Ovulation induction and subfertile untreated conception groups offer improved options for interpreting risks associated with ART.

PURPOSE: To identify and characterise appropriate comparison groups for population studies of health outcomes in ART-conceived births: ovulation induction (OI), subfertile untreated and fertile natural conceptions. Our secondary objective was to examine whether known risks of pregnancy complications and adverse birth outcomes in ART births are elevated in comparison with subfertile (untreated and OI) conception groups. METHODS: We linked State and Commonwealth datasets to identify all live and stillbirths (≥ 20 weeks) in Western Australia from 2003 to 2014 by method of conception. Demographic characteristics, maternal pre-existing conditions, adverse obstetric history and pregnancy complications were compared across conception groups. Generalised estimating equations were used to estimate adjusted risk ratios (aRRs) and 95% confidence intervals (CI) for pregnancy complications and birth outcomes in singletons. RESULTS: We identified 9456 ART, 3870 OI, 11,484 subfertile untreated and 303,921 fertile naturally conceived deliveries. OI and subfertile untreated groups more closely resembled the ART group than the fertile group; however, some differences remained across parity, maternal age, pre-existing conditions and obstetric history. In multivariate analyses, ART singletons had greater risks of placental problems (e.g. placenta praevia aRR 2.42 (95% CI 1.82-3.20)) and adverse birth outcomes (e.g. preterm birth aRR 1.38 (95% CI 1.25-1.52)) than the subfertile untreated group, while OI singletons were more similar to the subfertile group with higher risk of preeclampsia and gestational diabetes. CONCLUSION: OI and subfertile untreated conception groups offer improved options for interpreting health outcomes in ART births. Pregnancy complications (particularly placental disorders) and adverse outcomes at delivery are more common following ART.

The Australian Genetic Heart Disease Registry: Protocol for a Data Linkage Study.

BACKGROUND: Genetic heart diseases such as hypertrophic cardiomyopathy can cause significant morbidity and mortality, ranging from syncope, chest pain, and palpitations to heart failure and sudden cardiac death. These diseases are inherited in an autosomal dominant fashion, meaning family members of affected individuals have a 1 in 2 chance of also inheriting the disease ("at-risk relatives"). The health care use patterns of individuals with a genetic heart disease, including emergency department presentations and hospital admissions, are poorly understood. By linking genetic heart disease registry data to routinely collected health data, we aim to provide a more comprehensive clinical data set to examine the burden of disease on individuals, families, and health care systems. OBJECTIVE: The objective of this study is to link the Australian Genetic Heart Disease (AGHD) Registry with routinely collected whole-population health data sets to investigate the health care use of individuals with a genetic heart disease and their at-risk relatives. This linked data set will allow for the investigation of differences in outcomes and health care use due to disease, sex, socioeconomic status, and other factors. METHODS: The AGHD Registry is a nationwide data set that began in 2007 and aims to recruit individuals with a genetic heart disease and their family members. In this study, demographic, clinical, and genetic data (available from 2007 to 2019) for AGHD Registry participants and at-risk relatives residing in New South Wales (NSW), Australia, were linked to routinely collected health data. These data included NSW-based data sets covering hospitalizations (2001-2019), emergency department presentations (2005-2019), and both state-wide and national mortality registries (2007-2019). The linkage was performed by the Centre for Health Record Linkage. Investigations stratifying by diagnosis, age, sex, socioeconomic status, and gene status will be undertaken and reported using descriptive statistics. RESULTS: NSW AGHD Registry participants were linked to routinely collected health data sets using probabilistic matching (November 2019). Of 1720 AGHD Registry participants, 1384 had linkages with 11,610 hospital records, 7032 emergency department records, and 60 death records. Data assessment and harmonization were performed, and descriptive data analysis is underway. CONCLUSIONS: We intend to provide insights into the health care use patterns of individuals with a genetic heart disease and their at-risk relatives, including frequency of hospital admissions and differences due to factors such as disease, sex, and socioeconomic status. Identifying disparities and potential barriers to care may highlight specific health care needs (eg, between sexes) and factors impacting health care access and use. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48636.

Pioglitazone use in Australia and the United Kingdom following drug safety advisories on bladder cancer risk: An interrupted time series study.

