of the Exclusion Restriction Assumption, which is a standard assumption when using instrumental variables such as the start date of a new policy. This assumption requires the instrumental variable to be independent of subject characteristics, such as income and health status. The validity of an evaluation therefore depends on the ability to measure and adjust for these characteristics. Given the lack of such data, randomization of the policy may be a more valid study design. [ABSTRACT FROM AUTHOR]

Background: Increasing copayments for higher-priced prescription medications has been suggested as a means to help finance drug coverage for elderly patients, but evaluations of the impact of such policies are rare. The objective of this study was to analyze the effect of reference-based pricing of angiotensin-converting enzyme (ACE) inhibitors on drug utilization, cost savings and potential substitution with other medication classes.Methods: We analyzed 36 months of claims data from British Columbia for 2 years before and 1 year after implementation of reference-based pricing (in January 1997). The 119,074 patients were community-living Pharmacare beneficiaries 65 years of age or older who used ACE inhibitors during the study period. The main outcomes were changes over time in use of ACE inhibitors, use of antihypertensive drugs and expenditures for antihypertensive drugs, as well as predictors of medication switching related to reference-based pricing.Results: We observed a sharp decline (29%) in the use of higher-priced cost-shared ACE inhibitors immediately after implementation of the policy (p < 0.001). After a transition period, the post-implementation utilization rate for all ACE inhibitors was 11% lower than projected from pre-implementation data. However, overall utilization of antihypertensives was unchanged (p = 0.40). The policy saved $6.7 million in pharmaceutical expenditures during its first 12 months. Patients with heart failure or diabetes mellitus who were taking a cost-shared ACE inhibitor were more likely to remain on the same medication after implementation of reference-based pricing (OR 1.12 [95% confidence interval, CI, 1.06-1.19] and 1.28 [95% CI 1.20-1.36] respectively). Patients with low-income status were more likely than those with high-income status to stop all antihypertensive therapy (OR 1.65 [95% CI 1.43-1.89]), which reflects a general trend toward discontinuation of therapy among these patients even before implementation of reference-based pricing.Interpretation: Reference-based pricing in British Columbia achieved a sustained reduction in drug expenditures, and no changes in overall use of antihypertensive therapy were observed. Further research is needed on the overall health and economic effects of such policies. [ABSTRACT FROM AUTHOR]

Background: Exposure to opioid analgesics have historically raised concern for a risk of developing opioid use disorder. Prescriber audit-and-feedback interventions may reduce opioid prescribing, but some studies have shown detrimental effects for current users. We examined the effectiveness of an audit and feedback intervention, named Portrait, to reduce initiation of opioid analgesics among opioid-naïve patients experiencing pain., Methods: REDONNA was a single-blinded, two-arm (Early vs Delayed mailing) randomized trial of a portrait for eligible family physicians (FPs) in British Columbia (BC), Canada. The primary outcome was the change in the number of initiations of opioid analgesic prescriptions written by FPs for acute/chronic pain management. We compared outcomes for a 6-month window before vs. after each mailed intervention, using differences in percent differences (DPD) with 95% confidence intervals (CI) and odds ratios (OR) from logistic regressions adjusted for clustering of patients by FP., Results: In the Early (n = 2260) and Delayed (n = 2156) groups, opioid initiations per month were the same in the Before (2.10 Early; 2.06 Delayed) and After (1.94 Early; 1.95 Delayed) windows. The DPD was -2.1% (CI: -4.4% to 0.3%), and ORs were: 0.98 (CI: 0.96 to 1.01) for any opioid, 0.97 (CI: 0.94 to 1.01) for codeine (62% of initiations), and 1.0 (CI: 0.97 to 1.07) for tramadol (25% of initiations). There were no differences in mean quantity of tablets, mean milligrams of morphine equivalents (MME), or mean number of days., Conclusion: Portrait had no impact on FPs' rates of prescribing opioid analgesics to opioid-naïve patients experiencing pain., Trial Registration: The study was registered prospectively on 30 March 2020 at the ISRCTN Register (https://www.isrctn.com/ISRCTN34246811)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: This study monitors for early changes in health services utilization after a mandatory policy to switch patients from originator to biosimilar insulin glargine in British Columbia, Canada., Methods: We conducted a prospective cohort study of patients treated with originator insulin glargine. The policy cohort included patients treated with originator insulin glargine in the 6 months before the policy change (May 27, 2019). Three historical control cohorts included users of originator insulin glargine during the 6 months before May 27 each year in 2016, 2017, and 2018. Patients who discontinued or switched use of the originator insulin glargine and those without cost coverage by the provincial drug plan were excluded. Using likelihood ratios, we compared the daily use of medications, outpatient visits, and hospitalizations in the 12 months after the policy change with the daily use in 3 historical control cohorts. A sustained likelihood ratio above a predefined threshold of 7.1 was interpreted as an early signal of a possible policy impact., Findings: Each cohort included 15,344 to 17,310 patients. In the first year of the policy, we observed increases in (1) insulin glargine use (the cumulative incidence increased by 2.5% compared with the mean of the 3 historical cohorts), (2) oral antidiabetic medication use (increased by 2.8%), and (3) outpatient visits (increased by 1.4%). Likelihood ratios greater than the threshold of 7.1 were detected for these 3 outcomes., Implications: We observed marginal changes in health services utilization without detecting signals of negative health impacts on patients targeted by the British Columbia policy of mandatory switching from originator to biosimilar insulin glargine., Competing Interests: Declaration of Interest None declared., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Drug coverage policies that incentivize switching patients from originator to biosimilar products may result in significant health care savings. Our study aimed to detect early impacts on health services utilization following a mandated switch from originator to biosimilar etanercept in British Columbia (BC), Canada., Methods: We conducted a prospective, population-based cohort study using linked administrative health data from BC (2010-2020). The policy cohort consisted of patients with inflammatory arthritis who used originator etanercept in 2019, prior to BC's Biosimilars Initiative switching policy. Three historical cohorts included patients with inflammatory arthritis who used originator etanercept in the years 2016, 2017, and 2018. We compared the daily cumulative incidences of drug refills and outpatient and inpatient services between the policy and historical cohorts. A likelihood ratio sustained (≥ 31 days) at 7.1 or higher compared with the null hypothesis was chosen a priori as a threshold for a potential impact of the policy., Results: Each cohort contained between 1694 and 1963 patients. We detected several potential impacts: 1) a transient increase in etanercept refills between months three and eight (cumulative incidence difference of + 3.0%); 2) an anticipated increase in visits to physicians of any specialty between months three and eight (+ 2.6%); and 3) an anticipated increase in visits to a rheumatologist from the end of month three onwards (+ 12.8%). The policy had no impact on incidences of switching to a different biologic antirheumatic drug, visits to emergency departments, or admissions to hospitals., Conclusions: Only transient and/or anticipated increases in drug refills and physician visits were observed during the study period. Additional research on clinical outcomes is recommended to strengthen the evidence that no long-term unintended negative health impacts are associated with BC's Biosimilars Initiative [switching policy]., (© 2022. The Author(s).)

