The risks and costs of multiple-generic substitution of topiramate.

OBJECTIVE: To investigate clinical and economic consequences following generic substitution of one vs multiple generics of topiramate (Topamax; Ortho-McNeil Neurologics, Titusville, NJ). METHODS: Medical and pharmacy claims data of Régie de l'Assurance-Maladie du Québec from January 2006 to October 2007 were used. Patients with epilepsy treated with topiramate were selected. An open-cohort design was used to classify the observation period into periods of brand, single-generic, and multiple-generic use. One-year generic-switch and switchback-to-brand rates were estimated using Kaplan-Meier methodology. Medical resource utilization and costs were compared among the three periods using multivariate regression analysis. RESULTS: In total, 948 patients were observed during 1,105 person-years of brand use, 233 person-years of single-generic use, and 92 person-years of multiple-generic use. A total of 23% of generic users received at least two different generic versions. Compared to brand use, multiple-generic use was associated with higher utilization of other prescription drugs (incidence rate ratio [IRR] = 1.27, 95% confidence interval [CI] = 1.24-1.31), higher hospitalization rates (0.48 vs 0.83 visit/person-year, IRR = 1.65, 95% CI = 1.28-2.13), and longer hospital stays (2.6 vs 3.9 days/person-year, IRR = 1.43, 95% CI = 1.27-1.60), but the effect was less pronounced in single-generic use (hospitalization: IRR = 1.08, 95% CI = 0.88-1.34, length of stay: IRR = 1.12, 95% CI = 1.03-1.23). The risk of head injury or fracture was nearly three times higher (hazard ratio = 2.84, 95% CI = 1.24-6.48) following a generic-to-generic switch compared to brand use. The total annualized health care cost per patient was higher in the multiple-generic than brand periods by C$1,716 (cost ratio = 1.21, p = 0.0420). CONCLUSION: Multiple-generic substitution of topiramate was significantly associated with negative outcomes, such as hospitalizations and injuries, and increased health care costs.

Adherence to weekly oral bisphosphonate therapy: cost of wasted drugs and fractures.

UNLABELLED: In an observational cohort of patients treated with biphosphonates (BP), we observed that poor adherence to these drugs causes important expenditures in terms of avoidable fractures. Of particular interest are the amounts of money wasted by patients who did not take their BPs long enough to obtain a clinical benefit. INTRODUCTION: A large proportion of patients initiated with oral weekly BP therapy stop their treatment within the first year. The objective of this study was to estimate the impact of the poor adherence to BPs in terms of drug wasted and avoidable fractures. METHODS: The study was done on primary and secondary prevention cohorts from the Régie de l'assurance maladie du Québec (Québec). The concept of the "point of visual divergence" was used to determine the amount of wasted drug. The risk of fracture was estimated using Cox regression models. The hazard ratios of compliant patients (+80%) versus non compliant patients were used to estimate the number of fractures saved. RESULTS: The cost of wasted drugs was $25.87 per patient initiated in the primary prevention cohort and $30.52 in the secondary prevention cohort. If all patients had been compliant, 110 fractures would have been avoided in the primary prevention cohort and 19 fractures in the secondary prevention cohort. The cost of these avoidable fractures per patient initiated on BP therapy was $62.95 in primary prevention cohort and $330.84 in secondary prevention cohort. CONCLUSIONS: This study confirms that poor adherence to oral BPs leads to a significant waste of money and avoidable fractures.

Differences in persistence among different weekly oral bisphosphonate medications.

