Prevention is crucial for improving health at both the individual and population level. Research supporting the development and implementation of preventive interventions has however become a highly specialized field with increasingly advanced methods to investigate harms and benefits of prevention and to demonstrate its impact and cost-effectiveness.
The aim of this ACE is to strengthen the collaboration between prevention-focused research groups within Erasmus MC (and their collaboration with external partners), in order to accelerate innovations and facilitate effective interventions in prevention, both in patient care and in the population at large.
Erasmus MC is in an excellent position to contribute to developments in ‘precision preventive medicine’ and to design, implement and evaluate new prevention programs; to apply innovative research and evaluation methods and to quantify and predict outcomes of prevention; and contribute to timely deployment of the best evidence on prevention at multiple levels of care (from primary to specialized care) swiftly and efficiently. The research in this ACE starts with a focus on cancer, cardio-metabolic, neuro-vascular, musculoskeletal, and psychiatric diseases.
Research Activities
We bring together a core group of prevention experts from the Health Sciences and a number of top clinical and public health specialists in- and outside Erasmus MC.
The research is clearly multidimensional: fundamental (pathobiology, mainly in vitro cell work and limited mouse work), translational (in all aspects, translation from basic findings up to implementation in clinic and subpopulations), clinical (human cohort studies, trial participation, implementation research), and epidemiological/public health (cohort and case-control studies, large scale trial mimicking studies, population studies, large-scale RCTs, screening and primary preventive programs). Future research activities will build upon and expand current activities (but we anticipate important cross-fertilization), and include: - Development of strategies for identification of individuals at risk for disease, including biomarkers and imaging - Development of health behavior interventions in patient care settings - Testing of implementation strategies for sustainable preventive interventions - Understanding the contribution of lifestyle to burden of disease and health inequalities - Identification of optimal approaches for screening in cardiovascular, neurological, oncological, locomotor and psychiatric diseases, including personalized approaches.
Current research activities include for instance: - Evaluation of effective screening and preventive interventions in hospital patient care as part of Koers 18. - Comparative effectiveness of colorectal cancer screening, in subpopulations and patient groups - Risk prediction for efficient surveillance in Barrett's patients, based on pathological, biomarker and imaging characteristics - Building structured, evidence-based lifestyle modification programs into stroke units - Developing e-health applications that allows access to personal education, life style interventions, coaching and smart technology. - Assessing different detection methods to identify disturbed glucose metabolism, and studying the pathophysiology and prognosis of these disorders and develop individualized treatment strategies - Evaluating risk modifiers of familial hypercholesterolemia - Assessing efficacy of cardiovascular prevention, e.g., with novel imaging techniques, both large-scale population wide (ROBINSCA) and in patient groups - Improved understanding of causes of health behaviors in socially vulnerable populations
The groups are strong international collaborators, of which we mention some here: - Cancer Intervention and Surveillance Modeling Network - consortium by US National Cancer Institute - EU-TOPIA: Towards improved cancer screening in all of Europe - Horizon 2020 project including key European institutes and all 27 EU-countries at policy and research level on cancer screening - Leading role worldwide in clinical trials for secundary prevention after a TIA or minor stroke, such as the Dutch TIA Study, the European Atrial Fibrillation Trial, and the ESPRIT Trial. - MINDMAP: promoting mental well being in the ageing urban population (Horizon 2020 coordinator, with 13 European, US and Canadian institutes)
4-IN THE LUNG-RUN: towards INdividually tailored INvitations, screening INtervals, and INtegrated co-morbidity reducing strategies in lung cancer screening.
With 338,000 EU-deaths annually, lung cancer is a devastating problem. CT screening has the potential to prevent tenthousands of lung cancer deaths annually. The positive results of the Dutch-Belgian screening trial (NELSON), with relatively low referral rates, and the NLST in the USA provided conclusive evidence. However, implementation is likely to be limited, slow and of variable quality throughout Europe, and current guidelines could easily require up to 25 million CT screens annually. The most optimal strategy in risk-based lung-thoracic screening is still unknown regarding the optimal and most cost-effective (e.g., targeted) strategy 1) to recruit, 2) to integrate smoking cessation and co-morbidity-reducing services, and 3) to determine the (risk-based) screening interval. Personalised regimens based on the baseline CT result can potentially retain 85% of the mortality reduction achievable through screening at 45% less screens, thus potentially saving much unnecessary harm associated with screening, and 0.5-1 billion Euros per year. The heart of 4-IN-THE-LUNG-RUN is a randomised controlled trial amongst 24,000 individuals evaluating whether it is safe to have risk-based less intensive screening intervals after a negative baseline CT. Various methods to improve participation of hard-to-reach individuals will be assessed in five different healthcare settings. Innovative co-morbidity reducing strategies will be tested including other markers on CT imaging, as Calcium Score and COPD. Cost impact and cost-effectiveness analyses using a natural history model will steer implementation. The experienced consortium will strongly interact with key stakeholders, and discuss interim results with key other international initiatives on CT screening, biomarkers, and smoking cessation practices. This proposal will form the evidence base for risk-based lung cancer screening with huge benefits for the EU, on health outcomes, cost savings, and innovation in the long run.