Background: Beta-blockers are commonly used in the treatment of hypertension. We do not know whether the blood pressure (BP) lowering efficacy of beta-blockers varies across the day. This review focuses on the subclass of beta-blockers with partial agonist activity (BBPAA)., Objectives: To assess the degree of variation in hourly BP lowering efficacy of BBPAA over a 24-hour period in adults with essential hypertension., Search Methods: The Cochrane Hypertension Information Specialist searched the following databases for relevant studies up to June 2020: the Cochrane Hypertension Specialised Register; CENTRAL; 2020, Issue 5; MEDLINE Ovid; Embase Ovid; the World Health Organization International Clinical Trials Registry Platform; and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions., Selection Criteria: We sought to include all randomised and non-randomised trials that assessed the hourly effect of BBPAA by ambulatory monitoring, with a minimum follow-up of three weeks., Data Collection and Analysis: Two review authors independently selected the included trials and extracted the data. We assessed the certainty of the evidence using the GRADE approach. Outcomes included in the review were end-point hourly systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR), measured using a 24-hour ambulatory BP monitoring (ABPM) device., Main Results: Fourteen non-randomised baseline controlled trials of BBPAA met our inclusion criteria, but only seven studies, involving 121 participants, reported hourly ambulatory BP data that could be included in the meta-analysis. Beta-blockers studied included acebutalol, pindolol and bopindolol. We judged most studies at high or unclear risk of bias for selection bias, attrition bias, and reporting bias. We judged the overall certainty of the evidence to be very low for all outcomes. We analysed and presented data by each hour post-dose. Very low-certainty evidence showed that hourly mean reduction in BP and HR visually showed an attenuation over time. Over the 24-hour period, the magnitude of SBP lowering at each hour ranged from -3.68 mmHg to -17.74 mmHg (7 studies, 121 participants), DBP lowering at each hour ranged from -2.27 mmHg to -9.34 mmHg (7 studies, 121 participants), and HR lowering at each hour ranged from -0.29 beats/min to -10.29 beats/min (4 studies, 71 participants). When comparing between three 8-hourly time intervals that correspond to day, evening, and night time hours, BBPAA was less effective at lowering BP and HR at night, than during the day and evening. However, because we judged that these outcomes were supported by very low-certainty evidence, further research is likely to have an important impact on the estimate of effect and may change the conclusion., Authors' Conclusions: There is insufficient evidence to draw general conclusions about the degree of variation in hourly BP-lowering efficacy of BBPAA over a 24-hour period, in adults with essential hypertension. Very low-certainty evidence showed that BBPAA acebutalol, pindolol, and bopindolol lowered BP more during the day and evening than at night. However, the number of studies and participants included in this review was very small, further limiting the certainty of the evidence. We need further and larger trials, with accurate recording of time of drug intake, and with reporting of standard deviation of BP and HR at each hour., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Emergence coughing can harm the patient following completion of surgery, but it is unclear which medication is most effective at reducing this event. We conducted a systematic review and network meta-analysis of RCTs to determine the medications' relative efficacies on decreasing moderate to severe emergence coughing after general anaesthesia. Medications studied were lidocaine (i.v., intracuff, topical, or tracheal application), dexmedetomidine, remifentanil, and fentanyl., Methods: We searched eight different medical literature databases, conference abstracts, and article references. After screening, included citations were evaluated for bias and had their data extracted. Pooled odds ratios and 95% confidence intervals for each treatment comparison were calculated. A surface under the cumulative ranking curve analysis (SUCRA) determined the relative rank of each intervention to decrease moderate to severe emergence coughing. Subgroup analyses included severe coughing only, extubation times, type of maintenance anaesthetic, and dosages., Results: The network meta-analysis included 70 studies and 5286 patients. All study medications had favourable odds in reducing moderate and severe peri-extubation coughing compared with either no medication or placebo. No single medication was favoured over another. Dexmedetomidine had the highest SUCRA rank, followed in order by remifentanil, fentanyl, and lidocaine via intracuff, tracheal/topical, and i.v. routes. Remifentanil was ranked highest for decreasing severe coughing only. Intracuff lidocaine had higher odds of prolonging extubation times compared with placebo, dexmedetomidine, fentanyl, and remifentanil., Conclusion: All study medications were better than placebo or no medication in reducing moderate to severe emergence cough, with dexmedetomidine ranked the most effective., Systematic Review Registration: PROSPERO registration number: CRD42018102870., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Purpose: To explore the utility of physician prescribing preference as an instrumental variable., Methods: Expert (non-systematic) review of relevant literature on the appropriate selection of instrumental variables and theoretical exploration of individual physician and physician group prescriber preference., Results: An instrumental variable must satisfy three criteria: (1) It must predict the treatment received (strength of the instrument); (2) it cannot influence the outcome other that through the treatment received (exclusion restriction); and (3) it cannot be influenced by any factor that also influences the outcome (independence assumption). Arguments in favor of prescriber preference as an instrumental variable and suggestions for how to approach specific scenarios that may be encountered are offered., Conclusions: Prescriber preference, be it of individual physicians or groups of physicians, may, under the right conditions, be powerful instrumental variables. Empiric experimental data are required to determine the appropriateness of combining propensity matching and instrumental variable analysis., (© 2019 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.)

