Project title: Exclusion of patients with liver disease from interventional cardiovascular clinical trials: a meta-epidemiological study.

Potential Supervisors: Karen Waller

Project description: Chronic liver disease is increasing in prevalence, with metabolic associated steatotic liver disease (MASLD) estimated to affect at least 30% globally. Other liver diseases such as viral hepatitis, are less common, but affect 5-10% in some countries.

However, the leading cause of death among patients with MASLD is cardiovascular disease. The excess burden of death due to cardiovascular disease increases with worsening liver fibrosis. Understanding the safety and efficacy of medications for cardiovascular disease among this population is important for the long-term outcomes of this group.

Clinical trials in cardiovascular disease have been shown to routinely exclude key populations, including those with advanced age and chronic kidney disease. Exclusions related to liver function tests or the presence of liver disease have been shown in other trial populations (e.g. cancer), but the exclusion of patients with liver disease from cardiovascular trials has not been studied.

Main research question: This project aims to understand whether patients with liver disease have been systematically excluded from cardiovascular clinical trials. Specifically, it will ascertain the rate and nature of liver-related exclusions from a systematic review of key cardiovascular trials.

Research methodology: A systematic review of cardiovascular clinical trials will be undertaken using clinical trial registries and journal databases. Listed exclusions relating to liver function test abnormalities (including ALT elevation, thrombocytopenia), imaging findings, presence of liver diseases (including viral hepatitis) or cirrhosis will be noted for each trial. Results will be reported as per reporting guidelines for meta-epidemiological studies.

The summer scholar will gain specific experience with systematic review and meta-epidemiological study methodologies. They will also develop transferrable research skills, including quantitative analysis in the synthesis of results. The scholar would be supported to develop results towards conference presentation and manuscript preparation, with co-authorship depending on the contribution made. There are opportunities to extend this work into further formal research programs for a well-performing candidate.

Project title: Interventions during study design and conduct to reduce the risk of bias in interventional studies.

Potential Supervisors:  Aidan Tan, Lene Seidler and Angela Webster

Project description: The number of publications in the field of medicine and health has rapidly increased over the past decade. Yet, the rising number of studies may not meaningfully contribute to evidence syntheses (e.g., systematic reviews and meta-analyses) which inform clinical guidelines and evidence-based practice if they are at high risk of bias. Bias refers to a systematic deviation of the observed effect from the true value and could result in overestimation or underestimation of an effect. While bias is difficult to quantify, risk of bias can be qualified or evaluated, and studies with low risk of bias are more likely to produce results closer to the true value.

A review of 205 meta-analyses from the Cochrane database found that more than 40% of randomized controlled trials (RCTs) included in meta-analyses were at high risk of bias. At least half of the studies had incomplete reports, resulting in the outcomes of these studies being unusable and not reproducible. These problems are even greater in non-randomized studies. In 2014, The Lancet published a series of articles exploring the impact of low-quality medical research on the value of scientific research and the waste of resources, and high risk of bias studies do not return the benefits that expensive research funding deserves. Additionally, biased research can be regarded as unethical because participants put themselves at risk to advance medical research, which may not lead to useful findings.

The aim of this scoping review is to synthesize interventions during study design or conduct to reduce risk of bias in interventional studies.

Main research question: What interventions during study design or conduct have been implemented to reduce risk of bias in interventional studies? How effective are these interventions?

As a research intern, you will work with a team of expert supervisors. You will learn many useful and transferrable research skills including information management, study design and administration, critical appraisal, database management, data entry and cleaning, data analysis and synthesis and report drafting. The applicant will also develop skills in preparing a manuscript for publication in a peer-reviewed journal. The successful applicant who contributes well will be rewarded with co-authorship on any resulting conference presentations or publications. There may be opportunities to develop and extend this topic area into further projects suitable for honours, MD projects, or MPhil work. Preference will be given to applicants who explain their interest and personal objectives.

Project title: A scoping review of evidence criteria used to inform recommendations for surveillance strategies following primary cancer treatment.