Collaborations
The groups are strong international collaborators, of which we mention some here: - Cancer Intervention and Surveillance Modeling Network - consortium by US National Cancer Institute - EU-TOPIA: Towards improved cancer screening in all of Europe - Horizon 2020 project including key European institutes and all 27 EU-countries at policy and research level on cancer screening - Leading role worldwide in clinical trials for secundary prevention after a TIA or minor stroke, such as the Dutch TIA Study, the European Atrial Fibrillation Trial, and the ESPRIT Trial. - MINDMAP: promoting mental well being in the ageing urban population (Horizon 2020 coordinator, with 13 European, US and Canadian institutes)
Contributions
There is a very strong component of education in the health sciences section (partially in NIHES), and all clinical departments have huge responsibilities in education (Ba), also often nationally (resident AIOS-level).
We are further also participating in an education program embedded in theme 2 (stroke) and theme 6 (vascular clinical epidemiology), in the cardiovascular research school (COEUR), in several Minors (also TU Delft), and the PhD program of the Heart Foundation.
NIHES attracts students from all over the world, and holds a very strong international position. It cooperates with a global network of leading research centres in Europe, Asia, Latin America and the USA. The MSc programmes have received accreditation by KNAW, NVAO, and the Netherlands Epidemiology Society.
At the last graduation (August 2015) 70 students received their MSc and an additional 8 students received a DSc. Over 50% of students is from abroad. The majority of these students have conducted a research project linked to the aims of the ACE Prevention. The "Prevention entirely"-courses are: Bachelor (Medicine): Theme Ba.3.C.2 (400 students each year); (Research) Master: MSc in Health Sciences (NIHES), specialised courses in Methods of Public Health Research (0.7 ECTs); Primary and Secondary Prevention Research (0.7 ECTs); Public Health Research: intervention development and evaluation (2.1 ECTs); Planning and Evaluation of Screening (1.4 ECTs); Women's Health (Each of these courses include 20-40 students each year); PhD education: NIHES PhD programme, see specific courses in MSc. Global health.
All these courses are generally rated with grade 4 or higher (scale up to 5) in the evaluations, and great care is put into improving courses based on feedback from students. Also the latest evidence with respect to effective learning and teaching is incorporated into the courses. The community projects in Theme Ba.3.C.2, in which students form groups to address and evaluate a community problem, are an example of such an innovation, based on a US teaching model. Currently, several bachelor and post-graduate courses are being re-assessed to deem their suitability for a more e-learning and self-study based approach compared to the current standard teaching model. Our objective is to connect our education better with all groups of the Prevention ACE.
Care Activities
Clinical care is organized in large multidisciplinary teams consisting of physicians, specialized nurses, assistants, psychologists, and dieticians. All participating clinical participating departments have similar objectives and organizational structures, enabling to focus on prevention in their respective fields. In this ACE Prevention, patient care as such is a more limited part, but the patient population at risk will be an important potential target.
Early detection (and thereby primary and secondary prevention) of many potentially chronic diseases is a main focus in general practice of course. Promotion of healthy life style is another major theme in general practice, as well as the prevention of too much medicine and overdiagnosis. It would be too much to elaborate on patient care for all departments, but we describe the 2 large clinical participating centers here: The Department of Neurology of Erasmus MC offers acute care to more than 600 patients with stroke or TIA annually and is a tertiary center for acute stroke treatment, including mechanical thrombectomy. It works in close collaboration with surrounding hospitals, general practitioners and rehabilitation units within the regional stroke network covering an area of almost 2500 stroke patients per year. Following its landmark publication of the MR CLEAN trial, the Department has taken the lead in the formation of the Erasmus MC Stroke Center.
