UK Prospective Diabetes Study
UKPDS United Kingdom Prospective Diabetes Study
|Dates:||Ongoing since 1995|
|Funding:||Medical Research Council, National Institutes of Health, Diabetes UK, and a consortium of pharmaceutical companies|
|Collaborators:||Diabetes Trials Unit, University of Oxford|
|Information:||Jose Leal, Philip Clarke, Maria Alva|
The number of people globally with diabetes is now over 360 million and rapidly rising, making this a leading health problem of the 21st century. Type 2 diabetes, the most common type, can cause severe health problems, including heart disease, amputation and loss of sight. Major clinical trials have shown that diet, exercise and drugs can greatly reduce these risks.
Since the mid-1990s HERC has been involved in a collaboration with the Diabetes Research Laboratories and Diabetes Trials Unit of the University of Oxford in a series of economic analyses based on the UK Prospective Diabetes Study (UKPDS), a multi-centre prospective randomised controlled clinical trial of 5102 newly-diagnosed Type 2 diabetic patients designed to determine whether improved blood glucose control, and improved blood pressure control in hypertensive patients, prevent complications and reduce the associated morbidity and mortality. This landmark trial showed conclusively the benefits of good glucose and blood pressure control and helped change medical practice around the world.
An economic analysis was not initially included in the study design of the UKPDS. However, data were collected throughout the study on hospital drugs and medications used, and these were supplemented near the end of the study by cross-sectional surveys of non-inpatient health care use and quality of life.
Evaluations of tight versus less tight blood pressure control, intensive versus less conventional blood glucose control, and metformin, showed that each was highly cost-effective and that all could be provided at modest total cost. Further analyses showed that amputations and stroke had particularly severe consequences for quality of life, and that amputations and non-fatal MI had high cost consequences. Finally, patient-level data were used to construct a diabetes outcomes model, which estimates the probability of longer-term complications from patient-specific risk factors, lifetime costs and (quality-adjusted) life expectancy and can be applied to populations at different stages of diabetes progression.
The economic analyses arising from the UKPDS have provided new evidence to clinicians, policy-makers and researchers on the consequences of diabetes and the cost-effectiveness of interventions, thereby assisting the development of treatment guidelines and improved standards of care. The analyses also illustrated a number of methodological innovations.
The main clinical and economic results have been published in a series of papers covering different management strategies for diabetes. This has included cost-effectiveness evaluations of tight blood pressure control and intensive blood glucose control and estimating the budget impact of implementing these interventions in England as part of the National Service Framework for Diabetes. Studies estimating the effect complications have on quality of life and costs have also been published.
UKPDS Outcomes Model
The UKPDS Outcomes Model is a computer simulation model for estimating the long-term impact of health interventions for people with type 2 diabetes. The UKPDS Outcomes model version 1 (UKPDS-OM1) was completed in 2004 and gained widespread acceptance as a validated tool for long-term economic and clinical prediction in diabetes.
A paper describing the UKPDS-OM1 was published in Diabetologia in October 2004. The UKPDS-OM1 is based on patient data collected in the United Kingdom Prospective Diabetes Study up until 1997. It is a computer simulation model designed to assess the total burden of disease over an extrapolated lifetime for populations with Type 2 diabetes. The UKPDS–OM1 uses a wide variety of input data, including knowledge of previous events for individuals, and has the ability to take into account changes in some risk factor levels over time. If these updated risk factor levels are not available the model will, by default, extrapolate the risk factor levels entered. The UKPDS-OM1 outputs are estimated Life Expectancy and Quality Adjusted Life Expectancy for each member of a given population.
The UKPDS-OM1 was shown to be internally valid and closely match the outcomes observed during the UKPDS trial itself. The external validity of the model was also demonstrated by closely matching the results of clinical trials such as the Collaborative Atorvastatin Diabetes Study and the PROactive study and event rates in non trial populations such as US National Health and Nutritional Examination Survey participants. Recently we have published papers showing that the model reasonably predicts event rates in an Italian diabetic population, and also reasonably predicts future events in a follow-up study of patients in the original trial.
