This section includes research papers, white/grey papers and published books.

  • Author:
    Category: Research Papers
    Date: 2019-06-20 15:10:43

  • Author:
    Category: Research Papers
    Date: 2019-04-25 11:58:06

    Highlighted in an accompanying Commentary:

    Stüve O, Cutter GR. Multiple sclerosis drugs: how much bang for the buck? Lancet Neurol. 2015 May;14(5):460-1. doi: 10.1016/S1474-4422(15)00016-2. Epub 2015 Apr 1.

  • Author:
    Category: Research Papers
    Date: 2019-04-25 11:55:25

  • Author:
    Category: Research Papers
    Date: 2019-04-25 11:53:54

  • Author:
    Category: Research Papers
    Date: 2019-04-25 11:52:19

  • Author:
    Category: Research Papers
    Date: 2019-04-24 19:20:32

  • Author:
    Category: Research Papers
    Date: 2019-04-24 19:12:48

  • Author:
    Category: Research Papers
    Date: 2019-04-24 19:09:17

  • Author:
    Category: Research Papers
    Date: 2019-04-24 19:07:48

  • Author:
    Category: Research Papers
    Date: 2019-04-24 18:25:49

    Worldwide, the beta interferons remain the most commonly prescribed disease-modifying drugs for multiple sclerosis. However, it is unclear if they alter survival. We investigated the association between beta interferon and mortality in the ‘real-world’ setting. This was a multi-centre population-based observational study of patients with relapsing-onset multiple sclerosis who were initially registered at a clinic in British Columbia, Canada (1980–2004) or Rennes, France (1976–2013). Data on this cohort were accessed from the clinical multiple sclerosis databases and from individually linked health administrative data; all data were collected prospectively. Participants were followed from the latter of their first multiple sclerosis clinic visit, 18th birthday or 1 January 1996; until death, emigration or 31 December 2013. Only those who were naı¨ve to disease-modifying therapy and immunosuppressant treatment of multiple sclerosis at the start of their follow-up were included in the analysis. A nested case-control approach was used. Up to 20 controls, matched to cases (deaths) by country, sex, age 5 years, year and disability level at study entry, were randomly selected from the cohort by incidence density sampling. The associations between all-cause mortality and at least 6 months beta interferon exposure, and also cumulative exposure (‘low’, 6 months to 3 years; and ‘high’, 43 years), were estimated by conditional logistic regression adjusting for treatment with other disease-modifying therapies and age in years. Further analyses included separate analyses by sex and country, additional adjustment for comorbidity burden in the Canadian cohort, and estimation of the association between beta interferon and multiple sclerosis-related death in both countries. Among 5989 participants (75% female) with a mean age of 42 (standard deviation, SD 11) years at study entry, there were 742 deaths (70% female) and the mean age at death was 61 (SD 13) years. Of these cases, 649 were matched to between one and 20 controls. Results of the conditional logistic regression analyses are expressed as adjusted odds ratios with 95% confidence intervals. The odds of beta interferon exposure were 32% lower among cases than controls (0.68; 0.53–0.89). Increased survival was associated with `3 years beta interferon exposure (0.44; 0.30–0.66), but not between 6 months and 3 years exposure (1.00; 0.73–1.38). Findings were similar within sex and country, and for multiple sclerosis-related death. Beta interferon treatment was associated with a lower mortality risk among people with relapsing-onset multiple sclerosis. Findings were consistent between two geographically distinct regions in North America and Europe.

  • Author:
    Category: Research Papers
    Date: 2018-12-06 16:50:47

    Comparative Effectiveness and Safety of Biosimilar and Legacy Drugs Protocol

  • Author: Lim LSH, Feldman BM, Lix LM
    Category: Research Papers
    Date: 2018-10-17 13:45:52

    Longitudinal cohort designs (with three or more measurement occasions) are invaluable to investigate between- and within-individual variation in outcomes. However, traditional longitudinal designs require a lengthy implementation and data collection period and impose a substantial burden on participants and investigators. We discuss alternative longitudinal designs, including planned missing data designs and retrospective cohort studies with secondary data, which require a shorter period for data accrual and reduce participant burden while maintaining statistical power. We also discuss analysis strategies to maximize data use and produce unbiased estimates of treatment effectiveness, including models for recurrent or multistate events and time-varying covariates.