PURPOSE: National regulators in Australia and the United Kingdom issued safety advisories on the association between pioglitazone use and bladder cancer in July 2011. The Australian advisory noted that males were at higher risk of bladder cancer than females, while the UK advisory highlighted a new recommendation, suggest careful consideration in the elderly due to increasing risk with age. This study examined whether these differences in the advisories had different age- and sex-based impacts in each country. METHODS: Interrupted time series analysis was used to compare pioglitazone use (prescriptions/100000 population) in Australia and the United Kingdom for the 24 months before and 11 months after the July 2011 safety advisories (study period July 2009-June 2012). Separate models were used to compare use by sex and age group (≥65 years vs. <65 years) in each country. RESULTS: Pioglitazone use fell in Australia (17%) and the United Kingdom (24%) following the safety advisories. Use of pioglitazone fell more for males (18%) than females (16%) in Australia, and more for females (25%) than males (23%) in the United Kingdom; however, neither difference was statistically significant (Australia p = 0.445, United Kingdom p = 0.462). Pioglitazone use fell to a similar extent among older people than younger people in the United Kingdom (23% vs. 26%, p = 0.354), and did not differ between age groups in Australia (both 18%, p = 0.772). CONCLUSIONS: The results indicate that differences in the Australian and UK safety advisories resulted in substantial reductions in pioglitazone use at the population level in both countries, however, differences by sub-groups were not observed.

Hydroxyzine Initiation Following Drug Safety Advisories on Cardiac Arrhythmias in the UK and Canada: A Longitudinal Cohort Study.

INTRODUCTION: Regulatory advisories on hydroxyzine and risk of QT prolongation and Torsade de pointes (TdP) were issued in the UK in April 2015 and Canada in June 2016. We hypothesized patients with risk factors for QT prolongation and TdP, compared with those without risk factors, would be less likely to initiate hydroxyzine in the UK and in British Columbia (BC), Canada, following advisories. METHODS: We conducted a longitudinal study with repeated measures, and evaluated hydroxyzine initiation in a UK cohort and a concurrent BC control cohort (April 2013-March 2016) as well as in a BC advisory cohort (June 2014-May 2017). RESULTS: This study included 247,665 patients in the UK cohort, 297,147 patients in the BC control cohort, and 303,653 patients in the BC advisory cohort. Over a 12-month post-advisory period, hydroxyzine initiation decreased by 21% in the UK (rate ratio 0.79, 95% confidence interval 0.66-0.96) relative to the expected level of initiation based on the pre-advisory trend. Hydroxyzine initiation did not change in the BC control cohort or following the Canadian advisory in the BC advisory cohort. The decrease in hydroxyzine initiation in the UK in the 12 months after the advisories was not significantly different for patients with risk factors compared with those without risk factors. CONCLUSION: Hydroxyzine initiation decreased in the UK, but not in BC, in the 12 months following safety advisories. The decrease in hydroxyzine initiation in the UK was not significantly different for patients with versus without risk factors for QT prolongation and TdP.

Influence of drug safety advisories on drug utilisation: an international interrupted time series and meta-analysis.

OBJECTIVE: To evaluate the association between regulatory drug safety advisories and changes in drug utilisation. DESIGN: We conducted controlled, interrupted times series analyses with administrative prescription claims data to estimate changes in drug utilisation following advisories. We used random-effects meta-analysis with inverse-variance weighting to estimate the average postadvisory change in drug utilisation across advisories. STUDY POPULATION: We included advisories issued in Canada, Denmark, the UK and the USA during 2009-2015, mainly concerning drugs in common use in primary care. We excluded advisories related to over-the-counter drugs, drug-drug interactions, vaccines, drugs used primarily in hospital and advisories with co-interventions within ±6 months. MAIN OUTCOME MEASURES: Change in drug utilisation, defined as actual versus predicted percentage change in the number of prescriptions (for advisories without dose-related advice), or in the number of defined daily doses (for dose-related advisories), per 100 000 population. RESULTS: Among advisories without dose-related advice (n=20), the average change in drug utilisation was -5.83% (95% CI -10.93 to -0.73; p=0.03). Advisories with dose-related advice (n=4) were not associated with a statistically significant change in drug utilisation (-1.93%; 95% CI -17.10 to 13.23; p=0.80). In a post hoc subgroup analysis of advisories without dose-related advice, we observed no statistically significant difference between the change in drug utilisation following advisories with explicit prescribing advice, such as a recommendation to consider the risk of a drug when prescribing, and the change in drug utilisation following advisories without such advice. CONCLUSIONS: Among safety advisories issued on a wide range of drugs during 2009-2015 in 4 countries (Canada, Denmark, the UK and the USA), the association of advisories with changes in drug utilisation was variable, and the average association was modest.