Secondary stroke prevention is an important focus of the Erasmus MC Stroke Center. Our goal is to reduce stroke recurrence by education, treatment and support of patients with stroke or TIA. The outpatient secondary stroke prevention clinic provides an individualized, multidisciplinary and evidence based secondary prevention program to all patients admitted with TIA or stroke. This program focuses on both traditional risk factors and life style modification. Patients are consulted by a nurse practitioner or physician assistant in close collaboration with a stroke neurologist.
At the section Pharmacology, Vascular and Metabolic Diseases of the department of Internal Medicine family based approaches are employed to screen for and install early preventive treatment of dyslipidemias, diabetes mellitus, hypertension and severe coronary artery disease in families with an unparalleled burden from these diseases. In addition, high-risk cohorts receive preventive measures, like diabetes with multiple co-morbidities, statin-resistant dyslipidemias, and a number of orphan diseases. The latter is organized in a number of NFU centers of rare conditions. We are also the Expertise Center Erasmus MC Vascular Genetics (homozygous FH and LPL deficiency).
Societal Relevance to Research, Education and Patient Care
The societal relevance of this ACE on prevention is undisputable. As described before, the ACE closely matches the research targets of the national and international research agendas. Furthermore, since a large proportion of the ACE research agenda ultimately applies to the population as a whole, the potential population health impact is considerable.
Partners are also key in establishing (inter-)national cohorts, like the PROBAR and Proregal cohorts on Barrett's. Previous research related to this ACE has been shown to be able to inform and change public and health policy, including but not limited to: - the national breast, cervical and colorectal cancer screening programmes in the Netherlands and abroad - guidelines for colonoscopy surveillance in adenoma patients - guidelines for not treating prostate cancer patients (immediately) - guidelines for clinical management of familial hypercholesterolemia - new global guidelines for cardiovascular prevention - predicting the impact of asbestosis and other work-related diseases - reducing and tackling socio-economic inequalities worldwide Three mere illustrations from methodological research to change in society and societal impact:
- in the Netherlands: We conducted research into behavioural determinants of bicycle spoke injuries. We used a safety checklist and made direct observations of bicycle transport of 173 young children in two regions. It was found that young children are not transported safely in almost 75% of bicycle rides, with the absence of spoke protection being the major problem. The lack of safety increased when the parents perceive lower benefits of prevention. Based on this research, novel instruction materials were developed by Safety Netherlands and a campaign was launched.
- US: We developed a microsimulation model (MISCAN), which we calibrated to individual-level data of the NLST, the largest RCT on CT screening for lung cancer. After calibration, we performed analyses on the harms and benefits of almost 600 different screening scenarios (start & stop age, interval, risk level). These were considered by the USPSTF, and lead to US-Medicare coverage of our "advantageous scenario" in 2015.
- patient care: Erasmus MC performed the 2nd largest RCT on CT screening for lung cancer, and by analyzing the ten-thousands of nodules detected on CT, and their respective 6-year lung cancer risk, we have created a nomogram (published in Lancet Oncology), applicable to nodules found on CT scans in clinical care.
Viability of Research, Education and Patient Care
The ACE Prevention is characterized by research groups with in general a very approachable leadership, ensuring balanced advanced knowledge sharing across ages. The research groups are all large long-standing centres of excellence in their respective fields, indicating that continuity of research is guaranteed.
All partners have a Mean Normalized Citation Score (MNCS) above world average, and many substantially higher, e.g., Effects of Screening (2.5), Urology (2.1), MDL (2.0) & Clin Neuro (1.8). The research is internationally recognized for its high quality and relevance.
This clearly shows from the large amount of international papers in high-impact journals. All 58 PhD students are required to write international papers in top journals, and encouraged to participate in international conferences. In addition, talent review programs are in place to identify the most promising PhD candidates for future research careers at Erasmus MC at 2-year intervals. Within international consortia, like CISNET from NIH, an international training program for future researchers has been set up, and most PhD students start within the NIHES training programme.
Their leaders are key researchers worldwide, e.g., Van Lenthe is Fellow of the International Society of Behavioural Nutrition and Physical Activity, Sijbrands is key advisor in international guidelines on Familial Hypercholesterolemia Panel, Bierma is the 4th leading expert worldwide in osteoarthritis (of 22,000 selected papers), de Koning member of the European Code on Cancer Screening Taskforce, and Mackenbach has received several honourable doctorates and been appointed Fellow of the Royal Society UK due to its work on socio-economic inequalities.