SUMMARY: We evaluated the differences in persistence with weekly oral bisphosphonate therapy according to the initial drug. Persistence to weekly oral preparations remains suboptimal, particularly in patients who receive generic alendronate. Alternative solutions are needed to improve the real life effectiveness of osteoporosis therapies. INTRODUCTION: Poor persistence is widespread with oral osteoporosis (OP) therapy. The objective of this study was to evaluate the persistence among OP patients started on weekly oral bisphosphonates (BP). METHODS: Patients newly initiated on branded risedronate, branded alendronate, or generic alendronate once weekly were selected from the Régie de l'Assurance Maladie du Québec databases. The cohort included patients with and without a previous OP fracture. The probability and the risk factors for early discontinuation were estimated using Cox regression models. RESULTS: The study cohort included 32,804 patients. After 1 year, a significant difference in persistence on oral BP therapy was found. The patients started on branded risedronate were 11% more likely to stop OP therapy than patients started on branded alendronate. Risk of discontinuation doubled in patients initiated with generic alendronate compared to patients started on branded alendronate. Male gender was associated with a 25% increase risk of early discontinuation. No statistical association was found between previous OP fracture and early discontinuation. CONCLUSION: This study provides further evidence of poor persistence to newly initiated oral weekly BP therapies, particularly for the patients started on generic alendronate.

Clinical consequences of generic substitution of lamotrigine for patients with epilepsy.

OBJECTIVES: To measure the proportions of patients switching from generic to branded drugs among users of antiepileptic drugs (AED) compared to other therapeutic areas and to investigate medical services utilization associated with generic switching of lamotrigine. METHODS: Medical and pharmacy claims data from Régie de l'Assurance Maladie du Québec database from April 1998 to July 2006 were used. Patients with an epilepsy diagnosis (International Classification of Diseases-9 345) and treated with lamotrigine for >60 of the 90 days before the entry date of generic lamotrigine in Quebec (February 1, 2003) were selected. The proportion of patients switching back to brand were calculated for lamotrigine, for other AEDs (clobazam, carbamazepine CR, gabapentin) and for non-AED chronic medications (carvedilol, fosinopril, simvastatin). Medical resource utilization was compared between periods of branded vs generic use of lamotrigine. RESULTS: Of 671 patients treated with branded lamotrigine, 187 patients (27.9%) switched to a generic, and 51 of these patients (27.5%) switched back to the branded medication. Rates of switchback were from 20.8% to 44.1% for various AEDs and from 7.7% to 9.1% for non-AEDs. Relative to the branded lamotrigine use period, generic lamotrigine use period was associated with a 5.1% increase in mean daily dose of lamotrigine (239.1 vs 251.4 mg; p = 0.0149), a higher number of dispensations for other AEDs (20.4 vs 23.9 dispensations per person-year; p < 0.001) as well as non-AED drugs (26.4 vs 32.8 dispensations per person-year; p < 0.0001), a higher utilization rate of medical services (8.7 vs 9.8 visits per person-year; p < 0.0001), and a longer hospital length of stay (3.29 days vs 4.86 days per person-year; p < 0.0001). CONCLUSION: A higher propensity to switch back to branded medications was observed among antiepileptic drug users compared to users of antihypertensives and antihyperlipidemics, similar to findings from Andermann et al. Switch to generic lamotrigine was significantly associated with increased physician visits and hospitalizations.

Osteoporosis among patients with type 1 and type 2 diabetes.

Both diabetes and fractures are prevalent in adults. The relationship between diabetes and osteoporosis is complex and, although it has been investigated extensively, the subject remains controversial. While low bone mineral density (BMD) is consistently observed in type 1 diabetes, the relationship is less clear in type 2 diabetes, with some studies reporting modestly increased or unchanged BMD. Both type 1 and type 2 diabetes have been associated with a higher risk of fractures. Despite discrepancies between BMD and fracture rates, clinical trials uniformly support the fact that new bone formation and bone microarchitecture and, thus, bone quality, are altered in both types of diabetes. Although a causal association between diabetes and osteoporosis cannot be established on the basis of existing data, it is possible to conclude from many studies and from a better understanding of the physiopathology of diabetes that it can increase the risk of fractures through skeletal (decreased BMD and bone quality) and extraskeletal (increased risk of falls) factors. Even though osteoporosis screening or prophylactic treatment in all patients with type 1 and type 2 diabetes is not being recommended at present, such patient populations should be given general guidelines regarding calcium and vitamin D intakes, exercise and the avoidance of potential risk factors for osteoporosis. The extent of diagnostic and therapeutic interventions should be based on the individual's risk profile for fractures.

