WORKING P A P E R Project Retrosight Understanding the returns from cardiovascular and stroke research Case Studies ALEXANDRA POLLITT, STEVEN WOODING, STEPHEN HANNEY, MARTIN BUXTON AND JONATHAN GRANT WR-836-RS March 2011 Prepared on behalf of the Project Retrosight Team Approved for public release, distribution unlimited This product is part of the RAND Europe working paper series. RAND working papers are intended to share researchers’ latest findings and to solicit informal peer review. They have been approved for circulation by RAND Europe but have not been formally edited or peer reviewed. Unless otherwise indicated, working papers can be quoted and cited without permission of the author, provided the source is clearly referred to as a working paper. RAND’s publications do not necessarily reflect the opinions of its research clients and sponsors. is a registered trademark. Preface This report presents a set of 29 case studies of cardiovascular and stroke research grants funded in three countries between 1989 and 1993. The case studies focused on the individual grants but considered the development of the investigators and ideas involved in the research projects from initiation to the present day. Basic biomedical and clinical cardiovascular and stroke research grants awarded in Australia, Canada and the UK were selected through a stratified random selection approach that aimed to include both high- and low-impact grants. Case studies were constructed around the Payback Framework1, a research evaluation framework that is both a tool for evaluating a range of potential outputs from research and a logic model that provides a mechanism for conceptualising the process through which outputs are created. The structured case studies were used to assess the impact of the research grants in detail and to draw conclusions about the relationship between impact and a range of factors. The key messages from the project are as follows. The cases reveal that a large and diverse range of impacts arose from the 29 grants studied. There are variations between the impacts derived from basic biomedical and clinical research. There is no correlation between knowledge production and wider impacts. The majority of economic impacts identified come from a minority of projects. We identified factors that appear to be associated with high and low impact. This report presents the case studies. As far as possible, they are presented in the form used in the analysis. Case studies were initially approved by the PI for the research examined and each case study was then peer reviewed by independent researchers in the cardiovascular and stroke field. These reviews were used by the rating panel in assessing the impacts of the research described. Twenty-four of the case studies were reviewed by two independent researchers; for the remaining five we were only able to secure one reviewer in each case. Buxton, M., and S. Hanney. “How can payback from health services research be assessed?” Journal of Health Services Research and Policy 1 (1996): 35–43. i The Policy Report2 presents the project’s findings and their implications for policy, and the Methodology Report3 provides a detailed account of the methodology used, including the review process. This work was led by RAND Europe in collaboration with the Health Economics Research Group (HERG) at Brunel University. RAND Europe is an independent not-for- profit policy research organisation that serves the public interest by improving policy- making and informing public debate. The Health Economics Research Group is a Specialist Research Institute of Brunel University dedicated to conducting accessible, policy-relevant research of a high academic quality focused on improving the efficiency and cost-effectiveness of resources devoted to health care and to research. For more information about RAND Europe or this document, please contact: Steven Wooding Research Leader RAND Europe Westbrook Centre, Milton Road Cambridge, CB4 1YG United Kingdom Email: [email protected] or [email protected] 2 Wooding, S., S. Hanney, A. Pollitt, M. Buxton, and J. Grant. Project Retrosight. Understanding the returns from cardiovascular and stroke research: Policy Report. Cambridge, UK: RAND Europe, MG-1079-RS, 2011. 3Pollitt, A., S. Wooding, S. Hanney, M. Buxton, and J. Grant. Project Retrosight. Understanding the returns from cardiovascular and stroke research: Methodology Report. Cambridge, UK: RAND Europe, TR-925-RS, 2011 ii Contents Preface ............................................................................................................. i Acknowledgements and detailed authorship .................................................................. v CHAPTER 1 To conduct studies of a high density lipoprotein conversion factor ............................................................................................... 1 CHAPTER 2 Fibrillin deficiency in Marfan syndrome and overlapping syndromes (familial mitral valve prolapse, familial ascending aortic aneurysm): diagnosis and risk stratification ......................... 33 CHAPTER 3 ‘Heartstart Scotland’ – analysis of the results of a national programme .................................................................................... 55 CHAPTER 4 Haemostatic markers in acute transient ischaemic attacks .............. 83 CHAPTER 5A follow-up study of heart attack patients ................................... 103 CHAPTER 6 Coronary lesions and vasoactivity ................................................ 131 CHAPTER 7 The organisation and nature of formed elements within the paracellular clefts of capillary endothelia ..................................... 155 CHAPTER 8 Low-intensity warfarin and thrombosis ....................................... 179 CHAPTER 9 Analysis of the glucose transporter compliment and function in metabolically important tissues of the Milan hypertensive rat ................................................................................................ 197 CHAPTER 10 The role of coagulation and fibrinolysis in the pathogenesis of recurrent stroke ............................................................................ 219 CHAPTER 11 Nimodipine binding in cerebral ischaemia ................................... 237 CHAPTER 12 Genetic and cellular determinants of increased growth of vascular smooth muscle in spontaneously hypertensive rats ......... 261 iii CHAPTER 13 The study of the role of the regulatory gene, Mlx1, in cardiac development and disease, and the creation of animal models for myocardial dysfunction .......................................................... 281 CHAPTER 14 Effect of simulated stroke on developing astrocytes ..................... 305 CHAPTER 15 The effects of alcohol consumption on blood pressure, plasma lipoprotein cholesterol fractions and sympathetic nervous system function in man ................................................................ 323 CHAPTER 16 Electrophysiologic properties of cardiac myocytes in cardiomyopathy ........................................................................... 347 CHAPTER 17 To study the effects of angiotensin-converting enzyme inhibitors on tissue and cardiac angiotensin-converting enzyme ......................................................................................... 371 CHAPTER 18 Vasoactive substances and pathogenesis of essential hypertension ................................................................................ 399 CHAPTER 19 Immunoelectron microscopy of amine and peptide synapses on sympathetic preganglionic neurons ......................................... 419 CHAPTER 20 Right-hemisphere stroke: incidence, severity and recovery of language disorders ....................................................................... 439 CHAPTER 21 To study secondary prevention of hypertension ........................... 459 CHAPTER 22 The effects of lean meat diets on plasma lipids and haemostatic functions .................................................................. 487 CHAPTER 23 Cell–cell interactions in the disposition of natriuretic peptides in the bovine chromaffin cells ...................................................... 525 CHAPTER 24 Is hepatic synthesis and secretion of lecithin-cholesterol acyltransferase (LCAT) linked to lipoprotein production by the liver and intestine? ................................................................. 547 CHAPTER 25 Modulation of nitric oxide biosynthesis by polyamines ............... 563 CHAPTER 26 Antiarrhythmic drug receptor ...................................................... 577 CHAPTER 27 Biobehavioural influences on hypertension and atherosclerosis .............................................................................. 597 CHAPTER 28 Prolonged heart and lung allograft preservation .......................... 623 CHAPTER 29 Stroke prevention in the elderly in primary care .......................... 649 iv Acknowledgements and detailed authorship We would like to start by acknowledging all the scientists who were willing to act as the participants for this study, particularly the principal investigators of the 29 case study grants. The study would clearly have been impossible without them. This study was initiated with internal funding from RAND Europe and HERG, with continuing funding from the UK National Institute for Health Research, the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada and the National Heart Foundation of Australia. The UK Stroke