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Background: Early evidence on COVID-19 vaccine efficacy came from randomised trials. Many important questions subsequently about vaccine effectiveness (VE) have been addressed using real-world studies (RWS) and have informed most vaccination policies globally. As the questions about VE have evolved during the pandemic so have data, study design, and analytical choices. This scoping review aims to characterise this evolution and provide insights for future pandemic planning-specifically, what kinds of questions are asked at different stages of a pandemic, and what data infrastructure and methods are used?, Methods and Analysis: We will identify relevant studies in the Johns Hopkins Bloomberg School of Public Health VIEW-hub database, which curates both published and preprint VE RWS identified from PubMed, Embase, Scopus, Web of Science, the WHO COVID Database, MMWR, Eurosurveillance, medRxiv, bioRxiv, SSRN, Europe PMC, Research Square, Knowledge Hub, and Google. We will include RWS of COVID-19 VE that reported COVID-19-specific or all-cause mortality (coded as 'death' in the 'effectiveness studies' data set).Information on study characteristics; study context; data sources; design and analytic methods that address confounding will be extracted by single reviewer and checked for accuracy and discussed in a small group setting by methodological and analytic experts. A timeline mapping approach will be used to capture the evolution of this body of literature.By describing the evolution of RWS of VE through the COVID-19 pandemic, we will help identify options for VE studies and inform policy makers on the minimal data and analytic infrastructure needed to support rapid RWS of VE in future pandemics and of healthcare strategies more broadly., Ethics and Dissemination: As data is in the public domain, ethical approval is not required. Findings of this study will be disseminated through peer-reviewed publications, conference presentations, and working-papers to policy makers., Registration: https://doi.org/10.17605/OSF.IO/ZHDKR., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Calcium channel blockers (CCB), a commonly prescribed antihypertensive (AHT) medicine, may be associated with increased risk of breast cancer. The proposed study aims to examine whether long-term CCB use is associated with the development of breast cancer and to characterise the dose-response nature of any identified association, to inform future hypertension management., Methods and Analysis: The study will use data from 2 of Australia's largest cohort studies; the Australian Longitudinal Study on Women's Health, and the 45 and Up Study, combined with the Rotterdam Study. Eligible women will be those with diagnosed hypertension, no history of breast cancer and no prior CCB use at start of follow-up (2004-2009). Cumulative dose-duration exposure to CCB and other AHT medicines will be captured at the earliest date of: the outcome (a diagnosis of invasive breast cancer); a competing risk event (eg, bilateral mastectomy without a diagnosis of breast cancer, death prior to any diagnosis of breast cancer) or end of follow-up (censoring event). Fine and Gray competing risks regression will be used to assess the association between CCB use and development of breast cancer using a generalised propensity score to adjust for baseline covariates. Time-varying covariates related to interaction with health services will also be included in the model. Data will be harmonised across cohorts to achieve identical protocols and a two-step random effects individual patient-level meta-analysis will be used., Ethics and Dissemination: Ethical approval was obtained from the following Human research Ethics Committees: Curtin University (ref No. HRE2022-0335), NSW Population and Health Services Research Ethics Committee (2022/ETH01392/2022.31), ACT Research Ethics and Governance Office approval under National Mutual Acceptance for multijurisdictional data linkage research (2022.STE.00208). Results of the proposed study will be published in high-impact journals and presented at key scientific meetings., Trial Registration Number: NCT05972785., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Observational studies are increasingly used to inform health decision-making when randomised trials are not feasible, ethical or timely. The target trial approach provides a framework to help minimise common biases in observational studies that aim to estimate the causal effect of interventions. Incomplete reporting of studies using the target trial framework limits the ability for clinicians, researchers, patients and other decision-makers to appraise, synthesise and interpret findings to inform clinical and public health practice and policy. This paper describes the methods that we will use to develop the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) reporting guideline., Methods/design: The TARGET reporting guideline will be developed in five stages following recommended guidance. The first stage will identify target trial reporting practices by systematically reviewing published studies that explicitly emulated a target trial. The second stage will identify and