Many of the key partners function in international societies, function in panels from the Health Council of the Netherlands and Royal Academy of Sciences, and are key lecturers at international conferences. In 2015 and 2019, the department of Public health organized the International Cancer Screening Network Meeting with over 300 participants. Partners are consultants at WHO and IARC.
We further realize that partners have a strong expertise on vulnerability of (patient and population) groups, and at the same time, collaborating partners see a huge workload in such groups being prevalent in the Rotterdam area specifically. Investing more in the hard-to-reach-groups (methodology & effective preventive interventions) is an example of (until now underused) cross-fertilization, and also shows the viability of our research in the Rotterdam area specifically.
Key and relevant publications of the last five years
- Heijnsdijk EAM et al. Quality-of-Life Effects of Prostate-Specific Antigen Screening. NEJM 2012;367:595-605.
- Harinck F et al. A multicentre comparative prospective blinded analysis of EUS and MRI for screening of pancreatic cancer in high-risk individuals (Dutch research group on pancreatic cancer surveillance in high-risk individuals). Gut. 2015 May 18
- Koning HJ de et al. Benefits and harms of CT lung cancer screening strategies: a comparative modeling study for the U.S. Preventive Services Task Force. Ann Intern Med. 2014 Mar 4; 160 (5): 311-320.
- Ligthart S et al. Lifetime risk of developing impaired glucose metabolism and eventual progression from prediabetes to type 2 diabetes: a prospective cohort study. Lancet Diabetes Endocrinol 2016;4:44-51.
- Schroder et al. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet 2014; 384 (9959): 2027-35.
- Magnée T et al. For better or worse: Synthesis of equity-specific subgroup analyses of 26 Dutch intervention studies for obesity prevention and promotion of physical activity and a healthy diet. Am J Prev Med 2013: 44; e57-e66.
- Runhaar J et al. Prevention of knee osteoarthritis in overweight females: the first preventive RCT in osteoarthritis. Am J Med 2015; 128 (8): 888-895
- Jonker M et al. Estimating the impact of health-related behaviors on geographic variation in cardiovascular mortality; a new approach based on the synthesis of ecological and individual-level data. Epidemiology 2015; 26: 888-897.
- Bos MJ et al. Modifiable etiological factors and the burden of stroke from the Rotterdam Study: a population-based cohort study. PLoS Med 2014;11:e1001634.
- Kavousi M et al. Comparison of applications of the ACC/AHA guidelines, Adult treatment Panel III guidelines, and ESC guidelines for cardiovascular prevention in a European cohort. JAMA 2014; 311 (14): 1416-23
- Koning, HJ de ;van der Aalst, CM ;de Jong, P ;Scholten, ETh ;Nackaerts, K ;Heuvelmans, MA ;Lammers, JWJ ;Weenink ;Yousaf, AU ;Horeweg, N ;van 't Westeinde, S ;Prokop, M ;Mali, W ;Mohamed Hoesein, FAA ;van Ooijen, PMA ;Aerts, JGJV ;Bakker, A ;Thunnissen, E ;Verschakelen, J ;Vliegenthart, R ;Walter JE ;ten Haaf, K ;Groen, HJM ;Oudkerk, M.
- Reduced lung-cancer mortality with volume CT screening in a randomized trial. NEJM 2020; 382(6):503-513. Epub Date: January 29 2020
PhD theses of the last five years
- Rozemeijer K. The Effect of New Screening Tests in the Dutch Cervical Cancer Screening Programme. January 21, 2016
- Goede SL. Modelling the effects and costs of colorectal cancer screening. June 23, 2015
- Ravesteyn NT van. The impact of breast cancer screening on population health. May 21, 2013 (Cum Laude)
- Kroep S. Exploring the Natural History of Esophageal Adenocarcinoma and Possibilities for Early Detection and Intervention. July 8, 2015
- Bokhorst L. Prostate cancer screening and active surveillance; can we increase survival without doing too much harm? June 22, 2016
- Hoeven T. Vascular pathology and ostoearthritis. 2015
- Beenackers MA. Physical activity. The interplay between individual and neighbourhood factors. 12 April 2013.
- Sedaghat S. Kidney and the brain; role of vascular dysfunction. September 24, 2015.
- Vitezova A. Vitamin D and cardiometabolic health in the elderly. September 30, 2015.
- Versmissen J. Coronary heart disease in familial hypercholesterolemia. September 19, 2012 (Cum Laude).