The impact of proposed price regulations on new patented medicine launches in Canada: a retrospective cohort study.

BACKGROUND: The Patented Medicine Prices Review Board (PMPRB), the agency that regulates the prices of patented medicines in Canada, published proposed amendments to the regulatory framework in December 2017. Because of a series of changes and delays, the revised policy has not yet been finalized. We sought to evaluate the potential early impact of the uncertainty about the PMPRB policy on patented-medicine launches. METHODS: We developed a retrospective cohort of patented medicines (molecules) sold in Canada and the 13 countries that the PMPRB currently uses or has proposed to use as price comparators, from sales data from the IQVIA MIDAS database for 2012-2021. The outcome was whether a molecule was launched (i.e., sold) in a specific country within 2 years of its global first launch (2-yr launch). We compared the change of 2-year launch before (2012-2017) and after the proposed amendments were published ("uncertain period," 2018-2021) in Canada with the change in the United States and the other 12 countries as a group ("other-countries group"), using interrupted time series and logistic regressions, respectively. We further conducted analyses for each individual country and subgroups by molecule characteristics, such as therapeutic benefit, separately. RESULTS: We included 242 and 107 new molecules launched before publication of the proposed amendments and during the uncertain period, respectively. The corresponding 2-year launch proportions were 45.0% and 30.8% in Canada, 81.4% and 82.2% in the US, and 83.9% and 70.1% in the other-countries group. All analyses showed changes in 2-year launch during the uncertain period in the US and in the other-countries group that were similar to the changes in Canada. Greater decreases were observed in Norway and Sweden than in Canada. The 2-year launch proportion for molecules with major therapeutic benefit decreased from 45.8% to 31.3% in Canada during the uncertain period and from 87.5% to 62.5% in the other-countries group, but increased from 91.7% to 100% in the US. INTERPRETATION: No negative impact of the PMPRB-policy uncertainty on molecule launches was observed when comparing Canada with price-comparator countries, except for molecules with major therapeutic benefit. The reduction in launches of medicines with major therapeutic benefit in Canada requires continuing investigation.

The impact of changing the reference countries on the list prices for patented medicines in Canada: A policy analysis.

BACKGROUND: Canada's Patented Medicine Prices Review Board (PMPRB) uses external and internal reference pricing (IRP) to regulate patented drug list prices. PMPRB has changed external reference countries from 7 to 11 to include countries with prices closer to the OECD median. We examined the impact on the list prices for patented medicines had the amendment been implemented from 2013. METHODS: Using IQVIA MIDAS® quarterly sales data, we selected branded products that were launched in Canada in 2013-2018. The list price for each product in each country was calculated as its average annual price during the 3rd year post Canadian launch. The median international price (MIP) was the median of the list prices of PMPRB7 (MIP7) and PMPRB11 (MIP11). We assumed the same IRP would be (scenario 1) or would not be used (scenario 2). RESULTS: Among the selected 400 products, 80.3 % (321) had MIP7 and MIP11 (launched in at least one reference country); 18.3 % did not have MIP11. The total current expenditures were $7,134.4 M. In scenario 1, MIP11 would not be binding for most products and expenditures would decline only by 0.7 %. If IRP were abolished, expenditures might decline by 14.1 % if the launching sequence would not change. CONCLUSIONS: MIP11 might not be binding for most medicines. The impact depends on whether to retain the IRP and approaches taken for medicines without MIP11.

Economic evaluation of prostate cancer risk assessment methods: A cost-effectiveness analysis using population data.