  • Author: Shiff NJ, Oen K, Kroeker K, Lix LM
    Category: Research Papers
    Date: 2018-10-17 13:22:04

    Abstract
    OBJECTIVE:
    To estimate juvenile idiopathic arthritis (JIA) incidence and prevalence for children <16 years of age in the province of Manitoba, Canada, and test for changes in estimates between 2000 and 2012.

    METHODS:
    JIA cases were ascertained from Manitoba’s administrative health data using a validated case-finding algorithm. Annual incidence and prevalence rates were estimated using a generalized linear model with generalized estimating equations (GEEs), adjusting for socio-demographic characteristics. Changes in estimates were tested using piecewise regression models.

    RESULTS:
    A total of 455 prevalence cases met the inclusion criteria. Sex and age-adjusted incidence estimates were 14.01 (95% CI 13.52, 14.53) in 2000/01 and 9.18 (95% CI 8.56, 9.85) in 2010/11; prevalence estimates were 65.33 (95% CI 63.87, 66.83) in 2000/01 and 59.61 (95% CI 58.17, 61.08) in 2010/11. A linear piecewise model provided the best fit to the data. There was a significant decrease in prevalence over the study period (-0.18; 95% CI -0.35, -0.02; p=0.0292) but no statistically significant change in incidence (-0.46; 95% CI -0.94, 0.01; p=0.0571). Sex-stratified models revealed a decrease for males in both prevalence (estimate -0.54; 95% CI -0.84, -0.25; p=0.0003) and incidence (estimate -1.02; 95% CI -2.02, -0.04; p=0.0439); there were no changes for females.

    CONCLUSION:
    Few population-based longitudinal epidemiologic studies of JIA have been conducted. Our findings suggest a decrease in overall JIA prevalence and in incidence and prevalence for males. Further research to validate these findings in other cohorts and explore factors contributing to this change will benefit healthcare planning for JIA. This article is protected by copyright. All rights reserved.

    https://www.ncbi.nlm.nih.gov/pubmed/29799673

  • Author: Natalie Jane, Kiem Oen, Rasheda Rabbani, Lisa M. Lix
    Category: Research Papers
    Date: 2017-09-11 16:43:05

    We validated case ascertainment algorithms for juvenile idiopathic arthritis (JIA) in the provincial health administrative databases of Manitoba, Canada. A population based pediatric rheumatology clinical database from April 1st 1980 to March 31st 2012 was used to test case definitions in individuals diagnosed at ≤15 years of age. The case definitions varied the number of diagnosis codes (1, 2, or 3), time frame (1, 2 or 3 years), time between diagnoses (ever, >1 day, or ≥8 weeks), and physician specialty. Positive predictive value (PPV), sensitivity, and specificity with 95% confidence intervals (CIs) are reported. A case definition of 1 hospitalization or ≥2 diagnoses in 2 years by any provider ≥8 weeks apart using diagnosis codes for rheumatoid arthritis and ankylosing spondylitis produced a sensitivity of 89.2% (95% CI 86.8, 91.6), specificity of 86.3% (95% CI 83.0, 89.6), and PPV of 90.6% (95% CI 88.3, 92.9) when seronegative enthesopathy and arthropathy (SEA) was excluded as JIA; and sensitivity of 88.2% (95% CI 85.7, 90.7), specificity of 90.4% (95% CI 87.5, 93.3), and PPV of 93.9% (95% CI 92.0, 95.8) when SEA was included as JIA. This study validates case ascertainment algorithms for JIA in Canadian administrative health data using diagnosis codes for both rheumatoid arthritis (RA) and ankylosing spondylitis, to better reflect current JIA classification than codes for RA alone. Researchers will be able to use these results to define cohorts for population-based studies.

