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Impact of British Columbia's reduction in generic drug prices on statin adherence Mushashi, Fidela 2016

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IMPACT OF BRITISH COLUMBIA’S REDUCTION IN GENERIC DRUG PRICES ON STATIN ADHERENCE by  Fidela Mushashi  B.A., Berea College, 2014  A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF  MASTER OF SCIENCE in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Population and Public Health)  THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver)  December, 2016  © Fidela Mushashi, 2016 ii  Abstract  Background: The burden of cost of prescription medications for chronic conditions is substantial. Many patients do not take their medication as prescribed due to cost. In 2010 the government of British Columbia introduced policy changes that reduced generic prices over a period of four years. I studied the impact of five generic price reductions policy on adherence to statin medications.  Methods:  Using data from the British Columbia Ministry of Health through Population Data BC, I analyzed prescription claims of 433,945 residents who were on statins from 2008 to 2014. I measured medication adherence using proportion of days covered (PDC) with brand name statin users as my control group. Interrupted time series analysis was used to compare longitudinal trends before and after policy changes.  Results:    Residents on brand name statins on average had 89.9% (95% CI 0.8924 to 0.9059) proportion of days covered with medication prior to policy interventions. Pre-existing level of adherence to generic statins was 0.89 percentage points (-0.0007 to 0.0184) higher relative to the control. There was a sustained significant decrease of 0.05 percentage points (-0.0009 to -0.00001) per month in trend of brand name use (p=0.0473). Adherence to generics dropped by 0.02 percentage points (-0.0009 to 0.0005) relative to the control over the 24 months preceding policy interventions. After first policy intervention, adherence to brand name statins increased immediately by 1.1 percentage points (-0.0032 to 0.0245) while generics utilization decreased by 0.71 percentage points (-0.0267 to 0.0125) relative to the control. Trend in control decreased by iii  0.03 percentage points (-0.0026 to 0.0021). After the first policy, there was a rise in trend of generics adherence of 0.27 percentage points (-0.0006-0.0061) per month relative to the control. Further price reductions resulted in moderate improvement in adherence to generic statins.  Conclusion: Findings indicate that reductions in generic drug prices in BC yielded a modest improvement in pharmaceutical claims for statins. In the future, health policy makers may want to consider fewer but larger drug price reduction interventions for a more effective impact on medication adherence.   iv  Preface  I designed this study and conducted a literature review to inform this thesis. In addition, I performed all parts of this research including analysis of data and interpretation of findings.   The project was approved by the Behavioral Research Ethics Board of the University of British Columbia (Certificate No: H15-01690). Permission to use data was obtained from the British Columbia Ministry of Health through Population Data BC.  v  Table of Contents  Abstract .......................................................................................................................................... ii	Preface ........................................................................................................................................... iv	Table of Contents ...........................................................................................................................v	List of Tables .............................................................................................................................. viii	List of Figures ............................................................................................................................... ix	List of Symbols ...............................................................................................................................x	List of Abbreviations ................................................................................................................... xi	Acknowledgements .................................................................................................................... xiii	Dedication ................................................................................................................................... xiv	Chapter 1: Introduction ................................................................................................................1	1.1	 Research objectives ......................................................................................................... 3	Chapter 2: Literature Review .......................................................................................................5	2.1	 Introduction ..................................................................................................................... 5	2.2	 Burden of chronic disease ............................................................................................... 5	2.3	 Cardiovascular disease .................................................................................................... 6	2.4	 Statin treatment ............................................................................................................... 8	2.4.1	 Treatment guidelines ............................................................................................... 8	2.4.2	 Treatment uptake .................................................................................................. 10	2.5	 Adherence to medication .............................................................................................. 11	2.5.1	 Definitions and measures of adherence ................................................................ 11	2.5.1.1	 Calculating adherence ....................................................................................... 14	vi  2.5.2	 Conceptual frameworks of adherence ................................................................... 16	2.6	 Effect of policy intervention on medication adherence ................................................ 21	2.6.1	 Policy interventions that translate into improved adherence ................................ 23	2.6.1.1	 Reduced medication co-payment ...................................................................... 23	2.6.1.2	 Decreased medication co-insurance .................................................................. 23	2.6.1.3	 Full prescription drug coverage ........................................................................ 24	Chapter 3: Methods .....................................................................................................................25	3.1	 Study design .................................................................................................................. 25	3.1.1	 Data sources .......................................................................................................... 25	3.2	 Cohort definition ........................................................................................................... 27	3.2.1	 Cohort selection steps ........................................................................................... 27	3.2.2	 Inclusion and exclusion criteria ............................................................................ 29	3.3	 Study variables .............................................................................................................. 29	3.3.1	 Outcome variables ................................................................................................ 29	3.4	 Analytic plan ................................................................................................................. 32	Chapter 4: Results ........................................................................................................................35	4.1	 Cohort characteristics .................................................................................................... 35	4.2	 Diagnostic tests ............................................................................................................. 37	4.2.1	 Normality of outcome data ................................................................................... 37	4.2.2	 Addressing autocorrelation ................................................................................... 38	4.3	 Interrupted time series model ........................................................................................ 39	4.3.1	 Changes in adherence to statins ............................................................................ 42	4.3.2	 Residuals around the model .................................................................................. 43	vii  Chapter 5: Discussion ..................................................................................................................44	5.1	 Overall adherence ......................................................................................................... 44	5.2	 Key factors influencing adherence ................................................................................ 45	5.2.1	 Cost of medication ................................................................................................ 45	5.2.2	 Co-occurring events in history .............................................................................. 46	5.3	 Strengths and limitations ............................................................................................... 46	5.4	 Conclusion .................................................................................................................... 49	References .....................................................................................................................................50	Appendix A: Summary of recently published studies on health policy and medication adherence ......................................................................................................................................59	Appendix B: List of statins requested from PharmaNet ..........................................................67	Appendix C: Inventory model of drug supply ..........................................................................93	 viii  List of Tables  Table 1.1 Generic drug price reductions in BC .............................................................................. 3	Table 4.1 Cohort characteristics ................................................................................................... 36	Table 4.2 Segmented regression estimates and associated 95% confidence intervals for 406,622 patients during study period .......................................................................................................... 41	 ix  List of Figures  Figure 2.1 WHO's five dimensions of adherence ......................................................................... 16	Figure 2.2 Interacting factors of adherence .................................................................................. 20	Figure 3.1 Cohort selection model ................................................................................................ 28	Figure 3.2 Inventory model of drug supply .................................................................................. 30	Figure 3.3 Hypothetical drug use profile ...................................................................................... 31	Figure 3.4 Interrupted time series model ...................................................................................... 32	Figure 3.5 Final model .................................................................................................................. 34	Figure 4.1 QQ-plot showing normal outcome data ...................................................................... 37	Figure 4.2 Autocorrelation and partial autocorrelation ................................................................. 38	Figure 4.3 Monthly adherence to statins during study time .......................................................... 42	Figure 4.4 Residuals around the model ......................................................................................... 43	 x  List of Symbols  β Beta  Error  xi  List of Abbreviations  4S  Scandinavian Simvastatin Survival Study ATC  Anatomical therapeutic chemical  ACF  Autocorrelation function  BC  British Columbia CCS  Canadian Cardiovascular Society  CCHS  Canadian Community Health Survey  CI  Confidence interval CVD  Cardiovascular disease CHSPR UBC Center for Health Services and Policy Research DIN  Drug identification number HMG-CoA Hydroxymethylglutaryl CoenzymeA  HR  Hazard ratio ITS  Interrupted time series  LDL-C Low-density lipoprotein cholesterol MI  Myocardial infarction  Mmol/L Millimole per liter  MPR  Medication possession ratio NNT  Number needed to treat OR  Odds ratio PDC  Proportion of days covered Q-Q plot Quantile-Quantile plot xii  RCMP  Royal Canadian Mounted Police ReComp Refill compliance RR  Relative risk Rx  Recipe  SAS  Statistical analysis system SD  Standard deviation SMD  Standardized mean difference WHO  World Health Organization  xiii  Acknowledgements  I offer my enduring gratitude to Dr. R. Kassam, under whose supervision I have thrived and have been inspired to continue my work in research.   I owe particular thanks to Dr. J. Sutherland, whose penetrating questions taught me to question more deeply.   Many thanks to Lucy Cheng for providing statistical assistance.   I thank Dr. M. Law for enlarging my vision of health policy and health economics and providing coherent answers to my endless questions.   I would like to acknowledge the Michael Smith Foundation for Health Research and the Canadian Agency for Drugs and Technologies in Health (CADTH) for funding this research study.   Special thanks are owed to my family, who have supported me throughout my years of education, both morally and financially. xiv  Dedication  This thesis is dedicated to my father the late Antoine Ruzigamanzi with whom my education began. My father was the person who first saw potential in me and invested in my education, thus trading off other equally important concerns, he homeschooled me when traditional schools were out of reach, and he introduced me to his colleagues who later saw me through to higher learning when he was no longer with me. These are just a few of the ways in which this journey began with my father.    1  Chapter 1: Introduction  The burden of chronic disease is substantial. The World Health Organization (WHO) estimated 38 million deaths in 2012 due to chronic diseases, of which 16 million occurred at a premature age (before the age of 70 years) (1). Among other chronic diseases, cardiovascular disease (CVD) alone accounted for 17.5 million deaths annually (1). In Canada, CVD had the highest estimated economic burden ($11,692.7 billion, 6.8%) in direct cost among all diagnosed diseases in 2008 (2).   Among six cardiovascular diseases, myocardial infarction (MI) is of particular interest. Myocardial infarction is the most common type of CVD in Canada and other industrialized countries in the world (3). Myocardial infarction is responsible for a high proportion of the days in hospital and the non-diagnosed events and fatal events occurring outside of hospital (4).  Evidence-based practice guidelines support the use of statins for the secondary prevention of CVD (5). The use of statins has been increasing rapidly over time. Patients who filled a statin prescription increased from 4.2% in 1992 to 79.2% in 2005 (6). An estimated 2.8 million Canadian adults (about 1 in 10) were treated with statin drugs between 2007 and 2011 (7). Although statins play a large role in reducing poor health and mortality associated with CVD, their effectiveness is notably compromised by poor adherence to medication regimens (8).    Rates of use of medication regimens can be quantified using adherence measures. Adherence explains the level at which patients take their medications as prescribed with respect to timing 2  and dosage, and it is commonly measured as the proportion of days covered, in an interval for which patients have medication available to them (9,10). Although patients start to see benefits shortly after consistent use of statins, between 40% and 75% of the patients discontinue their statin therapy after one year of treatment, for various reasons (11).   Medication adherence is complex and is affected by several factors, but the impact of policy intervention on adherence is manifested at a broader level. Adherence to prescription drugs is improved by policies that reduce out-of-pocket expenses (12,13). New medication users are said to be sensitive to the price of prescription drugs (14).    Drug pricing in Canada is regulated through a combination of federal and provincial governments. Generic drug pricing is regulated by varying provincial and territorial policies (15). British Columbia has a universal income-based drug-financing program and other drug coverage plans for specific groups (16). The Fair PharmaCare Plan provides BC residents with coverage for eligible prescription drugs based on their net income. PharmaCare BC sets a maximum drug price and dispensing fee, and normally covers a maximum of a 100-day supply for drugs intended for long term use (16).  In July 2010, the Government of British Columbia (BC) reached an agreement with the BC Pharmacy Association and the Canadian Association of Chain Drug Stores to reduce prices of generic drugs over a period of three years (17). The reductions moved generic prices in the province from 65% of the brand-name product cost to 35%. In May 2012, the Pharmaceutical Services Act authorized the Minister of Health to regulate the prices of prescription drugs (18). 3  Generic drug prices were further reduced to 20% of their branded counterparts in the subsequent two years, as seen in Table 1.1 (18).   Table 1.1 Generic drug price reductions in BC Before 2010 October 2010 July 2011 April 2012 April 2013 April 2014 65% 50% 40% 35% 25% 20%  Published literature agrees that policy interventions such as reduced medication co-payments and co-insurance, and full prescription drug coverage translate into improved adherence. (19–23). Thus, my research question is: What is the impact of generic drug price reductions on adherence to statin medications?   The succeeding chapters contain the literature review I conducted to inform this thesis, the methods I used to answer my research question, my results, and a discussion of my findings. I am hoping that by answering this question on a current issue, I am contributing to the body of knowledge on health policy and adherence to chronic disease medications.     1.1 Research objectives Factors influencing medication adherence are well documented, but little is known about the effect of BC’s recent policy changes to adherence behavior for statin users in particular.     