BACKGROUND: The current prostate cancer (PCa) screening standard of care (SOC) leads to unnecessary biopsies and overtreatment because decisions are guided by prostate-specific antigen (PSA) levels, which have low specificity in the gray zone (3-10 ng/mL). New risk assessment tools (RATs) aim to improve biopsy decision-making. We constructed a modeling framework to assess new RATs in men with gray zone PSA from the British Columbia healthcare system's perspective. METHODS: We evaluated the cost-effectiveness of a new RAT used in biopsy-naïve men aged 50+ with a PSA of 3-10 ng/mL using a time-dependent state-transition model. The model was informed by engaging patient partners and using linked administrative health data, supplemented with published literature. The incremental cost-effectiveness ratio and the probability of the RAT being cost-effective were calculated. Probabilistic analysis was used to assess parameter uncertainty. RESULTS: In the base case, a RAT based on an existing biomarker's characteristics was a dominant strategy associated with a cost savings of $44 and a quality-adjusted life years (QALY) gain of 0.00253 over 18 years of follow-up. At a cost-effectiveness threshold of $50,000/QALY, the probability that using a RAT is cost-effective relative to the SOC was 73%. Outcomes were sensitive to RAT costs and accuracy, especially the detection rate of high-grade PCa. Results were also impacted by PCa prevalence and assumptions about undetected PCa survival. CONCLUSIONS: Our findings showed that a more accurate RAT to guide biopsy can be cost-effective. Our proposed general model can be used to analyze the cost-effectiveness of any novel RAT.

Health Care Costs Attributable to Prostate Cancer in British Columbia, Canada: A Population-Based Cohort Study.

We aimed to estimate the total health care costs attributable to prostate cancer (PCa) during care phases by age, cancer stage, tumor grade, and primary treatment in the first year in British Columbia (BC), Canada. Using linked administrative health data, we followed a cohort of men aged ≥ 50 years at diagnosis with PCa between 2010 and 2017 (Cohort 1) from the diagnosis date until the date of death, the last date of observation, or 31 December 2019. Patients who died from PCa after 1 January 2010, were selected for Cohort 2. PCa attributable costs were estimated by comparing costs in patients to matched controls. Cohort 1 (n = 22,672) had a mean age of 69.9 years (SD = 8.9) and a median follow-up time of 5.2 years. Cohort 2 included 6942 patients. Mean PCa attributable costs were the highest during the first year after diagnosis ($14,307.9 [95% CI: $13,970.0, $14,645.8]) and the year before death ($9959.7 [$8738.8, $11,181.0]). Primary treatment with radiation therapy had significantly higher costs each year after diagnosis than a radical prostatectomy or other surgeries in advanced-stage PCa. Androgen deprivation therapy (and/or chemotherapy) had the highest cost for high-grade and early-stage cancer during the three years after diagnosis. No treatment group had the lowest cost. Updated cost estimates could inform economic evaluations and decision-making.

The Impact of Tiered-Pricing Framework on Generic Entry in Canada.

BACKGROUND: Generic drug prices have been capped at specified percentages of the interchangeable branded drug's price by the Canadian provincial public drug plans since 1993. The Pan-Canadian Pharmaceutical Alliance, formed as a coalition by the provinces/territories in Canada, implemented an alternative approach, a tiered-pricing framework (TPF) for new generic drugs on April 1, 2014, under which the percentage varies with the number of generic firms in each market. We evaluate the impact of the TPF on generic entry, ie, listing in public drug plans in Canada. METHODS: Our study compared the pre-TPF period (01/01/2012-03/31/2014) with the TPF period (04/01/2014- 06/30/2016). Prescription drugs from nine provincial public drug plans were grouped into a "market" if they had the same active ingredient and strength, route of administration, and dosage form. Each "market" was contestable by generics and met the eligibility criteria for TPF. At the "market" level, Cox proportional-hazards models with time-varying covariates were used to measure the impact of the TPF on the first generic listing in any provincial public drug plan in Canada relative to the first launch date worldwide. RESULTS: A total of 189 markets in Canada were selected for the analyses. Generic drugs in small markets were more likely to be listed in Canada during the TPF period compared to the pre-TPF period (hazard ratio [HR], 95% CI: 3.81, 1.51-9.62). There was no significant difference in generic drug listings in large markets between the two policy periods. CONCLUSION: TPF speeds up generic entry in small markets and generates the benefits of generic competition while avoiding the pitfalls of the previously employed price-cap regulations.

Factors associated with drug shortages in Canada: a retrospective cohort study.