refine items to be considered for inclusion in the TARGET guideline by consulting content experts using sequential online surveys. The third stage will prioritise and consolidate key items to be included in the TARGET guideline at an in-person consensus meeting of TARGET investigators. The fourth stage will produce and pilot-test both the TARGET guideline and explanation and elaboration document with relevant stakeholders. The fifth stage will disseminate the TARGET guideline and resources via journals, conferences and courses., Ethics and Dissemination: Ethical approval for the survey has been attained (HC220536). The TARGET guideline will be disseminated widely in partnership with stakeholders to maximise adoption and improve reporting of these studies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Purpose: The POPPY II cohort is an Australian state-based cohort linking data for a population of individuals prescribed opioid medicines, constructed to allow a robust examination of the long-term patterns and outcomes of prescription opioid use., Participants: The cohort includes 3 569 433 adult New South Wales residents who initiated a subsidised prescription opioid medicine between 2003 and 2018, identified through pharmacy dispensing data (Australian Pharmaceutical Benefits Scheme) and linked to 10 national and state datasets and registries including rich sociodemographic and medical services data., Findings to Date: Of the 3.57 million individuals included in the cohort, 52.7% were female and 1 in 4 people were aged ≥65 years at the time of cohort entry. Approximately 6% had evidence of cancer in the year prior to cohort entry. In the 3 months prior to cohort entry, 26.9% used a non-opioid analgesic and 20.5% used a psychotropic medicine. Overall, 1 in 5 individuals were initiated on a strong opioid (20.9%). The most commonly initiated opioid was paracetamol/codeine (61.3%), followed by oxycodone (16.3%)., Future Plans: The POPPY II cohort will be updated periodically, both extending the follow-up duration of the existing cohort, and including new individuals initiating opioids. The POPPY II cohort will allow a range of aspects of opioid utilisation to be studied, including long-term trajectories of opioid use, development of a data-informed method to assess time-varying opioid exposure, and a range of outcomes including mortality, transition to opioid dependence, suicide and falls. The duration of the study period will allow examination of population-level impacts of changes to opioid monitoring and access, while the size of the cohort will also allow examination of important subpopulations such as people with cancer, musculoskeletal conditions or opioid use disorder., Competing Interests: Competing interests: The authors declare no direct competing interests relevant to this study. LD has received untied educational grant funding from Indivior, Mundipharma, Seqirus, and Reckitt Benckiser. AD has received untied educational grant funding from Braeburn/Camerus, Indivior, and Mundipharma. SL has received untied educational grant funding from Indivior. AW is paid by the Australian Commonwealth government as the chair of the Pharmaceutical Benefits Advisory Committee (PBAC). SAP is a member of the Drug Utilisation Sub-Committee (DUSC) of the PBAC., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: In Australia, suicide is the leading cause of death for people aged 15-44 years. Health professionals deliver most of our key suicide prevention strategies via health services, but other efficacious population-level strategies include means restriction and public awareness campaigns. Currently, we have no population-level data allowing us to determine which individuals, in what parts of Australia, are likely to use our most promising interventions delivered by health services. The aims of this study are to describe: (1) health service utilisation rates in the year prior to death by suicide, and how this varies by individual case characteristics; (2) prescribed medicines use in the year prior to death by suicide, medicines used in suicide by poisoning and how this varies by individual case characteristics., Methods and Analysis: This is a population-based case series study of all suicide cases in Australia identified through the National Coronial Information System (NCIS) from 2013 to 2019. Cases will be linked to administrative claims data detailing health service use and medicines dispensed in the year before death. We will also obtain findings from the coronial enquiry, including toxicology. Descriptive statistics will be produced to characterise health service and prescribed medicine use and how utilisation varies by age, sex, method of death and socioeconomic status. We will explore the geographical variability of health service and medicine use, highlighting regions in Australia associated with more limited access., Ethics and Dissemination: This project involves the use of sensitive and confidential data. Data will be linked using a third-party privacy-preserving protocol meaning that investigators will not have access to identifiable information once the data have been linked. Statistical analyses will be carried out in a secure environment. This study