4  My objective for this thesis is: To measure adherence to statin medications before and after generic drug price reductions in British Columbia.   5  Chapter 2: Literature Review  2.1 Introduction  The goal of my thesis is to explore the impact of drug price policy intervention on medication adherence, specifically, by investigating adherence to statin medications following reductions in generic drug pricing in British Columbia. The purpose of this literature review is to elucidate reasoning behind my research question and hypothesis, and to position this thesis in context. To inform this thesis, I conducted a review of literature in the areas of: 1) Cardiovascular disease, 2) Statin treatment, 3) Definition and measures of adherence, and 4) Policy intervention. Additionally, I highlighted conceptual frameworks of adherence, and reviewed several analyses on the relationship between drug cost and medication adherence.   2.2 Burden of chronic disease  The global burden of chronic diseases is considerable. Chronic diseases generally have a slow progression and are normally expected to have a lasting duration. The WHO estimated that 38 million deaths in 2012 were due to chronic diseases; sixteen million chronic disease deaths occurred at a premature age (before the age of 70 years) (1). Four groups of diseases (cardiovascular disease (CVD), cancer, respiratory disease and diabetes) account for 82% of all chronic disease deaths; cardiovascular disease alone accounts for most chronic disease deaths, estimated at 17.5 million deaths annually (1). As well as associated mortality, chronic diseases play a role as a source of daily disability (24).  6  Although mortality rates from various forms of CVD have decreased significantly over the past 30 years, the burden of cardiovascular diseases remains high. In Canada, from 1979 to 2003, age- standardized mortality per 100,000 declined by 53% in men and women (25). The second leading cause of death was cardiovascular disease, accounting for 60,910 deaths, 25% of all deaths in 2011 (26). Approximately 20.6% or 24,987 males and 18.7% or 22,649 females died of heart disease in the same year (26). The burden of CVD remained high in the 45-to-64 age group, with 16% or 6,414 deaths attributable to heart disease (26). Cardiovascular diseases outranked cancer and Alzheimer’s disease in the 85-and-over age category, claiming 51,346 lives in that age group (26). In 2008, CVD had the highest estimated economic burden ($11,692.7, 6.8%) in direct cost (hospital care, physician care, and drug expenditures) among all diagnosed diseases (2). Chronic diseases are believed to contribute to the dollar value of lost production.   2.3 Cardiovascular disease  Cardiovascular disease encompasses a variety of diseases including coronary heart disease (e.g. myocardial infarction or heart attack, angina), cerebrovascular disease (ischaemic and haemorrhagic stroke), peripheral artery disease, rheumatic heart disease, congenital heart disease, and heart failure (27). Traditional risk factors for CVD including high blood pressure, dyslipidemia, obesity, diabetes, and smoking are highly prevalent. Although smoking prevalence has decreased over time as a result of public health interventions, other risk factors for CVD are relatively increasing. According to the 2001-2012 study of the Canadian Community Health Survey (CCHS) in Ontario, smoking prevalence declined by more than 20%, while prevalence of obesity exceeded 50% for white and black males, and 46% for South Asian males (28). 7  Similarly, the prevalence of diabetes increased from 6.7% to 15.2% among South Asian males and from 6.3% to 12.2% among black females (28). These rising factors combined with further aging of the population considerably increase the possibility of CVD and recurrent cardiovascular events.  Among cardiovascular diseases, myocardial infarction is of particular importance. Myocardial infarction is the most common type of CVD in Canada and other industrialized countries in the world (3). In 2011, MI alone accounted for 19% of all deaths in Canada (29). From a disease surveillance perspective, MI is responsible for a high proportion of days in hospital, as well as non-diagnosed events and fatal events occurring outside of hospital (4).  An important aspect of cardiovascular disease treatment and the focus of my thesis project is the pharmacotherapy of cardiovascular diseases using statins. Statins are cholesterol-lowering drugs that play a large part in reducing morbidity and mortality associated with cardiovascular diseases (30). Statins inhibit an enzyme called Hydroxymethylglutaryl CoenzymeA (HMG-CoA) reductase, which controls cholesterol production in the liver (31,32). The American Heart Association described cholesterol as a substance produced and released in the bloodstream by liver cells. Low-density lipoprotein cholesterol (LDL-C), also known as ‘bad’ cholesterol, deposits cholesterol in the artery walls and forms plaque (33). The plaque buildup narrows arteries and prevents the heart from getting enough blood and this when prolonged, leads to cardiovascular events (34).   8  2.4 Statin treatment  There are six groups of statins currently marketed in Canada, where all statins are now available as generics. These medications exist under several different generic and brand names: atorvastatin (lipitor), pravastatin (pravachol), rosuvastatin (crestor ), simvastatin (zocor), fluvastatin (lescol), and lovastatin (mevacor) (35). The most potent statins are rosuvastatin and atorvastatin while fluvastatin and pravastatin are the least potent (36,37). Statin is the first-choice treatment therapy for the secondary prevention of cardiovascular events.  2.4.1 Treatment guidelines  The Canadian Cardiovascular Society (CCS) treatment guidelines for the prevention of cardiovascular diseases with medicine are based on cholesterol levels and risk factors (5). The guidelines rule that low-density lipoprotein cholesterol remains the primary target of therapy, and screening for dyslipidemia should begin at age 40 years and over for men, and age 50 years and over (or post-menopause) for women (5). Additionally, the guidelines emphasize statin treatment of higher risk patients including those with chronic kidney disease and high risk hypertension, and recommend a target LDL-C of less than or equal to 2.0 mmol/L or an over 50% reduction of LDL-C (5). Pharmacotherapy is recommended for low risk individuals with LDL-C greater than or equal to 5.0 mmol/L (5). For subjects for whom the need for statin therapy is unclear, a judicious use of secondary testing is recommended (5).  9  Statin trials with randomized double-blind treatment groups began in 1994 with the Scandinavian Simvastatin Survival Study (4S) (38). The 4S study, consisting of 4444 participants with a history of angina or MI treated with simvastatin, noted a reduction in total mortality of 30% (RR: 0.7; 95% CI: 0.58-0.85). Additionally, the study reported a 37% reduction (P<0.00001) in the risk of undergoing a myocardial revascularization procedure (38). A systematic review and meta-analysis of randomized studies demonstrates that statins have been shown to lower LDL-C concentration by an average of 1.8 mmol/L, which in turn lowers the risk for ischaemic heart disease by 60% and stroke by 17% (36).  Statins have been shown to be beneficial in reducing the risk for CVD in people without documented pre-existing cardiovascular disease. A recent systematic review of randomized control trials comparing any statins with a placebo or the usual care for primary prevention of CVD, revealed that statins significantly reduced the risk of major adverse cardiovascular events (OR: 0.82; 95%CI: 0.74-0.92) in subjects of age 65 years and over (39). Men and women, young and old, otherwise healthy individuals at high risk of CVD, seem to benefit from the protective effect of statins as deduced from systematic and meta-analysis studies (40,41).  Randomized clinical trials indicate the efficacy of intensive lipid-lowering statin therapy in the secondary prevention of cardiovascular events (42–46). Among 4,162 patients with stable coronary disease placed on either an intensive statin regimen of 80 mg atorvastatin daily or a standard-dose pravastatin of 40 mg daily, a 16% reduction in hazard ratio in favor of atorvastatin (P=0.005; 95% CI:5-26) was achieved (44). A large double-blind randomized trial incorporating 12,064 subjects, confirms that for individuals with a history of myocardial infarction high-dose 10  80 mg simvastatin daily reduces cardiovascular events by 6% (RR:0.94; 95% CI:0.88-1.01; P=0.1) compared to low-dose 20 mg simvastatin daily (45).  Although statins have proven to be effective in reducing cardiovascular morbidity and mortality, the adverse effects associated with statins are not clear. A population-based case-control study revealed weak but significant results linking statins with an associated risk of peripheral neuropathy (OR: 1.19; 95% CI:1.0-1.4) (47). Side effects linked to statins include muscle damage (as evidenced by elevated creatine kinase, muscle pain or weakness) and in rare cases rhabdomyolysis (48,49). Meta- and systematic analysis of randomized control trials failed to show significant cognitive impairment to be an adverse effect of statins (SMD: 0.01; 95% CI: -0.01-0.03; P=0.42) (50). A more recent study revealed that given optimal adherence, statin treatment prevented 18,900 CVD events annually (NNT: 15 over 10 years) (7).  2.4.2 Treatment uptake  Use of statins for secondary prevention of cardiac events has been increasing rapidly over time. A cross-sectional study measured rates of medication use for a population cohort discharged from hospital with a diagnosis of myocardial infarction (6). The percentage of patients who filled a statin prescription increased from 4.2% in 1992 to 79.2% in 2005 (6). A follow-up of the study revealed that the rate of statin use after discharge was higher among patients treated by a cardiologist than among patients treated by a non-cardiologist, and having a physician with 29 or more years of experience compared to having a physician who had graduated within the past 15 years was concomitant with higher use of statins (OR: 0.81; 95% CI: 0.64-0.97) (51). 11  Temporal patterns in statin use were reported in diabetic patients receiving or not receiving hemodialysis in Ontario. A linked health administrative study showed a rising use of statins from 597 per 1000 patients, 11 years prior to the study’s publication, to 676 per 1000 patients 2.5-years after the study’s publication in 2009 (52). The use of statins in this patient population appeared to be influenced by factors other than hemodialysis alone.   2.5  Adherence to medication  2.5.1 Definitions and measures of adherence  Adherence is generally defined by the  World Health Organization as, “the extent to which a person’s behavior taking medication, following a diet, and/or executing lifestyle changes, corresponds with agreed recommendations from a health care provider” (9). Definition of adherence specifically to medication is defined as, “the extent to which a patient acts in accordance with prescribed interval and dose of a dosing regimen” (53). Adherence and compliance are used interchangeably; however, compliance is less favored because it implies that the patient is to abide by a prescribed contract instead of reaching an agreement with the provider on the best treatment regimen (10). Medication adherence at a population level is measured as the proportion of days with possession of medication in a period of time, also known as proportion of days covered (PDC) (54,55). The medication possession ratio (MPR) is another measure of medication adherence from pharmacy claims data. However, it does not identify gaps in medication supply nor does it provide accuracy in the continuity of medication usage (56). 12  Measurements of medication adherence are classified in two categories: direct and indirect. Direct methods involve the laboratory detection of drugs in biological fluid, or the laboratory detection of biological markers, and direct observation of patient taking medication (57). A problem with this method is the cost and impracticality for outpatient settings or studies with a large sample size. The indirect method encompasses pharmacy refill rates, self-reporting, pill counts, and electronic adherence monitoring. Although this method is relatively simple and less costly, it provides no proof of patient consumption of medication and may be susceptible to information bias through recall bias and social desirability; hence it often overestimates adherence (57).  Assessment of the availability of medication, derived from pharmacy records, is a major strength of the indirect technique of adherence measurement. In closed pharmacy systems which offer pharmaceutical care to a select group of patients, or in jurisdictions with public drug coverage, where all dispensed medications are stored in a single computerized database, the rate of prescription fills over time can be used to estimate adherence to medications (10). Secondary use of administrative data can be used to study the entire target population where direct measure of medication consumption is not feasible. The data are anonymized for research purposes, which rules out information bias related to patients being aware of observation of their drug-taking behavior (57).  A number of Canadian databases have been validated for pharmacoepidemiological research owing to their comprehensiveness and accuracy (58–60). Pharmacy records are valuable in determining adherence for long-term medications, yet the method is not effective for short-term 13  treatments. Similarly, pharmacy records cannot capture primary non-adherence where patients fail to fill a prescription in the first place or fill a prescription outside of the pharmacy system (57). Important limitations with adherence measures using pharmacy data is that pharmacy refill records measure how frequently a patient filled a prescription but not whether a patient consumed a prescription or whether the consumption took place at the prescribed time (61); also the records do not identify contextual influence on adherence because data was collected for administrative and not research interests.  Both direct and indirect measures of adherence have strengths and limitations with no gold standard of validation of measurement methods. In an attempt to validate their use, pharmacy records have been compared to a number of direct and indirect methods of adherence measurements with results showing moderate but statistically significant relationships between calculated pharmacy data and other measures (48,49).  A study conducted on the Manitoba prescription claims database compared with pill count medication adherence revealed a concordance of 79% (p = 0.68) for overall medications taken by each patient (63). The high concordance between pharmacy records and pill counts suggested that the rate at which patients fill their prescriptions is consistent with the rate at which patients consume their medications (63). To evaluate the validity of patient reporting, pharmacy dispensing records, and pill counts, patients on monotherapy with prescription drug coverage for hypertension were investigated (62). The outcome claimed a moderate correlation between pill counts (r = 0.52) and prescription refill adherence (r = 0.32) (62). A review of  eight studies that assessed the validity of adherence calculated with pharmacy data found significant but moderate 14  association between prescription refill records and direct measures of adherence, for example serum drug levels or physiologic drug effects (r = 0.21 to r = 0.47) (65).  Generally, it is problematic to compare validation studies for adherence measures from pharmacy claims databases because studies use various comparators, have different target populations, and they target different groups of drugs, all of which may influence adherent or non-adherent behavior. Also, different methods of measuring adherence are appropriate for different contexts and study designs. For example, pharmacy records are appropriate for measuring adherence for long-term treatments covering a large population, while direct methods of adherence are suitable for short-term treatments and for smaller populations such as in clinical settings. Understanding the limitations of both direct and indirect methods of adherence measures is important.  2.5.1.1 Calculating adherence  Rates of adherence using pharmacy data can be calculated in many different ways depending largely on the research questions being asked. An important requirement in adherence calculation using pharmacy claims is for patients to have more than one prescription fill to infer a value for adherence. Regardless of the rates used, there are 3 parameters for measures of adherence: the evaluated number of refill intervals, either single or multiple intervals; assessment of availability of treatment or gaps in treatment; and the distribution of adherence variables, either continuous or dichotomous (65).  15  For parameters concerning refill intervals, adherence can be measured for single refill intervals or a combination of periods with multiple refill intervals (65). In the assessment of the availability of treatment, the days’ supply of medication is calculated in the numerator. In measures of medication gaps the numerator is calculated as the number of days in the interval of interest minus the days’ supply (65). Continuous measures of adherence are expressed in percentages representing the proportion of days in which a patient had access to medication, while dichotomous measures classify patients as ‘adherent’ or ‘non-adherent’ by ruling threshold values for the continuous measures of adherence. Normally, a threshold of 80% or higher separates adherent against non-adherent behavior; these thresholds, however, are arbitrary and do not have clinical or pharmacological rationale (65). Yet, the threshold of 80% or higher has been established as beneficial in clinical trials (66) and in statin adherence literature (12,67).   The most frequently used measures of adherence known as the medication possession ratio (MPR) and the proportion of days covered (PDC), are continuous measures of medication availability calculated as the number of days with medication available divided by a defined interval (54). A review compared the above measures of adherence and reported slight differences between the measures. The proportion of days covered measure includes the date of the last medication claim while the MPR does not. These measures showed approximately similar values for adherence (54). The above methods offer no single dominant measure of adherence. However, owing to the nature of pharmacy data, the simplest calculation requiring fewer variables may be the ideal measure.   16  2.5.2 Conceptual frameworks of adherence  I approached my study on adherence by considering two published conceptual frameworks specific to adherence: WHO’s 5 dimensions of adherence and Osterberg and Blaschke’s  provider, patient, and system interactions for adherence (9,10). As alluded to earlier, WHO’s definition of adherence is broad and is not limited to adherence to medications only, an idea reflected in the framework as seen in Figure 2.1.  