BACKGROUND: To monitor the magnitude of the drug shortage problem in Canada, since 2017, Health Canada has required manufacturers to report drug shortages. This study aimed to identify the factors associated with drug shortages in Canada. METHODS: We conducted a retrospective cohort study of all prescription drugs available on the market between Mar. 14, 2017, and Sept. 12, 2018, in Canada. All drugs of the same active ingredient, dosage form, route of administration and strength were grouped into a "market." Our main outcome was shortages at the market level, determined using the Drug Shortages Canada database. We used logistic regression to identify associated factors such as market structure, route or dosage form, and Anatomic Therapeutic Chemical (ATC) classification. RESULTS: Among the 3470 markets included in our analysis, 13.3% were reported to be in shortage. Markets with a single generic manufacturer were more likely to be in shortage than other markets. Markets with oral nonsolid route or dosage form were more likely to be in shortage than those that were oral solid with regular release (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.11 to 2.49). Markets for sensory organs were more likely to be in shortage than most other ATC classes. Markets with a higher proportion of drugs covered by public insurance programs were more likely to be in shortage (OR 1.03, 95% CI 1.00 to 1.05 per 10% increase). INTERPRETATION: Markets with a single generic manufacturer were most likely to be in shortage. To ensure the security of drug supply, governments should be vigilant in monitoring markets with a single generic manufacturer, with complex manufacturing processes, with higher demand from public programs or those that are in certain ATC classes.

Cost-effectiveness of diacetylmorphine versus methadone for chronic opioid dependence refractory to treatment.

BACKGROUND: Although diacetylmorphine has been proven to be more effective than methadone maintenance treatment for opioid dependence, its direct costs are higher. We compared the cost-effectiveness of diacetylmorphine and methadone maintenance treatment for chronic opioid dependence refractory to treatment. METHODS: We constructed a semi-Markov cohort model using data from the North American Opiate Medication Initiative trial, supplemented with administrative data for the province of British Columbia and other published data, to capture the chronic, recurrent nature of opioid dependence. We calculated incremental cost-effectiveness ratios to compare diacetylmorphine and methadone over 1-, 5-, 10-year and lifetime horizons. RESULTS: Diacetylmorphine was found to be a dominant strategy over methadone maintenance treatment in each of the time horizons. Over a lifetime horizon, our model showed that people receiving methadone gained 7.46 discounted quality-adjusted life-years (QALYs) on average (95% credibility interval [CI] 6.91-8.01) and generated a societal cost of $1.14 million (95% CI $736,800-$1.78 million). Those who received diacetylmorphine gained 7.92 discounted QALYs on average (95% CI 7.32-8.53) and generated a societal cost of $1.10 million (95% CI $724,100-$1.71 million). Cost savings in the diacetylmorphine cohort were realized primarily because of reductions in the costs related to criminal activity. Probabilistic sensitivity analysis showed that the probability of diacetylmorphine being cost-effective at a willingness-to-pay threshold of $0 per QALY gained was 76%; the probability was 95% at a threshold of $100,000 per QALY gained. Results were confirmed over a range of sensitivity analyses. INTERPRETATION: Using mathematical modelling to extrapolate results from the North American Opiate Medication Initiative, we found that diacetylmorphine may be more effective and less costly than methadone among people with chronic opioid dependence refractory to treatment.

Health related quality of life trajectories of patients in opioid substitution treatment.