Background: Emergence coughing and bucking, secondary to endotracheal tube stimulation of the tracheal mucosa, frequently occurs after the general anesthetic recedes. Besides general unpleasantness, coughing has important physiological sequelae that may be detrimental to the postoperative patient. Multiple pharmacological strategies have been published, but prior systematic reviews on this topic have neither been comprehensive enough in their literature or medication search, nor provided us the answer regarding what the best pharmacological method is to prevent or minimize peri-extubation coughing. Our systematic review and network meta-analysis' primary objective is to determine the relative efficacies of different pharmacological methods on decreasing coughing (none to mild compared to moderate to severe, as defined by the modified Minogue scale) during emergence after a general anesthetic with endotracheal intubation in adult elective surgeries. Medications of interest are lidocaine or lignocaine (intravenous (IV), intracuff alkalinized, intracuff non-alkalinized, topical, endotracheal application), dexmedetomidine IV, remifentanil IV, and fentanyl IV. These medications were selected based on a preliminary review of the literature., Methods: Using a predefined search strategy, we will search MEDLINE, Cochrane Central Register of Controlled Trials, Embase, Cochrane Database of Systematic Reviews, ACP Journal Club, Database of Abstracts of Reviews of Effects, and the Cochrane Methodology Register, with no date or language restrictions. Gray literature search will encompass conference abstracts, Web of Science, and references from publications selected for full-text review. Two reviewers will independently screen the retrieved literature using predetermined inclusion criteria, process publications selected for full-text review, extract data from publications chosen for study inclusion, and evaluate for bias using the Cochrane risk of bias assessment. Risk ratios and 95% confidence intervals will be calculated for each study, and a surface under the cumulative ranking curve will determine the relative rank of each intervention in its ability to prevent coughing on emergence., Discussion: The proposed systematic review and network meta-analysis will not only provide a more thorough review of common medications used to decrease emergence coughing, but also inform clinicians which of these pharmacological strategies is the best approach., Systematic Review Registration: PROSPERO CRD42018102870.