In its 2003 report on adherence and long-term therapies, WHO identified five dimensions of adherence, namely: social and economic, health system related, condition related, patient related, and therapy related factors (9). Moreover, WHO recognized that adherence to any regimen reflects behavior of one type or another.   Figure 2.1 WHO's five dimensions of adherence Copyright © 2003 World Health Organization  WHO's	5	dimensions	of	adherenceHealth	SystemSocial/economicTherapy-relatedPatient-related17  A. Social and economic factors Socio-economic status is not a consistent independent predictor of adherence; however in developing countries low socioeconomic status may put patients in the position of having to choose between demanding family needs and health care. Social and economic factors affecting adherence encompass a wide spectrum of issues. Some factors which significantly and negatively affect adherence include: poverty, unemployment, illiteracy, low levels of education, lack of effective social support networks, unstable living conditions, distance from treatment center, high cost of transportation, high cost of medication, changing environmental situations, culture and lay beliefs about illness and treatment, and family dysfunction (9).  Organizational factors were found to be more related to adherence than socio-demographic factors, depending on the setting. With regard to affecting patients’ adherence, WHO stated that organizational variables including time spent with the doctor, continuity of care by the doctor, communication style of the doctor and interpersonal style of the doctor are far more important than socio-demographic variables (gender, marital status, age, educational level, and health status).  Race is a strong predictor of adherence both in the patients’ country of origin and their country of residence. Cultural beliefs are said to be behind these racial differences; however, more often social inequalities confound these findings. The report also shows that civil wars have an influence on adherence to therapies. Adherence behavior is affected by the conditions of the aftermath of war including economic hardship, lack of medical control, fatalism, and anarchy.   18  Age has been found to have a mixed effect on adherence to medication regimens, although poor adherence to medication regimens affects all age groups (9). The prevalence of cognitive and functional impairments, combined with multiple co-morbidities and complex medical regimens, further complicates adherence behaviors in elderly patients. The increased number of single and working parents has shifted the responsibility for disease management to the children. The WHO revealed that children and adolescents who assume early sole responsibility for their treatment regimens are less adherent and exhibit poorer control of their disease management.   B. Health care team and system-related factors A good patient-provider relationship is said to improve adherence to therapy. However, there are system-related factors that negatively influence adherence, including poorly developed health services with inadequate or non-existent reimbursement by health insurance plans, a poor medication distribution system, lack of knowledge and training for health care providers on managing chronic diseases, overworked health care providers, lack of incentives and feedback on performance, short consultations, the weak capacity of the system to educate patients and provide patient follow-up, poor or no established community support, and lack of knowledge about adherence, and effective interventions to improve it (9).  C. Condition related factors The condition of illness reflects the demands of the illness and this has been shown to be a modifying factor of adherent behavior. Patient adherence to medication depends largely on the severity of the symptoms, the level of disability (physical, psychological, social, and vocational), the rate of progression, the severity of the disease and the availability of effective treatment (9). 19  Co-morbidities including depression, and drug and alcohol abuse also influence patient adherent behavior (9).  D. Therapy related factors Therapy related factors have mixed effects on adherence. The most pronounced therapy factors are those related to the complexity of the medical regimen, the duration of the treatment, the previous treatment failures, the frequent changes in treatment, the nearness of beneficial effects, the side-effects and the availability of medical support to deal with all of them (9). Also, adherence behavior is notably influenced by the purpose of therapy; that is, whether a therapy is prescribed for primary or secondary prevention of a disease.  E. Patient-related factors The influence of patient- related interacting factors on adherence behavior are not yet fully understood. Disease symptoms, expectations and illness cognitions often influence perceptions of the personal need for medication (9). Other patient-related factors reported to affect adherence include misunderstanding and non-acceptance of the disease, disbelief in the diagnosis, negative beliefs regarding the efficacy of the treatment, fear of dependence, frustration with health care providers, lack of attendance at follow-up or at counselling, motivational, behavioral, or psychotherapy classes, and feeling stigmatized by the disease (9).     World views characterized by concerns about chemicals in food and the environment, and about science, medicine and technology, are related to negative perspectives about medicines as a whole, and suspicions that physicians over-prescribe medicines (9). Moreover, the patients’ 20  decision to follow a regimen depends on the value placed on medication and confidence in their ability to engage in illness-management behaviors.  Osterberg and Blaschke described the conceptual framework of adherence as seen in Figure 2.2.             Copyright © 2005 Stanford University  A. Provider-patient communication Communication between patient and provider determines the patient’s understanding of the disease, the benefits and risks of treatment, and the proper use of the medication, all of which influence adherence. Also, physician prescription of an overly complex medication regimen is a barrier to medication adherence (10).  Patient Provider Healthcar-e system Figure 2.2 Interacting factors of adherence 21  B. Patient interaction with the health care system The patient’s interaction with the health care system largely affects their decision to take the medication as prescribed. Poor access to medication, health care facilities, and pharmacies, and missed medical appointments negatively influence adherence. The high cost of medication and switching to a different formulary similarly contribute to poor medication adherence (10). System level health policy interventions play a substantial role in patient adherence to prescription medication.  C. Physician interaction with the health care system Physician interaction with the health care system augments overall patient adherence to medication. The providers’ poor knowledge of drug costs and insurance coverage of different formularies is an impediment to medication adherence (10). Additionally, the providers’ low level of job satisfaction is believed to indirectly enlarge non-adherent behavior (10).   Medication adherence is a multidimensional concept as demonstrated by the frameworks discussed. For the purpose of this thesis, I will focus on the effect of policy intervention on medication adherence.  2.6 Effect of policy intervention on medication adherence  There have been several analyses of the relationship between drug costs and adherence to medications, seemingly recognizing the economic burden of chronic diseases and the potential for improved adherence to decrease morbidity and mortality. Despite this emphasis, there is a 22  paucity of information in literature addressing the effect of recent health policy changes on adherence to chronic disease treatment. It is clear from the literature that long-term adherence to chronic disease medication is unsatisfactory and the factors influencing adherence are complex, but the role of recent policy changes is not necessarily well understood.  For my review of the literature relating to health policy changes and adherence to medications, 18 studies were directly relevant to my research question. The studies are summarized in Appendix A. I searched Medline (with PubMed) and Web of Science using combinations of the keywords: drug cost, prescription drug coverage, adherence, cost sharing, drug policy change, pharmaceutical fees, statin, lipid lowering drugs, hypertension, primary and secondary CVD prevention, and interrupted time series (ITS). I also picked studies referenced in reviewed articles. I selected studies published within the past 10 years, from North America, and papers that used pharmacy claims data, and or administrative data or population data.  Nine of these studies measured adherence as the proportion of days covered with at least 80% of the days with medication available (PDC ≥ 0.80) for a given follow-up period, normally one year. Only two studies used a self-reported method while five studies applied the medication possession ratio as a measure of adherence to medication due to cost. Two studies estimated adherence using refill compliance (ReComp algorithm) which is a method better suited for shorter observation intervals with repeated measures (68).    23  2.6.1 Policy interventions that translate into improved adherence  As indicated in Appendix A, many studies have investigated the relationship between health policy intervention and adherence to medications. I identified three policy interventions for discussion: reduced medication co-payment, decreased co-insurance, and full prescription coverage.  2.6.1.1 Reduced medication co-payment  Findings from all studies suggest that policy interventions that decrease out-of-pocket expenses contribute to improving adherence to medications. Elimination of co-payments for statins was associated with an immediate 4.2% increase in monthly adherence (20). Also reduced co-payment rates for both generic and brand-name medication decreased nonadherence by 7% to 14% for different groups of drugs (23). Policies that increased co-payment were found to negatively influence adherence behavior for all drugs investigated.  2.6.1.2 Decreased medication co-insurance  Policies that decrease medication co-insurance costs improved adherence. New statin users were more price-sensitive across varying health policies compared to continuous users of co-insurance plans (14). Most notably, beneficiaries of co-insurance plans who had to be fully responsible for drug costs after reaching the ‘donut hole’ or coverage cap, exhibited poor medication adherence immediately (21,69,70).  24  2.6.1.3 Full prescription drug coverage  Health policies that offer full drug coverage to patients on lipid lowering, hypertension, and diabetes medications consistently improved adherence over time (71,72). On the other hand, policy plans with partial drug coverage or coverage of limited groups of drugs did not provide evidence for improving adherence to medications. 25  Chapter 3: Methods  3.1 Study design  To address my research question, namely what is the impact of generic drug price reductions on adherence to statin medications? I used a historical (or retrospective) study design (93) allowing me to observe prescription drug use over time. Using administrative data, I identified residents in BC who had a statin prescription between 2006 and 2014. A retrospective study design was the only appropriate study design for addressing my research question, because it enabled me to study nearly the entire population of BC on statins over eight years, using existing well-validated data. Using administrative data to measure my outcome of interest, namely adherence, may introduce less information bias than other methods of measurement that involve contact between researchers and patients (57).  3.1.1 Data sources  This study was conducted using secondary data from BC PharmaNet, a comprehensive population health care database. PharmaNet claims history includes records of all medications dispensed in community pharmacies in BC except records for individuals who are federally insured (Veterans, RCMP, Armed Forces and beneficiaries of Non-Insured Health Benefits including First Nations people on-reserve) (73). I used data from 2008 to 2014 to build a measure of adherence for my analysis, as described in section 3.3.1. PharmaNet contains records of outpatient prescription claims with information on drug identification, quantity dispensed, 26  date of dispensation, number of days’ supply, and limited information about the prescriber and the payer.  I obtained a total of 714 statin drug identification numbers (DIN) (see Appendix B) from PharmaNet drug list of May 2016 and the Health Canada Drug Product database using the following steps:  Step 1: PharmaNet drug list I selected all drugs with an anatomical therapeutic chemical (ATC) that start with C10AA code. The ATC divides drugs into different groups according to the organ or system on which they act and their chemical, pharmacological and therapeutic properties (74). Then I selected other ATC codes containing a combination of any statin ingredient. Thereafter, I included statin brand names that may have ATC codes other than C10AA. This step yielded a total of 681 different statin DINs.   Step 2: Health Canada drug product database First I searched for ATC C10AA and included on my list all statin identification numbers not included in step 1. Next, I searched for each ingredient name and brand name and included any DIN that was not included previously. Then I searched for generic names within each brand name and added any statin not included before. Finally, I searched for cancelled post market statins to obtain drugs that were marketed at one point but are not currently marketed. This enabled me to capture prescriptions dispensed several years before the policy interventions. I obtained an additional 33 DINs from this step.    27  The project was approved by the Behavioral Research Ethics Board of the University of British Columbia, and permission to use data was obtained from the BC Ministry of Health through Population Data BC.  3.2 Cohort definition I created a cohort selection model for my study as illustrated in Figure 3.1.  3.2.1 Cohort selection steps   Step 1: First cohort selection (January 1, 2006 – September 31, 2008) In this step, I included all patients who filled a statin prescription at any point between January 1, 2006 and September 31, 2008.  A group of first time statin users (determination is described in detail in section 3.2.2) was included to study the adherence behaviour of new statin users. Studies show low adherence levels ranging from PDC of 35%-78% for new users of chronic disease medications (75,76). If patients continued on statin beyond September 31, 2008, they were computed in the rolling cohort.  Data collected here included; patient study ID, medication ID, dispensed date, dispensed quantity, dispensed number of days’ supply, and total patient paid cost. Monthly adherence to statins at all steps of the cohort selection was calculated as described in section 3.3.1.  Step 2: Pre-intervention rolling cohort (October 1, 2008 – September 31, 2010) I created a rolling cohort which I defined as a group of patients who continued to be in the study from step 1 if they remained on statins, patients newly included if they started on a new statin, or 28  patients who left the cohort at any time if their statin was discontinued.  Patient data (the same data as in step 1) was obtained with the purpose of establishing trends in adherence behaviour two years before the new drug pricing policy intervention.  Step 3: Post-intervention rolling cohort (October 1, 2010 – September 31, 2014) To learn of the effect of drug price reduction intervention on statin adherence, I collected and analyzed patient data (the same data as in step 2). Patients continued to enter or leave the rolling cohort until the end of the study (for various reasons including moving out of the province, discontinuation of statin, death, and other).      PDC                                                                                                Post-intervention                                First cohort selection                                                                     Pre-intervention              Statin free             2005          2006                     2008                         2010   2011   2012  2013   2014   Figure 3.1 Cohort selection model   29  3.2.2 Inclusion and exclusion criteria  In order to establish adherence behavior of first time statin users, I requested the Ministry of Health to exclude data of patients who filled a statin prescription within one year (January 1 to December 31, 2005) prior to the beginning of my selection cohort. Past research studies have allowed 1 to 2 years of adherence behavior observation prior to policy change to establish adherence behavior before policy intervention (19,77). I purposely included first time statin users because new statin users were anticipated to join in at any time throughout the study period.  To be included in the study, patients had to have filled a statin prescription at any time between January 1, 2006 and September 30, 2014. Because the policy changes happened over the course of 4 consecutive years, observation points ranged between 6 and 12 after each policy change depending on the calendar date on which the policy intervention was implemented. Previous studies have allowed between 3 and 24 observation points post policy intervention (14,21,22).  3.3 Study variables  3.3.1 Outcome variables  The outcome of interest in this study, adherence, was calculated by first creating a supply diary for each individual’s monthly medication availability with a basic inventory model. To construct my variables, I used the fields “date of service” and “days’ supply dispensed” for each prescription recorded in PharmaNet for a given patient. To verify the reliability of “days’ supply 30  dispensed” field, I examined the lengths of prescriptions received to confirm they were common supplies in clinical practice (78). I populated an array of variables, based on dispensing dates and reported days’ supply for each month from the entry date into the rolling cohort (October 1, 2008) to the end of study date (September 30, 2014). On days when drugs were dispensed to the patients, their supply in-hand increased by the dispensed days’ supply, as illustrated on the vertical axis in Figure 3.2. On each day between prescription fills, their supply in-hand decreased by one, to a minimum of 0.     