Application of lag-time into exposure definitions to control for protopathic bias.

PURPOSE: To control for protopathic bias, some studies have incorporated the concept of lag-time into their exposure definition (time period before the index date that was not considered in assessing exposure). The objective of this study was to introduce a procedure to identify the best lag-time to be applied in studies where control for protopathic bias is required. METHODS: We used data from a case-control study carried out to assess the association between exposure to proton pump inhibitors (PPIs) and risk of gastric cancer, using RAMQ databases. Exposure was defined as the number of defined daily doses of PPIs dispensed during the 5-year period prior to the index date (divided into four quartiles). Thirty-one different lag-times were applied (0-30 months) based on 1-month intervals. Logistic regression was used to estimate the matched odds ratio (OR) for each lag-time. The change point in the ln(ORs) was identified by applying a two-compartmental model and a segmented regression model. RESULTS: A trend of decreasing ORs was found with the application of an increasing lag-time. As an illustration, the ORs for the 1st quartile of defined daily doses, when applying the 31 different lag-times, ranged between 3.52 when applying a 0 lag-time and 0.97 when applying a 30 months lag-time. Applying the two methods for the different lag-times showed that the ORs stabilized at around 6 months. CONCLUSION: For the purpose of controlling for protopathic bias in pharmacoepidemiological studies, we have provided a method to assess the most appropriate lag-time that should be applied for the assessment of drug exposure.

Assessment of Canadian provincial expenditures in depressed patients treated with venlafaxine XR versus SSRIs: the APEX Study.

OBJECTIVE: Empirical studies of antidepressant cost-effectiveness suggest that the use of venlafaxine may be no more costly than selective serotonin reuptake inhibitors (SSRIs) in the treatment of depression. The objectives of this study were to identify patients' characteristics and factors associated with the choice of antidepressant and to assess differences in persistence, healthcare utilization and direct medical costs associated with venlafaxine and SSRIs pharmacotherapy. RESEARCH DESIGN AND METHODS: We examined demographic and clinical characteristics of patients (n = 17 144) who received both a diagnosis of depression and a prescription for venlafaxine or an SSRI between 1996 and 2004 using the Quebec health administrative databases. Logistic regression models were used to identify factors independently associated with the choice of antidepressant. Persistence to treatment and overall direct medical costs during 12 months after initiation of therapy were assessed using Cox proportional hazard and GLM models, respectively. RESULTS: Age, sex, provider specialty, and prior 12-month healthcare utilization significantly influenced initial antidepressant choice. Fewer venlafaxine-treated patients discontinued their initial therapy relative to SSRIs' (persistence to initial treatment: 38.4% vs. 29.4% and 24.4% vs. 15.8% at 6 and 12 months, respectively; p < 0.0001), and they were less likely to require treatment switching. Overall 12-month direct medical costs for SSRI- and venlafaxine-treated patients were Can$2759 and Can$2604, respectively. Patients treated with SSRIs had significantly higher expenditures in a univariate analysis (cost ratio: 1.06 [95% CI: 1.02, 1.10]). However, after controlling for potential confounding factors such as patients' characteristics, prior healthcare utilization, and comorbid conditions in multivariate analyses, the overall expenditures were similar in both groups (cost ratio: 1.03 [95% CI: 0.99, 1.07]). CONCLUSIONS: Direct medical costs were generally similar among patients with depression treated with venlafaxine and SSRIs. In a 'real world' setting, the higher acquisition cost of venlafaxine is offset by savings due to fewer hospitalizations and fewer outpatient medical visits. Differences in treatment persistence may also, in part, explain the observed differences in average direct medical costs between venlafaxine and SSRIs.

Drug utilization review of celecoxib in Ontario.