BACKGROUND: While opioid substitution treatment (OST) provides the opportunity for substantial improvements in health related quality of life (HRQoL), this relationship is seldom documented and poorly understood. Our objectives were to identify differences in trajectories of HRQoL among chronic opioid-dependent patients and factors associated with improvement and deterioration in HRQoL following enrolment in opioid substitution treatment. METHODS: In the North American Opiate Medication Initiative (NAOMI) randomized controlled trial, the Euroqol (EQ-5D) and other measures of demographic, health and drug use characteristics were collected at baseline and quarterly follow-up. Latent class growth analysis was applied to identify classes of HRQoL trajectories during treatment, while baseline correlates of class membership and factors associated with changes in HRQoL were identified in multivariate analyses. RESULTS: Three classes of individual HRQoL growth trajectories were identified: class 1: low and constant (19.5%), class 2: moderate and improved (61.2%), and class 3: high and constant (19.3%). Class 1 members were younger and more likely to be female, while class 3 members were less likely to have chronic conditions and had lower illicit drug use severity at baseline. Changes in HRQoL were associated with improvements in housing status (positive), medical events (negative) and decreases in illicit drug use (positive). CONCLUSIONS: Insight into the extent of HRQoL response and characteristics of patients responding to treatment can be used to design interventions that maximize HRQoL improvement. Given its role in economic evaluation and subsequent resource allocation decisions, HRQoL should be considered an endpoint in treatment evaluations for opioid dependence.

The effect of motivational status on treatment outcome in the North American Opiate Medication Initiative (NAOMI) study.

Dropout and recidivism from addiction treatment has been found to be associated with individuals' readiness for change. Motivation for treatment among participants entering the North American Opiate Medication Initiative (NAOMI) randomized controlled trial, which compared heroin assisted treatment (HAT) to optimized methadone maintenance treatment (MMT), was assessed. Through multivariate regression, we aimed to determine whether baseline motivational status was predictive of four treatment outcomes: early dropout, 12-month retention, 12-month response to treatment, and time to discontinuation of treatment. Among the 251 out-of-treatment chronic opioid dependent patients recruited in Montreal, Quebec and Vancouver, British Columbia, 52% reported having a high level of motivation for treatment. HAT was statistically significantly more effective than MMT on each of the outcomes assessed. Baseline motivational status did not predict retention or time to discontinuation in either HAT or MMT. However, while patients were retained in HAT regardless of motivational status, motivated patients showed a more favourable response to treatment in terms of decreases in crime and illicit drug use. These results suggest that HAT successfully retains opioid dependent patients who otherwise may not have been attracted into existing treatment options, and may enhance the odds of successful rehabilitation among patients motivated for treatment.

The quality of eight health status measures were compared for chronic opioid dependence.

OBJECTIVE: To provide a comparative analysis of the psychometric properties of eight measures of health status among chronic opioid-dependent patients. STUDY DESIGN AND SETTING: Longitudinal data were analyzed for 251 patients enrolled in the North American Opiate Medication Initiative randomized controlled trial, conducted in Vancouver, British Columbia and Montreal, Quebec, Canada. Content validity, evidence of floor and ceiling effects, internal consistency, construct validity, and responsiveness were assessed for the Addiction Severity Index (ASI) medical and psychiatric (ASImed and ASIpsych) composite scores, the Maudesley Addiction Profile (MAP) physical and mental health scores (MAP-physical health score [MAP-PHS], MAP-mental health score [MAP-MHS]), the World Health Organization Disability Assessment Schedule-II, the EuroQol Group's EQ-5D index score and visual analog scale, EuroQol visual analog scale (EQ-VAS), and the Short Form SF-6D index score. RESULTS: ASImed was best able to discriminate among patients with and without chronic conditions. The MAP-PHS and MAP-MHS were not unidimensional. ASImed and ASIpsych had prominent ceiling effects. ASImed, MAP-MHS, MAP-PHS, EQ-VAS, and EQ-5D were all responsive to decreases in illicit drug use. CONCLUSION: None of the instruments performed uniformly as "best" or "worst." The EQ-5D appeared to be the preferable generic, indirect utility measure. Our results provide an evidence base to inform selection and further development of health status measures in opioid-dependent populations.

The concurrent validity and responsiveness of the health utilities index (HUI 3) among patients with advanced HIV/AIDS.