  • Author: Michael P. Wallace,Erica E. M. Moodie, David A. Stephens
    Category: Research Papers
    Date: 2017-09-11 16:39:38

    With the increasing interest in personalized medicine, over the last decade, sequential multiple assignment randomized trials (SMARTs) have become a more common fixture of the clinical trial landscape. Primarily of use in the identification of dynamic treatment regimes, they have experienced a shift from the more complex designs of the past to the considerably streamlined versions seen today. In this review, we summarize their history, outline recent and ongoing examples, and discuss some of the important methodological developments for their design and implementation

  • Author: Bénédicte Delcoigne, Edoardo Colzani, Michaela Prochazka, Giovanna Gagliardi, Per Hall, Michal Abrahamowicz, Kamila Czene, Marie Reilly
    Category: Research Papers
    Date: 2017-02-27 19:57:23

    Abstract
    Objective: To demonstrate the advantage of using weighted Cox regression to analyze nested case-control data in overcoming limitations
    encountered with traditional conditional logistic regression.
    Study Design and Setting: We analyzed data from 1,051 women who were sampled in a case-control study of lung cancer nested
    within a cohort of breast cancer patients. We investigated how lung cancer risk is associated with radiation therapy and modified by smoking,
    with both conditional logistic regression and weighted Cox regression models.
    Results: In contrast to logistic regression, weighted Cox regression exploited the information regarding radiation dose received by each
    individual lung. The weighted method also mitigated a problem of overmatching apparent in the data and revealed that the risk of
    radiotherapy-associated lung cancer was modified by smoking (P 5 0.026) with a hazard ratio of 4.09 (2.31, 7.24) in unexposed smokers
    and 8.63 (5.04, 14.79) in smokers receiving doses O13 Gy. The cumulative risk of lung cancer increased steadily with increasing radiotherapy
    dose in smokers, whereas no such effect was found in nonsmokers.
    Conclusion: The weighted Cox regression makes optimal and versatile use of the information in a nested case-control design, allowing
    dose-response analysis of exposure to paired organs and enabling the estimation of cumulative risk.

  • Author: Moura CS, Abrahamowicz M, Beauchamp M-E, Lacaille D, Wang Y, Boire G, Fortin PR, Bessette L, Bombardier C, Widdifield J, Hanly JG, Feldman D, Maksymowych W, Peschken C, Barnabe C, Edworthy S, Bernatsky S and CAN-AIM
    Category: Research Papers
    Date: 2016-05-26 18:39:05

    Abstract

    INTRODUCTION: Use of disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) may prevent joint damage and potentially reduce joint replacement surgeries. We assessed the association between RA drug use and joint replacement in Quebec, Canada.

    METHODS: A cohort of new-onset RA patients was identified from Quebec’s physician billing and hospitalization databases from 2002-2011. The outcome was defined using procedure codes submitted by orthopedic surgeons. Medication use was obtained from pharmacy databases. We used alternative Cox regression models with time-dependent variables measuring the cumulative effects of past use during different time windows (one model focussing on the first year after cohort entry) for methotrexate (MTX), and other DMARDs. Models were adjusted for baseline sociodemographics, co-morbidity and prior health service use, time-dependent cumulative use of other drugs (anti-tumor necrosis factor [anti-TNF] agents, other biologics, cyclooxygenase-2 inhibitors [COXIBs], nonselective nonsteroidal antiinflammatory drugs [NSAIDs], and systemic steroids), and markers of disease severity.

    RESULTS: During follow-up, 608 joint replacements occurred among 11,333 patients (median follow-up: 4.6 years). The best-fitting model relied on the cumulative early use (within the first year after cohort entry) of MTX and of other DMARDs, with an interaction between MTX and other DMARDs. In this model, greater exposure within the first year, to either MTX (adjusted hazard ratio, HR = 0.95 per 1 month, 95% confidence interval, 95% CI 0.93-0.97) or other DMARDs (HR = 0.97, 95% CI 0.95-0.99) was associated with longer time to joint replacement.

    CONCLUSIONS: Our results suggest that longer exposure to either methotrexate (MTX) or other DMARDs within the first year after RA diagnosis is associated with longer time to joint replacement surgery.