Cyclooxygenase (COX)-2-specific inhibitors were developed to circumvent the gastrointestinal toxicity of non-specific non-steroidal anti-inflammatory drugs while maintaining efficacy. However, the higher acquisition cost of COX-2-specific inhibitors has resulted in the implementation of a programme for cost containment in the Ontario public drug program. This programme consists of limited use (LU) criteria that need to be met for drug reimbursement of patients with osteoarthritis (OA) or rheumatoid arthritis (RA). Determining the proportion of patients eligible for reimbursement for celecoxib according to the LU criteria (based on prior treatment failure and the presence or history of serious ulcer-related gastrointestinal complications) can provide an indication of the extent of adherence to suggested guidelines. Using a patient-based survey and an analysis of the Ontario Drug Benefit Program database, the proportion of patients prescribed celecoxib who met rigorous or pragmatic definitions of the LU criteria was determined. The extent of coprescription of gastroprotective agents among patients taking celecoxib was also determined. Using the pragmatic definition, the majority of patients in the patient-based survey (53% for OA and 81% for RA) met the LU criteria. Similarly, in the database analysis, the majority of patients (76% for OA and 78% for RA) met the LU criteria. These data suggest that physician prescribing of celecoxib is consistent with the LU criteria. Concomitant prescription of gastroprotective agents in patients taking celecoxib was approximately 40%. It is recommended that further investigations be performed to determine the long-term impact of LU criteria on clinical and economic outcomes, since these criteria may also serve to restrict use in patients who may benefit from taking COX-2-specific inhibitors.

The science of health technology assessment--clinical effectiveness of therapeutic interventions.

Important information is not, and cannot, be available at the time a new drug enters the market. Delaying registration is not the answer because most of this information can only be obtained in a real life situation. Several types of postmarketing (phase IV studies) can be identified. The active pharmacovigilance cohort who allows large number of patients to be followed for long periods of time can answer questions about the incidence of rare events (less than one of 3000 patients). The prospective effectiveness cohort can answer questions on long term efficacy (more than two years). The simplified clinical trial, which implies randomly assigning patients and then following them with a 'naturalistic' protocol can answer questions about effectiveness (efficacy in real life). The drug use study is the only way to answer questions of key importance to drug plan managers such as 'which drug(s) is it going to replace?' and 'is it going to be used as first line or second line?'. Phase IV studies, which in some cases should be mandatory (conditional registration), are essential for the protection of the patients and the proper use of public funds to reimburse drugs.

Cost of prescribed NSAID-related gastrointestinal adverse events in elderly patients.

AIMS: It is well established that nonsteroidal anti-inflammatory drugs (NSAIDs) have gastrointestinal (GI) side-effects. However, the cost of health care resources spent on preventing and managing these side-effects is not clear. The objective of this study was to estimate the direct cost of NSAID-related GI events in an elderly population. METHODS: From the Régie de l'assurance-maladie du Québec (RAMQ) database, we obtained medical, pharmaceutical and demographic records of a 10% random sample (n = 49 033) of seniors who, between January 1, 1993 and December 31, 1997, had a dispensed prescription of a NSAID. Patients who did not have any GI events during the year prior to their first dispensed prescription were included in the cohort. All patients were followed-up for 2 years. The daily direct Canadian dollar costs of GI events that were incurred by these patients while they were on NSAID therapy were compared with those of GI events that were incurred by these same patients while they were not on NSAID therapy. The difference in these daily costs was attributed to NSAIDs. RESULTS: A total of 12 082 new NSAID users were included in the study. Two hundred and seventeen (1.8%) were hospitalized for GI-related problems; of these, 130 (60%) had their GI hospitalization as their first GI event; 3257 (27.0%) used gastroprotective agents (GPAs), and 857 (26.3%) took GPAs without any apparent prior GI symptoms; 801 (6.6%) had GI diagnostic tests; and 661 (5.5%) died. The average direct costs of GI side-effects per patient-day on NSAIDs were 3.5 times higher than those of a patient-day not on NSAIDs. The direct cost of GI side-effects per patient-day on NSAIDs was $1.34, of which more than 70% ($0.94) was attributed to GI events resulting from NSAID treatment. CONCLUSIONS: Approximately one Canadian dollar was added to patient costs for every day he/she was on NSAID therapy. Safer therapies and appropriate patient risk management may potentially reduce NSAID-related health care resource use.