The UKPDS-OM1 was developed primarily to assess the lifetime benefits of diabetes-related interventions. In particular, it is intended to facilitate economic evaluations by estimating changes in outcomes such as life expectancy and quality adjusted life expectancy, when risk factors such as blood glucose level, blood pressure, lipid levels and smoking status are changed. It can be applied to any population with type 2 diabetes. Other potential applications include:
• Assisting health service planning for populations with diabetes
• Estimating life expectancy of people with type 2 diabetes when writing premiums for life insurance
• Calculating expected event rates for sample size calculations when designing clinical trials.
The UKPDS-OM1 is already being used in a range of applications in the United Kingdom, Australia and Canada. It is available under license from ISIS Innovation, University of Oxford. Non-commercial and commercial licenses to use the model have been issued to users in many countries. Licenses are issued by ISIS Innovation, University of Oxford.
In 2008, the UKPDS-OM1 was used to develop a set of tables that quantify the expected lifetime health outcomes for people with type 2 diabetes. Also in 2008, the MRC awarded HERC a three-year grant to develop, validate and disseminate a new version of the model.
In 2009, Maria Alva started research for a DPhil, using UKPDS data to examine the impact of diabetes related complications. She explored the relationship between quality of life data and diabetes-related complications by estimating the impact of diabetes related complications on utility-based measures of quality of life and by examining whether index scores based on the EQ-5D are independent predictors of major complications and mortality in patients with Type 2 diabetes. She is also analysing the impact of diabetes related complications on healthcare costs (hospital inpatient costs and non-in-patient costs) using both HES (hospital episode statistics) and UKPDS data. Finally, she will also estimate the long-term impact of health interventions for people with type 2 diabetes on both life expectancy and QALYs.
Working closely with colleagues in Oxford, Sydney and Melbourne, we have recently published Version 2 of the Outcomes Model (UKPDS-OM2). This is based on a larger dataset which included additional data on events and risk factors collected during the UKPDS 10 year post-trial monitoring period (1997-2007). Version 2 shares the same objectives as the previous version and incorporates revised complication equations that include many additional risk factors (e.g. eGFR, heart rate, white blood cell count), a new complication equation (lower extremity ulcer), and new equations for the prediction of second events for myocardial infarction, stroke and amputation. We hope that UKPDS-OM2 will also be widely used by other researchers and agencies. In time we will also release an updated approved software version. The UKPDS trial will never be repeated, but in this way information from the study can continue to help improve cost-effective diabetes care around the world.
Work is also ongoing using hospital record-linked data for England to ascertain trends in and best estimates of the current fatality rates from stroke, myocardial infarction and heart failure in the sub-population with diagnosed diabetes, by age, sex and existing co-morbidities. The aim is to compare these estimates with the existing model equations and make these user-modifiable. Furthermore, a systematic review was undertaken to identify diabetes trial and compare their actual outcomes against predictions based on the UKPDS Outcomes models. This will enable us to further ascertain the models’ external validity.
Supporting material available for download
Web Appendix: The Effect of Diabetes Complications on Health-related Quality of life: the importance of longitudinal data to address patient heterogeneity. Supporting material for related article Alva, M, Gray, A, Mihaylova, B and Clarke, P.
Economics, Modelling and Diabetes: the Mount Hood Five Challenge
The Mount Hood Five Challenge was held at the Clinical Research Centre, University of Lund, Malmo, Sweden on 18-19 September 2010. More
Economics, Modelling and Diabetes: The Mt Hood 2012 Challenge
The Mount Hood 2012 Challenge was held at the Johns Hopkins Mount Washington Conference Center, Baltimore, Maryland, USA on 7-8 June 2012. More
Visit the DTU website for more information about the model and licensing arrangements.