The Comparative Effectiveness of Varenicline and Nicotine Patches for Smoking Abstinence During Pregnancy: Evidence From a Population-based Cohort Study.

INTRODUCTION: In the general population, varenicline is consistently shown to be more efficacious for smoking cessation than nicotine replacement therapy (NRT). Current clinical guidelines for the management of smoking during pregnancy recommend against the use of varenicline, whilst supporting the use of NRT. However, little is known about the comparative effectiveness of these smoking cessation therapies among pregnant women. AIMS AND METHODS: Routinely-collected records of all births in two Australian States during 2011 and 2012 were used to create a population-based cohort of women who smoked during the first half of pregnancy. Pharmaceutical dispensing data were used to identify varenicline and nicotine patch dispensings in the first half of pregnancy. Propensity score matching was used to account for the potentially different distribution of confounding factors between the treatment groups. The outcome was defined as smoking abstinence during the second half of pregnancy. RESULTS: After propensity score-matching, our cohort comprised 60 women who used varenicline and 60 who used nicotine patches during the first half of pregnancy. More varenicline users (33.3%, 95% CI: 21.7%-46.7%) quit smoking than nicotine patch users (13.3%, 95% CI: 5.9%-24.6%). The adjusted rate difference was 24.2% (95% CI: 10.2%-38.2%) and the adjusted relative risk was 2.8 (95% CI: 1.4-5.7). CONCLUSIONS: Varenicline was almost three times more effective than nicotine patches in assisting pregnant women to quit smoking. Further studies are needed to corroborate our results. Together with data on the safety of varenicline during pregnancy, evidence regarding the relative benefit of varenicline and NRT during pregnancy important for informing clinical decisions for pregnant smokers. IMPLICATIONS: This study is the first to measure the comparative effectiveness of varenicline and nicotine patches during pregnancy - women using varenicline were almost three times as likely to quit smoking than those using nicotine patches. This study addressed a clinically important question using an observational study, noting that there is an absence of evidence from randomized controlled trials because of the ethical issues associated with including pregnant women in clinical trials of medicines of unknown safety.

Exploring the association between stroke and acute myocardial infarction and statins adherence following a medicines co-payment increase.

OBJECTIVES: Patient contributions (co-payments) for one months' supply of a publicly-subsidised medicine in Australia were increased by 21% in January 2005 (US$2.73-$3.31 for social security recipients and $17.05-$20.58 for others). This study investigates the relationship between patients' use of statin medication and hospitalisation for acute coronary syndrome and stroke, following this large increase in co-payments. METHODS: We designed a retrospective cohort study of all patients in Western Australia who were dispensed statin medication between 2004 and 05. Data for the cohort was obtained from State and Federal linked databases. We divided the cohort into those who discontinued, reduced or continued statin therapy in the first six months after the co-payment increase. The primary outcome was two-year hospitalisation for acute coronary syndrome or stroke-related event. Analysis was conducted using Fine and Gray competing risk methods, with death as the competing risk. RESULTS: There were 207,066 patients using statins prior to the co-payment increase. Following the increase, 12.5% of patients reduced their use of statin medication, 3.3% of patients discontinued therapy, and 84.2% continued therapy. There were 4343 acute coronary syndrome and stroke-related hospitalisations in the two-year follow-up period. Multivariate analysis demonstrated that discontinuing statins increased the risk of hospitalisation for acute coronary syndrome or stroke-related events by 18% (95%CI = 0.1%-40%) compared to continuing therapy. Subgroup analysis showed that men aged <70 years were at increased risk of 54-63% after discontinuing statins compared to those continuing, but that women and older men were not. CONCLUSION: Discontinuing statin medication after a large increase patient cost contribution was associated with higher rates of acute coronary syndrome and stroke-related hospitalisation in men under 70 years. The findings highlight the importance of continued adherence to prescribed statin medication, and that discontinuing therapy for non-clinical reasons (such as cost) can possibly have negative consequences particularly for younger men.

Increased risk of 2-year death in patients who discontinued their use of statins.