has been approved by the following ethics committees: (1) the Justice Department Human Research Ethics Committee (REF: CF/17/23250), (2) the Western Australian Coroners Court (REF: EC 14/18 M0400), (3) the Australian Institute of Health and Welfare (REF: EO2017/4/366) and (4) NSW Population & Health Services Research Ethics Committee (REF: 2017/HRE1204). Findings will be published in peer-reviewed journals, presented at conferences and communicated to regulatory authorities, clinicians and policy-makers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To explore the perspectives of general practitioners (GPs) concerning the risk of opioid misuse in people with cancer and pain and related clinical considerations., Design: A qualitative approach using semistructured telephone interviews. Analysis used an integrative approach., Setting: Primary care., Participants: Australian GPs with experience of prescribing opioids for people with cancer and pain., Results: Twenty-two GPs participated, and three themes emerged. Theme 1 ( Misuse is not the main problem ) contextualised misuse as a relatively minor concern compared with pain control and toxicity, and highlighted underlying systemic factors, including limitations in continuity of care and doctor expertise. Theme 2 ( 'A different mindset' for cancer pain ) captured participants' relative comfort in prescribing opioids for pain in cancer versus non-cancer contexts, and acknowledgement that compassion and greater perceived community acceptance were driving factors, in addition to scientific support for mechanisms and clinical efficacy. Participant attitudes towards prescribing for people with cancer versus non-cancer pain differed most when cancer was in the palliative phase, when they were unconcerned by misuse. Participants were equivocal about the risk-benefit ratio of long-term opioid therapy in the chronic phase of cancer, and were reluctant to prescribe for disease-free survivors. Theme 3 ( 'The question is always, 'how lazy have you been?' ) captured participants' acknowledgement that they sometimes prescribed opioids for cancer pain as a default, easier option compared with more holistic pain management., Conclusions: Findings highlight the role of specific clinical considerations in distinguishing risk of opioid misuse in the cancer versus non-cancer population, rather than diagnosis per se. Further efforts are needed to ensure continuity of care where opioid prescribing is shared. Greater evidence is needed to guide opioid prescribing in disease-free survivors and the chronic phase of cancer, especially in the context of new treatments for metastatic disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The aims of this program of research are to use linked health and law enforcement data to describe individuals presenting to emergency and inpatient healthcare services with an acute alcohol harm or problematic alcohol use; measure their health service utilisation and law enforcement engagement; and quantify morbidity, mortality, offending and incarceration., Methods and Analysis: We will assemble a retrospective cohort of people presenting to emergency departments and/or admitted to hospitals between 1 January 2005 and 31 December 2014 in New South Wales, Australia with a diagnosis denoting an acute alcohol harm or problematic alcohol use. We will link these data with records from other healthcare services (eg, community-based mental healthcare data, cancer registry), mortality, offending and incarceration data sets. The four overarching areas for analysis comprise: (1) describing the characteristics of the cohort at their first point of contact with emergency and inpatient hospital services in the study period with a diagnosis indicating an acute alcohol harm and/or problematic alcohol use; (2) quantifying health service utilisation and law enforcement engagement; (3) quantifying rates of mortality, morbidity, offending and incarceration; and (4) assessing predictors (eg, age, sex) of mortality, morbidity, offending and incarceration among this cohort., Ethics and Dissemination: Ethics approval has been provided by the New South Wales Population and Health Services Research Ethics Committee. We will report our findings in accordance with the REporting of studies Conducted using Observational Routinely collected health Data (RECORD) statement and Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER) where appropriate. We will publish data in tabular, aggregate forms only. We will not disclose individual results. We will disseminate project findings at scientific conferences and in peer-reviewed journals. We will aim to present findings to relevant stakeholders (eg, addiction medicine and emergency medicine specialists, policy makers) to maximise translational impact of research findings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To examine the prevalence, costs and trends (2010-2014) for 21 low-value inpatient procedures in a privately insured Australian patient cohort., Design: We developed indicators for 21 low-value procedures from evidence-based lists such as Choosing Wisely, and applied them to a claims data set of hospital admissions. We used narrow and broad indicators where multiple