Gastrointestinal-related healthcare resource usage associated with a fixed combination of diclofenac and misoprostol versus other NSAIDs.

OBJECTIVE: To compare gastrointestinal (GI) healthcare resource use (HCRU) and associated costs in patients taking a fixed combination of diclofenac and misoprostol versus other nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: We analysed a sample (49,033 patients) of the Government of Quebec Health Insurance Agency database. Patients were included in the study if they did not have GI events during the year preceding the date of their first NSAID prescription dispensing (the index date). Patients were followed up for 2 years. A 3-stage model was used to determine the factors that influenced the direct medical costs of GI HCRU: (i) a logistic regression model (model 1) to estimate the risk of GI HCRU; (ii) a linear regression model (model 2) to estimate the direct costs of GI HCRU for those who had such events; (iii) multiplying the estimated risks from model 1 by the estimated costs from model 2 gave the estimated direct costs of GI HCRU for all patients. STUDY PERSPECTIVE: Provincial government of Quebec, Canada. RESULTS: 1,533 patients were prescribed diclofenac/misoprostol at the index date and 10,540 another NSAID. Comorbidity markers were not significantly different between the 2 groups. Of the diclofenac/misoprostol patients, 23 (1.5%) were hospitalised for GI problems compared with 194 (1.8%) of the NSAID group; 403 (26.3%) of diclofenac/misoprostol patients used gastroprotective agents compared with 2,849 (27.0%) of the NSAID patients; 118 (7.7%) of diclofenac/misoprostol patients had GI diagnostic tests compared with 682 (6.5%) of the NSAID patients. The average direct medical cost of GI HCRU was 310.52 Canadian dollars ($Can)/patient (1997 values) in the diclofenac/misoprostol group compared with $Can231.19/patient (1997 values) in the NSAID group. When adjusted for baseline factors, the ratio of the total direct medical cost of GI HCRU in the diclofenac/misoprostol group to that of the NSAID group was 1.15 (95% confidence interval: 0.89, 1.48). CONCLUSIONS: Our data showed no significant differences in GI HCRU among patients taking diclofenac/misoprostol compared with those taking NSAIDs.

Do statins cause cancer? A meta-analysis of large randomized clinical trials.

PURPOSE: Although the short-term safety and tolerability of statins has been well established, their potential carcinogenicity in the long term is still debated. The goal of this study was to determine whether long-term treatment with statins is associated with an increased risk of fatal and nonfatal cancers. METHODS: We searched the Medline database between January 1966 and December 1999 for randomized, controlled trials of human subjects in which monotherapy with a statin was compared with placebo. No language restrictions were applied. Only trials with a minimum treatment duration of 4 years and a minimum of 1,000 subjects were included. Studies that did not provide information on fatal or nonfatal cancers were excluded. Data on fatal and nonfatal cancers and all-cause mortality were extracted by a single nonblinded reviewer. Overall crude estimates of risk difference were computed by summing the numerators and denominators of trial-specific risk estimates. RESULTS: Five trials met the inclusion criteria. The estimated differences in absolute risk between treatment and placebo were as follows (negative risks indicate that treatment was safer than placebo): all nonfatal cancers, 0.0% (95% confidence interval [CI]: -0.8% to 0.8%); all fatal cancers, -0.1% (95% CI: -0.7% to 0.4%); all fatal and nonfatal cancers combined, -0.1% (95% CI: -1.0% to 0.7%); and all-cause mortality, -1.5% (95% CI: 2.8% to 0.2%). CONCLUSION: This study demonstrates no association between statin use over a 5-year period and the risk of fatal and nonfatal cancers. This conclusion is limited by the relatively short follow-up of the studies analyzed. Similar analyses of data from studies with longer follow-up periods would be valuable.