OBJECTIVE: This study examined the association between statin usage (discontinued, reduced or continued) and two-year death following a 21% increase in the Pharmaceutical Benefits Scheme (PBS) consumer co-payment in Western Australia. METHODS: A retrospective observational study in Western Australia using linked administrative Commonwealth PBS data and State hospital inpatient and death data (n = 207,066) was undertaken. We explored the two-year all-cause and ischemic heart disease(IHD)/stroke-specific-death in individuals who discontinued, reduced or continued statin medication following the January 2005 PBS co-payment increase, overall, by beneficiary status (general population vs. social security recipients) and by a history of admission for ischemic heart disease or stroke. Non-cardiovascular (CVD)-related death was also considered. RESULTS: In the first six months of 2005, 3.3% discontinued, 12.5% reduced and 84.2% continued statin therapy. We found those who discontinued statins were also likely to discontinue at least two other medicines compared to those who continued therapy. There were 4,607 all-cause deaths. For IHD/stroke-specific death, there were 1,317. For all non-CVD-related death, there were 2,808 deaths during the 2-year follow-up period. Cox regression models, adjusted for demographic and clinical characteristics, showed a 39%-61% increase in the risk of all-cause death for individuals who reduced or discontinued statin medication compared to those who continued their statin medication (Discontinued: Adj HR = 1.61, 95% CI 1.40-1.85; Reduced: Adj HR = 1.39, 95% CI 1.28-1.51). For IHD/stroke-specific death, there was an increased risk of death by 28-76% (Discontinued: Adj sHR = 1.76, 95% CI 1.37-2.27; Reduced: Adj sHR = 1.28, 95% CI 1.10-1.49), and for non-CVD-related death, there was an increased risk of death by 44-57% (Discontinued: Adj sHR = 1.57, 95% CI 1.31-1.88; Reduced: Adj sHR = 1.44, 95% CI 1.30-1.60), for individuals who discontinued or reduced their statin medication compared to those who continued. CONCLUSIONS: Patients who discontinued their statin therapy had a significantly increased risk of IHD and stroke death. Health professionals should be aware that large co-payment changes may be associated with patients discontinuing or reducing medicines to their health detriment. Factors that lead to such changes in patient medication-taking behaviour need to be considered and addressed at the clinical and policy levels.

Frequent general practitioner visits are protective against statin discontinuation after a Pharmaceutical Benefits Scheme copayment increase.

Objective This study assessed the effect of the frequency of general practitioner (GP) visitation in the 12 months before a 21% consumer copayment increase in the Pharmaceutical Benefits Scheme (PBS; January 2005) on the reduction or discontinuation of statin dispensing for tertiary prevention. Methods The study used routinely collected, whole-population linked PBS, Medicare, mortality and hospital data from Western Australia. From 2004 to 2005, individuals were classified as having discontinued, reduced or continued their use of statins in the first six months of 2005 following the 21% consumer copayment increase on 1 January 2005. The frequency of GP visits was calculated in 2004 from Medicare data. Multivariate logistic regression models were used to determine the association between GP visits and statin use following the copayment increase. Results In December 2004, there were 22495 stable statin users for tertiary prevention of prior coronary heart disease, prior stroke or prior coronary artery revascularisation procedure. Following the copayment increase, patients either discontinued (3%), reduced (12%) or continued (85%) their statins. Individuals who visited a GP three or more times in 2004 were 47% less likely to discontinue their statins in 2005 than people attending only once. Subgroup analysis showed the effect was apparent in men, and long-term or new statin users. The frequency of GP visits did not affect the proportion of patients reducing their statin therapy. Conclusions Patients who visited their GP at least three times per year had a lower risk of ceasing their statins in the year following the copayment increase. GPs can help patients maintain treatment following rises in medicines costs. What is known about the topic? Following the 21% increase in medication copayment in 2005, individuals discontinued or reduced their statin usage, including for tertiary prevention. What does this paper add? Patients who visited their GP at least three times per year were less likely to discontinue their statin therapy for tertiary prevention following a large copayment increase. What are the implications for practitioners? This paper identifies the important role that GPs have in maintaining the continued use of important medications following rises in medicines costs.

Use of analgesics following rescheduling of codeine in Australia: An interrupted time series analysis in the veteran population.