low-value procedure definitions exist., Setting and Participants: A cohort of 376 354 patients who claimed for an inpatient service from any of 13 insurance funds in calendar years 2010-2014; approximately 7% of the privately insured Australian population., Main Outcome Measures: Counts and proportions of low-value procedures in 2014, and relative change between 2010 and 2014. We also report both the Medicare (Australian government) and the private insurance financial contributions to these low-value admissions., Results: Of the 14 662 patients with admissions for at least 1 of the 21 procedures in 2014, 20.8%-32.0% were low-value using the narrow and broad indicators, respectively. Of the 21 procedures, admissions for knee arthroscopy were highest in both the volume and the proportion that were low-value (1607-2956; 44.4%-81.7%).Seven low-value procedures decreased in use between 2010 and 2014, while admissions for low-value percutaneous coronary interventions and inpatient intravitreal injections increased (51% and 8%, respectively).For this sample, we estimated 2014 Medicare contributions for admissions with low-value procedures to be between $A1.8 and $A2.9 million, and total charges between $A12.4 and $A22.7 million., Conclusions: The Australian federal government is currently reviewing low-value healthcare covered by Medicare and private health insurers. Estimates from this study can provide crucial baseline data and inform design and assessment of policy strategies within the Australian private healthcare sector aimed at curtailing the high volume and/or proportions of low-value procedures., Competing Interests: Competing interests: KC receives salary support via a doctoral scholarship from the Capital Markets Cooperative Research Centre-Health Market Quality Program, and consulting fees from Queensland Health Department. TB-P receives salary support via a doctoral scholarship from the Capital Markets Cooperative Research Centre-Health Market Quality Program, and consulting fees from Queensland Health Department. AGE receives salary support as the HCF Research Foundation Professorial Research Fellow and is a Ministerial appointee to the Australian Medicare Benefits (MBS) Review Taskforce, receives consulting sitting fees from Cancer Australia, the Capital Markets Cooperative Research Centre-Health Quality Program, NPS MedicineWise (facilitator of Choosing Wisely Australia), The Royal Australasian College of Physicians (facilitator of the EVOLVE programme) and the Australian Commission on Safety and Quality in Health Care, and Queensland Health (state department of health), and is on the advisory board of the NSW Bureau of Health Information; S-AP is a member of the Drug Utilisation Sub-Committee of the Pharmaceutical Benefits Advisory Committee (PBAC) and receives consulting fees from NPS MedicineWise., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To characterise trends in self-poisoning and psychotropic medicine use in young Australians., Design: Population-based retrospective cohort study., Setting: Calls taken by the New South Wales and Victorian Poisons Information Centres (2006-2016, accounting for 70% of Australian poisoning calls); medicine dispensings in the 10% sample of Australian Pharmaceutical Benefits Scheme data (July 2012 to June 2016)., Participants: People aged 5-19 years., Main Outcome Measures: Yearly trends in intentional poisoning exposure calls, substances taken in intentional poisonings, a prevalence of psychotropic use (dispensing of antidepressants, antipsychotics, benzodiazepines and medicines for attention deficit hyperactivity disorder (ADHD))., Results: There were 33 501 intentional poisonings in people aged 5-19 years, with an increase of 8.39% per year (95% CI 6.08% to 10.74%, p<0.0001), with a 98% increase overall, 2006-2016. This effect was driven by increased poisonings in those born after 1997, suggesting a birth cohort effect. Females outnumbered males 3:1. Substances most commonly taken in self-poisonings were paracetamol, ibuprofen, fluoxetine, ethanol, quetiapine, paracetamol/opioid combinations, sertraline and escitalopram. Psychotropic dispensing also increased, with selective serotonin reuptake inhibitors (SSRIs) increasing 40% and 35% July 2012 to June 2016 in those aged 5-14 and 15-19, respectively. Fluoxetine was the most dispensed SSRI. Antipsychotics increased by 13% and 10%, while ADHD medication dispensing increased by 16% and 10%, in those aged 5-14 and 15-19, respectively. Conversely, dispensing of benzodiazepines to these age groups decreased by 4% and 5%, respectively., Conclusions: Our results signal a generation that is increasingly engaging in self-harm and is increasingly prescribed psychotropic medications. These findings indicate growing mental distress in this cohort. Since people who self-harm are at increased risk of suicide later in life, these results may foretell future increases in suicide rates in Australia., Competing Interests: Competing interests: RC is an associate investigator on an untied educational grant from Seqirus to study tapentadol misuse. This has no relation to the current study. All other authors declare no conflicts to disclose., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To