Introduction: Anticoagulants are arguably the most important drug family of all, based on the frequency and duration of their use, and the clinical importance and frequency of benefits and harms. Several direct acting oral anticoagulants (DOACs) have recently joined warfarin for the treatment of atrial fibrillation, with a resultant significant expansion in use of oral anticoagulants (OACs). Our objectives are to compare safety and effectiveness of DOACs versus warfarin in a full population where anticoagulation management is good and to identify which types of patients do better with DOACs versus warfarin and vice versa., Methods and Analysis: This is a retrospective cohort study of all adults living in British Columbia who have a diagnosis of atrial fibrillation in hospital or medical service data, and a first prescription for an OAC. Coprimary outcomes are ischaemic stroke and systemic embolism (benefit) and major bleeding (harm). Secondary outcomes include net clinical benefit (composite of stroke, systemic embolism, major bleeds, myocardial infarction, pulmonary embolism and death), drug discontinuation and individual composite item occurrence. We will estimate the effects of treatment in a 2-year follow-up period, using time-to-event models with propensity score adjustment to control confounding. Secondary analyses will examine 'as treated' outcomes., Ethics and Dissemination: The protocol, data creation plan, privacy impact statement and data sharing agreements have been approved. Dissemination is planned via conferences and publications as well as directly to drug policy leaders. Information on the overall comparative effectiveness and safety of DOACs versus warfarin in a country with high quality anticoagulation management, as well as for vulnerable subgroups, will be an important addition to the literature., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Aim: Domperidone is preferentially used over other antiemetic agents to treat digestive symptoms in Parkinson's disease (PD). Concerns have been raised regarding an increased risk of ventricular tachyarrhythmia and sudden cardiac death (VT/SCD) associated with domperidone in the general population. However, the risk in PD is unknown., Methods: We conducted a multicentre retrospective cohort study using administrative databases from seven Canadian provinces and the UK Clinical Practice Research Datalink. Using a nested case-control analysis, we estimated the rate ratios (RRs) of VT/SCD associated with domperidone use compared to no use in patients newly-diagnosed with PD. VT/SCD events were identified using administrative medical records and vital statistics with a manual review of all potential cases. Meta-analytic methods were used to estimate overall effects across sites., Results: Among 214 962 patients with PD, 2907 cases of VT/SCD were identified during 886 581 person-years of follow-up (incidence rate 3.28 per 1000 persons per year). Current use of domperidone was associated with a non-statistically significant 22% increased risk of VT/SCD (RR 1.22; 95% CI 0.99-1.50) compared with no use. The risk was significantly elevated in those with a history of cardiovascular disease (RR 1.38; 95% CI 1.07-1.78), but not in those without (RR 1.21; 95% CI 0.81-1.81). Dose and duration of use did not affect the magnitude of the risk., Conclusion: Domperidone use may increase the risk of VT/SCD in patients with PD, particularly those with a history of cardiovascular disease. This risk may be underestimated because of imprecision in identifying VT/SCD events., (© 2016 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Isotretinoin, a teratogen, is widely used to treat cystic acne. Although the risks of pregnancy during isotretinoin therapy are well recognized, there are doubts about the level of adherence with the pregnancy prevention program in Canada. Our objective was to evaluate the effectiveness of the Canadian pregnancy prevention program in 4 provinces: British Columbia, Saskatchewan, Manitoba and Ontario., Methods: Using administrative data, we identified 4 historical cohorts of female users of isotretinoin (aged 12-48 yr) for the period 1996 to 2011. We defined pregnancy using International Statistical Classification of Diseases and billing codes. One definition included only cases with documented pregnancy outcomes (high-specificity definition); the other definition also included individuals recorded as receiving prenatal care (high-sensitivity definition). We studied new courses of isotretinoin and detected pregnancies in 2 time windows: during isotretinoin treatment only and up to 42 weeks after treatment. Live births were followed for 1 year to identify congenital malformations., Results: A total of 59 271 female patients received 102 308 courses of isotretinoin. Between 24.3% and 32.9% of participants received prescriptions for oral contraceptives while they were taking isotretinoin, compared with 28.3% to 35.9% in the 12 months before isotretinoin was started. According to the high-specificity definition of pregnancy, there were 186 pregnancies during isotretinoin treatment (3.1/1000 isotretinoin users), compared with 367 (6.2/1000 users) according to the high-sensitivity definition. By 42 weeks after treatment, there were 1473 pregnancies (24.9/1000 users), according to the high-specificity definition. Of these, 1331 (90.4%) terminated spontaneously or were terminated by medical intervention. Among the 118 live births were 11 (9.3%) cases of congenital malformation. Pregnancy rates during isotretinoin treatment remained constant between 1996 and 2011., Interpretation: Adherence to the isotretinoin pregnancy prevention program in Canada was poor during the 15-year period of this study., (© 2016 Canadian Medical Association or its licensors.)