BACKGROUND: The Australian medicines regulator, the Therapeutic Goods Administration (TGA), rescheduled all codeine-containing medicines to be available only on prescription on 1 February 2018. This study was conducted to determine whether use of analgesics changed following codeine re-scheduling to prescription only status, and whether there was a change in the use of codeine preparations and a therapeutic shift to stronger opioids or other analgesics in the Australian veteran population following the change. METHODS: Interrupted time series analysis using Repatriation Pharmaceutical Benefits Scheme (RPBS) claims data from the Australian Government Department of Veterans' Affairs (DVA) for clients with dispensing of opioid and non-opioid analgesics between January 2015 and April 2019. Trends in the monthly rate of analgesic dispensings (opioid and non-opioid) were compared for the period between January 2015 and January 2018 with the period February 2018 to April 2019. RESULTS: Paracetamol with codeine 8mg was the only analgesic with an increased rate of dispensing following the February 2018 codeine scheduling changes. Prior to codeine re-scheduling, the rate of dispensing of paracetamol with codeine 8mg was decreasing by 0.9% each month. Immediately after the scheduling changes, dispensing of paracetamol with codeine 8mg increased by 45% (95%CI=1.282-1.676, p<0.001) and in the fifteen month period thereafter (February 2018 to April 2019), the rate of dispensing increased by 4% each month (95%CI=1.027-1.054, p<0.001). Therapeutic shift from over-the-counter codeine products to other opioids was not observed, with no increase in the rate of dispensing of any of the other opioid (or non-opioid) analgesics following the codeine scheduling changes. CONCLUSION: A significant increase in prescription use of paracetamol with codeine 8mg was observed after the February 2018 codeine re-scheduling. Therapeutic shift to stronger opioid analgesics was not observed in the study population.

Predictors of ceasing or reducing statin medication following a large increase in the consumer copayment for medications: a retrospective observational study.

OBJECTIVES: Previous Australian research has shown that following the 21% increase in patient copayments for medications on the Pharmaceutical Benefits Scheme (PBS) in 2005, the use of lipid-lowering therapy declined by 5%. This study aimed to determine the demographic and clinical characteristics of individuals who continued, reduced or ceased their use of statin medication in 2005. STUDY TYPE: Retrospective observational study using routinely collected administrative data. METHOD: We used pharmaceutical claims, hospital separations and mortality records from 2000 to 2005 for the Western Australian population. The cohort comprised stable users of statin medication in 2004. Based on changes in statin use between 2004 and 2005, we identified individuals who: 1) continued using statins; 2) reduced their use by ≥20%; or 3) ceased therapy for at least the first 6 months in 2005. Multivariate logistic regression models were used to determine whether the demographic and clinical characteristics of the three groups differed. RESULTS: There were 205 924 statin users identified in Western Australia as of December 2004. After the January 2005 Pharmaceutical Benefits Scheme (PBS) copayment increase, 3.2% of users ceased their regular statin therapy, 12.9% reduced statin use and 83.9% continued statin use. This represented a 2.1% increase in statin users reducing or ceasing therapy compared to 2004. Predictors of cessation and reduction of statin therapy included younger age, greater socio-economic disadvantage, residing in very remote areas, having general beneficiary status, being a new statin user, having no prior history of ischaemic heart disease, having no prior history of a coronary artery revascularisation procedure, taking no other cardiovascular medication or diabetic medication, taking an increased number of medications, and having a lower level of adherence to statin medication in 2004. CONCLUSION: Compared to 2004, an additional 2.1% of statin users reduced or discontinued medication use in 2005, which may be attributed to an increase in the medication copayment. Individuals with general beneficiary status, and younger and healthier people were at particular risk of cessation or reduction in statin use in 2005.

Use of smoking cessation pharmacotherapies during pregnancy is not associated with increased risk of adverse pregnancy outcomes: a population-based cohort study.