Days supply        10                  7            0      7             14                    24        31                                Time (days) Figure 3.2 Inventory model of drug supply  The inventory model of drug supply was constructed for all patients on any statin (see Appendix C for details). In order to infer accurate value for adherence, patients with a record of one prescription were omitted from the study. This is due to the inventory model I used which would result in adherence of 100% for patients with only one prescription record. Switching from a brand name to a generic product with the same active statin ingredient and switching from one 31  generic statin to another was not considered an interruption in therapy. The arrays were then used to calculate individual adherence to statin medication for each calendar month.   Adherence I measured adherence using the proportion of days with medication available (also called the proportion of days covered, or PDC). I used an interval-based approach, which is a measure of adherence during a given interval (79). I calculated PDC as the number of days’ supply of medication supplied from all prescriptions during a month (numerator) divided by the total number of days in that month (denominator) for each subject. If the numerator exceeded the denominator, any excess supply available was added to a subsequent month (78). Figure 3.3 shows the interval-based adherence approach (79) applied to a hypothetical drug use profile where t is the total number of days in the interval, and xy is the days supplied from the last prescription.                                    Date of first Rx                                                       Date of last Rx                                                                 0                                                                                     x-------y        t                                                                                                --------                                                                                                      Numerator: Total days supplied       Denominator: Total days in interval Figure 3.3 Hypothetical drug use profile    32  3.4 Analytic plan  To analyze the effect of policy interventions on adherence to statin medications, I used interrupted time series analysis, one of the strongest quasi-experimental designs (80). I assessed price-related changes in the use of statins following each successive reduction in generic drug prices as illustrated in Figure 3.4 where X represents interventions and O represents observation points. I constructed a non-randomized control series as represented by dash lines using brand name products for all statins.   Figure 3.4 Interrupted time series model  I used the following linear regression to model outcome measure in each time interval pre-and post-policy interventions:  Outcome (adherence) = β0 + β1*timet + β2*Policy1 + β3*timet*Policy1 + β4*Policy2 + β5*timet*Policy2 + β6*Policy3 + β7*timet*Policy3 +β8*Policy4 + β9*timet*Policy4 + β10*Policy5 + β11*timet*Policy5 +   O1 O2 …O23 O24    X1 O25 …O32 O33      X2 O34…O41 O42    X3 O43…O53 O54     X4 O55…O65 O66    X5 O67…O71 O72 _____________________________________________________________________________________________________________________________________  O1 O2 …O23 O24    X1 O25 …O32 O33      X2 O34…O41 O42    X3 O43…O53 O54     X4 O55…O65 O66    X5 O67…O71 O72   October     October         July          April                    April                    April   2008         2010          2011                    2012                     2013                     2014  33  In this model, β0 represents the intercept, time represents any given month before or after the policy change (1, 2, 3…).  Policy is an intervention representing a price reduction in generics (50%, 40%, 35%, 25%, and 20%).  The parameters of interest are β2,4,6,8,10 which show direct change in the level of outcome, and β3,5,7,9,11 which indicate any change in the trend of outcome over time following generic price changes. Standard errors were adjusted for, represented by  in the regression equation.   A generalized least-squares model which included autoregressive terms to control for correlation over time was used. The presence of serial autocorrelation was assessed by examining the autocorrelation values at various lags using autocorrelation and partial autocorrelation functions. I calculated counterfactual values of adherence to learn what would have been observed in the absence of policy intervention.   My final model included both generic statin users (intervention group) and brand name statin users (control). Prices for brand name drugs were not affected by the BC generic drug pricing policy changes hence brand name statins served as a reasonable estimate for the control group. The final model as seen in Figure 3.5 below shows highlighted terms as the variables of interest, which are differences in level and trend in the intervention group relative to the control.     34  Outcomejt = β0 + β1*timet + β2*groupk + β3*groupk*timet + β4*level1t + β5*trend1t  β6*level2t + β7*trend2t  + β8*level3t  + β9*trend3t + β10*level4t + β11*trend4t  + β12*level5t + β13*trend5t  + β14*level1t* groupk + β15*trend1t* groupk + β16*level2t* groupk + β17*trend2t* groupk  + β18*level3t* groupk + β19*trend3t* groupk + β20*level4t* groupk + β21*trend4t* groupk + β22*level5t* groupk + β23*trend5t* groupk +  ɛjkt                                                                                      PDC                                     β15 β17   β19 β21      β23                                                   β3                                     β2                   β14      β16     β18  β20     β22                                                                       Pre-intervention                                 Post-intervention    Figure 3.5 Final model  I evaluated the model fit by running diagnostic tests. I ran a quantile-quantile plot to evaluate the normality of outcome data. Also, I produced a residual plot to investigate the distribution of residuals around the model.   All statistical analyses were done using R statistical software package, version 3.2.5, and data preparation was done using SAS version 9.4 for Windows (SAS Institute Inc., Cary, NC).        35  Chapter 4: Results  4.1 Cohort characteristics  There were 433,945 patients in British Columbia who filled a statin prescription between October 2008 and September 2014. The characteristics of the study cohort according to patients’ use of statins are shown in Table 4.1. Among statin users, 42.42% were female and 57.57% were male. The majority of statin users (57.36%) appeared to be older adults in the 51 to 70 years’ age category. Overall, 34.1% of statin prescription claims had 30 or less days’ supply and 53.83% of all claims had between 60 and 100 days’ supply. These values indicate realistic prescription lengths, mainly given the 100-day supply limit coverage in BC. A total of 27,323 (6.3%) patients had only one pharmaceutical claim. For an accurate value of adherence to be obtained using the proportion of days covered measure, patients must have at least two prescription claims. Upon exclusion of patients with one prescription record only, a total of 406,622 statin users remained and were included in my segmented regression analysis.      36  Table 4.1 Cohort characteristics  Characteristic  Total n = 433 945  Percent of Total Sex   Female 184 096 42.42                             Male 249 807 57.57 Unknown  42 0.01 Age (year)   £30 3 685 0.85 31-50 80 181 18.48 51-70 248 918 57.36 ≥ 71 101 161 23.31 Medication Supply (day)   £30 147 721 34.1 31-60 43 603 10.06 61-100 233 906 53.83 101-200 8 715 2.01 Prescription Claim   <2 27 323 6.3 ≥ 2 406 622 93.7 37   4.2 Diagnostic tests  4.2.1 Normality of outcome data  I produced a diagnostic test, a normal quantile-quantile plot comparing randomly generated outcome data (monthly proportion of days covered or PDC) on the vertical axis to a standard normal population on the horizontal axis. The linearity of observed points on the Q-Q plot indicates that the outcome data are reasonably normally distributed, as seen in Figure 4.1.   Figure 4.1 QQ-plot showing normal outcome data 38  4.2.2 Addressing autocorrelation  Results from my preliminary analysis indicated the existence of an autoregressive process that needed to be addressed in my model. Figure 4.2 shows autocorrelation plots to assess for correlation of residuals in the model. We see an exponential decay in the autocorrelation function (ACF) plot and significant lags which spike at 15 before dropping to zero in the Partial ACF plot. I addressed the autocorrelation by including autoregressive terms in my final model to adjust for the correlation of observations over time.    Figure 4.2 Autocorrelation and partial autocorrelation      39  4.3 Interrupted time series model  Time series models were fitted to assess for changes in the level (step) and trend (slope) in adherence to generic statins (intervention group) and brand name statins (control group). On average, the measured monthly adherence rate for both groups of statin users in BC during my study period exceeded the PDC of 80% threshold that separates adherent from non-adherent behavior.   Results from the generalized least-squares model revealed that among statin users, price reduction was associated with high monthly adherence to generic statins (Table 4.2). At the beginning of the study, brand name statin users had a mean proportion of days covered with medication of 89.9% per month (95% CI 0.8924 to 0.9059). The pre-existing level of adherence to generic statins was 0.89 percentage points (95% CI -0.0007 to 0.0184) higher, relative to adherence to brand name statins. There was a sustained significant decrease of 0.05 percentage points (95% CI -0.0009-(-0.00001)) per month in the trend of the brand name use (p=0.0473). Adherence to generics saw a monthly drop of 0.02 percentage points (95% CI -0.0009 to 0.0005) relative to the control group over the 24 months preceding policy intervention.   At the time the first policy intervention was introduced, there was an immediate increase in the level of adherence to statins. The level in use of brand name statins increased by 1.1 percentage points (95% CI -0.0032 to 0.0245) while the level in use of generics decreased by 0.71 percentage points (95% CI -0.0267 to 0.0125) relative to its brand name counterpart. There was a decrease in the trend of the control group of 0.03 percentage points (95% CI -0.0026 to 0.0021). 40  The trend in generics increased by 0.27 percentage points (95% CI -0.0006 to 0.0061) per month higher relative to the control. However, this increase in the trend of generic statins after the first policy intervention was not significant.  After the second policy intervention, which reduced generic drug prices from 50% to 40% of the brand name price, there was a small increase in the level of adherence to the brand name statin of 0.61 percentage points (95% CI -0.008 to 0.0203). There was also a small increase of 0.01 percentage points (95% CI -0.0041 to 0.0042) in the trend of the control group afterwards. I observed a rise in the trend of generic use of 0.03 percentage points (95% CI -0.0056 to 0.0063) relative to the control. Further drug price reductions were not associated with a statistically significant increase in monthly adherence among statin users.   41  Table 4.2 Segmented regression estimates and associated 95% confidence intervals for 406,622 patients during study period Variable Differential change in monthly PDC  (generics) p-value for (differential change in monthly PDC for generics) Monthly PDC for control group (brand name) p-value for monthly PDC for control  (brand name) Intercept 24 months pre-intervention 0.0089 (-0.0007-0.0184) 0.0705 0.8992 (0.8924-0.9059) 0.0000 Pre-intervention trend -0.0002 (-0.0009-0.0005) 0.5714 -0.0005 (-0.0009-(-0.00001)) 0.0473 Change in level after first intervention  -0.0071 (-0.0267-0.0125) 0.4785 0.0107 (-0.0032-0.0245) 0.1339 Change in level after second intervention -0.0167 (-0.0368-0.0033) 0.1046 0.0061 (-0.0080-0.0203) 0.3977 Change in level after third intervention 0.0015 (-0.0193-0.0222) 0.8865 0.0007 (-0.0139-0.0154) 0.9207 Change in level after fourth intervention 0.0164 (-0.0053-0.0381) 0.1418 -0.0155 (-0.0309-(-0.0002)) 0.0500 Change in level after fifth intervention -0.0007 (-0.0262-0.0248) 0.9586 0.0016 (-0.0164-0.0196) 0.8628 Change in trend after first intervention  0.0027 (-0.0006-0.0061) 0.1147 -0.0003 (-0.0026-0.0021) 0.8271 Change in trend after second intervention 0.0003 (-0.0056-0.0063) 0.9163 0.0001 (-0.0041-0.0042) 0.9812 Change in trend after third intervention -0.004 (-0.0097-0.0016) 0.1655 0.001 (-0.003-0.005) 0.6256 Change in trend after forth intervention -0.0019 (-0.0071-0.0032) 0.4662 0.0037 (0.000-0.0073) 0.0521 Change in trend after fifth intervention 0.0058 (-0.0045-0.0161) 0.2701 -0.0075 (-0.0148-(-0.0002)) 0.0470 42   4.3.1 Changes in adherence to statins  My model showed changes between the counterfactual and the observed adherence behavior at any point in the post intervention period. Counterfactual lines projected forward in Figure 4.3 indicate that we would have expected to see a sustained decrease in adherence to statins had policy interventions not taken place.   Figure 4.3 Monthly adherence to statins during study time 43  4.3.2 Residuals around the model  A visual inspection of the patterns of residuals in Figure 4.4 shows a scattered cloud of residuals around the model. This indicates that the variation around the regression line is constant.   Figure 4.4 Residuals around the model 44  Chapter 5: Discussion  5.1 Overall adherence  Before the 2010 policy intervention which reduced the price of generic drugs in British Columbia, pharmaceutical claims for statin medication were consistently decreasing for two years. A small but statistically insignificant rise in adherence to generic statin was observed at each stage of the five policy interventions. However, when the policy interventions were combined, the cumulative effect of the reduced generic pricing yielded a modest and significant increase in adherence.    Overall, statin medication adherence in BC occurred on the high end of medication adherence measures. Mean adherence measured as the monthly proportion of days covered (PDC) was higher post intervention relative to pre-existing measures. This finding is consistent with outcomes examined by studies on drug utilization and cost (19,69,81,82). As explained in literature earlier (12,66,67), my results confirm that on average statin users are sensitive to the  price of medication.  Sensitivity to the price of medication, however, manifested itself in insignificant measures. Policy changes were implemented in a ‘phase in’ approach where prices were reduced in stages over a four-year period (17). The first two policy changes resulted in a small rise in the trend of generics use. Subsequent price reductions from 35% to 25% to 20% of the brand name price had equally small improvements on adherence to generic statin medication.  45  While the implementation of generic pricing might explain the incremental improvement in adherence observed in the generic statin arm over the brand statin arm, it is worth noting that adherence to statins improved in both arms between 2010 and 2014. Given that the BC pricing policy did not affect brand name prices, this finding suggests that in all likelihood other factors were active during this period, influencing adherence across both arms. One possible explanation might be the implementation of the Medication Review Services in BC in 2011. The objective of this service was to promote safe and effective use of medicines (83). A study evaluating the impact of Medication Review Services between May 2012 and June 2013 found a significant improvement in statin adherence among patients who participated in this review process (increase of 0.52% (95% CI 0.19% to 0.86%, P = 0.005) (83).      5.2 Key factors influencing adherence  5.2.1 Cost of medication  My study showed that price reductions were associated with increases in the use of generic statins. This study provides evidence of cost-related adherence behavior as a result of policy intervention. Furthermore, previous studies have consistently found that the cost of medication plays a large role in patient adherence behavior (14,72,84).     46  5.2.2 Co-occurring events in history  There were prescription drug-related events that occurred at two time periods during the course of my study. Canada opened the market for generic drug manufacturers to sell two highly prescribed medications in May 2010 and March 2012. Atorvastatin became available as a generic in mid-May 2010 followed by the BC government’s announcement of policy changes to generic drug pricing in July 2010 (85). The last statin to go off patent, Rosuvastatin, was approved as a generic for the first time in Canada in March 2012 (86). The availability of generic Crestor was preceded by the BC government’s announcement of further price reductions in February 2012.    An interruption in adherence patterns was observed around the time these events took place. Lower adherence behavior was seen during these months compared to other time periods in the study. Patient adherence behavior in reaction to these events supplements my claim that policy intervention did impact adherence behavior to prescription medication at a population level.   5.3 Strengths and limitations  My study uncovers the state of statin medication adherence behavior following recent policy interventions using a rich, population-wide administrative dataset. Pharmaceutical claims data enabled me to create individual monthly drug profiles and aggregate patients’ drug taking behavior to examine the effect of policy at a population level. Also, this study has a long observation period. From October 2008 to September 2014, I was able to measure, at a system level, the impact of policy interventions on medication adherence.  47   Furthermore, the study engaged a rigorous analysis of policy. Through the application of interrupted time series analysis and use of a comparable control group, I was able to compare adherence behaviors for both generic and brand name statin users for a period of six years. Moreover, the analysis allowed me to show trends in statin medication use had policy changes not taken place.     Furthermore, the study investigated a total of 714 different drugs claimed at pharmacies. Thus, my findings are relevant to closed pharmacy systems in jurisdictions where all dispensed medications are stored in a single computerized database.  A major limitation of this study is that it considered the cost of medication alone as a potential influencing factor of adherence. However, both the WHO and Osterberg and Blaschke frameworks suggest that multiple factors come together to influence an individual’s decision related to adherence. With adherence improving in both the generic and brand arms of this study, findings from this study also insinuate that other factors in addition to cost contributed to adherence. These factors include but not limited to other parallel health systems policies,  level of income, health status, social support, and multiple drug use (9,10). Future research that considers these additional factors is needed to validate the modest but important incremental improvement in adherence observed in the generic arm versus the brand arm in this study.    