  • Author: Madeleine Durand, Yishu Wang, François Venne, Jacques Lelorier, Cécile L Tremblay and Michal Abrahamowics
    Category: Research Papers
    Date: 2015-11-26 17:43:33

  • Author: Natasha Nanwa, Tetyana Kendzerska, Murray Krahn, Jeffrey C Kwong, Nick Daneman, William Witteman, Nicole Mittmann, Suzanne M Cadarette, Laura Rosella and Beate Sander
    Category: Research Papers
    Date: 2015-11-25 21:03:35

  • Author: John G Hanly, Kara Thompson, Chris Skedgel
    Category: Research Papers
    Date: 2015-11-25 20:10:51

    Objective: To validate and compare the decision rules to identify rheumatoid arthritis (RA) in administrative databases.
    Methods: A study was performed using administrative health care data from a population of 1 million people who had access to universal health care. Information was available on hospital discharge abstracts and physician billings. RA cases in health administrative databases were matched 1:4 by age and sex to randomly selected controls without inflammatory arthritis. Seven case definitions were applied to identify RA cases in the health administrative data, and their performance was compared with the diagnosis by a rheumatologist. The validation study was conducted on a sample of individuals with administrative data who received a rheumatologist consultation at the Arthritis Center of Nova Scotia.
    Results: We identified 535 RA cases and 2,140 non-RA, noninflammatory arthritis controls. Using the rheumatologist’s diagnosis as the gold standard, the overall accuracy of the case definitions for RA cases varied between 68.9% and 82.9% with a kappa statistic between 0.26 and 0.53. The sensitivity and specificity varied from 20.7% to 94.8% and 62.5% to 98.5%, respectively. In a reference population of 1 million, the estimated annual number of incident cases of RA was between 176 and 1,610 and the annual number of prevalent cases was between 1,384 and 5,722.
    Conclusion: The accuracy of case definitions for the identification of RA cases from rheumatology clinics using administrative health care databases is variable when compared to a rheumatologist’s assessment. This should be considered when comparing results across studies. This variability may also be used as an advantage in different study designs, depending on the relative importance of sensitivity and specificity for identifying the population of interest to the research question

  • Author: Mylotte D, Quenneville SP, Kotowycz MA, Xie X, Brophy JM, Ionescu-Ittu R, Martucci G, Pilote L, Therrien J, Marelli AJ
    Category: Research Papers
    Date: 2015-11-25 19:30:19

  • Author: Mylotte D, Pilote L, Ionescu-Ittu R, Abrahamowicz M, Khairy P, Therrien J, Mackie AS, Marelli AJ.
    Category: Research Papers
    Date: 2015-11-25 19:01:03

    Abstract

    Clinical guidelines recommend specialized care for adult congenital heart disease (ACHD) patients. In reality, few patients receive such dedicated care. We sought to examine the impact of specialized care on ACHD patient mortality.
    We examined referral rates to specialized-ACHD centers and ACHD patient mortality rates between 1990 and 2005 in the population-based Quebec Congenital Heart Disease (CHD) database (n=71,467). This period covers several years before and after publication of guidelines endorsing specialized care for ACHD patients. A time-series design, based on Joinpoint and Poisson regression analyses, was used to assess changes in annual referral and patient mortality rates. The association between specialized-ACHD care and all-cause mortality was assessed in both case-control and cohort studies. The time-series analysis demonstrated a significant increase in referral rates to specialized-ACHD centers in 1997 (Rate Ratio [RR] +7.4%; 95% CI +6.6% to +8.2%). In parallel, a significant reduction in expected ACHD patient mortality was observed after year 2000 (RR -5.0%;95% CI -10.8% to -0.8%). In exploratory post-hoc cohort and case-control analyses, specialized-ACHD care was independently associated with reduced mortality (Hazard Ratio (HR), 0.78;95% CI, 0.65-0.94) and a reduced odds of death (adjusted odds ratio: 0.82;95% CI 0.08-0.97), respectively. This effect was predominantly driven by patients with severe CHD (HR, 0.38;95% CI 0.22-0.67).
    A significant increase in referrals to specialized-ACHD centers followed the introduction of clinical guidelines. Moreover, referral to specialized-ACHD care was independently associated with a significant mortality reduction. Our findings support a model of specialized care for all ACHD patients.