Background: Calcium channel blockers are a heterogeneous class of drugs, including dihydropyridine and non-dihydropyridine subgroups, commonly used in the treatment of hypertension. A systematic review of the 24-hour time course of the blood pressure-lowering effect has not been published., Objectives: To assess how much variation there is in hourly systolic and diastolic blood pressure lowering by dihydropyridine calcium channel blockers over a 24-hour period in people with hypertension aged 18 years or over, with baseline systolic blood pressure of at least 140 mmHg or diastolic blood pressure of at least 90 mmHg, or both., Search Methods: We performed electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 1, 2014), MEDLINE (1946 to February 2014), EMBASE (1974 to February 2014), and ClinicalTrials.gov (to February 2014). We also screened references of published studies and reviews to identify additional trials., Selection Criteria: We included all randomized, placebo-controlled trials assessing the hourly effects of dihydropyridine calcium channel blockers by ambulatory blood pressure monitoring in adults with hypertension with a follow-up of at least three weeks., Data Collection and Analysis: Two authors independently selected the included trials, evaluated the risk of bias, and analyzed the data., Main Results: We included 16 randomized controlled trials of dihydropyridine calcium channel blockers in this systematic review, with 2768 randomized participants. Drugs studied included amlodipine, lercanidipine, mandipine, nifedipine, and felodipine (all administered once daily) and nicardipine (administered twice daily). We analyzed and presented data by hour post dose. The blood pressure-lowering effect was stable over time; there were no clinically important differences in blood pressure-lowering effect of calcium channel blockers between each hour for either systolic blood pressure (estimated mean hourly differences ranged between 9.45 mmHg and 13.2 mmHg) or diastolic blood pressure (estimated mean hourly differences ranged between 5.85 mmHg and 8.5 mmHg). However, there was a moderate risk of bias for this finding. Once-daily dihydropyridine calcium channel blockers appeared to lower blood pressure by a relatively constant amount throughout the 24-hour dosing interval., Authors' Conclusions: Six dihydropyridine calcium channel blockers studied in this review lowered blood pressure by a relatively similar amount each hour over the course of 24 hours. The benefits and harms of this pattern of blood pressure lowering are unknown. Further trials are needed with accurate recording of time of drug intake and with reporting of standard deviation of blood pressure at each hour. We did not attempt to assess adverse effects in this review due to the lack of reporting and the short duration of follow-up.

Background: Tablet splitting, in which a higher-dose tablet is split to get 2 doses, reduces patients' drug costs. Statins can be split safely. General practitioners (GPs) may not direct their patients to split statins because of safety concerns or unawareness of costs. Medical chart inserts provide cost-effective education to physicians., Objective: The aim of this study was to assess whether providing GPs with statin-splitting chart inserts would increase splitting rates, and to identify predictors of splitting., Methods: In 2005 and 2006, we faxed a statin chart insert to British Columbia GPs with a request for a telephone interview. Consenting GPs were mailed 3 statin chart inserts and interviewed by phone (the intervention). In an interrupted time series, we compared monthly rates of statin-splitting prescriptions among intervention and nonintervention GPs before, during, and after the intervention. In multivariate logistic regressions accounting for patient clustering, predictors of splitting included physician and patient demographics and the specific statin prescribed., Results: Of 5051 GPs reached, 282 (6%) agreed to the intervention. Before the intervention, GPs' splitting rate was 2.6%; after intervention, GPs' splitting rate was 7.5%. The rate for the nonintervention GPs was 4.4%. Intervention GPs were 1.68 (95% CI, 1.12-2.53) times more likely to prescribe splitting after the intervention than were nonintervention GPs. Other predictors were a patient's female sex (odds ratio [OR] = 1.26; 95% CI, 1.18-1.34), lower patient income (OR = 1.33; 95% CI, 1.18-1.34), and a lack of drug insurance (OR = 1.89; 95% CI, 1.69-2.04)., Conclusions: An inexpensive intervention was effective in producing a sustained increase in GPs' splitting rate during 22 months of observed follow-up. Expanding statin-splitting education to all GPs might reduce prescription costs for many patients and payors., (Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.)