Another limitation faced by this study is the existence of a parallel policy change in BC. In 2009 a policy change in BC allowed pharmacists to independently renew existing prescriptions for 48  chronic disease medications. One of the intended results was to improve patient access and adherence to medicines (87). This policy however, had an extremely low uptake with only 0.17% prescriptions renewed during the time the policy was in place (88). The 2009 policy change is not expected to influence the results of my study.  As with any study using administrative data this study faces similar limitations. Adherence measured using pharmaceutical claims data assumes that patients take their medications as prescribed. Nonetheless, as alluded to in the literature review, prescription claims do not necessarily state that patients actually take their medications.  I did not have access to medical records, and for that reason I could not differentiate between patients who discontinued medication therapy on the advice of their physicians, and patients who are cost-related non-adherers. Further information is needed to address qualitative factors related to medication taking behavior.   It is well documented that the price of prescription medication plays a large role in patient adherence behavior(70,77,82,89). The optimal level of pricing for prescription medications is yet to be realized. This topic is beyond the scope of my study; however, future studies should investigate the threshold at which drug pricing policies become effective.      49  5.4  Conclusion  Policy analysis in this study shows that out-of-pocket cost incurred by patients in British Columbia indeed determines their adherence to medication behavior. As referred to in the literature review, patients without or with partial prescription medication insurance are likely to report cost-related nonadherence to treatment (84). Literature also shows that patients on publicly ensured medication plans are more adherent to their medication regimen than those whose prescription drugs are privately insured (90). Additionally, reduced prescription copayments and full medication coverage were reported to improve adherence to medications (19,23,71,91).  Findings indicate that reductions in generic drug prices in BC yielded a modest improvement in pharmaceutical claims for statins. This study provides a novel contribution in the area of policy research by representing the first quantitative evaluation of five health policy interventions in Canada. Given that cumulative model demonstrated greater medication adherence compared to any of the five policy interventions (assessed individually), suggests that large generic pricing reduction are needed to have a meaningful impact on statin adherence. In the future, health policy makers may want to consider fewer but larger drug price reduction interventions for a more effective impact.       50  References 1.  WHO. Global status report on noncommunicable diseases 2014 [Internet]. WHO. [cited 2015 Oct 22]. Available from: http://www.who.int/nmh/publications/ncd-status-report-2014/en/ 2.  Government of Canada PHA of C. Economic Burden of Illness in Canada, 2005-2008 [Internet]. 2014 [cited 2015 Oct 18]. Available from: http://www.phac-aspc.gc.ca/publicat/ebic-femc/2005-2008/index-eng.php 3.  Government of Canada PHA of C. Six types of cardiovascular disease - Public Health Agency Canada [Internet]. 2008 [cited 2016 Apr 28]. 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Matched Retrospective cohort PDC Higher cost for privately insured (CAD$41.52) than publicly insured (CAD$32.21). 1 year Publicly insured patients on 1 antihypertensive drugs were more adherent (65%) than privately insured patients (58.8%)   Law et, al 2012 (84) Canada Community Health Survey (2007) from 5732 respondents. Population-based analysis  Self-reported Investigation of insured and non-insured individuals. 1 year Cost-related nonadherence predicted rates of  35.6% (95% CI: 26.1%-44.9%) among non-insured and 3.6% (95% CI: 2.4-4.5) insured Schneeweiss et, al 2007 (19) British Columbia residents aged 66 years and older. 51561 residents on statins with and without MI. Cohort time series study PDC Full drug coverage, copay with $10 or $25, coverage with a 25% coinsurance benefit. 9 months after each policy change Relative to full coverage, adherence reduced for fixed copayment policy from 55.8% to 50.5% (95% CI:-6.4%to-4.4) and for coinsurance policy (95% CI:-6.3%to-4.4)  60  Summary of recently published studies on health policy and medication adherence (cont.) Source Study Sample Study design Adherence  Intervention Follow up Key findings Choudhry et, al 2010 (20) Beneficiaries of Pitney Bowes insurance plan were compared to Horizon Blue Cross Blue Shield of New Jersy beneficiaries. 2,830 people eligible for copayment reductions on statins and Clopidogrel. Controlled Retrospective cohort PDC Elimination of copayments for statins and Clopidogrel. 1 year Elimination of copayments associated with an immediate 4.2% increase in monthly adherence in the intervention group Heisler et, al 2010 (22) Health and Retirement Study (HRS) national survey of adults aged 50 to 85. Data collected from over 11536 individuals with at least one CVD. Retrospective biannual cohort Self-reported Examination of cost-related hospitalization and deaths. 2 years Cost-related medication underuse respondents were more likely to be hospitalized than those reporting no underuse (54% compared with 42% P < 0.001)  61  Summary of recently published studies on health policy and medication adherence (cont.) Source Study Sample Study design Adherence  Intervention Follow up Key findings Chernew et, al 2008 (23) ActiveHealth Management (AHM) employees and dependents aged 18-64 were compared to other disease management (DM) programs firms. Controlled before after MPR Reduced copayment rates for generics from $5 to zero, brand name $25 to 12.5 for preferred drugs and from $45 to $22.50 for non-preferred drugs. 2 years A 7-14% reduction in nonadherence for four classes of medications (p < 0.001) after reduced copayment  policy Hsu et, al 2006 (71) Adults aged 65 years total of 157275 medicare +choice beneficiaries with capped drug benefits and 41904 beneficiaries with unlimited drug benefits. Prospective cohort PDC Copayments of $10 for generics and $15 to $30 for brand-name with either $1000 cap or no cap  1 year Subjects with capped benefits had higher odds ratio of nonadherence to lipid-lowering drugs (OR: 1.27; 95% CI: 1.19 to 1.34), antihypertensive drugs (OR: 1.30; 95% CI:1.23 to 1.38) and antidiabetic drugs (OR: 1.33; 95% CI: 1.18 to 1.48)      62  Summary of recently published studies on health policy and medication adherence (cont.) Source Study Sample Study design Adherence  Intervention Follow up Key findings Zhang et, al 2010 (72) Adults aged 65 years or older in a large Pennsylvania insurer's Medicare Before-after (no control group) MPR Observation of individuals before drug coverage and after drug coverage 1years Improved adherence in the group without prior drug coverage by 13.4% (95% CI: 10.1-16.8), 17.9  (95% CI:13.7-22.1), and 13.5 (95% CI: 11.5-15.5) for those with hyperlipidemia, diabetes, and hypertension Li et al, 2012 (21) Medicare beneficiaries with diagnosis of hypertension and hyperlipidaemia. 83921 adults aged 65 years and over. Controlled before and after PDC Increased copayment when patients without coverage reached the donut hole 6 months Non-adherence increased when patients were subjected to copayments. Hypertension (OR: 1.6; 95% CI:1.5-1.71) Lipid lowering (OR: 1.59; 95% CI: 1.5-1.68)   63  Summary of recently published studies on health policy medication adherence (cont.) Source Study Sample Study design Adherence  Intervention Follow up Key findings Gibson et al, 2006 (14) Statin users were selected from Medstat MarketScan database. 142341 new statin users and 92344 continuing statin users were sampled. Cross-sectional time-series MPR Statin co-payment variation across health plans 3 years Copayment increase lowered monthly adherence rates for statins by 2.6% and 1.1% (OR: 0.949P < 0.01) among new and continuous users respectively. New statin users were more price-sensitive Maciejewski et al, 2010 (82) Veterans diagnosed with hypertension or diabetes on or not on statins exempted or not exempted from copayments. Average age 65.5 years 2138 in diabetes group, 7090 in hypertension group were selected.  Retrospective cohort ReCOMP algorithm Increased copayment from $2-$7  12 months before 23 months after Increase non-adherence when subjected to copayment in statin group (OR: 1; 95% CI: 0.8522-1.1733 diabetes group (OR: 1.48; 95% CI: 1.23-1.79),9), Hypertension group (OR: 1.13; 95% CI: 1.029-1.2481) 64  Summary of recently published studies on health policy and medication adherence (cont.) Source Study Sample Study design Adherence  Intervention Follow up Key findings Taira et al, 2006 (81) Selected 114232 patients who filled prescriptions for antihypertensive medication.  Repeated cross-sectional MPR Three copayment levels: $5, $20, and $20-$165  1 year Relative to drugs with a $5 co-payment, odds ratio for adherence to drugs having a $20 copayment was 0.76 (95% CI: 0.75-0.78) and drugs requiring a $20-$165 copayment odds ratio was 0.48 (95% CI: 0.47-0.49) Fung et al, 2010 (70) California residents over 65 years prescribed oral diabetes, hypertension and hyperlipidaemia medicines. A total of 7059 people were recruited. Cohort study PDC Increased copayment when patients without coverage  reached the donut hole 3 months Non-adherence increased when patients were subjected to copayment. Lipid lowering (OR: 1.45; 95% CI: 1.36-1.54), hypertension (OR: 1.28; 95% CI: 1.2-1.35), diabetes (OR: 1.2; 95% CI: 1.14-1.26)  65  Summary of recently published studies on health policy and medication adherence (cont.) Source Study Sample Study design Adherence  Intervention Follow up Key findings Goldman et al,2006 (12) Selected 62274 patients aged 20 years and older initiated on cholesterol therapy between 1997 and 2001. Repeated cross-sectional MPR Increased copayment from $10 to $20 1 year The fraction of fully adherent patients dropped by 6 to 10 percentage points (P <0.05) Doshi et al, 2009 (92) 5604 veterans on lipid lowering medicines in Philadelphia Controlled before after PDC Increased copayment from $2-$7 2 years Increase non-adherence when subjected to copayment was (OR: 3.04; 95% CI: 2.29-4.03) compared to copay exempt  Polinski et al, 2011 (69) Medicare beneficiaries total of 663850 aged 65 and over on CVD, diabetes, depression and rheumatoid arthritis were followed until coverage gap or "donut hole" Cohort study PDC Increased copayment to 100% of drug cost when in donut hole 3.6 months Subjects exposed to copayment were more likely to have reduced adherence (OR: 1.07; 95% CI: 0.98-1.18)  66  Summary of recently published studies on health policy and medication adherence (cont.) Source Study Sample Study design Adherence  Intervention Follow up Key findings Wang et al, 2011 (77) Veterans diagnosed with hypertension (7852) were compared with those with diabetes (2426) for all aged 65+ Retrospective cohort ReCOMP algorithm Increased copayment from $2-$7 12 months before 11 months after Non-adherence increased when patients were subject to copayment. Hypertension low morbidity (OR: 1.19; 95% CI: 1.101 to 1.2789). Hypertension high morbidity (OR: 1.44; 95% CI:1.2 to 1.71). Diabetes low morbidity (OR: 1.38; 95% CI: 1.191-1.611). Diabetes high morbidity (OR: 1.66; 95% CI: 1.25-2.21) Gu et al, 2010 (91) Medicare Part D beneficiaries with diabetes totaling 12881 were included in the sample Controlled before and after PDC Increased copay when patients without coverage reached coverage gap. Prices ranges $18.63 to $69.2 1 year When subjected to copayment non-adherence behavior increased (OR: 0.617; 95% CI:0.523-0.728; P < 0.0001)   67  Appendix B: List of statins requested from PharmaNet DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	795860 LOVASTATIN TAB 20MG MEVACOR MERCK CANADA INC  Cancelled Post Market  December 31, 1988 June 6, 2014  795852 LOVASTATIN TAB 40MG MEVACOR MERCK CANADA INC  Cancelled Post Market  December 31, 1990 June 6, 2014  884332 SIMVASTATIN TAB 10MG ZOCOR MERCK CANADA INC  Marketed  December 31, 1990  Approved 893757 PRAVASTATIN TAB 20MG PRAVACHOL  BRISTOL-MYERS SQUIBB CANADA  Marketed  December 31, 1990  Approved 893749 PRAVASTATIN TAB 10MG PRAVACHOL  BRISTOL-MYERS SQUIBB CANADA  Marketed  December 31, 1990  Approved 884324 SIMVASTATIN TAB 5MG ZOCOR MERCK CANADA INC  Marketed  December 31, 1991  Approved 2061570 FLUVASTATIN CAP 40MG LESCOL  NOVARTIS PHARMACEUTICALS CANADA INC  Marketed  December 31, 1994  Approved 884340 SIMVASTATIN TAB 20MG ZOCOR MERCK CANADA INC  Marketed  December 31, 1994  Approved 2061562 FLUVASTATIN CAP 20MG LESCOL  NOVARTIS PHARMACEUTICALS CANADA INC Marketed  December 31, 1994  Approved 884359 SIMVASTATIN TAB 40MG ZOCOR MERCK CANADA INC  Marketed  August 14, 1996  Approved 2222051 PRAVASTATIN TAB 40MG PRAVACHOL  BRISTOL-MYERS SQUIBB CANADA  Marketed  August 21, 1996  Approved 2230713 ATORVASTATIN TAB 20MG LIPITOR PFIZER CANADA INC  Marketed  March 5, 1997  Approved 2230711 ATORVASTATIN TAB 10MG LIPITOR PFIZER CANADA INC  Marketed  March 5, 1997  Approved 2230714 ATORVASTATIN TAB 40MG LIPITOR PFIZER CANADA INC  Marketed  March 5, 1997  Approved 2220172 LOVASTATIN TAB 20MG  APOTEX INC  Marketed  March 27, 1997  Approved 2220180 LOVASTATIN TAB 40MG  APOTEX INC  Marketed  March 27, 1997  Approved 2237325 CERIVASTATIN TAB .2MG BAYCOL  BAYER INC  Cancelled Post Market  March 11, 1998 October 26, 2001  2237326 CERIVASTATIN TAB .3MG BAYCOL  BAYER INC  Cancelled Post Market  March 11, 1998 October 26, 2001  2240332 SIMVASTATIN TAB 80MG ZOCOR MERCK CANADA INC Cancelled Post Market  July 21, 1999 May 6, 2014  2241466 CERIVASTATIN TAB .4MG BAYCOL BAYER INC  Cancelled Post Market  January 6, 2000 October 26, 2001  2237374 PRAVASTATIN TAB 20MG  LINSON PHARMA CO.   Cancelled Post Market  July 13, 2000 May 29, 2006  2237373 PRAVASTATIN TAB 10MG  LINSON PHARMA CO.   Cancelled Post Market  July 13, 2000 May 29, 2006  2237375 PRAVASTATIN TAB 40MG  LINSON PHARMA CO.   Cancelled Post Market  July 13, 2000 May 29, 2006  2243223 CERIVASTATIN TAB .8MG BAYCOL BAYER INC Cancelled Post Market  December 28, 2000 October 26, 2001  2243127 LOVASTATIN TAB 20MG  MYLAN PHARMACEUTICALS ULC  Marketed  February 8, 2001  Approved 2243129 LOVASTATIN TAB 40MG  MYLAN PHARMACEUTICALS ULC  Marketed  February 8, 2001  Approved 68  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2243506 PRAVASTATIN TAB 10MG  APOTEX INC Marketed  February 27, 2001  Approved 2243507 PRAVASTATIN TAB 20MG  APOTEX INC Marketed  February 27, 2001  Approved 2243508 PRAVASTATIN TAB 40MG  APOTEX INC Marketed  February 27, 2001  Approved 2243097 ATORVASTATIN TAB 80MG LIPITOR PFIZER CANADA INC  Marketed  June 29, 2001  Approved 2242865 PRAVASTATIN TAB 10MG  BIOENHANCE MEDICINES INC. Cancelled Post Market  July 12, 2001 February 27, 2003  2242866 PRAVASTATIN TAB 20MG  BIOENHANCE MEDICINES INC. Cancelled Post Market  July 12, 2001 February 27, 2003  2242867 PRAVASTATIN TAB 40MG  BIOENHANCE MEDICINES INC. Cancelled Post Market  July 12, 2001 February 27, 2003  2244351 PRAVASTATIN TAB 20MG  NU-PHARM INC Cancelled Post Market  May 2, 2002 September 4, 2012  2244350 PRAVASTATIN TAB 10MG  NU-PHARM INC Cancelled Post Market  May 13, 2002 September 4, 2012  2244352 PRAVASTATIN TAB 40MG  NU-PHARM INC Cancelled Post Market  May 16, 2002 September 4, 2012  2245822 LOVASTATIN TAB 20MG  RATIOPHARM INC DIVISION OF TEVA CANADA LIMITED Cancelled Post Market  May 22, 2002 January 9, 2013  2245823 LOVASTATIN TAB 40MG  RATIOPHARM INC DIVISION OF TEVA CANADA LIMITED Cancelled Post Market  May 22, 2002 January 9, 2013  2246013 LOVASTATIN TAB 20MG  PHARMASCIENCE INC  Marketed  July 12, 2002  Approved 2247011 SIMVASTATIN TAB 5MG  APOTEX INC  Marketed  December 20, 2002  Approved 2247012 SIMVASTATIN TAB 10MG  APOTEX INC  Marketed  December 20, 2002  Approved 2247014 SIMVASTATIN TAB 40MG  APOTEX INC  Marketed  December 20, 2002  Approved 2247015 SIMVASTATIN TAB 80MG  APOTEX INC  Marketed  December 20, 2002  Approved 2247013 SIMVASTATIN TAB 20MG  APOTEX INC  Marketed  December 20, 2002  Approved 2243824 PRAVASTATIN TAB 10MG  PRO DOC LIMITEE  Marketed  December 23, 2002   2243825 PRAVASTATIN TAB 20MG  PRO DOC LIMITEE  Marketed  December 23, 2002   2243826 PRAVASTATIN TAB 40MG  PRO DOC LIMITEE  Marketed  December 23, 2002   2246989 LOVASTATIN TAB 20MG  PHARMEL INC Marketed  January 7, 2003   2246990 LOVASTATIN TAB 40MG  PHARMEL INC Marketed  January 7, 2003   2247008 PRAVASTATIN TAB 10MG  TEVA CANADA LIMITED  Marketed  January 8, 2003  Approved 2247010 PRAVASTATIN TAB 40MG  TEVA CANADA LIMITED  Marketed  January 8, 2003  Approved 2247009 PRAVASTATIN TAB 20MG  TEVA CANADA LIMITED  Marketed  January 8, 2003  Approved 2246737 SIMVASTATIN TAB 20MG  MYLAN PHARMACEUTICALS ULC Marketed  January 15, 2003  Approved 2246585 SIMVASTATIN TAB 80MG  MYLAN PHARMACEUTICALS ULC Marketed  January 15, 2003  Approved 69  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2246582 SIMVASTATIN TAB 5MG  MYLAN PHARMACEUTICALS ULC Marketed  January 15, 2003  Approved 2246583 SIMVASTATIN TAB 10MG  MYLAN PHARMACEUTICALS ULC Marketed  January 15, 2003  Approved 2246584 SIMVASTATIN TAB 40MG  MYLAN PHARMACEUTICALS ULC Marketed  January 15, 2003  Approved 2246542 LOVASTATIN TAB 20MG  TEVA CANADA LIMITED Marketed  January 20, 2003  Approved 2246543 LOVASTATIN TAB 40MG  TEVA CANADA LIMITED Marketed  January 20, 2003  Approved 2246932 PRAVASTATIN TAB 40MG  RATIOPHARM INC DIVISION OF TEVA CANADA LIMITED Cancelled Post Market  February 3, 2003 September 19, 2014  2246930 PRAVASTATIN TAB 10MG  RATIOPHARM INC DIVISION OF TEVA CANADA LIMITED Cancelled Post Market  February 3, 2003 September 19, 2014  2246931 PRAVASTATIN TAB 20MG  RATIOPHARM INC DIVISION OF TEVA CANADA LIMITED Cancelled Post Market  February 3, 2003 September 19, 2014  2247163 ROSUVASTATIN TAB 20MG CRESTOR  ASTRAZENECA CANADA INC  Marketed  February 19, 2003  Approved 2247164 ROSUVASTATIN TAB 40MG CRESTOR  ASTRAZENECA CANADA INC  Marketed  February 19, 2003  Approved 2247162 ROSUVASTATIN TAB 10MG CRESTOR  ASTRAZENECA CANADA INC  Marketed  February 19, 2003  Approved 2247231 LOVASTATIN TAB 20MG  DOMINION PHARMACAL  Marketed  February 25, 2003   2247232 LOVASTATIN TAB 40MG  DOMINION PHARMACAL  Marketed  February 25, 2003   2247056 LOVASTATIN TAB 20MG  SANDOZ CANADA INCORPORATED  Marketed  February 27, 2003   2247057 LOVASTATIN TAB 40MG  SANDOZ CANADA INCORPORATED  Marketed  February 27, 2003   2247297 SIMVASTATIN TAB 5MG  LABORATOIRE RIVA INC Marketed  March 10, 2003  Approved 2247299 SIMVASTATIN TAB 20MG  LABORATOIRE RIVA INC Marketed  March 10, 2003  Approved 2247300 SIMVASTATIN TAB 40MG  LABORATOIRE RIVA INC Marketed  March 10, 2003  Approved 2247301 SIMVASTATIN TAB 80MG  LABORATOIRE RIVA INC Marketed  March 10, 2003  Approved 2247298 SIMVASTATIN TAB 10MG  LABORATOIRE RIVA INC Marketed  March 10, 2003  Approved 2248103 SIMVASTATIN TAB 5MG  ACTAVIS PHARMA COMPANY  Marketed  March 26, 2003  Approved 2247221 