Objective
Our overarching vision is that general population screening for type 1 diabetes will be implemented in routine healthcare in Australia to decrease the burden of life-threatening diabetic ketoacidosis and improve lifelong health outcomes. Several general population screening models for type 1 diabetes have been proposed in research trials internationally. However, there is no clear optimal model for the Australian setting with advantages and limitations to both approaches. We therefore propose a clinical research program to compare the feasibility, acceptability, efficacy and cost-effectiveness of three screening models for type 1 diabetes in the Australian paediatric general population. The overall goal is to develop the evidence base to determine the most appropriate screening model for routine population-wide screening for type 1 diabetes in Australia.
We will achieve this through 3 objectives. Firstly, to compare the feasibility and acceptability of three different general population screening models in Australia through a clinical trial comparing them head-to-head. Secondly, to review the published evidence on the efficacy, benefits and harms of the three screening models through a comprehensive review and then model the cost-effectiveness of each model using Australian health costs and pilot data. Finally, to develop and begin enacting a stakeholder engagement and communication strategy with families, the type 1 diabetes community, primary and tertiary healthcare professionals, community and professional organisations and with government and policymakers, to build support for the adoption of routine general population screening for type 1 diabetes.
Background Rationale
Over 120,000 Australians have type 1 diabetes, with almost 3,500 newly diagnosed each year1. However, one in three Australian children are diagnosed with type 1 diabetes too late, being admitted to intensive care with life-threatening diabetic ketoacidosis (DKA)3. This start to disease is traumatic and has lifelong implications for cognitive function, long-term blood glucose control and the serious diabetes complications, such as blindness, kidney failure and amputation. Early diagnosis and initiation of treatment is essential to prevent DKA at diagnosis, in order to reduce the trauma to the child and family and improve their long-term health.
Screening for early type 1 diabetes, before symptoms become apparent, provides the opportunity for early diagnosis. Screening of family members has been underway for 20 years in Australia, however 90% of those who will develop type 1 diabetes have no family history of the condition. Therefore, the only way to identify the vast majority of children early is through general population screening. Indeed, rates of DKA in international screening programs are less than 5%, compared with a population average of 30%. Screening also offers the potential to speed up possible treatments to prevent type 1 diabetes, as these clinical trials rely on participants with early stage type 1 diabetes who normally difficult to identify in the general population.
Several general population screening models have been proposed in research trials internationally. Chiefly, screening for type 1 diabetes-related autoantibodies in the blood, which identifies early, presymptomatic disease OR a two-step approach with genetic screening from blood or saliva, with ongoing autoantibody testing in children with a higher genetic risk. However, there is no clear optimal model for the Australian setting with advantages and limitations to both approaches. For example, genetic screening is a lifelong result, whereas autoantibodies can appear at any stage and therefore screening needs to be repeated in order to identify children as they develop autoantibodies. Genetic screening also has the advantage that it can identify more future cases of type 1 diabetes than autoantibody screening (78% vs 50%) but it requires ongoing monitoring for 1 in 10 children, the majority of whom will never develop type 1 diabetes. Given selecting the right screening model is critical to the success of a screening program in routine healthcare, a comprehensive review and testing of the different screening options in the local environment is essential in order to make compelling, evidence-based decisions regarding the roadmap towards screening in routine health.
Description of Project
Children are often diagnosed with type 1 diabetes too late, with 1 in 3 admitted to ICU with life-threatening diabetic ketoacidosis (DKA). This start to disease is traumatic and has lifelong implications for cognitive impairment, long-term blood glucose levels, and the risk of serious complications. Early diagnosis and starting treatment is essential to prevent DKA, reduce trauma and improve long-term health.
Screening for type 1 diabetes provides the opportunity for early diagnosis. Up to 90% of those who will develop type 1 diabetes have no family history of the condition. Therefore, the only way to identify the vast majority of children early is through general population screening. Our overarching vision is that general population screening for type 1 diabetes will be implemented in Australia to decrease the burden of DKA and its multiple health consequences. Australia is ideally suited to screening programs, given our centralised healthcare system with screening federally mandated, funded and managed.
Several screening models have been proposed in research trials internationally, however, there is no clear optimal model for the Australian setting with advantages and limitations to all approaches. We therefore propose a clinical research program to compare the feasibility, acceptability, efficacy and cost-effectiveness of three screening models for type 1 diabetes in the Australian paediatric general population. The overall goal is to develop the evidence base to determine the most appropriate screening model for routine population-wide screening for type 1 diabetes in Australia.