BACKGROUND: Varenicline, bupropion and nicotine replacement therapy (NRT) are three effective pharmacotherapies for smoking cessation, but data about their safety in pregnancy are limited. We assessed the risk of adverse perinatal outcomes and major congenital anomalies associated with the use of these therapies in pregnancy in Australia. METHODS: Perinatal data for 1,017,731 deliveries (2004 to 2012) in New South Wales and Western Australia were linked to pharmaceutical dispensing, hospital admission and death records. We identified 97,875 women who smoked during pregnancy; of those, 233, 330 and 1057 were exposed to bupropion, NRT and varenicline in pregnancy, respectively. Propensity scores were used to match exposed women to those who were unexposed to any smoking therapy (1:10 ratio). Propensity scores and gestational age at exposure were used to match varenicline-exposed to NRT-exposed women (1:1 ratio). Time-dependent Cox proportional hazards models estimated hazard ratios (HR) with 95% confidence intervals (95% CI) for any adverse perinatal event (a composite of 10 unfavourable maternal and neonatal outcomes) and any major congenital anomaly. RESULTS: The risk of any adverse perinatal event was not significantly different between bupropion-exposed and unexposed women (39.2% versus 39.3%, HR 0.93, 95% CI 0.73-1.19) and between NRT-exposed and unexposed women (44.8% vs 46.3%, HR 1.02, 95% CI 0.84-1.23), but it was significantly lower in women exposed to varenicline (36.9% vs 40.1%, HR 0.86, 95% CI 0.77-0.97). Varenicline-exposed infants were less likely than unexposed infants to be born premature (6.5% vs 8.9%, HR 0.72, 95% CI 0.56-0.92), be small for gestational age (11.4% vs 15.4%, HR 0.68, 95% CI 0.56-0.83) and have severe neonatal complications (6.6% vs 8.2%, HR 0.74, 95% CI 0.57-0.96). Among infants exposed to varenicline in the first trimester, 2.9% had a major congenital anomaly (3.5% in unexposed infants, HR 0.91, 95% CI 0.72-1.15). Varenicline-exposed women were less likely than NRT-exposed women to have an adverse perinatal event (38.7% vs 51.4%, HR 0.58, 95% CI 0.33-1.05). CONCLUSIONS: Pregnancy exposure to smoking cessation pharmacotherapies does not appear to be associated with an increased risk of adverse birth outcomes. Lower risk of adverse birth outcomes in varenicline-exposed pregnancies is inconsistent with recommendations that NRT be used in preference to varenicline.

Using Post-market Utilisation Analysis to Support Medicines Pricing Policy: An Australian Case Study of Aflibercept and Ranibizumab Use.

OBJECTIVES: To describe how post-market utilisation analysis in Australia informs cost-effectiveness assessment and pricing decisions, using aflibercept and ranibizumab as case studies. METHODS: Pharmaceutical claims were used to identify initiators of aflibercept and ranibizumab in the year after aflibercept-listing (December 2012), and ranibizumab initiators in the year before aflibercept listing. The dispensing rates for each cohort were calculated, and their demographic and clinical characteristics compared using Kruskal-Wallis tests. RESULTS: Aflibercept and ranibizumab each accounted for half the age-related macular degeneration market following aflibercept listing. Aflibercept initiators had similar dispensing rates to ranibizumab initiators in the pre- and post-aflibercept era (~ three scripts during the first 90 days, and eight to nine scripts during the following 12 months). All cohorts were similar in terms of their age, sex, residential aged-care status and geographic remoteness, and no differences were observed in their overall co-morbidity scores and history of thromboembolic events. CONCLUSIONS: Contrary to clinical trial protocols, post-market utilisation research for ranibizumab and aflibercept demonstrates equivalent use in practice in terms of dose frequency, and the demographic and clinical characteristics of initiators. This supports Australia's decision to pay the same price for each rather than giving a premium to aflibercept. Many other countries are likely overpaying for aflibercept if their utilization patterns are similar to Australia's, and could benefit from incorporating routine utilisation assessment.

Pricing policies for generic medicines in Australia, New Zealand, the Republic of Korea and Singapore: patent expiry and influence on atorvastatin price.

Background: Little is known about how the different policies available to promote use of generic medicines affect the price per unit supplied or sold. This study compares the influence of pricing policies for generic medicines on atorvastatin prices in Australia, New Zealand, the Republic of Korea and Singapore, after market entry of generic atorvastatin. Methods: The annual price of atorvastatin per defined daily dose supplied (price/DDD) was examined for each country from 2006 to 2015 (≥2 years before and ≥4 years after generic market entry). Prices were converted to international dollars and cumulative percentage price reductions were calculated for the first 4 years following generic entry. Results: Prior to market entry of generic atorvastatin, New Zealand had the lowest price ($0.10/DDD), and the Republic of Korea the highest ($2.89/DDD). The price/DDD fell immediately after generic entry in all countries except New Zealand, which already had low prices. The largest immediate decrease was observed in Singapore (46%, year 1). By the fourth year after generic entry, the price had fallen by 46-80% in all countries; however, large price differences between countries remained. Conclusion: New Zealand's tendering system and use of preferred medicines resulted in very low atorvastatin prices well before patent expiry. Pricing policies in the other three countries were effective in reducing atorvastatin prices, with reductions of between 46% and 80% within 4 years of generic entry. Where tendering and use of preferred medicines were the mechanisms for atorvastatin procurement (New Zealand), prices were lowest before and after generic entry. Mandatory price cuts, combined with price-disclosure policies (Australia), produced similar relative price reductions to tendering systems (New Zealand, Singapore) at 4 years. By comparison, mandatory price cuts upon generic entry as the sole measure, while initially effective, were associated with the smallest relative reduction in price after 4 years (Republic of Korea).