SIMVASTATIN TAB 10MG  PRO DOC LIMITEE  Marketed  April 10, 2003   2247222 SIMVASTATIN TAB 20MG  PRO DOC LIMITEE  Marketed  April 10, 2003   2247223 SIMVASTATIN TAB 40MG  PRO DOC LIMITEE  Marketed  April 10, 2003   2247655 PRAVASTATIN TAB 10MG  PHARMASCIENCE INC  Marketed  July 21, 2003  Approved 2247657 PRAVASTATIN TAB 40MG  PHARMASCIENCE INC  Marketed  July 21, 2003  Approved 2247656 PRAVASTATIN TAB 20MG  PHARMASCIENCE INC  Marketed  July 21, 2003  Approved 2247858 PRAVASTATIN TAB 40MG  SANDOZ CANADA INCORPORATED Marketed  August 12, 2003   70  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2247857 PRAVASTATIN TAB 20MG  SANDOZ CANADA INCORPORATED Marketed  August 12, 2003   2239955 LOVASTATIN TAB 20MG  PRO DOC LIMITEE  Cancelled Post Market  August 15, 2003 July 9, 2008  2239956 LOVASTATIN TAB 40MG  PRO DOC LIMITEE Cancelled Post Market  August 15, 2003 July 9, 2008  2247531 SIMVASTATIN TABLETS 5MG  PREMPHARM INC  Cancelled Post Market  September 3, 2003 August 5, 2005  2247535 SIMVASTATIN TABLETS 80MG  PREMPHARM INC  Cancelled Post Market  September 3, 2003 August 5, 2005  2247534 SIMVASTATIN TABLETS 40MG  PREMPHARM INC  Cancelled Post Market  September 3, 2003 August 5, 2005  2247532 SIMVASTATIN TABLETS 10MG  PREMPHARM INC  Cancelled Post Market  September 3, 2003 August 5, 2005  2247533 SIMVASTATIN TABLETS 20MG  PREMPHARM INC  Cancelled Post Market  September 3, 2003 August 5, 2005  2248104 SIMVASTATIN TAB 10MG  ACTAVIS PHARMA COMPANY  Marketed  September 26, 2003  Approved 2248105 SIMVASTATIN TAB 20MG  ACTAVIS PHARMA COMPANY  Marketed  September 26, 2003  Approved 2248106 SIMVASTATIN TAB 40MG  ACTAVIS PHARMA COMPANY  Marketed  September 26, 2003  Approved 2248107 SIMVASTATIN TAB 80MG  ACTAVIS PHARMA COMPANY  Marketed  September 26, 2003  Approved 2247068 SIMVASTATIN TAB 10MG  RATIOPHARM INC DIVISION OF TEVA CANADA LIMITED Cancelled Post Market  October 27, 2003 September 19, 2014  2247069 SIMVASTATIN TAB 20MG  RATIOPHARM INC DIVISION OF TEVA CANADA LIMITED Cancelled Post Market  October 27, 2003 September 19, 2014  2247070 SIMVASTATIN TAB 40MG  RATIOPHARM INC DIVISION OF TEVA CANADA LIMITED Cancelled Post Market  October 27, 2003 September 19, 2014  2247071 SIMVASTATIN TAB 80MG  RATIOPHARM INC DIVISION OF TEVA CANADA LIMITED Cancelled Post Market  October 27, 2003 September 19, 2014  2247067 SIMVASTATIN TAB 5MG  RATIOPHARM INC DIVISION OF TEVA CANADA LIMITED Cancelled Post Market  October 27, 2003 September 19, 2014  2247827 SIMVASTATIN TAB 5MG  SANDOZ CANADA INCORPORATED Marketed  October 29, 2003   2247831 SIMVASTATIN TAB 40MG  SANDOZ CANADA INCORPORATED Marketed  October 29, 2003   2247833 SIMVASTATIN TAB 80MG  SANDOZ CANADA INCORPORATED Marketed  October 29, 2003   2247828 SIMVASTATIN TAB 10MG  SANDOZ CANADA INCORPORATED Marketed  October 29, 2003   2247856 PRAVASTATIN TAB 10MG  SANDOZ CANADA INCORPORATED Marketed  December 8, 2003   2248182 PRAVASTATIN TAB 10MG  ACTAVIS PHARMA COMPANY  Marketed  December 9, 2003  Approved 2248183 PRAVASTATIN TAB 20MG  ACTAVIS PHARMA COMPANY  Marketed  December 9, 2003  Approved 2248184 PRAVASTATIN TAB 40MG  ACTAVIS PHARMA COMPANY  Marketed  December 9, 2003  Approved 2250152 SIMVASTATIN TAB 10MG  TEVA CANADA LIMITED Marketed  March 22, 2004  Approved 2250160 SIMVASTATIN TAB 20MG  TEVA CANADA LIMITED Marketed  March 22, 2004  Approved 2250144 SIMVASTATIN TAB 5MG  TEVA CANADA LIMITED Marketed  March 22, 2004  Approved 71  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2250179 SIMVASTATIN TAB 40MG  TEVA CANADA LIMITED Marketed  March 22, 2004  Approved 2250187 SIMVASTATIN TAB 80MG  TEVA CANADA LIMITED Marketed  March 22, 2004  Approved 2250330 PRAVASTATIN TAB 80MG PRAVACHOL BRISTOL-MYERS SQUIBB CANADA Approved March 26, 2004    2250527 FLUVASTATIN TAB 80MG LESCOL XL NOVARTIS PHARMACEUTICALS CANADA INC  Marketed  April 5, 2004  Approved 2252635 SIMVASTATIN TAB 10MG  PHARMASCIENCE INC  Marketed  May 7, 2004   2252619 SIMVASTATIN TAB 5MG  PHARMASCIENCE INC  Marketed  May 7, 2004   2252643 SIMVASTATIN TAB 20MG  PHARMASCIENCE INC  Marketed  May 7, 2004   2252651 SIMVASTATIN TAB 40MG  PHARMASCIENCE INC  Marketed  May 7, 2004   2252678 SIMVASTATIN TAB 80MG  PHARMASCIENCE INC  Marketed  May 7, 2004   2249731 PRAVASTATIN TAB 20MG  DOMINION PHARMACAL Marketed  May 12, 2004   2249758 PRAVASTATIN TAB 40MG  DOMINION PHARMACAL Marketed  May 12, 2004   2249723 PRAVASTATIN TAB 10MG  DOMINION PHARMACAL Marketed  May 12, 2004   2247072 SIMVASTATIN TAB 5MG  NU-PHARM INC  Cancelled Post Market  June 21, 2004 September 4, 2012  2247077 SIMVASTATIN TAB 40MG  NU-PHARM INC  Cancelled Post Market  June 21, 2004 September 4, 2012  2247078 SIMVASTATIN TAB 80MG  NU-PHARM INC  Cancelled Post Market  June 21, 2004 September 4, 2012  2247075 SIMVASTATIN TAB 10MG  NU-PHARM INC  Cancelled Post Market  June 21, 2004 September 4, 2012  2247076 SIMVASTATIN TAB 20MG  NU-PHARM INC  Cancelled Post Market  June 21, 2004 September 4, 2012  2247830 SIMVASTATIN TAB 20MG  SANDOZ CANADA INCORPORATED Marketed  June 23, 2004   2249782 PRAVASTATIN TAB 40MG  MELIAPHARM INC Cancelled Post Market  July 22, 2004 June 25, 2014  2249766 PRAVASTATIN TAB 10MG  MELIAPHARM INC Cancelled Post Market  July 22, 2004 June 25, 2014  2249774 PRAVASTATIN TAB 20MG  MELIAPHARM INC Cancelled Post Market  July 22, 2004 June 25, 2014  2248572 LOVASTATIN TAB 20MG  ACTAVIS PHARMA COMPANY  Marketed  July 28, 2004  Approved 2248573 LOVASTATIN TAB 40MG  ACTAVIS PHARMA COMPANY  Marketed  July 28, 2004  Approved 2253690 SIMVASTATIN TAB 5MG  PHARMEL INC Marketed  August 11, 2004   2253739 SIMVASTATIN TAB 80MG  PHARMEL INC Marketed  August 11, 2004   2253747 SIMVASTATIN TAB 5MG  DOMINION PHARMACAL Marketed  August 11, 2004   2253771 SIMVASTATIN TAB 40MG  DOMINION PHARMACAL Marketed  August 11, 2004   2253712 SIMVASTATIN TAB 20MG  PHARMEL INC Marketed  August 11, 2004   72  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2253763 SIMVASTATIN TAB 20MG  DOMINION PHARMACAL Marketed  August 11, 2004   2253755 SIMVASTATIN TAB 10MG  DOMINION PHARMACAL Marketed  August 11, 2004   2253704 SIMVASTATIN TAB 10MG  PHARMEL INC Marketed  August 11, 2004   2253720 SIMVASTATIN TAB 40MG  PHARMEL INC Marketed  August 11, 2004   2253798 SIMVASTATIN TAB 80MG  DOMINION PHARMACAL Marketed  August 11, 2004   2256878 PRAVASTATIN TAB 20MG  LABORATOIRE RIVA INC Cancelled Post Market  October 22, 2004 June 30, 2005  2256886 PRAVASTATIN TAB 40MG  LABORATOIRE RIVA INC Cancelled Post Market  October 22, 2004 June 30, 2005  2256851 PRAVASTATIN TAB 10MG  LABORATOIRE RIVA INC Cancelled Post Market  October 22, 2004 June 30, 2005  2231434 LOVASTATIN TAB 20MG  NU-PHARM INC  Marketed  December 17, 2004   2265656 SIMVASTATIN TAB 5MG  BAKER CUMMINS INC  Approved March 2, 2005    2265664 SIMVASTATIN TAB 10MG  BAKER CUMMINS INC  Approved March 2, 2005    2265699 SIMVASTATIN TAB 80MG  BAKER CUMMINS INC  Approved March 2, 2005    2265672 SIMVASTATIN TAB 20MG  BAKER CUMMINS INC  Approved March 2, 2005    2265680 SIMVASTATIN TAB 40MG  BAKER CUMMINS INC  Approved March 2, 2005    2265540 ROSUVASTATIN TAB 5MG CRESTOR  ASTRAZENECA CANADA INC Marketed  March 18, 2005  Approved 2257092 PRAVASTATIN TAB 10MG  MYLAN PHARMACEUTICALS ULC Marketed  April 7, 2005  Approved 2257114 PRAVASTATIN TAB 40MG  MYLAN PHARMACEUTICALS ULC Marketed  April 7, 2005  Approved 2257106 PRAVASTATIN TAB 20MG  MYLAN PHARMACEUTICALS ULC Marketed  April 7, 2005  Approved 2267969 LOVASTATIN TAB 20MG  RANBAXY PHARMACEUTICALS CANADA INC.  Cancelled Post Market  July 5, 2005 June 13, 2012  2267977 LOVASTATIN TAB 40MG  RANBAXY PHARMACEUTICALS CANADA INC.  Cancelled Post Market  July 5, 2005 June 13, 2012  2265885 SIMVASTATIN TAB 10MG  TARO PHARMACEUTICALS INC  Cancelled Post Market  August 10, 2005 April 1, 2014  2265893 SIMVASTATIN TAB 20MG  TARO PHARMACEUTICALS INC  Cancelled Post Market  August 10, 2005 April 1, 2014  2265907 SIMVASTATIN TAB 40MG  TARO PHARMACEUTICALS INC  Cancelled Post Market  August 10, 2005 April 1, 2014  2270250 PRAVASTATIN TAB 40MG  LABORATOIRE RIVA INC  Marketed  October 28, 2005   2270234 PRAVASTATIN TAB 10MG  LABORATOIRE RIVA INC  Marketed  October 28, 2005   2270242 PRAVASTATIN TAB 20MG  LABORATOIRE RIVA INC  Marketed  October 28, 2005   2269260 SIMVASTATIN TAB 10MG  PHARMASCIENCE INC  Marketed  November 3, 2005  Approved 2269295 SIMVASTATIN TAB 80MG  PHARMASCIENCE INC  Marketed  November 3, 2005  Approved 73  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2269287 SIMVASTATIN TAB 40MG  PHARMASCIENCE INC  Marketed  November 3, 2005  Approved 2269252 SIMVASTATIN TAB 5MG  PHARMASCIENCE INC  Marketed  November 3, 2005  Approved 2269279 SIMVASTATIN TAB 20MG  PHARMASCIENCE INC  Marketed  November 3, 2005  Approved 2270439 LOVASTATIN / NICOTINIC ACID 20 / 500 TAB MG ADVICOR SEPRACOR PHARMACEUTICALS INC Cancelled Post Market  November 8, 2005 August 2, 2012  2270447 LOVASTATIN / NICOTINIC ACID 20 / 1000 TAB MG ADVICOR SEPRACOR PHARMACEUTICALS INC Cancelled Post Market  November 9, 2005 August 2, 2012  2272288 LOVASTATIN TAB 20MG  LABORATOIRE RIVA INC  Marketed  December 1, 2005   2272296 LOVASTATIN TAB 40MG  LABORATOIRE RIVA INC  Marketed  December 7, 2005   2273241 AMLODIPINE BESYLATE / ATORVASTATIN 5/20 TAB MG CADUET PFIZER CANADA INC  Marketed  December 23, 2005   2273268 AMLODIPINE BESYLATE / ATORVASTATIN 5/40 TAB MG CADUET PFIZER CANADA INC  Marketed  December 23, 2005   2273292 AMLODIPINE BESYLATE / ATORVASTATIN 10/20 TAB MG CADUET PFIZER CANADA INC  Marketed  December 23, 2005   2273306 AMLODIPINE BESYLATE / ATORVASTATIN 10/40 TAB MG CADUET PFIZER CANADA INC  Marketed  December 23, 2005   2273314 AMLODIPINE BESYLATE / ATORVASTATIN 10/80 TAB MG CADUET PFIZER CANADA INC  Marketed  December 23, 2005   2273233 AMLODIPINE BESYLATE / ATORVASTATIN 5/10 TAB MG CADUET PFIZER CANADA INC  Marketed  December 23, 2005   2273284 AMLODIPINE BESYLATE / ATORVASTATIN 10/10 TAB MG CADUET PFIZER CANADA INC  Marketed  December 23, 2005   2273276 AMLODIPINE BESYLATE / ATORVASTATIN 5/80 TAB MG CADUET PFIZER CANADA INC  Marketed  December 23, 2005   2272415 PRAVASTATIN SODIUM / ACETYLSALICYLIC ACID 10/81 TAB MG  PALADIN LABS INC  Cancelled Post Market  January 13, 2006 July 31, 2015  2272423 PRAVASTATIN SODIUM / ACETYLSALICYLIC ACID 20/81 TAB MG  PALADIN LABS INC  Cancelled Post Market  January 13, 2006 July 31, 2015  2272431 PRAVASTATIN SODIUM / ACETYLSALICYLIC ACID 40/81 TAB MG  PALADIN LABS INC  Cancelled Post Market  January 13, 2006 July 31, 2015  2284421 PRAVASTATIN TAB 10MG  RANBAXY PHARMACEUTICALS CANADA INC. Marketed  May 16, 2006  Approved 2281546 SIMVASTATIN TAB 5MG  PHARMEL INC Marketed  July 21, 2006   2281554 SIMVASTATIN TAB 10MG  PHARMEL INC Marketed  July 21, 2006   2281562 SIMVASTATIN TAB 20MG  PHARMEL INC Marketed  July 21, 2006   2281570 SIMVASTATIN TAB 40MG  PHARMEL INC Marketed  July 21, 2006   2281589 SIMVASTATIN TAB 80MG  PHARMEL INC Marketed  July 21, 2006   2281619 SIMVASTATIN TAB 5MG  DOMINION PHARMACAL Marketed  August 2, 2006   2281627 SIMVASTATIN TAB 10MG  DOMINION PHARMACAL Marketed  August 2, 2006   2281651 SIMVASTATIN TAB 80MG  DOMINION PHARMACAL Marketed  August 2, 2006   2281635 SIMVASTATIN TAB 20MG  DOMINION PHARMACAL Marketed  August 2, 2006   74  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2281643 SIMVASTATIN TAB 40MG  DOMINION PHARMACAL Marketed  August 2, 2006   2293501 NIACIN / LOVASTATIN 1000/40 TAB 1MG ADVICOR SEPRACOR PHARMACEUTICALS INC Cancelled Post Market  May 15, 2007 July 26, 2010  2284456 PRAVASTATIN TAB 40MG  RANBAXY PHARMACEUTICALS CANADA INC. Marketed  May 16, 2007  Approved 2284448 PRAVASTATIN TAB 20MG  RANBAXY PHARMACEUTICALS CANADA INC. Marketed  May 16, 2007  Approved 2246014 LOVASTATIN TAB 40MG  PHARMASCIENCE INC  Marketed  July 16, 2007  Approved 2312670 LOVASTATIN TAB 20MG  PRO DOC LIMITEE Marketed  July 9, 2008   2312689 LOVASTATIN TAB 40MG  PRO DOC LIMITEE Marketed  July 9, 2008   2317451 PRAVASTATIN TAB 10MG  MINT PHARMACEUTICALS INC  Marketed  February 6, 2009  Approved 2317478 PRAVASTATIN TAB 20MG  MINT PHARMACEUTICALS INC  Marketed  February 6, 2009  Approved 2317486 PRAVASTATIN TAB 40MG  MINT PHARMACEUTICALS INC  Marketed  February 6, 2009  Approved 2300907 SIMVASTATIN TAB 5MG  ZYMCAN PHARMACEUTICALS INC Cancelled Post Market  February 26, 2009 June 16, 2014  2300915 SIMVASTATIN TAB 10MG  ZYMCAN PHARMACEUTICALS INC Cancelled Post Market  February 26, 2009 June 16, 2014  2301806 PRAVASTATIN TAB 20MG  SORRES PHARMA INC  Cancelled Post Market  February 26, 2009 June 20, 2014  2301814 PRAVASTATIN TAB 40MG  SORRES PHARMA INC  Cancelled Post Market  February 26, 2009 June 20, 2014  2300931 SIMVASTATIN TAB 40MG  ZYMCAN PHARMACEUTICALS INC Cancelled Post Market  February 26, 2009 June 16, 2014  2300974 SIMVASTATIN TAB 80MG  ZYMCAN PHARMACEUTICALS INC Cancelled Post Market  February 26, 2009 June 16, 2014  2300923 SIMVASTATIN TAB 20MG  ZYMCAN PHARMACEUTICALS INC Cancelled Post Market  February 26, 2009 June 16, 2014  2301792 PRAVASTATIN TAB 10MG  SORRES PHARMA INC  Cancelled Post Market  February 26, 2009 June 20, 2014  2247224 SIMVASTATIN TAB 80MG  PRO DOC LIMITEE  Marketed  June 25, 2009   2329174 SIMVASTATIN TAB 40MG  RANBAXY PHARMACEUTICALS CANADA INC.  Marketed  July 20, 2009  Approved 2329131 SIMVASTATIN TAB 5MG  RANBAXY PHARMACEUTICALS CANADA INC.  Marketed  July 20, 2009  Approved 2329158 SIMVASTATIN TAB 10MG  RANBAXY PHARMACEUTICALS CANADA INC.  Marketed  July 20, 2009  Approved 2329182 SIMVASTATIN TAB 80MG  RANBAXY PHARMACEUTICALS CANADA INC.  Marketed  July 20, 2009  Approved 2329166 SIMVASTATIN TAB 20MG  RANBAXY PHARMACEUTICALS CANADA INC.  Marketed  July 20, 2009  Approved 2331969 SIMVASTATIN TAB 5MG  RANBAXY PHARMACEUTICALS CANADA INC.  Approved August 13, 2009   Approved 2332019 SIMVASTATIN TAB 80MG  RANBAXY PHARMACEUTICALS CANADA INC.  Approved August 13, 2009   Approved 2331985 SIMVASTATIN TAB 10MG  RANBAXY PHARMACEUTICALS CANADA INC.  Approved August 13, 2009   Approved 2331993 SIMVASTATIN TAB 20MG  RANBAXY PHARMACEUTICALS CANADA INC.  Approved August 13, 2009   Approved 75  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2332000 SIMVASTATIN TAB 40MG  RANBAXY PHARMACEUTICALS CANADA INC.  Approved August 13, 2009   Approved 2332191 PRAVASTATIN TAB 10MG  RANBAXY PHARMACEUTICALS CANADA INC.  Approved August 20, 2009    2332213 PRAVASTATIN TAB 40MG  RANBAXY PHARMACEUTICALS CANADA INC.  Approved August 20, 2009    2332205 PRAVASTATIN TAB 20MG  RANBAXY PHARMACEUTICALS CANADA INC.  Approved August 20, 2009    2284723 SIMVASTATIN TAB 5MG  SANIS HEALTH INC  Marketed  October 22, 2009  Approved 2284731 SIMVASTATIN TAB 10MG  SANIS HEALTH INC  Marketed  October 22, 2009  Approved 2284774 SIMVASTATIN TAB 80MG  SANIS HEALTH INC  Marketed  October 22, 2009  Approved 2284758 SIMVASTATIN TAB 20MG  SANIS HEALTH INC  Marketed  October 22, 2009  Approved 2284766 SIMVASTATIN TAB 40MG  SANIS HEALTH INC  Marketed  October 22, 2009  Approved 2342332 PRAVASTATIN TAB 20MG  COBALT PHARMACEUTICALS COMPANY Approved January 26, 2010    2342340 PRAVASTATIN TAB 40MG  COBALT PHARMACEUTICALS COMPANY Approved January 26, 2010    2342472 SIMVASTATIN TAB 20MG  COBALT PHARMACEUTICALS COMPANY Approved January 26, 2010    2342480 SIMVASTATIN TAB 40MG  COBALT PHARMACEUTICALS COMPANY Approved January 26, 2010    2342499 SIMVASTATIN TAB 80MG  COBALT PHARMACEUTICALS COMPANY Approved January 26, 2010    2342324 PRAVASTATIN TAB 10MG  COBALT PHARMACEUTICALS COMPANY Approved January 26, 2010    2342464 SIMVASTATIN TAB 10MG  COBALT PHARMACEUTICALS COMPANY Approved January 26, 2010    2342456 SIMVASTATIN TAB 5MG  COBALT PHARMACEUTICALS COMPANY Approved January 26, 2010    2344335 LOVASTATIN TAB 20MG  COBALT PHARMACEUTICALS COMPANY  Approved February 15, 2010    2344343 LOVASTATIN TAB 40MG  COBALT PHARMACEUTICALS COMPANY  Approved February 15, 2010    2331047 SIMVASTATIN TAB 20MG  JAMP PHARMA CORPORATION  Cancelled Post Market  March 12, 2010 July 8, 2013  2331039 SIMVASTATIN TAB 10MG  JAMP PHARMA CORPORATION  Cancelled Post Market  March 12, 2010 July 8, 2013  2331063 SIMVASTATIN TAB 80MG  JAMP PHARMA CORPORATION  Cancelled Post Market  March 12, 2010 July 8, 2013  2331055 SIMVASTATIN TAB 40MG  JAMP PHARMA CORPORATION  Cancelled Post Market  March 12, 2010 July 8, 2013  2331020 SIMVASTATIN TAB 5MG  JAMP PHARMA CORPORATION  Marketed  March 23, 2010   2330954 PRAVASTATIN TAB 10MG  JAMP PHARMA CORPORATION  Marketed  April 1, 2010  Approved 2330970 PRAVASTATIN TAB 40MG  JAMP PHARMA CORPORATION  Marketed  April 1, 2010  Approved 2330962 PRAVASTATIN TAB 20MG  JAMP PHARMA CORPORATION  Marketed  April 1, 2010  Approved 2295288 ATORVASTATIN TAB 20MG  APOTEX INC  Marketed  May 19, 2010  Approved 76  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2302675 ATORVASTATIN TAB 10MG  NOVOPHARM LIMITED Cancelled Post Market  May 19, 2010 October 26, 2015  2302691 ATORVASTATIN TAB 40MG  NOVOPHARM LIMITED Cancelled Post Market  May 19, 2010 October 26, 2015  2302713 ATORVASTATIN TAB 80MG  NOVOPHARM LIMITED Cancelled Post Market  May 19, 2010 October 26, 2015  2310910 ATORVASTATIN TAB 40MG  ACTAVIS PHARMA COMPANY Marketed  May 19, 2010  Approved 2313448 ATORVASTATIN TAB 10MG  PHARMASCIENCE INC Marketed  May 19, 2010   2313456 ATORVASTATIN TAB 20MG  PHARMASCIENCE INC Marketed  May 19, 2010   2313464 ATORVASTATIN TAB 40MG  PHARMASCIENCE INC Marketed  May 19, 2010   2313472 ATORVASTATIN TAB 80MG  PHARMASCIENCE INC Marketed  May 19, 2010   2324946 ATORVASTATIN TAB 10MG  SANDOZ CANADA INCORPORATED Marketed  May 19, 2010  Approved 2333724 ATORVASTATIN TAB 10MG  PHARMASCIENCE INC Approved May 19, 2010    2333732 ATORVASTATIN TAB 20MG  PHARMASCIENCE INC Approved May 19, 2010    2350297 ATORVASTATIN TAB 10MG  TEVA CANADA LIMITED Marketed  May 19, 2010  Approved 2350327 ATORVASTATIN TAB 40MG  TEVA CANADA LIMITED Marketed  May 19, 2010  Approved 2295296 ATORVASTATIN TAB 40MG  APOTEX INC  Marketed  May 19, 2010  Approved 2310899 ATORVASTATIN TAB 10MG  ACTAVIS PHARMA COMPANY Marketed  May 19, 2010  Approved 2310929 ATORVASTATIN TAB 80MG  ACTAVIS PHARMA COMPANY Marketed  May 19, 2010  Approved 2333740 ATORVASTATIN TAB 40MG  PHARMASCIENCE INC Approved May 19, 2010    2348632 ATORVASTATIN TAB 20MG  RATIOPHARM INC DIVISION OF TEVA CANADA LIMITED Cancelled Post Market  May 19, 2010 June 27, 2013  2348640 ATORVASTATIN TAB 40MG  RATIOPHARM INC DIVISION OF TEVA CANADA LIMITED Cancelled Post Market  May 19, 2010 June 27, 2013  2350335 ATORVASTATIN TAB 80MG  TEVA CANADA LIMITED Marketed  May 19, 2010  Approved 2295261 ATORVASTATIN TAB 10MG  APOTEX INC  Marketed  May 19, 2010  Approved 2295318 ATORVASTATIN TAB 80MG  APOTEX INC  Marketed  May 19, 2010  Approved 2302683 ATORVASTATIN TAB 20MG  NOVOPHARM LIMITED Cancelled Post Market  May 19, 2010 October 26, 2015  2310902 ATORVASTATIN TAB 20MG  ACTAVIS PHARMA COMPANY Marketed  May 19, 2010  Approved 2324954 ATORVASTATIN TAB 20MG  SANDOZ CANADA INCORPORATED Marketed  May 19, 2010  Approved 2324962 ATORVASTATIN TAB 40MG  SANDOZ CANADA INCORPORATED Marketed  May 19, 2010  Approved 2324970 ATORVASTATIN TAB 80MG  SANDOZ CANADA INCORPORATED Marketed  May 19, 2010  Approved 2333759 ATORVASTATIN TAB 80MG  PHARMASCIENCE INC Approved May 19, 2010    77  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2348624 ATORVASTATIN TAB 10MG  PRO DOC LIMITEE Marketed  May 19, 2010   2348659 ATORVASTATIN TAB 80MG  RATIOPHARM INC DIVISION OF TEVA CANADA LIMITED Cancelled Post Market  May 19, 2010 June 27, 2013  2350319 ATORVASTATIN TAB 20MG  TEVA CANADA LIMITED Marketed  May 19, 2010  Approved 2288354 ATORVASTATIN TAB 20MG  GENMED A DIVISION OF PFIZER CANADA INC  Marketed  May 19, 2010  Approved 2288362 ATORVASTATIN TAB 40MG  GENMED A DIVISION OF PFIZER CANADA INC  Marketed  May 20, 2010  Approved 2288370 ATORVASTATIN TAB 80MG  GENMED A DIVISION OF PFIZER CANADA INC  Marketed  May 20, 2010  Approved 2313723 ATORVASTATIN TAB 40MG  RANBAXY PHARMACEUTICALS CANADA INC.  