Context: A US Food and Drug Administration advisory has warned that antidepressants may be associated with an increased risk of suicidal thoughts and behaviors in adolescents. This prompted a meta-analysis of trials in adults that found no overall increase in risk, but individual agents could not be studied., Objective: To assess the risk of suicide and suicide attempts associated with individual antidepressant agents., Design: Cohort study of incident users of antidepressant agents., Setting: Population-based health care utilization data of all residents of British Columbia, Canada, aged 18 years and older between January 1, 1997, and December 31, 2005., Patients: British Columbia residents who had antidepressant therapy initiated and had a recorded diagnosis of depression., Intervention: Initiation of various antidepressant medications., Main Outcome Measures: Combined suicide death or hospitalization due to self-harm., Results: In a population of 287,543 adults aged 18 years and older with antidepressant therapy initiated, we observed outcome rates ranging from 4.41/1000 person-years to 9.09/1000 person-years. Most events occurred in the first 6 months after treatment initiation. After extensive propensity score adjustment, we found no clinically meaningful variation in the risk of suicide and suicide attempt between antidepressant agents compared with fluoxetine hydrochloride initiation: citalopram hydrobromide, hazard ratio = 1.00 (95% confidence interval, 0.63-1.57); fluvoxamine maleate, hazard ratio = 0.98 (95% confidence interval, 0.63-1.51); paroxetine hydrochloride, hazard ratio = 1.02 (95% confidence interval, 0.77-1.35); and sertraline hydrochloride, hazard ratio = 0.75 (95% confidence interval, 0.53-1.05). Compared with selective serotonin reuptake inhibitors as a drug class, other classes including serotonin-norepinephrine reuptake inhibitors, tricyclic agents, and other newer and atypical agents had a similar risk. Restriction to patients with no antidepressant use in the past 3 years further reduced apparent differences between groups., Conclusions: Our finding of equal event rates across antidepressant agents supports the US Food and Drug Administration's decision to treat all antidepressants alike in their advisory. Treatment decisions should be based on efficacy, and clinicians should be vigilant in monitoring after initiating therapy with any antidepressant agent.

Background: Depression imposes enormous burdens on the elderly. Despite this, rates of initiation of and adherence to recommended pharmacotherapy are frequently low in this population. Although initiatives such as the Medicare Modernization Act (MMA) have improved seniors' access to antidepressants, there are concerns that the patient cost-sharing incorporated in the MMA may have unintended consequences if it reduces essential drug use. Age-related pharmacokinetic and pharmacodynamic changes could make seniors particularly vulnerable to antidepressant regimens used inappropriately to save costs, increasing their risks of morbidity, hospitalizations, and nursing home placements. Two sequential large-scale "natural experiments'' in British Columbia provide a unique opportunity to evaluate the effect of cost sharing on outcomes and mental health service use among seniors. In January 2002 the province introduced a CAD 25 copay (CAD10 for low-income seniors). In May 2003 this copay policy was replaced by a second policy consisting of an income-based deductible, 25% coinsurance once the deductible was met, and full coverage once an out-of-pocket ceiling was met. The transition between the two policies is analogous to what many U.S. seniors experience when they transition from private insurance requiring copays to Medicare Part D requiring deductibles and coinsurance., Aims: To evaluate whether declines in antidepressant initiation after the introduction of two drug cost-sharing policies in British Columbia were associated with increased use of physician services, hospitalizations, and nursing home admissions among all British Columbia residents aged 65+., Methods: Records of physician service use, inpatient hospitalizations, and residential care admissions were obtained from administrative databases. Population-level patterns over time were plotted, and effects of implementing the cost-sharing policies examined in segmented linear regression models., Results: Neither policy affected the rates of visits to physicians or psychiatrists for depression, hospitalizations with a depression diagnosis, or long-term care admissions., Discussion: The cost-sharing policies studied may have contained non-essential antidepressant use without substantially increasing mental health service utilization. However, it is possible that the policies had effects that we were unable to detect, such as increasing rates of visits to social workers or psychologists or forcing patients to reduce other spending. Further, the sequential implementation of the policy changes, makes it difficult to estimate the effect of a direct change from full coverage to a coinsurance/income-based deductible policy., Implications for Health Policies: It may be possible to design policies to contain non-essential antidepressant use without substantially increasing other service utilization or adverse events. However, because undertreatment remains a serious problem among depressed elderly, well-designed prescription drug policies should be coupled with interventions to address under-treatment.

Background: Public health advisories have warned that the use of atypical antipsychotic medications increases the risk of death among elderly patients. We assessed the short-term mortality in a population-based cohort of elderly people in British Columbia who were prescribed conventional and atypical antipsychotic medications., Methods: We used linked health care utilization data of all BC residents to identify a cohort of people aged 65 years and older who began taking antipsychotic medications between January 1996 and December 2004 and were free of cancer. We compared the 180-day all-cause mortality between residents taking conventional antipsychotic medications and those taking atypical antipsychotic medications., Results: Of 37 241 elderly people in the study cohort, 12 882 were prescribed a conventional antipsychotic medication and 24 359 an atypical formulation. Within the first 180 days of use, 1822 patients (14.1%) in the conventional drug group died, compared with 2337 (9.6%) in the atypical drug group (mortality ratio 1.47, 95% confidence interval [CI] 1.39-1.56). Multivariable adjustment resulted in a 180-day mortality ratio of 1.32 (1.23-1.42). In comparison with risperidone, haloperidol was associated with the greatest increase in mortality (mortality ratio 2.14, 95% CI 1.86-2.45) and loxapine the lowest (mortality ratio 1.29, 95% CI 1.19-1.40). The greatest increase in mortality occurred among people taking higher (above median) doses of conventional antipsychotic medications (mortality ratio 1.67, 95% CI 1.50-1.86) and during the first 40 days after the start of drug therapy (mortality ratio 1.60, 95% CI 1.42-1.80). Results were confirmed in propensity score analyses and instrumental variable estimation, minimizing residual confounding., Interpretation: Among elderly patients, the risk of death associated with conventional antipsychotic medications is comparable to and possibly greater than the risk of death associated with atypical antipsychotic medications. Until further evidence is available, physicians should consider all antipsychotic medications to be equally risky in elderly patients.