Impact of a cost-sharing drug insurance plan on drug utilization among older people.

OBJECTIVES: In August 1996, the Régie de l'assurance-maladie du QuEbec (RAMQ), the government body responsible for medical insurance in the Canadian province of Quebec, introduced a cost-sharing drug insurance plan. Before this plan, individuals age 65 years and older had to pay Canadian (CDN)$2 per prescription, with the remaining cost paid by the RAMQ. With the new plan, beneficiaries may have to pay an amount between CDN$200 and CDN$925 per year, depending on their income. Concerned that this financial constraint imposed on older people might have an impact on the use of medications, we investigated whether the consumption of four classes of medications, antihypertensive agents, anticoagulants, nitrates, and benzodiazepines, was affected by the drug plan implementation. DESIGN: Time series models with pre/post comparison group. SETTING: Administrative computerized databases of the RAMQ. PARTICIPANTS: Random sample of Quebec residents age 65 years and older registered in the provincial drug plan between August 1992 and June 1997: 54,771 users of nitrates, 133,146 users of antihypertensive agents, 45,534 users of anti-coagulants, and 26,165 users of benzodiazepines. MEASUREMENTS: We modeled the monthly consumption of the medications under study between August 1992 and June 1996. Monthly drug consumptions predicted from the models were compared with those observed for the 13 months (August 1996 to August 1997) following the implementation of the new drug plan using 95% confidence intervals. The number of prescriptions dispensed served as an indicator for drug consumption. RESULTS: During the study period we observed a nonstatistically significant decrease in number of prescriptions of 5.1% for nitrates, 1.1% for antihypertensive agents, and 0.8% for benzodiazepines, and a nonstatistically significant increase of 1.6% for anticoagulants. CONCLUSION: Residents of Quebec age 65 years and older were not found to have reduced significantly their consumption of nitrates, antihypertensive agents, anticoagulants, and benzodiazepines during the 13 months that followed the implementation of a cost-sharing drug insurance plan.

Age-related differences in in-hospital mortality and the use of thrombolytic therapy for acute myocardial infarction.

BACKGROUND: Recent guidelines have acknowledged that thrombolysis decreases mortality from acute myocardial infarction (AMI) independently of age. The purpose of this study was to determine the age-related rates of thrombolytic administration and in-hospital mortality and the variables related to the use of thrombolytic therapy for patients with AMI. METHODS: A prospective cohort analysis involved a registry of 44 acute care Quebec hospitals that enrolled 3741 patients with AMI between January 1995 and May 1996. The main outcomes of interest were crude and adjusted age-related in-hospital mortality rates and rates of use of thrombolytic therapy. RESULTS: In-hospital mortality rates increased dramatically with age from 2.1% in patients with AMI who were less than 55 years of age to 26.3% in those who were 85 years of age or older. Overall, 35.8% of the patients received thrombolysis. There was a pronounced inverse gradient in the use of thrombolysis with age, ranging from 46.2% in the youngest age group (< 55 years) to 9.5% in the oldest group (> or = 85 years). After adjustment for potential confounders, the older patients remained significantly less likely to receive thrombolytic therapy. Compared with patients who were less than 55 years of age, the odds ratio of receiving thrombolytic therapy was 0.68 (95% confidence interval [CI] 0.52-0.89) for patients aged 65-74 years, 0.48 (95% CI 0.35-0.65) for patients aged 75-84 years and 0.13 (95% CI 0.06-0.26) for patients aged 85 years or more. Other variables related to thrombolytic therapy were diabetes (odds ratio [OR] 0.77, 95% CI 0.59-1.00), cerebrovascular disease (OR 0.46, 95% CI 0.30-0.72), angina (OR 0.73, 95% CI 0.56-0.95), typical chest pain (OR 2.56, 95% CI 1.88-3.47); ST elevation (OR 8.93, 95% CI 7.24-11.00), Q wave MI (OR 5.26, 95% CI 4.20-6.60) and increased length of time between onset of symptoms and arrival at hospital. INTERPRETATION: Age is an important independent predictor of in-hospital mortality and lower thrombolytic use following AMI. Other studies are required to further evaluate the appropriateness of thrombolytic therapy for elderly patients.