Marketed  May 20, 2010  Approved 2313758 ATORVASTATIN TAB 80MG  RANBAXY PHARMACEUTICALS CANADA INC.  Marketed  May 20, 2010  Approved 2288346 ATORVASTATIN TAB 10MG  GENMED A DIVISION OF PFIZER CANADA INC  Marketed  May 20, 2010  Approved 2313707 ATORVASTATIN TAB 10MG  RANBAXY PHARMACEUTICALS CANADA INC.  Marketed  May 20, 2010  Approved 2313715 ATORVASTATIN TAB 20MG  RANBAXY PHARMACEUTICALS CANADA INC.  Marketed  May 20, 2010  Approved 2346486 ATORVASTATIN TAB 10MG  PRO DOC LIMITEE Marketed  May 21, 2010   2346508 ATORVASTATIN TAB 40MG  PRO DOC LIMITEE Marketed  May 21, 2010   2346516 ATORVASTATIN TAB 80MG  PRO DOC LIMITEE Marketed  May 21, 2010   2346494 ATORVASTATIN TAB 20MG  PRO DOC LIMITEE Marketed  May 21, 2010   2348721 ATORVASTATIN TAB 40MG  SANIS HEALTH INC Marketed  May 27, 2010  Approved 2348713 ATORVASTATIN TAB 20MG  SANIS HEALTH INC Marketed  May 27, 2010  Approved 2348705 ATORVASTATIN TAB 10MG  SANIS HEALTH INC Marketed  May 27, 2010  Approved 2348748 ATORVASTATIN TAB 80MG  SANIS HEALTH INC Marketed  May 27, 2010  Approved 2351765 ATORVASTATIN TAB 20MG  PRO DOC LIMITEE  Cancelled Post Market  June 1, 2010 July 27, 2011  2351773 ATORVASTATIN TAB 40MG  PRO DOC LIMITEE  Cancelled Post Market  June 1, 2010 July 27, 2011  2351781 ATORVASTATIN TAB 80MG  PRO DOC LIMITEE  Cancelled Post Market  June 1, 2010 July 27, 2011  2351757 ATORVASTATIN TAB 10MG  PRO DOC LIMITEE  Cancelled Post Market  June 1, 2010 July 27, 2011  2343169 SIMVASTATIN TAB 20MG  MELIAPHARM INC Cancelled Post Market  June 11, 2010 June 25, 2014  2343177 SIMVASTATIN TAB 40MG  MELIAPHARM INC Cancelled Post Market  June 11, 2010 June 25, 2014  2343142 SIMVASTATIN TAB 5MG  MELIAPHARM INC Cancelled Post Market  June 11, 2010 June 25, 2014  2343185 SIMVASTATIN TAB 80MG  MELIAPHARM INC Cancelled Post Market  June 11, 2010 June 25, 2014  2343150 SIMVASTATIN TAB 10MG  MELIAPHARM INC Cancelled Post Market  June 11, 2010 June 25, 2014  78  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2353229 LOVASTATIN TAB 20MG  SANIS HEALTH INC  Marketed  July 26, 2010  Approved 2353237 LOVASTATIN TAB 40MG  SANIS HEALTH INC  Marketed  July 26, 2010  Approved 2355647 ATORVASTATIN TAB 80MG  DOMINION PHARMACAL Approved August 25, 2010    2274507 PRAVASTATIN TAB 10MG  SANDOZ CANADA INCORPORATED Approved November 3, 2010    2274515 PRAVASTATIN TAB 20MG  SANDOZ CANADA INCORPORATED Approved November 3, 2010    2274523 PRAVASTATIN TAB 40MG  SANDOZ CANADA INCORPORATED Approved November 3, 2010    2356546 PRAVASTATIN TAB 10MG  SANIS HEALTH INC Marketed  November 23, 2010  Approved 2356554 PRAVASTATIN TAB 20MG  SANIS HEALTH INC Marketed  November 23, 2010  Approved 2356562 PRAVASTATIN TAB 40MG  SANIS HEALTH INC Marketed  December 1, 2010  Approved 2355620 ATORVASTATIN TAB 20MG  DOMINION PHARMACAL Marketed  December 17, 2010   2355639 ATORVASTATIN TAB 40MG  DOMINION PHARMACAL Marketed  December 17, 2010   2355612 ATORVASTATIN TAB 10MG  DOMINION PHARMACAL Marketed  December 17, 2010   2372940 SIMVASTATIN TAB 10MG  MINT PHARMACEUTICALS INC Marketed  July 9, 2011  Approved 2362759 AMLODIPINE/ATORVASTATIN 5/10 TAB MG GD-AMLODIPINE/ATORVASTATIN GENMED A DIVISION OF PFIZER CANADA INC Marketed  July 25, 2011   2362767 AMLODIPINE/ATORVASTATIN 5/20 TAB MG GD-AMLODIPINE/ATORVASTATIN GENMED A DIVISION OF PFIZER CANADA INC Marketed  July 25, 2011   2362783 AMLODIPINE/ATORVASTATIN 5/80 TAB MG GD-AMLODIPINE/ATORVASTATIN GENMED A DIVISION OF PFIZER CANADA INC Marketed  July 25, 2011   2362791 AMLODIPINE/ATORVASTATIN 10/10 TAB MG GD-AMLODIPINE/ATORVASTATIN GENMED A DIVISION OF PFIZER CANADA INC Marketed  July 25, 2011   2362775 AMLODIPINE/ATORVASTATIN 5/40 TAB MG GD-AMLODIPINE/ATORVASTATIN GENMED A DIVISION OF PFIZER CANADA INC Marketed  July 25, 2011   2362805 AMLODIPINE/ATORVASTATIN  10/20 TAB MG GD-AMLODIPINE/ATORVASTATIN GENMED A DIVISION OF PFIZER CANADA INC Marketed  July 25, 2011   2362813 AMLODIPINE/ATORVASTATIN  10/40 TAB MG GD-AMLODIPINE/ATORVASTATIN GENMED A DIVISION OF PFIZER CANADA INC Marketed  July 25, 2011   2362821 AMLODIPINE/ATORVASTATIN 10/80 TAB MG GD-AMLODIPINE/ATORVASTATIN GENMED A DIVISION OF PFIZER CANADA INC Marketed  July 25, 2011   2364239 LOVASTATIN TAB 20MG  AVANSTRA INC Cancelled Post Market  August 18, 2011 August 21, 2014  2364247 LOVASTATIN TAB 40MG  AVANSTRA INC Cancelled Post Market  August 18, 2011 August 21, 2014  2372959 SIMVASTATIN TAB 20MG  MINT PHARMACEUTICALS INC Marketed  September 7, 2011  Approved 2372967 SIMVASTATIN TAB 40MG  MINT PHARMACEUTICALS INC Marketed  September 7, 2011  Approved 2372932 SIMVASTATIN TAB 5MG  MINT PHARMACEUTICALS INC Marketed  September 7, 2011  Approved 2372975 SIMVASTATIN TAB 80MG  MINT PHARMACEUTICALS INC Marketed  September 7, 2011  Approved 2364018 SIMVASTATIN TAB 5MG  AVANSTRA INC Cancelled Post Market  October 11, 2011 August 21, 2014  79  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2364034 SIMVASTATIN TAB 20MG  AVANSTRA INC Cancelled Post Market  October 11, 2011 August 21, 2014  2364042 SIMVASTATIN TAB 40MG  AVANSTRA INC Cancelled Post Market  October 11, 2011 August 21, 2014  2364425 PRAVASTATIN TAB 20MG  AVANSTRA INC Cancelled Post Market  October 11, 2011 December 12, 2011  2364417 PRAVASTATIN TAB 10MG  AVANSTRA INC Cancelled Post Market  October 11, 2011 December 12, 2011  2364026 SIMVASTATIN TAB 10MG  AVANSTRA INC Cancelled Post Market  October 11, 2011 August 21, 2014  2364050 SIMVASTATIN TAB 80MG  AVANSTRA INC Cancelled Post Market  October 11, 2011 August 21, 2014  2364433 PRAVASTATIN TAB 40MG  AVANSTRA INC Cancelled Post Market  October 11, 2011 December 12, 2011  2373211 ATORVASTATIN TAB 20MG  MYLAN PHARMACEUTICALS ULC  Cancelled Post Market  October 17, 2011 May 20, 2016  2373238 ATORVASTATIN TAB 40MG  MYLAN PHARMACEUTICALS ULC  Cancelled Post Market  October 17, 2011 May 20, 2016 Approved 2373246 ATORVASTATIN TAB 80MG  MYLAN PHARMACEUTICALS ULC  Cancelled Post Market  October 17, 2011 May 20, 2016  2373203 ATORVASTATIN TAB 10MG  MYLAN PHARMACEUTICALS ULC  Cancelled Post Market  November 28, 2011 May 20, 2016  2364476 ATORVASTATIN TAB 40MG  AVANSTRA INC Cancelled Post Market  November 28, 2011 August 21, 2014  2364441 ATORVASTATIN TAB 10MG  AVANSTRA INC Cancelled Post Market  November 28, 2011 August 21, 2014  2364468 ATORVASTATIN TAB 20MG  AVANSTRA INC Cancelled Post Market  November 28, 2011 August 21, 2014  2364484 ATORVASTATIN TAB 80MG  AVANSTRA INC Cancelled Post Market  November 28, 2011 August 21, 2014  2376040 SIMVASTATIN TAB 5MG  SEPTA PHARMACEUTICALS INC Approved December 12, 2011   Approved 2376059 SIMVASTATIN TAB 10MG  SEPTA PHARMACEUTICALS INC Approved December 12, 2011   Approved 2376075 SIMVASTATIN TAB 40MG  SEPTA PHARMACEUTICALS INC Approved December 12, 2011   Approved 2376083 SIMVASTATIN TAB 80MG  SEPTA PHARMACEUTICALS INC Approved December 12, 2011   Approved 2376067 SIMVASTATIN TAB 20MG  SEPTA PHARMACEUTICALS INC Approved December 12, 2011   Approved 2375613 SIMVASTATIN TAB 20MG  JAMP PHARMA CORPORATION Marketed  January 9, 2012  Approved 2375648 SIMVASTATIN TAB 80MG  JAMP PHARMA CORPORATION Marketed  January 9, 2012  Approved 2375605 SIMVASTATIN TAB 10MG  JAMP PHARMA CORPORATION Marketed  January 9, 2012  Approved 2375621 SIMVASTATIN TAB 40MG  JAMP PHARMA CORPORATION Marketed  January 9, 2012  Approved 2375591 SIMVASTATIN TAB 5MG  JAMP PHARMA CORPORATION Marketed  January 9, 2012  Approved 2376288 ATORVASTATIN TAB 10MG  Q-GEN PHARMACEUTICALS INC  Approved January 16, 2012    2377314 SIMVASTATIN TAB 40MG  NT PHARMA CANADA LTD  Approved January 16, 2012    2376318 ATORVASTATIN TAB 40MG  Q-GEN PHARMACEUTICALS INC  Approved January 16, 2012    80  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2377322 SIMVASTATIN TAB 80MG  NT PHARMA CANADA LTD  Approved January 16, 2012    2376296 ATORVASTATIN TAB 20MG  Q-GEN PHARMACEUTICALS INC  Approved January 16, 2012    2376326 ATORVASTATIN TAB 80MG  Q-GEN PHARMACEUTICALS INC  Approved January 16, 2012    2377284 SIMVASTATIN TAB 5MG  NT PHARMA CANADA LTD  Approved January 16, 2012    2377292 SIMVASTATIN TAB 10MG  NT PHARMA CANADA LTD  Approved January 16, 2012    2377306 SIMVASTATIN TAB 20MG  NT PHARMA CANADA LTD  Approved January 16, 2012    2338874 SIMVASTATIN TAB 10MG  QD PHARMACEUTICALS ULC  Cancelled Post Market  February 3, 2012 August 21, 2015  2338882 SIMVASTATIN TAB 20MG  QD PHARMACEUTICALS ULC  Cancelled Post Market  February 3, 2012 August 21, 2015  2338890 SIMVASTATIN TAB 40MG  QD PHARMACEUTICALS ULC  Cancelled Post Market  February 3, 2012 August 21, 2015  2378892 SIMVASTATIN TAB 10MG  ODAN LABORATORIES LTD Cancelled Post Market  February 14, 2012 November 12, 2014  2378914 SIMVASTATIN TAB 40MG  ODAN LABORATORIES LTD Cancelled Post Market  February 14, 2012 November 12, 2014  2378884 SIMVASTATIN TAB 5MG  ODAN LABORATORIES LTD Cancelled Post Market  February 14, 2012 November 12, 2014  2378906 SIMVASTATIN TAB 20MG  ODAN LABORATORIES LTD Cancelled Post Market  February 14, 2012 November 12, 2014  2378922 SIMVASTATIN TAB 80MG  ODAN LABORATORIES LTD Cancelled Post Market  February 14, 2012 November 17, 2014  2379503 SIMVASTATIN TAB 5MG  BENTEC PHARMA INC Approved February 22, 2012    2379538 SIMVASTATIN TAB 20MG  BENTEC PHARMA INC Approved February 22, 2012    2379546 SIMVASTATIN TAB 40MG  BENTEC PHARMA INC Approved February 22, 2012    2379554 SIMVASTATIN TAB 80MG  BENTEC PHARMA INC Approved February 22, 2012    2338726 ROSUVASTATIN TAB 5MG  SANDOZ CANADA INCORPORATED  Marketed  March 15, 2012  Approved 2338742 ROSUVASTATIN TAB 20MG  SANDOZ CANADA INCORPORATED  Marketed  March 15, 2012  Approved 2354608 ROSUVASTATIN TAB 5MG  TEVA CANADA LIMITED Marketed  March 15, 2012  Approved 2354616 ROSUVASTATIN TAB 10MG  TEVA CANADA LIMITED Marketed  March 15, 2012  Approved 2354624 ROSUVASTATIN TAB 20MG  TEVA CANADA LIMITED Marketed  March 15, 2012  Approved 2354632 ROSUVASTATIN TAB 40MG  TEVA CANADA LIMITED Marketed  March 15, 2012  Approved 2378523 ROSUVASTATIN TAB 5MG  PHARMASCIENCE INC Marketed  March 15, 2012  Approved 2378566 ROSUVASTATIN TAB 40MG  PHARMASCIENCE INC Marketed  March 15, 2012  Approved 2381273 ROSUVASTATIN TAB 10MG  MYLAN PHARMACEUTICALS ULC Marketed  March 15, 2012  Approved 2381281 ROSUVASTATIN TAB 20MG  MYLAN PHARMACEUTICALS ULC Marketed  March 15, 2012  Approved 81  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2338750 ROSUVASTATIN TAB 40MG  SANDOZ CANADA INCORPORATED  Marketed  March 15, 2012  Approved 2378558 ROSUVASTATIN TAB 20MG  PHARMASCIENCE INC Marketed  March 15, 2012  Approved 2381265 ROSUVASTATIN TAB 5MG  MYLAN PHARMACEUTICALS ULC Marketed  March 15, 2012  Approved 2338734 ROSUVASTATIN TAB 10MG  SANDOZ CANADA INCORPORATED  Marketed  March 15, 2012  Approved 2378531 ROSUVASTATIN TAB 10MG  PHARMASCIENCE INC Marketed  March 15, 2012  Approved 2339773 ROSUVASTATIN TAB 10MG  ACTAVIS PHARMA COMPANY Marketed  March 16, 2012  Approved 2339781 ROSUVASTATIN TAB 20MG  ACTAVIS PHARMA COMPANY Marketed  March 16, 2012  Approved 2339803 ROSUVASTATIN TAB 40MG  ACTAVIS PHARMA COMPANY Marketed  March 16, 2012  Approved 2339765 ROSUVASTATIN TAB 5MG  ACTAVIS PHARMA COMPANY Marketed  March 16, 2012  Approved 2337975 ROSUVASTATIN TAB 5MG  APOTEX INC  Marketed  April 2, 2012  Approved 2337991 ROSUVASTATIN TAB 20MG  APOTEX INC  Marketed  April 2, 2012  Approved 2338009 ROSUVASTATIN TAB 40MG  APOTEX INC  Marketed  April 2, 2012  Approved 2382652 ROSUVASTATIN TAB 10MG  RANBAXY PHARMACEUTICALS CANADA INC Marketed  April 2, 2012  Approved 2382660 ROSUVASTATIN TAB 20MG  RANBAXY PHARMACEUTICALS CANADA INC Marketed  April 2, 2012  Approved 2337983 ROSUVASTATIN TAB 10MG  APOTEX INC  Marketed  April 2, 2012  Approved 2382644 ROSUVASTATIN TAB 5MG  RANBAXY PHARMACEUTICALS CANADA INC Marketed  April 2, 2012  Approved 2382679 ROSUVASTATIN TAB 40MG  RANBAXY PHARMACEUTICALS CANADA INC Marketed  April 2, 2012  Approved 2381303 ROSUVASTATIN TAB 40MG  MYLAN PHARMACEUTICALS ULC Marketed  April 17, 2012  Approved 2380013 ROSUVASTATIN TAB 5MG  LABORATOIRE RIVA INC  Marketed  June 11, 2012   2380056 ROSUVASTATIN TAB 10MG  LABORATOIRE RIVA INC  Marketed  June 11, 2012  Approved 2386321 SIMVASTATIN TAB 40MG  SIVEM PHARMACEUTICALS ULC Marketed  June 11, 2012  Approved 2386291 SIMVASTATIN TAB 5MG  SIVEM PHARMACEUTICALS ULC Marketed  June 11, 2012  Approved 2386305 SIMVASTATIN TAB 10MG  SIVEM PHARMACEUTICALS ULC Marketed  June 11, 2012  Approved 2386348 SIMVASTATIN TAB 80MG  SIVEM PHARMACEUTICALS ULC Marketed  June 11, 2012  Approved 2386313 SIMVASTATIN TAB 20MG  SIVEM PHARMACEUTICALS ULC Marketed  June 12, 2012  Approved 2380102 ROSUVASTATIN TAB 40MG  LABORATOIRE RIVA INC  Marketed  June 13, 2012  Approved 2380064 ROSUVASTATIN TAB 20MG  LABORATOIRE RIVA INC  Marketed  June 13, 2012  Approved 2386739 ROSUVASTATIN TAB 40MG  DOMINION PHARMACAL Approved June 19, 2012    82  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2387891 ATORVASTATIN TAB 10MG  SIVEM PHARMACEUTICALS ULC Approved June 26, 2012   Approved 2387913 ATORVASTATIN TAB 40MG  SIVEM PHARMACEUTICALS ULC Approved June 26, 2012   Approved 2387905 ATORVASTATIN TAB 20MG  SIVEM PHARMACEUTICALS ULC Approved June 26, 2012   Approved 2387921 ATORVASTATIN TAB 80MG  SIVEM PHARMACEUTICALS ULC Approved June 26, 2012   Approved 2389037 ROSUVASTATIN TAB 5MG  SIVEM PHARMACEUTICALS ULC Marketed  July 11, 2012  Approved 2389045 ROSUVASTATIN TAB 10MG  SIVEM PHARMACEUTICALS ULC Marketed  July 11, 2012  Approved 2389053 ROSUVASTATIN TAB 20MG  SIVEM PHARMACEUTICALS ULC Marketed  July 11, 2012  Approved 2389061 ROSUVASTATIN TAB 40MG  SIVEM PHARMACEUTICALS ULC Marketed  July 11, 2012  Approved 2389541 ATORVASTATIN TAB 10MG  RANBAXY PHARMACEUTICALS CANADA INC. Approved July 17, 2012    2389584 ATORVASTATIN TAB 80MG  RANBAXY PHARMACEUTICALS CANADA INC. Approved July 17, 2012    2389568 ATORVASTATIN TAB 20MG  RANBAXY PHARMACEUTICALS CANADA INC. Approved July 17, 2012    2389576 ATORVASTATIN TAB 40MG  RANBAXY PHARMACEUTICALS CANADA INC. Approved July 17, 2012    2389401 ROSUVASTATIN TAB 10MG  RANBAXY PHARMACEUTICALS CANADA INC. Approved July 18, 2012    2389436 ROSUVASTATIN TAB 40MG  RANBAXY PHARMACEUTICALS CANADA INC. Approved July 18, 2012    2389355 ROSUVASTATIN TAB 5MG  RANBAXY PHARMACEUTICALS CANADA INC. Approved July 18, 2012    2389428 ROSUVASTATIN TAB 20MG  RANBAXY PHARMACEUTICALS CANADA INC. Approved July 18, 2012    2381176 ROSUVASTATIN TAB 5MG  PRO DOC LIMITEE  Marketed  July 19, 2012   2381184 ROSUVASTATIN TAB 10MG  PRO DOC LIMITEE  Marketed  July 19, 2012   2381206 ROSUVASTATIN TAB 40MG  PRO DOC LIMITEE  Marketed  July 19, 2012   2381192 ROSUVASTATIN TAB 20MG  PRO DOC LIMITEE  Marketed  July 19, 2012   2389703 PRAVASTATIN TAB 10MG  SIVEM PHARMACEUTICALS ULC Marketed  July 23, 2012  Approved 2389738 PRAVASTATIN TAB 20MG  SIVEM PHARMACEUTICALS ULC Marketed  July 23, 2012  Approved 2389746 PRAVASTATIN TAB 40MG  SIVEM PHARMACEUTICALS ULC Marketed  July 23, 2012  Approved 2391066 ATORVASTATIN TAB 20MG  JAMP PHARMA CORPORATION  Marketed  September 10, 2012  Approved 2391082 ATORVASTATIN TAB 80MG  JAMP PHARMA CORPORATION  Marketed  September 10, 2012  Approved 2391058 ATORVASTATIN TAB 10MG  JAMP PHARMA CORPORATION  Marketed  September 10, 2012  Approved 2391074 ATORVASTATIN TAB 40MG  JAMP PHARMA CORPORATION  Marketed  September 10, 2012  Approved 2391260 ROSUVASTATIN TAB 10MG  JAMP PHARMA CORPORATION  Marketed  September 24, 2012  Approved 83  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2391252 ROSUVASTATIN TAB 5MG  JAMP PHARMA CORPORATION  Marketed  September 24, 2012  Approved 2391287 ROSUVASTATIN TAB 40MG  JAMP PHARMA CORPORATION  Marketed  September 24, 2012  Approved 2391279 ROSUVASTATIN TAB 20MG  JAMP PHARMA CORPORATION  Marketed  September 24, 2012  Approved 2299224 FLUVASTATIN CAP 20MG  TEVA CANADA LIMITED Marketed  December 11, 2012  Approved 2299232 FLUVASTATIN CAP 40MG  TEVA CANADA LIMITED Marketed  December 11, 2012  Approved 2375036 SIMVASTATIN TAB 5MG  MARCAN PHARMACEUTICALS INC  Marketed  December 20, 2012  Approved 2375052 SIMVASTATIN TAB 20MG  MARCAN PHARMACEUTICALS INC  Marketed  December 20, 2012  Approved 2375060 SIMVASTATIN TAB 40MG  MARCAN PHARMACEUTICALS INC  Marketed  December 20, 2012  Approved 2375044 SIMVASTATIN TAB 10MG  MARCAN PHARMACEUTICALS INC  Marketed  December 20, 2012  Approved 2375079 SIMVASTATIN TAB 80MG  MARCAN PHARMACEUTICALS INC  Marketed  December 20, 2012  Approved 2399512 ATORVASTATIN TAB 80MG  DOMINION PHARMACAL Approved January 2, 2013    2396432 ATORVASTATIN TAB 20MG  APOTEX INC  Marketed  January 7, 2013   2396440 ATORVASTATIN TAB 40MG  APOTEX INC  Marketed  January 7, 2013   2396459 ATORVASTATIN TAB 80MG  APOTEX INC  Marketed  January 7, 2013   2396424 ATORVASTATIN TAB 10MG  APOTEX INC  Marketed  January 7, 2013   2400774 AMLODIPINE/ATORVASTATIN 5/20 TAB MG  MYLAN PHARMACEUTICALS ULC Approved January 31, 2013    2400804 AMLODIPINE/ATORVASTATIN 10/10 TAB MG  MYLAN PHARMACEUTICALS ULC Approved January 31, 2013    2400812 AMLODIPINE/ATORVASTATIN 10/20 TAB MG  MYLAN PHARMACEUTICALS ULC Approved January 31, 2013    2400820 AMLODIPINE/ATORVASTATIN 10/40 TAB MG  MYLAN PHARMACEUTICALS ULC Approved January 31, 2013    2400839 AMLODIPINE/ATORVASTATIN 10/80 TAB MG  MYLAN PHARMACEUTICALS ULC Approved January 31, 2013    2400758 AMLODIPINE/ATORVASTATIN  5/10 TAB MG  MYLAN PHARMACEUTICALS ULC Approved January 31, 2013    2400782 AMLODIPINE/ATORVASTATIN 5/40 TAB MG  MYLAN PHARMACEUTICALS ULC Approved January 31, 2013    2400790 AMLODIPINE/ATORVASTATIN 5/80 TAB MG  MYLAN PHARMACEUTICALS ULC Approved January 31, 2013    2400235 FLUVASTATIN CAP 20MG  SANDOZ CANADA INCORPORATED Marketed  February 15, 2013  Approved 2400243 FLUVASTATIN CAP 40MG  SANDOZ CANADA INCORPORATED  Marketed  February 15, 2013  Approved 2400243 FLUVASTATIN CAP 40MG  SANDOZ CANADA INCORPORATED Marketed  February 15, 2013  Approved 2400235 FLUVASTATIN CAP 20MG  SANDOZ CANADA INCORPORATED  Marketed  February 15, 2013  Approved 2379511 SIMVASTATIN TAB 10MG  BENTEC PHARMA INC Cancelled Post Market  March 1, 2013 December 15, 2015  84  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2422786 ATORVASTATIN TAB 40MG  LABORATOIRE RIVA INC Marketed  March 20, 2013   2422794 ATORVASTATIN TAB 80MG  LABORATOIRE RIVA INC Marketed  March 20, 2013   2422786 ATORVASTATIN TAB 40MG  LABORATOIRE RIVA INC  Marketed  March 20, 2013   2399377 ATORVASTATIN TAB 10MG  PHARMASCIENCE INC  Marketed  March 26, 2013  Approved 2399393 ATORVASTATIN TAB 40MG  PHARMASCIENCE INC  Marketed  March 26, 2013  Approved 2399407 ATORVASTATIN TAB 80MG  PHARMASCIENCE INC  Marketed  March 26, 2013  Approved 2399385 ATORVASTATIN TAB 20MG  PHARMASCIENCE INC  Marketed  March 26, 2013  Approved 2404222 AMLODIPINE/ATORVASTATIN 5/10 TAB MG  PHARMASCIENCE INC Marketed  March 28, 2013  Approved 2404249 AMLODIPINE/ATORVASTATIN 10/10 TAB MG  PHARMASCIENCE INC Marketed  March 28, 2013  