OBJECTIVES: To assess the concurrent validity and responsiveness of the Health Utility Index 3 (HUI3) in patients with advanced HIV/AIDS, and to determine the responsiveness of this measure, the MOS-HIV and EQ-5D to HIV-related clinical events. METHODS: Data from the OPTIMA (OPTions In Management with Antiretrovirals) trial was analyzed. Two aspects of the validity of the HUI3 were considered: concurrent validity was evaluated using Spearman correlations with MOS-HIV component and summary scores. Responsiveness to AIDS-defining events (ADE) and all adverse events (our external change criterion) was assessed using area under the receiver operating characteristic (AUROC) curves. RESULTS: The study enrolled 368 patients (mean follow-up: 3.66 years); 82% had at least one severe adverse event and 27% had at least one ADE. The HUI3 scale and items showed good concurrent validity, with 85% of the expected relationships with the MOS-HIV subscales verified. The HUI3 was responsive to both adverse events (AUROC [95%CI]: 0.68 [0.57, 0.80]) and ADEs (0.62 [0.51, 0.74]). The EQ-5D was responsive to ADEs (0.66 [0.56, 0.76]), but not responsive to adverse events (0.56 [0.46, 0.68]). CONCLUSION: The HUI3 is a valid and responsive measure of the change in HRQoL associated with clinical events in an advanced HIV/AIDS population.

Quality of life of patients with advanced HIV/AIDS: measuring the impact of both AIDS-defining events and non-AIDS serious adverse events.

OBJECTIVE: To investigate the relative magnitude and duration of impact of AIDS-defining events (ADEs) and non-AIDS serious adverse events (SAEs) on health-related quality of life (HRQoL) among patients with advanced HIV/AIDS. METHODS: We use data from OPTIMA (OPTions In Management with Antiretrovirals), a multinational, randomized, open, control, clinical management trial of treatment strategies for patients with multidrug-resistant HIV and advanced immune disease. Longitudinal models were used to determine the effects of ADEs and SAEs on HRQoL across periods before, during, and after event onset. The Medical Outcomes Study HIV Health Survey (MOS-HIV) physical and mental health summary scores (MOS-PHS and MOS-MHS), EQ-5D, and the Health Utilities Index Mark 3 HRQoL measures were all assessed at regular follow-up intervals during the trial. RESULTS: ADEs occurred much less frequently than SAEs (n = 147 vs. n = 821) in the study sample population of 368 patients, during median follow-up of 3.96 years. Although both ADEs and SAEs had significant negative impacts on HRQoL, SAEs had at least as large an impact upon HRQoL as ADEs when both were included in a multivariate linear regression model, controlling for other covariates. However, the effect of ADEs on HRQoL was more persistent, with larger magnitude of effect across all instruments in time intervals further from the onset of the event. CONCLUSIONS: Non-AIDS SAEs occurring in patients with late-stage HIV/AIDS seem to have at least as important an immediate impact on patient HRQoL as ADEs; however, the impact of ADEs seems to be more persistent. Our findings call for a greater emphasis on the detection and active prevention of non-AIDS SAEs in patients with late-stage HIV/AIDS.

The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis.

BACKGROUND: Overweight and obese persons are at risk of a number of medical conditions which can lead to further morbidity and mortality. The primary objective of this study is to provide an estimate of the incidence of each co-morbidity related to obesity and overweight using a meta-analysis. METHODS: A literature search for the twenty co-morbidities identified in a preliminary search was conducted in Medline and Embase (Jan 2007). Studies meeting the inclusion criteria (prospective cohort studies of sufficient size reporting risk estimate based on the incidence of disease) were extracted. Study-specific unadjusted relative risks (RRs) on the log scale comparing overweight with normal and obese with normal were weighted by the inverse of their corresponding variances to obtain a pooled RR with 95% confidence intervals (CI). RESULTS: A total of 89 relevant studies were identified. The review found evidence for 18 co-morbidities which met the inclusion criteria. The meta-analysis determined statistically significant associations for overweight with the incidence of type II diabetes, all cancers except esophageal (female), pancreatic and prostate cancer, all cardiovascular diseases (except congestive heart failure), asthma, gallbladder disease, osteoarthritis and chronic back pain. We noted the strongest association between overweight defined by body mass index (BMI) and the incidence of type II diabetes in females (RR = 3.92 (95% CI: 3.10-4.97)). Statistically significant associations with obesity were found with the incidence of type II diabetes, all cancers except esophageal and prostate cancer, all cardiovascular diseases, asthma, gallbladder disease, osteoarthritis and chronic back pain. Obesity defined by BMI was also most strongly associated with the incidence of type II diabetes in females (12.41 (9.03-17.06)). CONCLUSION: Both overweight and obesity are associated with the incidence of multiple co-morbidities including type II diabetes, cancer and cardiovascular diseases. Maintenance of a healthy weight could be important in the prevention of the large disease burden in the future. Further studies are needed to explore the biological mechanisms that link overweight and obesity with these co-morbidities.