Randomized pragmatic trials of drugs, physician education and drug policies are needed to improve pharmacosurveillance and cost-effectiveness of prescribing. Since 1994, we have developed and tested methods for low-cost education and policy trials to improve prescribing in primary care in Canada. We review methodology for using drug claims and other health services data to evaluate prescribing improvement programs and policies. We apply the lessons to a proposed trial of physician education tools (PET) for quality improvement of prescribing. Design issues for the trial include defining the potential programme in causal terms using counterfactuals, narrowing the denominator to the population affected, excluding noise from the numerator, calculating the prescribing preference, adjusting for baseline differences, controlling for modifiers and confounders, accounting for uncertainty when measuring impacts, and grouping practices for feedback and recognition. Data from a randomized trial of academic detailing illustrate measurement challenges. A decade of progress on methods for evaluating prescribing improvement programs with drug claims data has enabled planning of routine randomized pragmatic trials of education and policies in primary care in Canada.

Objective: The purpose of this study was to assess the impacts of individualized prescribing feedback and interactive small group education aimed at encouraging evidence-based prescribing in family/general practice., Methods: A two-by-two factorial randomized controlled trial was carried out involving 200 family physicians in British Columbia, Canada. The physicians met monthly in 28 peer learning groups within the Practice-Based Small Group (PBSG) learning programme. Personalized prescribing feedback related to hypertension was provided through 'prescribing portraits' which graphically displayed comparative rates of individual and peer group prescribing, together with a concise guide for evidence-based prescribing. A case-based educational module, containing the same evidence-based message, was discussed in small groups. Groups were matched and randomized into four arms of seven groups each: control (n = 56), prescribing portrait only (n = 48), educational module only (n = 47), both portrait and module (n = 49). The main outcome measure was changes in 'prescribing preferences' to new patients among those medications used to treat hypertension (i.e. probability that a patient would receive the evidence-based medication as first-line therapy)., Results: Using data from the provincial pharmacy registry (PharmaNet), prescribing preferences for antihypertensive agents were determined for all groups for a 6 month period before and after the interventions, based on 4394 patients receiving a first-line antihypertensive. Significant absolute increases in prescribing preference for thiazides were documented for both the module +0.068 (confidence interval [CI] 0.022-0.115) and the portrait +0.065 (CI 0.018-0.111). Preference in the group receiving both module and portrait increased by +0.115 (CI 0.040-0.189)., Conclusions: Evidence-based educational interventions combining personalized prescribing feedback with interactive group discussion can lead to modest but meaningful changes in physician prescribing. Clear messages, proper trial design and sensitive outcomes are necessary to demonstrate these changes.

Background: Reference drug pricing (RP) is a cost-sharing strategy commonly used to control drug expenditures. Under RP, a benefit plan fully reimburses medications that are equally or less expensive than the reference price, and requires patients to pay the extra cost of therapeutically equivalent but higher priced drugs. Critics argued that drug plan savings are offset by administrative costs and increased spending on other health services., Objective: We evaluated net healthcare savings in beneficiaries >or=65 years from the perspective of the British Columbia provincial health insurance system after it applied RP to angiotensin-converting enzyme (ACE) inhibitors in 1997., Methods: We estimated savings in new users of antihypertensives after the start of RP plus associated administrative costs and savings from reductions in retail drug prices. Findings were integrated with earlier results on the consequences of RP on expenditures for drugs, physicians, and hospitalizations among all seniors who used ACE inhibitors before the introduction of RP., Results: During the first year after the implementation of RP, savings for continuous users were CAN dollars 6.0 million. Savings for new users were dollars 0.2 million. Approximately five sixths thereof were achieved by utilization changes and one sixth by cost shifting to patients. There were no savings through drug price changes. Administering RP cost dollars 0.42 million. Overall net savings were estimated to be dollars 5.8 million during the first year after the start of RP. The magnitude of these savings is equal to 6% of all cardiovascular drug expenditures in seniors. After 10 years, approximately 50% of savings will be achieved by new users., Conclusion: We observed substantial net savings from RP for ACE inhibitors for the provincial health insurance system in British Columbia, although there were generous exemptions from the policy. In other jurisdictions, savings could be higher if drug prices decline after the start of reference pricing.