quantify the relationship between home medicines review (HMR) receipt in older adults and sociodemographic, medication-related and health factors., Design: Prospective cohort analysis., Settings, Participants, Measurements: Questionnaire data from a population-based cohort study of individuals aged ≥45 years, Sydney, Australia were linked with primary healthcare data, medication and hospitalisation data, to ascertain factors associated with HMR receipt during the period July 2009-June 2014. Medication-related factors included exposure to five and more medications (polypharmacy), narrow therapeutic index medicines, potentially inappropriate prescribing defined using Beers Criteria medicines, and anticholinergic and sedative drugs, defined using the Drug Burden Index (DBI). Poisson and Cox regression models were used to evaluate HMR receipt in relation to sociodemographic, behavioural and health characteristics, and time-varying factors including medication use and hospitalisations., Primary Outcome: HMR receipt during the 5-year study period., Results: Over 5 years of follow-up, 4.7% (n=6115) of 131 483 participants received at least one HMR. Five-year HMR receipt was: 1.5% in people using <5 medications at baseline, 6.8% with 5-9 medications, 12.7% with ≥10 medications, 8.8% using Narrow Therapeutic Index medicines, 6.8% using Beers Criteria potentially inappropriate medicines and 7.4% using DBI medicines. Age-sex stratified HRs for HMR receipt were 6.07 (95% CI: 5.58 to 6.59) and 12.46 (11.42 to 13.59) for concurrent use of 5-9 and ≥10 versus <5 medications, respectively. The age-sex adjusted rate ratio for HMR receipt was 2.65 (2.51 to 2.80) with poor versus good self-reported health; this association was attenuated substantially following additional adjustment for polypharmacy., Conclusions: HMR was common in individuals using multiple medications, a formal indication for general practitioner referral and, to a lesser extent, with poorer health and other markers of high-risk prescribing. Despite this, HMR use over a 5-year period was generally below 10%, even in high-risk groups, suggesting substantial potential for improvement in uptake and targeting., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Advances in systemic therapy for early and metastatic breast cancer (BC) over the last two decades have improved patients' survival, but their impact on metastatic disease outcomes at a population level is not well described. The aim of this study is to investigate changes in the incidence, site and survival of metastatic disease for women with a first diagnosis of BC in 2001-2002 vs 2006-2007., Methods and Analysis: Population-based retrospective cohort study of women with first primary invasive BC registered in the New South Wales (NSW) Cancer Registry in 2001-2002 and 2006-2007. We will use linked records from NSW hospitals, dispensed medicines, outpatient services and death registrations to determine: women's demographic and tumour characteristics; treatments received; time to first distant metastasis; site of first metastasis and survival. We will use the Kaplan-Meier method to estimate cumulative incidence of distant metastasis, distant recurrence-free interval and postmetastasis survival by extent of disease at initial diagnosis, site of metastasis and treatment-defined tumour receptor type (hormone receptor-positive, human epidermal growth factor receptor-2-positive, triple negative). We will use Cox proportional hazards regression to estimate the relative effects of prognostic factors, and we will compare systemic therapy patterns by area-of-residence and area-level socioeconomic status to examine equity of access to healthcare., Ethics and Dissemination: Research ethics committee approval was granted by the Australian Institute of Health and Welfare (#EO2017/2/255), NSW Population and Health Services (#HREC/17/CIPHS/19) and University of Notre Dame Australia (#0 17 144S). We will disseminate research findings to oncology, BC consumer and epidemiology audiences through national and international conference presentations, lay summaries to BC consumer groups and publications in international peer-reviewed oncology and cancer epidemiology journals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Opioid prescribing has increased 15-fold in Australia in the past two decades, alongside increases in a range of opioid-related harms such as opioid dependence and overdose. However, despite concerns about increasing opioid use, extramedical use and harms, there is a lack of population-level evidence about the drivers of long-term prescribed opioid use, dependence, overdose and other harms., Methods and Analysis: We will form a cohort of all adult residents in New South Wales (NSW), Australia, who initiated prescribed opioids from 2002 using Pharmaceutical Benefits Scheme dispensing records. This cohort will be linked to a wide range of other datasets containing information on sociodemographic and clinical characteristics, health service use and adverse outcomes (eg, opioid dependence and non-fatal and fatal overdose). Analyses will initially examine patterns and predictors of prescribed opioid use and then apply regression and survival