Potential Supervisors: Sally Lord

Project description: Surveillance testing can be recommended after initial treatment of primary cancer, as an addition to clinical follow-up, for early detection of cancer progression that warrants new treatment. The trade-off between potential health benefits versus harms for testing and different testing intervals versus clinical follow-up depends on test accuracy, the benefits of earlier treatment, the risk of progression, and other patient-centered factors. Randomised controlled trials of surveillance strategies could ideally provide evidence to guide recommendations but are rarely conducted. As a result, surveillance recommendations are generally based on considering a range of criteria and types of evidence, and approaches may vary between guideline panels. Optimal surveillance strategies can be expected to change over time as more effective treatments are introduced, more accurate or more efficient tests are available eg. circulating tumour cells, and potentially models for classifying risk of progression. As a first step for developing an evidence framework and tools to support evidence generation and decision-making for assessing new surveillance strategies, the student will conduct a scoping review of Australian clinical guidelines for the 20 most common cancers in Australia to describe the current inclusion of surveillance recommendations, types of evidence considered, and evidence integration approaches.

Main research question: What criteria, types of evidence, and evidence integration approaches are used to formulate current clinical guideline recommendations for surveillance strategies following primary treatment of cancer.

Research methodology: This will be a scoping review. The five main steps will be: formulating the research question; searching for relevant clinical guidelines and identifying surveillance recommendations; categorizing evidence criteria, types of evidence and integration approach used to support recommendations; extracting data; and summarizing and reporting results.

The summer scholar will gain experience in scoping/systematic review methods, appraising clinical guideline recommendations, and research reporting. The results will be used to inform the development of a larger research project.

Project title: Researcher adherence to data sharing policies of funders and journals.

Potential Supervisors: Aidan Tan, Lene Seidler, Angela Webster

Project description: Billions of public funding are invested annually in clinical trials, $288 million in Australia alone. People put their trust in science by participating in clinical trials to advance health care. Yet, only about half of all studies publish their results in medical journals, and the ones that are published often do not report all their outcomes, or over emphasise benefits omitting less favourable findings. This means policy and clinical practice risk relying on biased or incomplete evidence. One solution is to champion data sharing and re-use for subsequent projects and analyses. On-sharing trial data maximises the value of trial investment, by ensuring data keep contributing to the evidence base beyond the end of the trial. One example is sharing of row-by-row individual participant data (IPD) of completed studies, to enable individual participant data meta-analysis. This can add tremendous value to trials, and is increasingly mandated by funders. In the scientific community, in-principle support for data sharing is strong, however the in-practice commitment to sharing data is low.

The practice of data sharing is influenced by data sharing policies. Over the past few decades, funders and journals have developed a wide range of data sharing policies. However, there has been little to no change in the gap between the high level of in-principle support for data sharing and low level of in-practice willingness to share data. This may be related to researcher adherence to the data sharing policies of journals.

This summer internship will investigate researcher adherence to data sharing policies of funders and journals. We are collecting data on study characteristics, initial data sharing plans in publicly available research protocols, and final data sharing plans in published data sharing statements. Once completed, we hope this work will contribute to the development of an improved data sharing toolkit, to maximise the implementation of widespread data sharing. This will leverage maximum contribution and minimise research waste and strengthen the public acceptability of data sharing.

Main research question: To what extent do researchers adhere to the data sharing policies of funders and journals?

As a research intern, you will work with a team of expert supervisors. You will learn many useful and transferrable research skills including information management, study design and administration, critical appraisal, database management, data entry and cleaning, data analysis and synthesis and report drafting. The applicant will also develop skills in preparing a manuscript for publication in a peer-reviewed journal. The successful applicant who contributes well will be rewarded with co-authorship on any resulting conference presentations or publications. There may be opportunities to develop and extend this topic area into further projects suitable for honours, MD projects, or MPhil work. Preference will be given to applicants who explain their interest and personal objectives.

Project title: Developing a framework for best practice IPD meta-analysis.