Approved 2404230 AMLODIPINE/ATORVASTATIN  5/20 TAB MG  PHARMASCIENCE INC Marketed  March 28, 2013   2404257 AMLODIPINE/ATORVASTATIN 10/20 TAB MG  PHARMASCIENCE INC Marketed  March 28, 2013   2405644 ROSUVASTATIN TAB 20MG  SANIS HEALTH INC  Marketed  June 12, 2013  Approved 2405652 ROSUVASTATIN TAB 40MG  SANIS HEALTH INC  Marketed  June 12, 2013  Approved 2405644 ROSUVASTATIN TAB 20MG  SANIS HEALTH INC Marketed  June 12, 2013  Approved 2405628 ROSUVASTATIN TAB 5MG  SANIS HEALTH INC  Marketed  June 12, 2013  Approved 2405628 ROSUVASTATIN TAB 5MG  LABORATOIRE RIVA INC  Marketed  June 12, 2013  Approved 2405636 ROSUVASTATIN TAB 10MG  SANIS HEALTH INC  Marketed  June 12, 2013  Approved 2405652 ROSUVASTATIN TAB 40MG  SANIS HEALTH INC Marketed  June 12, 2013  Approved 2407256 ATORVASTATIN TAB 10MG  AURO PHARMA INC Marketed  June 13, 2013  Approved 2407264 ATORVASTATIN TAB 20MG  AURO PHARMA INC Marketed  June 13, 2013  Approved 2407280 ATORVASTATIN TAB 80MG  AURO PHARMA INC Marketed  June 13, 2013  Approved 2407272 ATORVASTATIN TAB 40MG  AURO PHARMA INC Marketed  June 13, 2013  Approved 2397781 ROSUVASTATIN TAB 5MG  MINT PHARMACEUTICALS INC Marketed  July 2, 2013  Approved 2397811 ROSUVASTATIN TAB 20MG  MINT PHARMACEUTICALS INC Marketed  July 2, 2013  Approved 2397838 ROSUVASTATIN TAB 40MG  MINT PHARMACEUTICALS INC Marketed  July 2, 2013  Approved 2397803 ROSUVASTATIN TAB 10MG  MINT PHARMACEUTICALS INC Marketed  July 2, 2013  Approved 2405164 SIMVASTATIN TAB 20MG  AURO PHARMA INC Marketed  July 8, 2013  Approved 2405172 SIMVASTATIN TAB 40MG  AURO PHARMA INC Marketed  July 8, 2013  Approved 85  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2405156 SIMVASTATIN TAB 10MG  AURO PHARMA INC Marketed  July 8, 2013  Approved 2405148 SIMVASTATIN TAB 5MG  AURO PHARMA INC Marketed  July 8, 2013  Approved 2405180 SIMVASTATIN TAB 80MG  AURO PHARMA INC Marketed  July 8, 2013  Approved 2345730 PRAVASTATIN TAB 10MG  TEVA CANADA LIMITED  Approved July 31, 2013    2345749 PRAVASTATIN TAB 20MG  TEVA CANADA LIMITED  Approved July 31, 2013    2345757 PRAVASTATIN TAB 40MG  TEVA CANADA LIMITED  Approved July 31, 2013    2385511 ROSUVASTATIN TAB 5MG  TEVA CANADA LIMITED  Approved July 31, 2013    2385546 ROSUVASTATIN TAB 20MG  TEVA CANADA LIMITED  Approved July 31, 2013    2385554 ROSUVASTATIN TAB 40MG  TEVA CANADA LIMITED  Approved July 31, 2013    2385538 ROSUVASTATIN TAB 10MG  TEVA CANADA LIMITED  Approved July 31, 2013    2399482 ATORVASTATIN TAB 10MG  DOMINION PHARMACAL Marketed  August 9, 2013   2399490 ATORVASTATIN TAB 20MG  DOMINION PHARMACAL Marketed  August 9, 2013   2399504 ATORVASTATIN TAB 40MG  DOMINION PHARMACAL Marketed  August 9, 2013   2386704 ROSUVASTATIN TAB 5MG  DOMINION PHARMACAL Marketed  September 28, 2013   2386712 ROSUVASTATIN TAB 10MG  DOMINION PHARMACAL Marketed  September 28, 2013   2386720 ROSUVASTATIN TAB 20MG  DOMINION PHARMACAL Marketed  September 28, 2013   2411350 ATORVASTATIN TAB 10MG  SIVEM PHARMACEUTICALS ULC  Marketed  October 23, 2013  Approved 2411636 ROSUVASTATIN TAB 10MG  SIVEM PHARMACEUTICALS ULC  Marketed  October 23, 2013  Approved 2411652 ROSUVASTATIN TAB 40MG  SIVEM PHARMACEUTICALS ULC  Marketed  October 23, 2013  Approved 2411644 ROSUVASTATIN TAB 20MG  SIVEM PHARMACEUTICALS ULC  Marketed  October 23, 2013  Approved 2411385 ATORVASTATIN TAB 80MG  SIVEM PHARMACEUTICALS ULC  Marketed  October 23, 2013  Approved 2411644 ROSUVASTATIN TAB 20MG  SIVEM PHARMACEUTICALS ULC  Marketed  October 23, 2013  Approved 2411636 ROSUVASTATIN TAB 10MG  SIVEM PHARMACEUTICALS ULC  Marketed  October 23, 2013  Approved 2411652 ROSUVASTATIN TAB 40MG  SIVEM PHARMACEUTICALS ULC  Marketed  October 23, 2013  Approved 2411369 ATORVASTATIN TAB 20MG  SIVEM PHARMACEUTICALS ULC  Marketed  October 23, 2013  Approved 2411377 ATORVASTATIN TAB 40MG  SIVEM PHARMACEUTICALS ULC  Marketed  October 23, 2013  Approved 2411628 ROSUVASTATIN TAB 5MG  SIVEM PHARMACEUTICALS ULC  Marketed  October 23, 2013  Approved 2411628 ROSUVASTATIN TAB 5MG  SIVEM PHARMACEUTICALS ULC  Marketed  October 23, 2013  Approved 86  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2411253 AMLODIPINE/ATORVASTATIN 5/10 TAB MG  APOTEX INC  Marketed  November 15, 2013   2411261 AMLODIPINE/ATORVASTATIN  5/20 TAB MG  APOTEX INC  Marketed  November 15, 2013   2411296 AMLODIPINE/ATORVASTATIN 5/80 TAB MG  APOTEX INC  Marketed  November 15, 2013   2411318 AMLODIPINE/ATORVASTATIN 10/10 TAB MG  APOTEX INC  Marketed  November 15, 2013   2411334 AMLODIPINE/ATORVASTATIN  10/40 TAB MG  APOTEX INC  Marketed  November 15, 2013   2411342 AMLODIPINE/ATORVASTATIN  10/80 TAB MG  APOTEX INC  Marketed  November 15, 2013   2411288 AMLODIPINE/ATORVASTATIN  5/40 TAB MG  APOTEX INC  Marketed  November 15, 2013   2411326 AMLODIPINE/ATORVASTATIN  10/20 TAB MG  APOTEX INC  Marketed  November 15, 2013   2399180 ROSUVASTATIN TAB 20MG  GENERIC MEDICAL PARTNERS INC Marketed  November 23, 2013  Approved 2399172 ROSUVASTATIN TAB 10MG  GENERIC MEDICAL PARTNERS INC Marketed  November 27, 2013  Approved 2399199 ROSUVASTATIN TAB 40MG  GENERIC MEDICAL PARTNERS INC Marketed  November 27, 2013  Approved 2399164 ROSUVASTATIN TAB 5MG  GENERIC MEDICAL PARTNERS INC Marketed  November 27, 2013  Approved 2422751 ATORVASTATIN TAB 10MG  LABORATOIRE RIVA INC Marketed  March 20, 2014   2422778 ATORVASTATIN TAB 20MG  LABORATOIRE RIVA INC Marketed  March 20, 2014   2422751 ATORVASTATIN TAB 10MG  LABORATOIRE RIVA INC  Marketed  March 20, 2014   2422778 ATORVASTATIN TAB 20MG  LABORATOIRE RIVA INC  Marketed  March 20, 2014   2422794 ATORVASTATIN TAB 80MG  LABORATOIRE RIVA INC  Marketed  March 20, 2014   2438933 ROSUVASTATIN TAB 20MG  ACCORD HEALTHCARE INC  Approved  April 28, 2014   2392933 ATORVASTATIN TAB 10MG  MYLAN PHARMACEUTICALS ULC  Marketed  June 3, 2014  Approved 2392941 ATORVASTATIN TAB 20MG  MYLAN PHARMACEUTICALS ULC  Marketed  June 3, 2014  Approved 2392976 ATORVASTATIN TAB 80MG  MYLAN PHARMACEUTICALS ULC  Marketed  June 3, 2014  Approved 2392968 ATORVASTATIN TAB 40MG  MYLAN PHARMACEUTICALS ULC  Marketed  June 3, 2014  Approved 2413051 ROSUVASTATIN TAB 5MG  MARCAN PHARMACEUTICALS INC Marketed  June 26, 2014  Approved 2413086 ROSUVASTATIN TAB 20MG  MARCAN PHARMACEUTICALS INC Marketed  June 26, 2014  Approved 2413078 ROSUVASTATIN TAB 10MG  MARCAN PHARMACEUTICALS INC Marketed  June 26, 2014  Approved 2413108 ROSUVASTATIN TAB 40MG  MARCAN PHARMACEUTICALS INC Marketed  June 26, 2014  Approved 2427257 PRAVASTATIN TAB 10MG  PENDOPHARM DIVISION OF DE PHARMASCIENCE INC Approved July 31, 2014    2427265 PRAVASTATIN TAB 20MG  PENDOPHARM DIVISION OF DE PHARMASCIENCE INC Approved July 31, 2014    87  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2427257 PRAVASTATIN TAB 10MG  PENDOPHARM DIVISION OF DE PHARMASCIENCE INC Approved July 31, 2014    2427265 PRAVASTATIN TAB 20MG  PENDOPHARM DIVISION OF DE PHARMASCIENCE INC Approved July 31, 2014    2427702 AMLODIPINE/ATORVASTATIN  5/10 TAB MG  PENDOPHARM DIVISION OF DE PHARMASCIENCE INC  Approved August 5, 2014    2427729 AMLODIPINE/ATORVASTATIN  10/10 TAB MG  PENDOPHARM DIVISION OF DE PHARMASCIENCE INC  Approved August 5, 2014    2427710 AMLODIPINE/ATORVASTATIN  5/20 TAB MG  PENDOPHARM DIVISION OF DE PHARMASCIENCE INC  Approved August 5, 2014    2427737 AMLODIPINE/ATORVASTATIN 10/20 TAB MG  PENDOPHARM DIVISION OF DE PHARMASCIENCE INC  Approved August 5, 2014    2432064 PRAVASTATIN TAB 40MG  MARCAN PHARMACEUTICALS INC Approved November 10, 2014    2432048 PRAVASTATIN TAB 10MG  MARCAN PHARMACEUTICALS INC Approved November 10, 2014    2432056 PRAVASTATIN TAB 20MG  MARCAN PHARMACEUTICALS INC Approved November 10, 2014    2433125 ROSUVASTATIN TAB 5MG  COBALT PHARMACEUTICALS COMPANY  Approved November 21, 2014    2433168 ROSUVASTATIN TAB 40MG  COBALT PHARMACEUTICALS COMPANY  Approved November 21, 2014    2433141 ROSUVASTATIN TAB 20MG  COBALT PHARMACEUTICALS COMPANY  Approved November 21, 2014    2433133 ROSUVASTATIN TAB 10MG  COBALT PHARMACEUTICALS COMPANY  Approved November 21, 2014    2433168 ROSUVASTATIN TAB 40MG  COBALT PHARMACEUTICALS COMPANY  Approved November 21, 2014    2433133 ROSUVASTATIN TAB 10MG  COBALT PHARMACEUTICALS COMPANY  Approved November 21, 2014    2433141 ROSUVASTATIN TAB 20MG  COBALT PHARMACEUTICALS COMPANY  Approved November 21, 2014    2433125 ROSUVASTATIN TAB 5MG  COBALT PHARMACEUTICALS COMPANY  Approved November 21, 2014    2433761 ATORVASTATIN TAB 10MG  ACTAVIS PHARMA COMPANY  Approved November 24, 2014    2433788 ATORVASTATIN TAB 20MG  ACTAVIS PHARMA COMPANY  Approved November 24, 2014    2433796 ATORVASTATIN TAB 40MG  ACTAVIS PHARMA COMPANY  Approved November 24, 2014    2433818 ATORVASTATIN TAB 80MG  ACTAVIS PHARMA COMPANY  Approved November 24, 2014    2435292 ATORVASTATIN TAB 10MG  ACTAVIS PHARMA COMPANY  Approved December 19, 2014    2435306 ATORVASTATIN TAB 20MG  RANBAXY PHARMACEUTICALS CANADA INC. Approved December 19, 2014    2435314 ATORVASTATIN TAB 40MG  RANBAXY PHARMACEUTICALS CANADA INC. Approved December 19, 2014    2435322 ATORVASTATIN TAB 80MG  RANBAXY PHARMACEUTICALS CANADA INC. Approved December 19, 2014    2438917 ROSUVASTATIN TAB 5MG  ACCORD HEALTHCARE INC  Approved April 28, 2015    2438925 ROSUVASTATIN TAB 10MG  ACCORD HEALTHCARE INC  Approved April 28, 2015    2438941 ROSUVASTATIN TAB 40MG  ACCORD HEALTHCARE INC  Approved April 28, 2015    88  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2440644 PRAVASTATIN TAB 10MG  ACCORD HEALTHCARE INC  Approved April 29, 2015    2440652 PRAVASTATIN TAB 20MG  ACCORD HEALTHCARE INC  Approved April 29, 2015    2440660 PRAVASTATIN TAB 40MG  ACCORD HEALTHCARE INC  Approved April 29, 2015    2417936 ATORVASTATIN TAB 10MG  DR REDDYS LABORATORIES LTD Marketed  June 22, 2015  Approved 2417952 ATORVASTATIN TAB 40MG  DR REDDYS LABORATORIES LTD  Marketed  June 22, 2015  Approved 2417960 ATORVASTATIN TAB 80MG  DR REDDYS LABORATORIES LTD  Marketed  June 22, 2015  Approved 2417952 ATORVASTATIN TAB 40MG  DR REDDYS LABORATORIES LTD Marketed  June 22, 2015  Approved 2417960 ATORVASTATIN TAB 80MG  DR REDDYS LABORATORIES LTD Marketed  June 22, 2015  Approved 2417944 ATORVASTATIN TAB 20MG  DR REDDYS LABORATORIES LTD  Marketed  June 22, 2015  Approved 2417944 ATORVASTATIN TAB 20MG  DR REDDYS LABORATORIES LTD Marketed  June 22, 2015  Approved 2417936 ATORVASTATIN TAB 10MG  DR REDDYS LABORATORIES LTD  Marketed  June 22, 2015  Approved 2445379 PRAVASTATIN TAB 10MG  PHARMAPAR INC  Approved September 18, 2015    2445409 PRAVASTATIN TAB 40MG  PHARMAPAR INC  Approved September 18, 2015    2445409 ROSUVASTATIN TAB 40MG  PHARMAPAR INC Approved September 18, 2015    2446251 PRAVASTATIN TAB 10MG  BIOMED PHARMA Approved September 18, 2015    2446286 PRAVASTATIN TAB 40MG  BIOMED PHARMA Approved September 18, 2015    2446278 PRAVASTATIN TAB 20MG  BIOMED PHARMA Approved September 18, 2015    2445395 PRAVASTATIN TAB 20MG  PHARMAPAR INC  Approved September 18, 2015    2445379 ROSUVASTATIN TAB 10MG  PHARMAPAR INC Approved September 18, 2015    2445395 ROSUVASTATIN TAB 20MG  PHARMAPAR INC Approved September 18, 2015    2442574 ROSUVASTATIN TAB 5MG  AURO PHARMA INC Marketed  November 30, 2015   2442582 ROSUVASTATIN TAB 10MG  AURO PHARMA INC Marketed  November 30, 2015   2442590 ROSUVASTATIN TAB 20MG  AURO PHARMA INC Marketed  November 30, 2015   2442604 ROSUVASTATIN TAB 40MG  AURO PHARMA INC Marketed  November 30, 2015   2374625 SIMVASTATIN TAB 5MG  MARCAN PHARMACEUTICALS INC  Approved January 7, 2016    2374633 SIMVASTATIN TAB 10MG  MARCAN PHARMACEUTICALS INC  Approved January 7, 2016    2374641 SIMVASTATIN TAB 20MG  MARCAN PHARMACEUTICALS INC  Approved January 7, 2016    2374668 SIMVASTATIN TAB 40MG  MARCAN PHARMACEUTICALS INC  Approved January 7, 2016    89  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2374676 SIMVASTATIN TAB 80MG  MARCAN PHARMACEUTICALS INC  Approved January 7, 2016    2444976 ROSUVASTATIN TAB 10MG  BIOMED PHARMA  Approved January 19, 2016    2444984 ROSUVASTATIN TAB 20MG  BIOMED PHARMA  Approved January 19, 2016    2444992 ROSUVASTATIN TAB 40MG  BIOMED PHARMA  Approved January 19, 2016    2444968 ROSUVASTATIN TAB 5MG  BIOMED PHARMA  Approved January 19, 2016    2445417 ROSUVASTATIN TAB 5MG  PHARMAPAR INC Approved January 22, 2016    2445425 ROSUVASTATIN TAB 10MG  PHARMAPAR INC Approved January 22, 2016    2445433 ROSUVASTATIN TAB 20MG  PHARMAPAR INC Approved January 22, 2016    2445433 ROSUVASTATIN TAB 20MG  PHARMAPAR INC  Approved January 22, 2016    2445441 ROSUVASTATIN TAB 40MG  PHARMAPAR INC Approved January 22, 2016    2445417 ROSUVASTATIN TAB 5MG  PHARMAPAR INC  Approved January 22, 2016    2445425 ROSUVASTATIN TAB 10MG  PHARMAPAR INC  Approved January 22, 2016    2445441 ROSUVASTATIN TAB 40MG  PHARMAPAR INC  Approved January 22, 2016    2405636 ROSUVASTATIN TAB 10MG  SANIS HEALTH INC Marketed January 27, 2016   Approved 2410958 ROSUVASTATIN TAB 10MG  MARCAN PHARMACEUTICALS INC  Approved March 15, 2016    2430983 PRAVASTATIN TAB 40MG  MARCAN PHARMACEUTICALS INC Approved March 15, 2016    2410931 ROSUVASTATIN TAB 5MG  MARCAN PHARMACEUTICALS INC  Approved March 15, 2016    2430975 PRAVASTATIN TAB 20MG  MARCAN PHARMACEUTICALS INC Approved March 15, 2016    2410966 ROSUVASTATIN TAB 20MG  MARCAN PHARMACEUTICALS INC  Approved March 15, 2016    2410974 ROSUVASTATIN TAB 40MG  MARCAN PHARMACEUTICALS INC  Approved March 15, 2016    2430967 PRAVASTATIN TAB 10MG  MARCAN PHARMACEUTICALS INC Approved March 15, 2016    2181562 SIMVASTATIN TAB 20MG  PHARMEL INC      2247220 SIMVASTATIN TAB 5MG        2247536 LOVASTATIN TAB 20MG        2247537 LOVASTATIN TAB 40MG        2252929 LOVASTATIN TAB 20MG        2252937 LOVASTATIN TAB 40MG        2265613 PRAVASTATIN TAB 10MG        90  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2265621 PRAVASTATIN TAB 20MG        2265648 PRAVASTATIN TAB 40MG        2265877 SIMVASTATIN TAB 5MG        2265915 SIMVASTATIN TAB 80MG        2310759 PRAVASTATIN TAB 10MG  LABORATOIRE RIVA INC  Cancelled Post Market   January 28, 2016  2310767 PRAVASTATIN TAB 20MG  LABORATOIRE RIVA INC  Cancelled Post Market   January 28, 2016  2310775 PRAVASTATIN TAB 40MG  LABORATOIRE RIVA INC  Cancelled Post Market   January 28, 2016  2331586 PRAVASTATIN TAB 10MG        2331594 PRAVASTATIN TAB 20MG        2331608 PRAVASTATIN TAB 40MG        2331837 LOVASTATIN TAB 20MG        2331845 LOVASTATIN TAB 40MG        2338866 SIMVASTATIN TAB 5MG  QD PHARMACEUTICALS ULC  Cancelled Post Market   August 21, 2015  2338904 SIMVASTATIN TAB 80MG  QD PHARMACEUTICALS ULC  Cancelled Post Market   August 21, 2015  2340259 PRAVASTATIN TAB 10MG        2340267 PRAVASTATIN TAB 20MG        2340275 PRAVASTATIN TAB 40MG        2341476 LOVASTATIN TAB 20MG        2341484 LOVASTATIN TAB 40MG        2341956 SIMVASTATIN TAB 5MG        2341964 SIMVASTATIN TAB 10MG        2341972 SIMVASTATIN TAB 20MG        2341980 SIMVASTATIN TAB 40MG        2341999 SIMVASTATIN TAB 80MG        2343509 ROSUVASTATIN TAB 5MG  TEVA CANADA LIMITED Cancelled Post Market   October 16, 2015  2343517 ROSUVASTATIN TAB 10MG  TEVA CANADA LIMITED Cancelled Post Market   October 16, 2015  2343525 ROSUVASTATIN TAB 20MG  TEVA CANADA LIMITED Cancelled Post Market   October 16, 2015  2343533 ROSUVASTATIN TAB 40MG  TEVA CANADA LIMITED Cancelled Post Market   October 16, 2015  91  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2349922 SIMVASTATIN TAB 5MG        2349930 SIMVASTATIN TAB 10MG        2349949 SIMVASTATIN TAB 20MG        2349957 SIMVASTATIN TAB 40MG        2349965 SIMVASTATIN TAB 80MG        2370875 PRAVASTATIN TAB 10MG  QD PHARMACEUTICALS ULC Cancelled Post Market   August 21, 2015  2370891 PRAVASTATIN TAB 20MG  QD PHARMACEUTICALS ULC Cancelled Post Market   August 21, 2015  2370905 PRAVASTATIN TAB 40MG  QD PHARMACEUTICALS ULC Cancelled Post Market   August 21, 2015  2377632 SIMVASTATIN TAB 5MG        2377640 SIMVASTATIN TAB 10MG        2377659 SIMVASTATIN TAB 20MG        2377667 SIMVASTATIN TAB 40MG        2377675 SIMVASTATIN TAB 80MG        2379783 PRAVASTATIN TAB 10MG        2379791 PRAVASTATIN TAB 20MG        2379805 PRAVASTATIN TAB 40MG        2384787 ATORVASTATIN TAB 10MG  TEVA CANADA LIMITED  Cancelled Post Market   May 5, 2016  2384795 ATORVASTATIN TAB 20MG  TEVA CANADA LIMITED  Cancelled Post Market   May 5, 2016  2384809 ATORVASTATIN TAB 40MG  TEVA CANADA LIMITED  Cancelled Post Market   May 5, 2016  2384817 ATORVASTATIN TAB 80MG  TEVA CANADA LIMITED  Cancelled Post Market   May 5, 2016  2390182 ATORVASTATIN TAB 80MG        2390507 ROSUVASTATIN TAB 5MG  QD PHARMACEUTICALS ULC  Cancelled Post Market   August 21, 2015  2390523 ROSUVASTATIN TAB 10MG  QD PHARMACEUTICALS ULC  Cancelled Post Market   August 21, 2015  2390531 ROSUVASTATIN TAB 20MG  QD PHARMACEUTICALS ULC  Cancelled Post Market   August 21, 2015  2390558 ROSUVASTATIN TAB 40MG  QD PHARMACEUTICALS ULC  Cancelled Post Market   August 21, 2015  2397633 SIMVASTATIN TAB 5MG  FROSST A DIVISION OF MERCK CANADA INC Cancelled Post Market   May 5, 2016  2397641 SIMVASTATIN TAB 10MG  FROSST A DIVISION OF MERCK CANADA INC Cancelled Post Market   May 5, 2016  2397668 SIMVASTATIN TAB 20MG  FROSST A DIVISION OF MERCK CANADA INC Cancelled Post Market   May 5, 2016  92  DIN Generic name Brand name Manufacturer Current Status Approved Date Marketed Date Date Cancelled BC	Pharmacare	2397676 SIMVASTATIN TAB 40MG  FROSST A DIVISION OF MERCK CANADA INC Cancelled Post Market   May 5, 2016  2397684 SIMVASTATIN TAB 80MG  FROSST A DIVISION OF MERCK CANADA INC Cancelled Post Market   May 5, 2016  2397862 ATORVASTATIN TAB 10MG        2397870 ATORVASTATIN TAB 20MG        2397889 ATORVASTATIN TAB 40MG        2397897 ATORVASTATIN TAB 80MG        2398117 ATORVASTATIN TAB 10MG        2398125 ATORVASTATIN TAB 20MG        2398133 ATORVASTATIN TAB 40MG        2398141 ATORVASTATIN TAB 80MG        2400251 SIMVASTATIN TAB 5MG        2400278 SIMVASTATIN TAB 10MG        2400286 SIMVASTATIN TAB 20MG        2400294 SIMVASTATIN TAB 40MG        2400308 SIMVASTATIN TAB 80MG        2270429 NIACIN / LOVASTATIN 1000/40 TAB MG        93  Appendix C: Inventory model of drug supply  The following are steps I used to create the inventory model of drug supply Step 1: I collected each patient's daily supply of pills. Some patients switched from one statin to another. Switching from brand to generic product of the same active ingredient was not considered an interruption in therapy.   Step 2: On days patients filled prescription, their supply in-hand increased by the dispensed days’ supply. After patients filled prescriptions their daily supply was reduced by 1 each day to a minimum of 0.  Step 3: I translated the days’ supply in hand to an array of daily drug availability with availability coded as a binary variable indicating whether or not a patient had drug supply in-hand.  Step 4: Daily drug availability array was matched with calendar date indicating the month and year.  Step 5: Days’ supply for each month in a given year for each patient was determined by summing all days’ supply from every prescription dispensed in a month.  94  Step 6: Each patient's monthly PDC was calculated where the numerator was equal to step 5 above and denominator was equal to number of days in that month. If the numerator exceeded the denominator, the excess days’ supply was added to the subsequent month.  Step 7: For each calendar month, average PDC was calculated. 

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