analysis to quantify the risks and risk factors of adverse outcomes associated with prescribed opioid use., Ethics and Dissemination: This study has received full ethical approval from the Australian Institute of Health and Welfare Ethics Committee, the NSW Population and Health Services Research Committee and the ACT Health Human Research Ethics Committee. This will be the largest postmarketing surveillance study of prescribed opioids undertaken in Australia, linking exposure and outcomes and examining risk factors for adverse outcomes of prescribed opioids. As such, this work has important translational promise, with direct relevance to regulatory authorities and agencies worldwide. Project findings will be disseminated at scientific conferences and in peer-reviewed journals. We will also conduct targeted dissemination with policy makers, professional bodies and peak bodies in the pain, medicine and addiction fields through stakeholder workshops and advisory groups. Results will be reported in accordance with the REporting of studies Conducted using Observational Routinely collected Data (RECORD) Statement., Competing Interests: Competing interests: The authors declare no direct competing interests relevant to this study protocol. Some of the authors have received investigator-initiated untied educational grants from Reckitt Benckiser/Indivior for studies of buprenorphine-naloxone (LD and RPM), buprenorphine depot (LD and AD), naloxone (SL and LD), the development of an opioid-related behaviour scale (LD and RPM) and a study of opioid substitution therapy uptake among chronic non-cancer pain patients (LD and RPM). Some of the authors have also received investigator-initiated untied educational grants for postmarketing surveillance studies of a tamper-resistant opioid formulation from Mundipharma (LD) and for tapentadol from Seqirus Pty Ltd (LD). No company had any knowledge or involvement in this study. AW is paid by the Australian Commonwealth government as the chair of the Pharmaceutical Benefits Advisory Committee (PBAC). SAP is a member of the Drug Utilisation Sub-Committee (DUSC) of the PBAC., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The introduction of targeted therapies for cancer has contributed to dramatic improvements in patient survival. Nevertheless, several targeted therapies have been associated with 'off-target' adverse effects, based on varying levels of evidence. To date, this evidence has not been systematically synthesised. We will synthesise published systematic review evidence of cardiovascular toxicity associated with targeted cancer therapies., Methods and Analysis: We will include systematic reviews of randomised controlled trials and observational studies that report on cardiovascular outcomes for individual agents. We will identify systematic reviews by applying predeveloped, standardised search strategies within Embase, Medline and Cochrane Central. Two independent reviewers will identify reviews published up to 31 December 2016 using predefined eligibility criteria. They will resolve ambiguous cases through consensus, arbitrated by a third reviewer if required. The reviewers will extract and report data according to methodological guidelines for overviews provided by the Cochrane Collaboration, Joanna Briggs Institute and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. They will assess the quality of included reviews by applying the Assessment of Multiple Systematic Reviews tool. They will judge the quality of evidence in included reviews based on their assessment of bias and incorporation into the interpretation of findings. In synthesising the evidence, we will classify agents based on systematic review evidence of toxicity (sufficient, probable, possible or indeterminate) for specific cardiovascular outcomes (congestive heart failure, myocardial infarction, ischaemic heart disease, left ventricular ejection fraction decline, cerebrovascular disease, pulmonary embolism, thrombosis and hypertension). This will provide clinicians and patients with an accessible synthesis based on robust methodology., Ethics and Dissemination: Ethics approval is not required for overviews. We will conduct the study in collaboration with consumer representatives. We will submit results for peer-review publication, and disseminate them through established clinical and consumer networks., Prospero Registration Number: CRD42017080014., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: The management of human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) has changed dramatically with the introduction and widespread use of HER2-targeted therapies. However, there is relatively limited real-world information on patterns of use, effectiveness and safety in whole of population cohorts. The research programme detailed in this protocol will generate evidence on the prescribing patterns, safety monitoring and outcomes of patients with BC treated with HER2-targeted therapies in Australia., Methods/design: Our ongoing research programme will involve a series of retrospective cohort studies that include every patient accessing Commonwealth-funded HER2-targeted therapies for the treatment of early BC and advanced BC in Australia. At the time