Use of nonbiologic disease-modifying antirheumatic drugs and risk of infection in patients with rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is associated with increased frequency of and mortality from infections, which may be related to host factors, RA itself, inflammation, or medication side effects. This study was undertaken to determine the effect of nonbiologic disease-modifying antirheumatic drugs (DMARDs) on infection risk in RA. METHODS: We performed a retrospective, longitudinal study of a population-based RA cohort in British Columbia, Canada, followed from January 1996 to March 2003 using administrative data. We evaluated mild infections (requiring a physician visit or antibiotics) and serious infections (requiring or complicating hospitalization). Adjusted risk of mild and serious infections associated with DMARD exposure was estimated using generalized estimating equation extension of multivariate Poisson regression models, after adjusting for baseline covariates (age, sex, RA duration, socioeconomic status) and time-dependent covariates (corticosteroids, comorbidity, prior infections). RESULTS: A total of 27,710 individuals with RA provided 162,710 person-years of followup. Of these, 25,608 (92%) had at least 1 mild infection and 4,941 (18%) had at least 1 serious infection. Use of DMARDs without corticosteroids was associated with a small decrease in mild infection risk of statistical significance but unclear clinical significance (adjusted rate ratio [RR] 0.90, 95% confidence interval [95% CI] 0.88-0.93 relative to no corticosteroid or DMARD use). Use of DMARDs without corticosteroids was not associated with increased serious infection risk (adjusted RR 0.92, 95% CI 0.85-1.0). Use of corticosteroids increased the risk of mild and serious infections. CONCLUSION: Our results indicate that use of nonbiologic DMARDs, including methotrexate, does not increase the risk of infection in RA, whereas use of corticosteroids does. This has important implications for counseling individuals with RA concerning risks and benefits of DMARDs.

Impact of the recall period on measuring health utilities for acute events.

The impact of healthcare interventions on health utility values is most frequently measured using a preference-based instrument. Each of the available instruments instructs the respondent to report their health status over different recall periods ranging from the current day to the past month. In an ongoing randomised controlled trial in patients with advanced HIV disease, the impact of using a preference-based instrument with a 1-week recall period vs a 1-day recall period (e.g. today) for capturing recently resolved serious adverse events was measured. The results suggest that the instrument with a 1-week recall period gave lower utility values for recently resolved events in comparison with the instrument with a 1-day recall period. A plausible interpretation of these results is that the recall period was adhered to; for example, patients ignored the impact of recently resolved events in their response if the questionnaire asked them only about their health today. While there are limitations to our study, we believe further consideration should be given to the recall period used for preference-based instruments, and future research should examine other patient groups using a single instrument with multiple recall periods.

When patients have to pay a share of drug costs: effects on frequency of physician visits, hospital admissions and filling of prescriptions.