Potential Supervisors: Lene Seidler, and Sol Libesman

Project description: Meta-analyses summarise all available information to inform policy and practice. They bring together results from different studies to enable decisions on which treatment works best in practice. Traditionally meta-analyses were limited to extracting summary information of published literature. Individual participant data meta-analysis (IPD-MA) is an alternative approach involving collection of raw data for each participant from relevant trials. IPD-MA offers more flexible and powerful approaches to analysis, to better inform clinical decision-making. Furthermore, often the information provided in the published literature that would be required to perform an analysis is either not available or not able to be harmonised. IPD enhances the ability to gleam and harmonise the necessary information. For these reasons IPD-MA is considered the gold standard form of meta-analysis. However, IPD-MA analyses are a relatively new approach and heterogeneous methods with varying degrees of appropriateness are often applied. Understanding how IPD-MA are applied will help future research practice produce better and more reliable evidence for decision-making. Optimising IPD-MA methodologies will ensure maximum benefit is gained from the considerable resources they require.

This summer internship will investigate the practices of prior IPD-MAs of trials. It will involve the extraction of key characteristics and details of methodologies used. This will help identify the trends of current practices, including inconsistencies and shortcomings. Additionally, it will involve sending online surveys to authors of previous IPD-MAs to identify methodology gaps and uncertainties needing clarification. This work will culminate to perform a scoping review across the field of IPD-MAs. This will help us understand the strengths and limitations of what is currently considered the gold standard form of evidence synthesis, IPD MA.

Main research question: What is the landscape of current practices in IPD-MA methodologies and are there any shortfalls in these practices?

As a research intern, you will work with a team of expert supervisors. You will learn many useful and transferrable research skills including information management, study design and administration, critical appraisal, database management, data entry and cleaning, data analysis and synthesis and report drafting. The applicant will also develop skills in preparing a manuscript for publication in a peer-reviewed journal. The successful applicant who contributes well will be rewarded with co-authorship on any resulting conference presentations or publications. There may be opportunities to develop and extend this topic area into further projects suitable for honours, MD projects, or MPhil work. Preference will be given to applicants who explain their interest and personal objectives.

Project title: Routine exclusions of people with disabilities in cardiovascular clinical trials in low- and middle-income countries.

Potential Supervisors: Shiva Raj Mishra

Project description: Cardiovascular diseases (CVDs) are increasingly recognized as a major health challenge, disproportionately affecting marginalized and vulnerable populations. People with disabilities face up to eight times higher rates and earlier onset of CVD compared to general population. World Health Organisation estimates that nearly 1.3 billion population have some forms of disability worldwide, of which 80% live in low- and middle-income countries (LMICs). Cardiovascular diseases cover a wide range of heart and vascular conditions like coronary artery disease, heart failure, and arrhythmias, and have been persistently ranked as the primary causes of global mortality and morbidity. Reducing CVD deaths requires primary and secondary prevention measures such as through improved diagnosis, screening, and prevention. Randomized controlled trials (RCTs) serve as the gold standard for generating evidence for tackling burden of CVD. However, the high rate of routine exclusions in clinical trials introduces a significant challenge to the generalizability of their findings. This practice of excluding certain populations particularly those with disability from participation in RCTs can lead to uncertainty regarding the applicability of trial results to broader patient populations. Consequently, it is imperative to delve into the factors that contribute to routine exclusions in clinical trials and to understand their potential consequences.

Main research question: The objective of this study is to explore the prevalence of exclusions of people with disabilities in cardiovascular clinical trials in low- and middle-income countries (LMICs).

Research methodology: A meta-epidemiological study of recent cardiovascular clinical trials registered in clinical trials registers: WHO Clinical Trials Registry Platform or ClinicalTrials.gov from 2015 to 2022 using a combination of search terms. Exclusions of people with disabilities (including physical, mental, and social relationships) will be mapped along with their corresponding trial characteristics.

The summer scholar will have opportunity to learn transferable skills in literature review and meta epidemiological study. The summer scholar will be supported throughout the project to develop the research project, conduct literature review, data extraction and analysis of results. There will also be opportunity to develop the research project for a conference presentation and journal publication. There may be opportunities to develop and extend this topic area into further projects suitable for honours, MD projects, MPhil or PhD work.