Objective: Reference pricing is a medication cost-sharing policy that fully covers medications which are less expensive than a standard reference price and requires patients to pay the extra cost of higher-priced drugs in a class of therapeutically substitutable drugs. Little information exists on the clinical and economic consequences. We analyzed changes in drug utilization, physician visits, hospitalizations, long-term care admissions, and expenditures after the introduction of reference pricing for dihydropyridine calcium channel blockers (CCBs) among patients aged 65 years or older in British Columbia, Canada., Methods: This quasiexperimental longitudinal study was performed in the setting of Pharmacare, the state-funded drug benefits plan of all elderly persons in British Columbia. Study patients comprised all elderly residents of British Columbia who were enrolled in the provincial health insurance program and received dihydropyridine CCBs at the time of the policy change (35,886) and a subgroup of high-priced dihydropyridine CCB users (23,116). We studied the implementation of reference drug pricing on Jan 1, 1997, affecting all elderly Pharmacare beneficiaries. The main outcome measures were drug utilization, drug expenditures, physician visits, hospitalizations, long-term care, and net savings., Results: The start of reference pricing was followed by a significant reduction in high-priced dihydropyridine CCBs (-150 monthly doses per 10,000 elderly persons), with a corresponding increase in fully covered dihydropyridine CCBs (+116). Overall, antihypertensive use did not decline (P =.46). Low-income status was a risk factor for discontinuing treatment (odds ratio, 1.64; 95% confidence interval [CI], 1.36 to 1.99); however, this was already observed to a similar magnitude 12 months before reference pricing (odds ratio, 1.46). In the overall study cohort, there was no increase in rates of physician visits, hospitalizations, and long-term care admissions. However, the 9% of patients who actually switched medications showed an 18% increase (95% CI, 8% to 28%) in physician visits and an increase of Canadian $13 (95% CI, Canadian $3 to Canadian $24) in costs of physician visits per patient as compared with nonswitchers during the transition but not afterward. This temporary increase may have been a result of additional prescribing and monitoring in switchers. Changes in drug expenditures and physician services resulted in net savings of Canadian $1.6 million in the first 12 months of policy implementation., Conclusions: Reference pricing as implemented in British Columbia may be a model for successful pharmaceutical cost-containment without adversely affecting patients or cost-shifting.

Introduction: Statements of commitment to change are advocated both to promote and to assess continuing education interventions. However, most studies of commitment to change have used self-reported outcomes, and self-reports may significantly overestimate actual performance. As part of an educational randomized controlled trial, this study documented changes that family physicians committed to make in their prescribing and then used third-party data to examine actual changes., Method: Following participation in a continuing medical education program using interactive small groups, physicians were asked to identify changes that they planned to make in their practices. For prescribing changes related to four conditions, data from a provincial pharmacy registry were analyzed for 6-month periods before and after the educational intervention., Results: A total of 207 physicians participated in the project, which involved monthly meetings of 30 peer learning groups. Ninety-nine physicians received experimental case-based educational modules +/- personal prescribing feedback, and 91 of these indicated that they planned to make at least one change in practice. Of the 209 intended changes, 71% were directly related to the prescribing messages in the materials., Discussion: In three of four indicator conditions, physicians who expressed a commitment to change were significantly more likely to change their actual prescribing for the target medications in the following 6 months. The percentage of physicians who did change their prescribing varied significantly by condition. Further study of the process of translating commitment to change into real practice change is needed.

Background: The way in which dissemination of evidence changes medical practice needs to be better understood. Controversy about calcium-channel blockers (CCB) in the past 3 years has provided a natural experiment, enabling assessment of the impact of media stories, a national warning letter, a teleconference, small group workshops, and newsletters on first-line prescribing of antihypertensive drugs., Methods: We included all physicians (4403) in British Columbia who prescribed a thiazide diuretic, beta-blocker, inhibitor of angiotensin-converting enzyme (ACE), or CCB as the first antihypertensive agent for 36,507 residents aged 66 years and over, with no previous or concurrent sign of underlying cardiovascular disease. We used a database covering all prescriptions to elderly people to measure the change in proportion of newly treated patients who received each class of drug as first-line therapy. We used a matched cohort design for assessment of the teleconference and workshops, a randomised community design for the newsletters, and time-series analysis for the media impacts., Findings: The proportion of patients who received a CCB as first-line therapy declined gradually from 22% in early 1994 to 15% in late 1996. This proportion was not affected by two waves of adverse news about CCBs in 1995, but fell by 5% for 5 months and by 3% for 1 month after two waves in 1996. The proportion of patients who received either a CCB or an ACE inhibitor as first-line therapy, contrary to guidelines, was still 42% overall in 1996. The workshops and newsletters were followed by shifts from first-line CCB to first-line thiazide prescribing., Interpretation: Changes in prescribing practices occur gradually with the accumulation of small impacts from educational interventions and lay media attention.