BACKGROUND: Previous research has shown that patient cost-sharing leads to a reduction in overall health resource utilization. However, in Canada, where health care is provided free of charge except for prescription drugs, the converse may be true. We investigated the effect of prescription drug cost-sharing on overall health care utilization among elderly patients with rheumatoid arthritis. METHODS: Elderly patients (> or = 65 years) were selected from a population-based cohort with rheumatoid arthritis. Those who had paid the maximum amount of dispensing fees (200 dollars) for the calendar year (from 1997 to 2000) were included in the analysis for that year. We defined the period during which the annual maximum co-payment had not been reached as the "cost-sharing period" and the one beyond which the annual maximum co-payment had been reached as the "free period." We compared health services utilization patterns between these periods during the 4 study years, including the number of hospital admissions, the number of physician visits, the number of prescriptions filled and the number of prescriptions per physician visit. RESULTS: Overall, 2968 elderly patients reached the annual maximum cost-sharing amount at least once during the study periods. Across the 4 years, there were 0.38 more physician visits per month (p < 0.001), 0.50 fewer prescriptions filled per month (p = 0.001) and 0.52 fewer prescriptions filled per physician visit (p < 0.001) during the cost-sharing period than during the free period. Among patients who were admitted to the hospital at least once, there were 0.013 more admissions per month during the cost-sharing period than during the free period (p = 0.03). INTERPRETATION: In a predominantly publicly funded health care system, the implementation of cost-containment policies such as prescription drug cost-sharing may have the unintended effect of increasing overall health utilization among elderly patients with rheumatoid arthritis.

Gaps in care for rheumatoid arthritis: a population study.

OBJECTIVE: Treatment guidelines for rheumatoid arthritis (RA) now recommend early, aggressive, and persistent use of disease-modifying antirheumatic drugs (DMARDs) to prevent joint damage in all people with active inflammation, and evaluation by a rheumatologist, when possible. This research assesses whether care for RA, at a population level, is consistent with current treatment guidelines. METHODS: Using administrative billing data from the Ministry of Health in 1996-2000, all prevalent RA cases in British Columbia, Canada were identified. Data were obtained on all medications and all provincially-funded health care services. RESULTS: We identified 27,710 RA cases, yielding a prevalence rate of 0.76%, consistent with epidemiologic studies. DMARD use was inappropriately low. Only 43% of the entire RA cohort received a DMARD at least once over 5 years, and 35% over 2 years. When used, DMARDs were started in a timely fashion, but were not used consistently. Care by a rheumatologist increased DMARD use 31-fold. Yet, only 48% and 34% saw a rheumatologist over 5 and 2 years, respectively. DMARD use was significantly more frequent, persistent, and more often used as combination therapy with continuous rheumatologist care. DMARDs were used by 84% and 73%, 40%, and 10% of people followed by rheumatologists continuously and intermittently, internists, and family physicians, respectively (P < 0.001). NSAID use, physiotherapy, and orthopedic surgeries were similar across these 4 care groups. CONCLUSION: RA care in the British Columbia population was not consistent with current treatment guidelines. Efforts to educate family physicians and consumers about the shift in RA treatment paradigms and to improve access to rheumatologists are needed.

HIV-positive injection drug users who leave the hospital against medical advice: the mitigating role of methadone and social support.

BACKGROUND: Leaving the hospital against medical advice has been associated with increased morbidity and readmission. Factors associated with the risk of leaving against medical advice among HIV/AIDS patients or injection drug users have not been examined in detail. OBJECTIVES: To examine the clinical and social factors associated with leaving against medical advice (AMA) from a specialized HIV/AIDS ward among patients who reported a history of injection drug use. METHODS: All patients with a history of injection drug use admitted to the HIV/AIDS ward at St. Paul's Hospital, Vancouver, British Columbia (the largest specialized HIV/AIDS hospital ward in Canada) between April 1997 and October 2000 were reviewed retrospectively. A multivariate logistic regression model utilizing a generalized estimating equation algorithm identified factors associated with leaving the hospital AMA. RESULTS: Of the 1056 hospital admissions to the HIV/AIDS ward by patients with a history of injection drug use, 263 (24.9%) resulted in leaving the hospital AMA. Independent positive predictors of leaving AMA included recent injection drug use (adjusted odds ratio [AOR] = 2.08, 95% confidence interval [CI]: 1.41-3.07) and aboriginal ethnicity (AOR = 1.55, 95% CI: 1.05-2.28). Discharge AMA was also more likely to occur on weekends (AOR = 2.27, 95% CI: 1.49-3.48) and on days when social assistance payments were issued (AOR = 2.95, 95% CI: 1.70-5.10). Factors that independently reduced the odds of hospital discharge AMA included in-hospital methadone use (AOR = 0.49, 95% CI: 0.32-0.76), social support (AOR = 0.33, 95% CI: 0.21-0.51), and older age (per 10-year increment, AOR = 0.56, 95% CI: 0.43-0.73). CONCLUSIONS: Among HIV-positive patients with a history of injection drug use, the odds of leaving the hospital AMA were reduced for subjects who received inpatient methadone treatment, were of older age, or had social supports. Addiction treatment and interventions that enhance social supports in marginalized populations at risk for hospital discharge AMA should be further explored.