Association between the burden of disease and research funding by the Medical Research Council of Canada and the National Institutes of Health. A cross-sectional study.

BACKGROUND: The Medical Research Council of Canada (MRCC) is the major Canadian agency responsible for funding biomedical health research in this country. Disease-specific funding by the United States National Institutes of Health (NIH) has been studied and is not independent of burden-of-disease parameters. We tested the association between disease-specific MRCC funding, disease-specific NIH funding and various burden-of-disease parameters. METHOD: Information on 1994/99 MRCC funding was obtained from the MRCC database for 29 diseases. NIH funding and burden-of-disease counterparts for the year 1996 were gleaned from a recent publication. The association between data series was measured by correlation coefficients. RESULTS: Disease-specific incidence, mortality and years-of-life lost did not correlate significantly with 1994/99 disease-specific MRCC funding but prevalence (r = 0.54, p = 0.005) and disability-adjusted life-years did (r = 0.48, p = 0.009). A correlation coefficient of 0.50 (p = 0.006) was calculated between 1996 NIH funding and 1996/97 MRCC funding. Two disease categories, cirrhosis and alcohol abuse, received a greater percentage of funds from the NIH than from the MRCC. Two other disease categories, epilepsy and perinatal disease, received a greater percentage of funds from the MRCC than from the NIH. CONCLUSIONS: Disease-specific MRCC grants in the past 5 years correlated with 2 of the usual burden-of-disease parameters: disability-adjusted life-years and disease prevalence. A statistically-significant correlation was observed between disease-specific grants awarded by the MRCC and the NIH.

Predictors of persistence of use of the novel antidiabetic agent acarbose.

BACKGROUND: A carbose is the first of a new class of antidiabetic agents, the alpha-glucosidase inhibitors. This study characterizes and identifies predictors of persistence of use of acarbose. METHODS: Medical, pharmaceutical, and demographic records were extracted for 2 cohorts of patients (social assistance recipients and seniors) from the databases of Quebec's provincial health plan. Patients were eligible for inclusion if they had received their first dispensation of acarbose between August 1, 1996, and December 31, 1997. The observation period included at least 1 year before the first dispensation and a minimum of 4 months after. RESULTS: New users of acarbose included 216 social assistance recipients and 677 seniors who were followed up for 82 914 and 270 041 person-days, respectively. Median persistence with acarbose treatment was 83 days (95% confidence interval, 75-105 days) for social assistance recipients and 105 days (95% confidence interval, 90-119 days) for seniors. In both cohorts, treatment by an endocrinologist vs another physician predicted longer treatment persistence. In the seniors cohort, additional determinants of (earlier) treatment discontinuation included a higher initial daily dose, previous treatment with insulin, and consultation with a gastroenterologist after treatment initiation. CONCLUSIONS: New users of acarbose showed low persistence in 2 cohorts of beneficiaries of Quebec's provincial health plan. Prescribing specialist was an important predictor of persistence in seniors and the socially assisted. The importance of 4 additional factors in seniors only led to hypotheses concerning population differences in treatment expectations and in the occurrence and tolerance of adverse effects.

Estrogen replacement therapy: determinants of persistence with treatment.