We will achieve this through 3 objectives. Firstly, to compare the feasibility and acceptability of three different screening models in Australia by comparing them head-to-head in a pilot clinical trial. Children will either be recruited 1) as newborns for genetic screening analysed from dried bloodspots taken at the same time as the current newborn screening sample. Genetically at-risk children will be offered follow-up autoantibody testing in dried bloodspots from 12 months of age; 2) families of infants aged 6 months will be mailed invitations and offered genetic screening from a saliva sample. Similarly, genetically at-risk children will be offered follow-up autoantibody testing in dried bloodspots from 12 months of age OR 3) families of children aged 2-3 years old or 5-6 years old will be mailed invitations to participate in autoantibody screening from a dried bloodspot. Children with two or more autoantibodies are considered to have early stage type 1 diabetes. We are aiming to recruit 9,000 children, with 3,000 children in each group from across Australia. Each screening model will run in a unique geographical area with targeted public awareness and engagement campaigns. The three screening models will be compared to see which was the most feasible acceptable and lastly how expensive each model was. We will also produce a comprehensive technical review and report for the Government on the current evidence for general population screening. Economic modelling will reveal which screening option is most cost-effective based on the costs of screening in the pilot, the current costs of DKA to the Australian health system and the potential savings if DKA as reduced to a similar rate seen in international trials. Lastly the third objective of this pilot is to grow the support for type 1 diabetes screening amongst Australians and the Government. We are committed to build the support and momentum for screening by connecting with the community, government and strategic individuals.
Collectively, this is a pivotal first step in achieving our overarching vision for general population screening for type 1 diabetes to be implemented into routine healthcare across Australia, with the principal aim of reducing the burden of DKA and its lifelong health consequences for children.
Anticipated Outcome
This proposal will culminate in the feasibility, acceptability, efficacy and cost-effectiveness evidence to inform recommendations for the optimal screening pathway for type 1 diabetes in the general Australian population, taking into consideration the community and healthcare system impacts and benefits. It is locally focused but contributes to the global effort towards general population screening. The pilot is a novel and creative research program, providing the first head-to-head comparison of a broad coverage of screening models, with rapid and comprehensive assessment. We have strategically adopted a national, health systems-orientated approach that is sustainable and scalable to population-level. Through stakeholder mapping, engagement, consultation and workshopping, we will develop the national roadmap to implementation. This project will also enable the formalisation of the national type 1 diabetes general population screening network we are establishing in Australia and supports us to participate and contribute to the global network of researchers, clinicians, advocacy groups and industries, working towards general population screening. Collectively, this is a pivotal first step in achieving our overarching vision for general population screening for type 1 diabetes to be implemented into routine healthcare across Australia, with the principal aim of reducing the burden of DKA and its multiple lifelong health consequences.
Relevance to T1D
Diagnosis of type 1 diabetes is often delayed and traumatic. One in three Australian children are diagnosed too late and need to be admitted to hospital in intensive care with a potentially deadly condition called Diabetic Ketoacidosis (DKA). This is caused by a build-up of glucose and acidic ketones in the blood which, if left untreated, can cause coma and death. This DKA rate is even more alarming in regional Australia, with up to 80% presenting with DKA. Treatment of DKA requires expensive high-level medical care and causes significant post-traumatic stress for families.
Screening for type 1 diabetes in the general population offers the opportunity to identify those at risk of developing the condition or who already have an early stage but aren’t experiencing any symptoms. Education and ongoing monitoring means families and their healthcare professionals will be given warning as type 1 diabetes starts to develop, allowing treatment to start on time, reducing the threat of DKA. Studies in the USA and Germany have shown that screening substantially reduces the number of children developing DKA at diagnosis, from a population average of about 30% to less than 5%. This not only reduces the trauma and immediate health risks to the child but has lifelong improvements in their blood glucose levels, cognitive function and risk of serious diabetes complications.
Furthermore, screening offers the potential to speed up research into possible preventions for type 1 diabetes. Currently, there is no cure or established prevention for type 1 diabetes and management is complex and burdensome. Recent clinical trials have shown that certain medications can delay the onset or progression of type 1 diabetes. However, these trials rely on people who are in the very early stages of the disease, who are often difficult to identify in the general population. Screening therefore creates an opportunity to identify these individuals and offer enrolment in clinical trials. Faster recruitment can therefore accelerate the discovery of new treatments to prevent or further delay type 1 diabetes and offers substantial health and quality of life benefits to individuals at risk of type 1 diabetes.