  • Author: Bron M, Guerin A, Latremouille-Viau D, Ionescu-Ittu R, Viswanathan P, Lopez C, Wu EQ
    Category: Research Papers
    Date: 2015-11-25 18:58:33

  • Author: Langer C, Ravelo A, Hazard SJ, Guerin A, Ionescu-Ittu R, Latremouille-Viau D, Wu EQ, Ramalingam S
    Category: Research Papers
    Date: 2015-11-25 18:48:26

  • Author: Annie Guerin, Lei Chen, Raluca Ionescu-Ittu, Maryna Marynchenko, Roy Nitulescu, Robert Hiscock, Christopher Keir, Eric Quong Wu
    Category: Research Papers
    Date: 2015-11-25 18:30:30

  • Author: Ariane J. Marelli, MD, MPH; Raluca Ionescu-Ittu, PhD; Andrew S Mackie MD, SM; Liming Guo, MSC; Nandini Dendukuri, PhD; Mohammed Kaouache, PhD
    Category: Research Papers
    Date: 2015-11-25 17:58:28

  • Author: April W. Armstrong, MD, MPH, Annie Guerin MSc, Murali Sundaram MBA, PhD, Eric Qiong Wu PhD, Elizabeth Sara Faust BA, Raluca Ionescu-Itta PhD, Parvez Mulani PhD
    Category: Research Papers
    Date: 2015-11-25 17:55:19

    Data in this manuscript were presented as an e-poster at the 71st Annual Meeting of the American Academy of Dermatology in Miami, Florida, on March 1-5, 2013, and as a poster at the 21st Congress of the European Academy of Dermatology and Venereology in Prague, Czech Republic, on September 27-30, 2012.

  • Author: Ronen Rozenblum PhD, MPH, Ann Gianola MA, Raluca Ionescu-Ittu PhD, Amy Verstappen MEd, Michael Landzberg MD, Michelle Gurvitz MD MS, Kathy Jenkins MD,MPH, David W Bates MD, MSc, Ariane J Marelli MD, MPH
    Category: Research Papers
    Date: 2015-11-25 17:49:40

  • Author: Raluca Ionescu-Ittua, M Maria Glymour, Jay S Kaufman
    Category: Research Papers
    Date: 2015-11-25 17:38:57

    Abstract

    Objective

    The Universal Child Care Benefit (UCCB) is a 2006 Canadian federal policy of income supplementation that provides parents with $100 monthly in Canadian dollars for each child aged < 6 years. The study main objective was to estimate the causal effect of UCCB on self-reported food insecurity overall and in vulnerable subgroups.

    Method

    The Canadian Community Health Survey (2001–2009) was used to conduct a difference-in-differences (DID) regression analysis for the effect of the UCCB on self-reported food insecurity. Respondents were ages ≥ 12 in families with at least one child aged < 6 years (UCCB-eligible, n = 22,737) or a child aged 6–11 but no child < 6 years (control group, n = 17,664).

    Results

    Over the study period 16.3% of respondents experienced some level of food insecurity. Overall, UCCB reduced the proportion of respondents reporting food insecurity by 2.4% (95% CI: − 4.0%, − 0.9%). There was a significantly stronger impact on food insecurity for respondents from households with yearly income below the population median (− 4.3%, 95% CI: − 7.2%, − 1.4%) and respondents from single parent families (− 5.4%, 95% CI: − 10.3%, − 0.6%).

    Conclusion

    We found that a relatively small monthly income supplementation results in a significant reduction in food insecurity at the population level, with larger effects in vulnerable groups.

  • Author:
    Category: Research Papers
    Date: 2015-11-05 20:12:47

  • Rheumatoid arthritis prevalence in Quebec

    2015-11-05 20:08:41
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    Author: Sasha Bernatsky, Alaa Dekis, Marie Hudson, Christian A Pineau, Gilles Boire, Paul R Fortin, Louis Bessette, Sonia Jean, Ann L Chetaille, Patrick Belisle, Louise Bergeron, Debbie Ehrmann Feldman and Lawrence Joseph
    Category: Research Papers
    Date: 2015-11-05 20:08:41

  • Author: Mina Tadrous, Joshua J. Gagne, Til Stürmer, and Suzanne M. Cadarette
    Category: Research Papers
    Date: 2015-11-05 19:52:18

  • Author: Jordan M. Albaum, Soyoung Youn, Linda E. Lévesque, Andrea S. Gershon, Suzanne M. Cadarette
    Category: Research Papers
    Date: 2015-11-05 19:42:53

  • Author: Andrea M. Burden, J. Michael Paterson, Andrea Gruneir and Suzanne M. Cadarette
    Category: Research Papers
    Date: 2015-11-05 19:37:10