The validity of the Rx-Risk Comorbidity Index using medicines mapped to the Anatomical Therapeutic Chemical (ATC) Classification System.

OBJECTIVES: To provide a map of Anatomical Therapeutic Chemical (ATC) Classification System codes to individual Rx-Risk comorbidities and to validate the Rx-Risk Comorbidity Index. DESIGN: The 46 comorbidities in the Rx-Risk Index were mapped to dispensing's indicative of each condition using ATC codes. Prescription dispensing claims in 2014 were used to calculate the Rx-Risk. A baseline logistic regression model was fitted using age and gender as covariates. Rx-Risk was added to the base model as an (1) unweighted score, (2) weighted score and as (3) individual comorbidity categories indicating the presence or absence of each condition. The Akaike information criterion and c-statistic were used to compare the models. SETTING: Models were developed in the Australian Government Department of Veterans' Affairs health claims data, and external validation was undertaken in a 10% sample of the Australian Pharmaceutical Benefits Scheme Data. PARTICIPANTS: Subjects aged 65 years or older. OUTCOME MEASURES: Death within 1 year (eg, 2015). RESULTS: Compared with the base model (c-statistic 0.738, 95% CI 0.734 to 0.742), including Rx-Risk improved prediction of mortality; unweighted score 0.751, 95% CI 0.747 to 0.754, weighted score 0.786, 95% CI 0.782 to 0.789 and individual comorbidities 0.791, 95% CI 0.788 to 0.795. External validation confirmed the utility of the weighted index (c-statistic=0.833). CONCLUSIONS: The updated Rx-Risk Comorbidity Score was predictive of 1-year mortality and may be useful in practice to adjust for confounding in observational studies using medication claims data.

Tobacco policy reform and population-wide antismoking activities in Australia: the impact on smoking during pregnancy.

INTRODUCTION: This study examined the impact of antismoking activities targeting the general population and an advertising campaign targeting smoking during pregnancy on the prevalence of smoking during pregnancy in New South Wales (NSW), Australia. METHODS: Monthly prevalence of smoking during pregnancy was calculated using linked health records for all pregnancies resulting in a birth (800 619) in NSW from 2003 to 2011. Segmented regression of interrupted time series data assessed the effects of the extension of the ban on smoking in enclosed public places to include licensed premises (evaluated in combination with the mandating of graphic warnings on cigarette packs), television advertisements targeting smoking in the general population, print and online magazine advertisements targeting smoking during pregnancy and increased tobacco tax. Analyses were conducted for all pregnancies, and for the population stratified by maternal age, parity and socioeconomic status. Further analyses adjusted for the effect of the Baby Bonus maternity payment. RESULTS: Prevalence of smoking during pregnancy decreased from 2003 to 2011 overall (0.39% per month), and for all strata examined. For pregnancies overall, none of the evaluated initiatives was associated with a change in the trend of smoking during pregnancy. Significant changes associated with increased tobacco tax and the extension of the smoking ban (in combination with graphic warnings) were found in some strata. CONCLUSIONS: The declining prevalence of smoking during pregnancy between 2003 and 2011, while encouraging, does not appear to be directly related to general population antismoking activities or a pregnancy-specific campaign undertaken in this period.

Clinical consultations and investigations before and after discontinuation of endocrine therapy in women with primary breast cancer.