of writing, our cohorts consist of 11 406 patients with early BC and 5631 with advanced BC who accessed trastuzumab and lapatinib between 2001 and 2014. Pertuzumab and trastuzumab emtansine were publicly funded for metastatic BC in 2015, and future data updates will include patients accessing these medicines. We will use dispensing claims for cancer and other medicines, medical service claims and demographics data for each patient accessing HER2-targeted therapies to undertake this research., Ethics and Dissemination: Ethics approval has been granted by the Population Health Service Research Ethics Committee and data access approval has been granted by the Australian Department of Human Services (DHS) External Review Evaluation Committee. Our findings will be reported in peer-reviewed publications, conference presentations and policy forums. By providing detailed information on the use and outcomes associated with HER2-targeted therapies in a national cohort treated in routine clinical care, our research programme will better inform clinicians and patients about the real-world use of these treatments and will assist third-party payers to better understand the use and economic costs of these treatments., Competing Interests: BEK has received conference support and a speaker's honorarium from Roche., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Introduction: After medicines have been subsidised in Australia we know little about their use in routine clinical practice, impact on resource utilisation, effectiveness or safety. Routinely collected administrative health data are available to address these issues in large population-based pharmacoepidemiological studies. By bringing together cross-jurisdictional data collections that link drug exposure to real-world outcomes, this research programme aims to evaluate the use and impact of cancer medicines in a subset of elderly Australians in the real-world clinical setting., Methods and Analysis: This ongoing research programme involves a series of retrospective cohort studies of Australian Government Department of Veterans' Affairs (DVA) clients. The study population includes 104 635 veterans who reside in New South Wales, Australia, and were aged 65 years and over as of 1 July 2004. We will investigate trends in cancer medicines use according to cancer type and other sociodemographic characteristics as well as predictors of the initiation of cancer medicines and other treatment modalities, survival and adverse outcomes among patients with cancer. The programme is underpinned by the linkage of eight health administrative databases under the custodianship of the DVA and the New South Wales Ministry of Health, including cancer notifications, medicines dispensing data, hospitalisation data and health services data. The cancer notifications database is available from 1994 with all other databases available from 2005 onwards., Ethics and Dissemination: Ethics approval has been granted by the DVA and New South Wales Population and Health Service Research Ethics Committees., Results: Results will be reported in peer-reviewed publications, conference presentations and policy forums. The programme has high translational potential, providing invaluable evidence about cancer medicines in an elderly population who are under-represented in clinical trials.

Objective: The aim was to examine statin discontinuation rates in a cohort of elderly Australians with newly diagnosed cancer using population-based secondary health data., Design: Observational cohort study., Setting: New South Wales, the largest jurisdiction in Australia. The Pharmaceutical Benefits and Repatriation Pharmaceutical Benefits Schemes are national programmes subsidising prescription drugs to the Australian population and Australian Government Department of Veterans' Affairs clients., Participants: The cohort comprised 1731 cancer patients aged ≥65 years with evidence of statin use in the 90 days prior to diagnosis. They were matched to 3462 non-cancer patients prescribed statins in the same period., Main Outcome Measure: The authors compared statin discontinuation rates up to 4 years post-diagnosis and examined the factors associated with statin discontinuation., Results: The proportion of cancer patients discontinuing statin therapy at 4 years (27%) was comparable to the comparison cohort; however, significantly higher proportions of the cancer cohort discontinued statins than the comparison cohort at 3, 6 and 12 months of follow-up (9.7% vs 7.4% at 12 months, respectively). More than 30% of cancer patients who died were dispensed statins within 30 days of death. Discontinuation of statin therapy in cancer patients was associated with regionalised and distant disease spread at diagnosis (p<0.001), older age (p=0.006), upper gastrointestinal organs and liver cancer (aHR 2.95, 95% CI 1.92 to 4.53) and cancer of the lung, bronchus and trachea (aHR 1.99, 95% CI 1.32 to 3.00) and poorer survival., Conclusions: Medications should be rationalised at the time of a cancer diagnosis, especially in the setting of a poor prognosis. At least for some patients in our cohort, statin therapy may be inappropriately continued which adds unnecessarily to therapeutic burden.