    ABSTRACT
    Purpose Days supply (prescription duration) values are commonly used to estimate drug exposure and quantify adherence to therapy, yet
    accuracy is not routinely assessed, and potential inaccurate reporting has been previously identified. We examined the impact of cleaning
    days supply values on the measurement of adherence to oral bisphosphonates.
    Methods We identified new users of oral bisphosphonates among Ontario seniors (April 2001–March 2011). Days supply values were
    examined by dose, and we identified misclassification by comparing observed values to dose-specific expected values. Days supply values
    not matching expected values were cleaned using dose-specific algorithms. One-year adherence to therapy was defined using measures
    of compliance (mean proportion of days covered [PDC], and categorized into high [PDC ≥ 80%], medium [50%<PDC<80%], low
    [PDC ≤ 50%]) and persistence (30-day permissible gap). Estimates were compared using the observed and cleaned days supply values,
    stratified by site of patient residence (community or long-term care [LTC]).
    Results We identified 337 729 (5% LTC) eligible new users. Among LTC patients, adherence estimates increased significantly following
    data cleaning: mean PDC (59 to 83%), proportion with high compliance (47 to 76%), and proportion persisting with therapy (62 to 78%).
    Modest increases were identified among community-dwelling patients following data cleaning (mean PDC, 71 to 74%; high compliance, 54
    to 58%; and persistence, 56 to 61%).
    Conclusions Data cleaning to correct for exposure misclassification can influence estimates of adherence with oral bisphosphonate therapy,
    particularly in LTC. Results highlight the importance of developing data cleaning strategies to correct for exposure misclassification
    and improve transparency in pharmacoepidemiologic studies.

  • Author: Racquel Jandoc, Nathaniel Jembere, Saba Khan, Storm J. Russell, Yvon Allard , Suzanne M. Cadarett
    Category: Research Papers
    Date: 2015-11-05 19:31:05

    Half of Métis citizens, compared to less than 10 % of the general population of Ontario, reside in northern regions, with little access to bone mineral density (BMD) testing. Métis citizens had lower sex-specific and age-standardized rates of BMD testing, yet similar rates of fracture (both sexes) and pharmacotherapy (women only). The purpose of this study is to examine osteoporosis management and common osteoporosis-related fractures among Métis citizens compared to the general population of older adults residing in Ontario.

  • Author: Racquel Jandoc, Andrea M. Burden, Muhammad Mamdani, Linda E. Lévesque, Suzanne M. Cadarette
    Category: Research Papers
    Date: 2015-11-05 19:24:33

    This research was presented at the International Conference on Pharmacoepidemiology and Therapeutic Risk Management (ICPE) in Montreal, QC, Canada, August 2013; the Canadian Association for Population Therapeutics (CAPT) Annual Conference in Toronto, ON, Canada, November 2013; and the Canadian Association for Health Services and Policy Research (CAHSPR) Annual Conference in Toronto, ON, Canada, May 2014. Participation at ICPE was supported by an ICPE Travel Scholarship, participation at CAPT was supported by a CAPT Student Bursary and the Leslie Dan Faculty of Pharmacy Student Experience Fund, and participation at CAHSPR was supported by a University of Toronto School of Graduate Studies Conference Grant.

  • Author: Burden AM , Gruneir A, Paterson JM and Cadarette SM
    Category: Research Papers
    Date: 2015-11-05 18:59:27

    Introduction: Using pharmacy claims data we previously identified exposure misclassification in pharmacy
    claims data that underestimated oral bisphosphonate compliance, particularly in long-term care (LTC). In this study
    we examined the impact of exposure misclassification in pharmacy claims data on estimates of drug effectiveness
    using osteoporosis pharmacotherapy and hip fractures as a case example.

  • Author: Jessica Widdifield, PhD
    Category: Presentations, Research Papers
    Date: 2015-11-05 18:48:07

  • Author:
    Category: Research Papers
    Date: 2015-11-05 18:44:51

  • Author: Dickstein, Craig, and Renu Gehring. Administrative Healthcare Data: A Guide to Its Origin, Content, and Application Using SAS. SAS Institute, 2014.
    Category: Research Papers, Videos, Work In Progress
    Date: 2015-10-29 18:51:15