Lowering generic drug prices: less regulation equals more competition.

BACKGROUND: In Ontario, Canada, the 70/90 regulations were instituted in May 1993 to establish provincial government procurement prices for generic drugs. Accordingly, the first generic entrant's price could not exceed 70% of the incumbent's branded price. Subsequent entrants' prices could not exceed 90% of the first entrant's price. OBJECTIVE: These regulations' impact on generic market competitiveness are evaluated. DESIGN AND METHODS: Data on 518 drugs spanning nine therapeutic classifications were collected for the period of 04/01/1987 to 12/31/1998 from Ontario Drug Benefit formulary and IMS Canada. The period 04/01/1987 to 04/30/1993 was defined as the before period (BP) and 05/01/1993 to 12/31/1998 was the after period (AP). We compared the price ratio (P = P(G)/P(B) ) between BP and AP and performed regression analysis to assess the determinants of P. RESULTS: in both the BP and AP decreased as the number of generic firms increased within these periods. However, this decrease in was significantly less in the AP (median: 0.75 --> 0.68 --> 0.67) than in BP (0.71 --> 0.61 --> 0.53) as the number of generics increased from 1 to 2 to 3, respectively. The regression analysis showed that the price ratio in the AP was higher than that in the BP by 0.05, 0.09, and 0.13 for first, second, and third generic entrant respectively. CONCLUSIONS: Our findings show that the 70/90 regulations not only failed to achieve their goal of lowering the procurement price but instead the opposite occurred. The mandated procurement price became a focal point and resulted in a clustering of prices around the maximum allowable levels with little price dispersion.

Patterns of inhaled asthma medication use: a 3-year longitudinal analysis of prescription claims data from British Columbia, Canada.

STUDY OBJECTIVES: To assess trends in asthma management and to identify factors associated with increasing short-acting (SA) beta-agonist utilization in British Columbia using administrative prescription data. DESIGN: A retrospective cohort analysis. SETTING: All patients between 13 and 50 years of age who had received at least one prescription for a SA beta-agonist covered by BC Pharmacare between January 1, 1996, and December 31, 1998. METHODS: Cross-sectional analysis of all patients, and longitudinal analyses only of patients who had received at least one SA beta-agonist prescription in each of the 3 years. Trends in asthma medication use over time were evaluated using repeated-measures Mantel-Haenszel tests. Multiple logistic regression was used to identify factors associated with increasing SA beta-agonist use. RESULTS: A total of 78,758 patients were included in the cohort. No decrease in the annual prevalence of receiving more than four canisters per year of a SA beta-agonist was identified between 1996 and 1998. A total of 12,844 patients filled at least one SA beta-agonist prescription each year. Time-trend analysis showed an overall increasing probability of not receiving an inhaled corticosteroid (ICS) agent in this population (p = 0.002). In patients exhibiting low SA beta-agonist use, > 18 years of age (adjusted odds ratio [OR], 1.5), male gender (adjusted OR, 1.7), and in receipt of social assistance (adjusted OR, 2.3) were associated with receiving increasing amounts of SA beta-agonist agents over the 3 years. In patients with a high degree of use of SA beta-agonists, only the receipt of social assistance (adjusted OR, 1.3) was significantly associated with increasing use. CONCLUSIONS: Despite the development and dissemination of asthma management guidelines, there was no trend toward decreasing SA beta-agonist use. An unexpected trend toward decreasing ICS utilization was identified. Receiving social assistance was a risk factor for increasing SA beta-agonist use, independent of baseline utilization.