OBJECTIVE: To evaluate the persistence rate for estrogen therapy and to identify its determinants. METHODS: From the Quebec health insurance database we chose a cohort of 4527 women 35 years and older who received social assistance and were new users of estrogen between January 1989 and December 1997. Incident use was defined by the absence of any dispensed prescription of estrogen in the 3 years before the index date (date of first dispensed prescription). We estimated the cumulative persistence rate of treatment by Kaplan-Meier failure time analysis and identified its determinants with the Cox proportional hazards model. RESULTS: From the initial cohort, 3395 women (75%) renewed their first dispensed prescription and 905 (20%) continued treatment after 4 years. The determinants measured at the index date and significantly associated with a better persistence rate (relative risk [RR]) were younger than 60 years (RR 1.15, 95% confidence interval [CI] 1.01, 1.30), low dosage (RR 1.49, 95% CI 1.32, 1.70), continuous progestin combination (RR 1.40, 95% CI 1.27, 1.54), and a gynecologist as the first prescribing physician (RR 1.15, 95% CI 1.03, 1.21). Also, coronary heart disease or at least one risk factor for it in the year before the index date was associated with a better persistence rate for estrogen replacement therapy (RR 1.15, 95% CI 1.05, 1.22). CONCLUSIONS: The persistence rate for estrogen therapy is poor, implying that few women take it long enough to benefit from it.

Patterns of amlodipine and felodipine use in an elderly Quebec population.

OBJECTIVES: To assess drug prescription patterns and medical resource consumption in an elderly population in Quebec receiving amlodipine or felodipine for the treatment of hypertension. PATIENTS AND METHODS: Sociodemographic, clinical and drug claim data for a random sample of hypertensive patients 65 years of age and older with at least one claim for amlodipine or felodipine between August 1, 1990 and August 31, 1997 were extracted from the Régie de l'assurance maladie du Québec (RAMQ) database. Patterns of prescription renewal, drug switch and compliance rates, and health care resource use were established for both an amlodipine and a felodipine group. Long term persistence on treatment was quantified by survival curve analysis. RESULTS: The amlodipine (5188 patients) and felodipine (2630 patients) groups were similar in terms of sex ratio (66.7% female) and age (mean 74 years). Average compliance rates for amlodipine patients (67.9%) were significantly higher than for felodipine patients (66.2%) (P<0.01), and switch rates were 5.4-fold higher in the latter group. Patients initiating treatment with felodipine had a 27% increased rate of discontinuation (relative risk 1.27) compared with the amlodipine patients. In addition, patients with at least one year of follow-up data were more likely to maintain amlodipine as part of their antihypertensive regimens than felodipine. After adjustment, medical resource consumption patterns were similar for both groups except for an increase in the number of specialist visits for the amlodipine treatment group. CONCLUSIONS: Patients who received amlodipine, either as a monotherapy or as part of a multitherapy regimen, were more compliant and persistent with their treatment than patients on felodipine. The data suggest that amlodipine may provide more effective long term hypertension control than felodipine, and that the two drugs are not therapeutically equivalent.

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and the risk of cancer: a nested case-control study.

BACKGROUND: During the past 15 years there has been an exponential increase in the number of prescriptions for lipid-lowering drugs. Uncertainties remain about the long-term impact of these medications on cancer, which is particularly bothersome given that the duration of these treatments may extend for several decades. OBJECTIVE: To explore the association between 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and cancer incidence. METHODS: Using the administrative health databases of the Régie de l'Assurance-Maladie du Québec we performed a nested case-control study. We selected a cohort of 6721 beneficiaries of the health care plan of Quebec who were free of cancer for at least 1 year at cohort entry, 65 years and older, and treated with lipid-modifying agents. Cohort members were selected between 1988 and 1994 and were followed up for a median period of 2.7 years. From the cohort, 542 cases of first malignant neoplasm were identified, and 5420 controls were randomly selected. Users of HMG-CoA reductase inhibitors were compared with users of bile acid-binding resins as to their risk of cancer. Specific cancer sites were also considered. RESULTS: Users of HMG-CoA reductase inhibitors were found to be 28% less likely than users of bile acid-binding resins to be diagnosed as having any cancer (rate ratio, 0.72; 95% confidence interval, 0.57-0.92). All specific cancer sites under study were found to be not or inversely associated with the use of HMG-CoA reductase inhibitors. CONCLUSION: The results of our study provide some degree of reassurance about the safety of HMG-CoA reductase inhibitors.