OBJECTIVE: Although clinical trials recommend that women with hormone-dependent primary breast cancer remain on endocrine therapy for at least 5 years, up to 60% discontinue treatment early. We determined whether these women had consulted with clinicians or had investigations for cancer recurrence or metastasis around the time they discontinued endocrine therapy, and whether clinical contact continued after discontinuation. METHODS: We performed case-control and cohort studies of women from the 45 and Up Study who were diagnosed with invasive primary breast cancer between January 2003 and December 2008, and who had ≥12 months of anastrozole, exemestane, letrozole or tamoxifen subsequently dispensed. RESULTS: Women who consulted general practitioners and surgeons/oncologists, and women who had breast ultrasound/mammogram were just as likely to discontinue endocrine therapy within 30 days as those who did not consult these clinicians or have this investigation. In the 6 months after early discontinuation, women who discontinued endocrine therapy were less likely to consult general practitioners (adjusted risk ratio [RRadj] 0.80; 95% confidence interval [CI] 0.75, 0.86) and surgeons/oncologists (RRadj 0.62; 95% CI 0.54, 0.72) than those who remained on therapy. CONCLUSIONS: For most women, endocrine therapy discontinuation did not appear to follow consultation with doctors managing their breast cancer treatment or investigations for recurrence or metastasis. However, women who discontinued endocrine therapy were less likely to consult their general practitioner or surgeon/oncologist in the 6 months following discontinuation than those who remained on therapy. Of the clinician groups studied, general practitioners are best placed to engage and support women to continue pharmacotherapy. However, mechanisms are needed to prompt clinicians to do this at every visit.

High rates of general practice attendance by former prisoners: a prospective cohort study.

OBJECTIVES: To determine the rates at which people recently released from prison attend general practitioners, and to describe service users and their encounters. DESIGN, PARTICIPANTS AND SETTING: Prospective cohort study of 1190 prisoners in Queensland, interviewed up to 6 weeks before expected release from custody (August 2008 - July 2010); their responses were linked prospectively with Medicare and Pharmaceutical Benefits Scheme data for the 2 years after their release. General practice attendance was compared with that of members of the general Queensland population of the same sex and in the same age groups. MAIN OUTCOME MEASURES: Rates of general practice attendance by former prisoners during the 2 years following their release from prison. RESULTS: In the 2 years following release from custody, former prisoners attended general practice services twice as frequently (standardised rate ratio, 2.04; 95% CI, 2.00-2.07) as other Queenslanders; 87% of participants visited a GP at least once during this time. 42% of encounters resulted in a filled prescription, and 12% in diagnostic testing. Factors associated with higher rates of general practice attendance included history of risky opiate use (incidence rate ratio [IRR], 2.09; 95% CI, 1.65-2.65), having ever been diagnosed with a mental disorder (IRR, 1.32; 95% CI, 1.14-1.53), and receiving medication while in prison (IRR, 1.82; 95% CI, 1.58-2.10). CONCLUSIONS: Former prisoners visited general practice services with greater frequency than the general Queensland population. This is consistent with their complex health needs, and suggests that increasing access to primary care to improve the health of former prisoners may be insufficient, and should be accompanied by improving the quality, continuity, and cultural appropriateness of care.

Impact of consumer copayments for subsidised medicines on health services use and outcomes: a protocol using linked administrative data from Western Australia.

INTRODUCTION: Across the world, health systems are adopting approaches to manage rising healthcare costs. One common strategy is a medication copayments scheme where consumers make a contribution (copayment) towards the cost of their dispensed medicines, with remaining costs subsidised by the health insurance service, which in Australia is the Federal Government.In Australia, copayments have tended to increase in proportion to inflation, but in January 2005, the copayment increased substantially more than inflation. Results from aggregated dispensing data showed that this increase led to a significant decrease in the use of several medicines. The aim of this study is to determine the demographic and clinical characteristics of individuals ceasing or reducing statin medication use following the January 2005 Pharmaceutical Benefit Scheme (PBS) copayment increase and the effects on their health outcomes. METHODS AND ANALYSIS: This whole-of-population study comprises a series of retrospective, observational investigations using linked administrative health data on a cohort of West Australians (WA) who had at least one statin dispensed between 1 May 2002 and 30 June 2010. Individual-level data on the use of pharmaceuticals, general practitioner (GP) visits, hospitalisations and death are used.This study will identify patients who were stable users of statin medication in 2004 with follow-up commencing from 2005 onwards. Subgroups determined by change in adherence levels of statin medication from 2004 to 2005 will be classified as continuation, reduction or cessation of statin therapy and explored for differences in health outcomes and health service utilisation after the 2005 copayment change. ETHICS AND DISSEMINATION: Ethics approvals have been obtained from the Western Australian Department of Health (#2007/33), University of Western Australia (RA/4/1/1775) and University of Notre Dame (0 14 167F). Outputs from the findings will be published in peer reviewed journals designed for a policy audience and presented at state, national and international conferences.