From symptom to treatment International research centre for the diagnosis of cancer

Transcription

1 From symptom to treatment International research centre for the diagnosis of cancer Midway report October 2012 The Danish Cancer Society and the Novo Nordisk Foundation Research Centre for Cancer Diagnosis in Primary Care

2 From symptom to treatment International research centre for the diagnosis of cancer. Midway report October The Danish Cancer Society and the Novo Nordisk Foundation Research Centre for Cancer Diagnosis in Primary Care Research Unit for General Practice Aarhus University Bartholins Allé 2 DK 8000 Aarhus C T: E: cap@alm.au.dk W:

3 Content Introduction... 3 Background for the initiative... 3 Establishing the Research Centre for Cancer Diagnosis in Primary Care CaP... 4 Organisation of CaP... 5 Core function of the centre... 6 Studies at the CaP centre... 7 A. Patients aspect... 8 B. Diagnostic aspect C. Care management aspect D. Projects across all three aspects The interdisciplinary research team The medical psychological approach in CaP The medical anthropological approach in CaP The public health approach in CaP Epidemiology and data management at CaP The three CAP cohorts CAPS Sampling of incident cancer patients Variation The GP profile Data capture from general practice CaP in relation to the national and international parties Nationally Internationally Impact on research environment Impact on state of the art and health care development in early cancer diagnosis Infrastructure, location at and cooperation with Aarhus University Perspectives of the remaining project period ( ) Perspectives beyond the project period Concluding remarks and self evaluation Staff at CaP

4 CaP activities Selected events Publications PhD dissertations Original articles Reports, books and book chapters (selected) Popular science (selected) International presentations Selected presentations and posters Teaching, courses, CME and other activities Appendix Members of the national advisory board Members of the international advisory board

5 From symptom to treatment international research centre for the diagnosis of cancer Midway report Introduction This is the midway report for the CaP initiative taken by The Novo Nordisk Foundation and The Danish Cancer Society in 2009, an initiative based on the need for further knowledge and improvements in relation to the performance of the Danish health care system on cancer survival. Furthermore, cancer was seen as a case for the diagnosis of serious diseases in a modern health care system. Improvements and innovations within this area, based on the CaP research, should act as an engine for the whole health care system. In this way, the initiative could facilitate a positive, important and significant development of the whole health care system both in Denmark and internationally. Background for the initiative Since 2000, cancer has been the leading cause of death in Denmark. The lifetime risk of developing cancer is 30% before age 75 and 50% before age 85 years. In Denmark, almost 33,000 people receive a cancer diagnosis each year, and this number is increasing as the population gets older and treatment of e.g. cardiovascular diseases gets more effective. It is estimated that the cancer incidence will increase by at least 20% over the next 10 years. In Denmark, as well as in some other countries, it has been found that even though the health care system is considered very modern, its results are not satisfactory in comparison with other health care systems. For example, the 1 year and 5 year relative cancer survival in Denmark and the UK are among the lowest in the European Union. Danish women have the highest cancer mortality rate among all the EU countries. Studies suggest that Danish cancer patients are diagnosed and treated at a later stage of disease than patients in the other Nordic countries. Thus, although Denmark may be providing state of theart cancer treatment, it has been suggested that the delay from first symptom to start of treatment may be the key to the disappointing results. There was a need for research into this. For the health care system to react to and diagnose cancer, people need to contact their physician for symptoms and signs. However, we know that many people wait a while before they present to their general practitioner (GP). This may be due to the social context, psychological factors or knowledge, beliefs and awareness of cancer and cancer symptoms. Furthermore, there may be difficulties with access to GP/health care services and with the doctor patient relationship. Therefore, we need much more knowledge about people s interpretation of symptoms and their reactions and beliefs about cancer. General practice plays a crucial role in diagnosing cancer as 85% of primary cancer investigation takes place in general practice. A Danish GP has approx face to face consultations per year, and among these contacts, a GP has to diagnose in average 8 10 patients with cancer per year. Benign conditions and rarely a specific cancer disease most often cause symptoms seen in general practice. The predictive values of even 3

6 serious cancer symptoms are often less than 5%. Therefore, the health care system must be able to make prompt and effective investigations of a number of patients with suspected cancer although most of these patients may not have cancer when properly examined. In clinical practice, it is often noted that many patients do not present with classical symptoms. This puts extreme pressure on the GP and on the possibility to have relevant and fast diagnostic procedures done. We need more knowledge on how to obtain a correct and prompt diagnosis after a person has presented a symptom to the health care system. Due to the increasing incidence and the need for better performance, the health care system will have to become very efficient in the way the diagnostic pathways for cancer suspicion are planned. However, the diagnostic cancer pathway has been shown to last for up to several months. Thus, an increased incidence may worsen the diagnostic performance unless we obtain new knowledge about how to organise the diagnostic pathway in an effective and high quality manner. The question is how to improve this performance and still be efficient. Thus, we raised the question whether introducing specific diagnostic pathways for suspected cancer (fast track referrals) would have an effect on waiting times and whether other pathways would have to be implemented to support general practice. It has often been suggested that waiting time for treatment does not have a significant effect on prognosis as the tumour has often developed over many years or even over decades. However, many studies may have been based on the false assumption that less waiting time was associated with worse outcome due to the waiting time paradox. There was a need for more research and better methods to investigate the association between the diagnostic process, especially time intervals, and the prognosis. In conclusion, the primary cancer diagnosis is entirely dependent on three factors: A) that persons address their signs and symptoms and contact the health care system, B) that general practice is able to identify the relevant symptoms and take quick action and, C) that there are well defined diagnostic pathways to confirm or rule out the suspicion of cancer. To improve cancer outcome, precisely these three elements had to be explored by cutting edge research, as they are some of the tools to improve cancer treatment in Denmark as well as in an international setting. Establishing the Research Centre for Cancer Diagnosis in Primary Care CaP In the process leading to the establishment of CaP, the Novo Nordisk Foundation funded a national project on improving patients experiences of the cancer pathway. This primary care based project initiated different studies at different research institutions. A main partner was the Research Unit for General Practice, Aarhus University, and we used this initiative to focus on the state of the art of cancer diagnosis. Thus, in 2008, we published a report on waiting times and cancer diagnosis and reinforced the need for research within the area. Two PhD projects had already been started: one on lung cancer (Marianne Bjerager) and one on delay in cancer diagnosis (Rikke Pilegaard Hansen). The report formed the basis for the discussion between the Novo Nordisk Foundation and the Danish Cancer Society about funding a project on early cancer diagnosis and was the beginning of the foundation of the initiative later forming the CaP. The relevance of the formation of CaP was indeed supported by an initiative from the Danish Cancer Society, whose official strategy was to support a long term strategic initiative in the field of early diagnosis. 4

7 Together with the Novo Nordisk Foundation, the Danish Cancer Society thus announced the donation of 30 million DKK (approx. 4 million Euros or 3.2 million ) for this area to be applied for in free competition. A group led by Peter Vedsted and substantially supported by Research Director Frede Olesen made the application. CaP won the funding after significant and important feedback from the assessment committee. On 8 January 2010, CaP was officially opened with a symposium on early cancer diagnosis. It was a brilliant and well attended event with many interesting contributions from, among others, The Novo Nordisk Foundation, Director, Professor Birgitte Nauntofte; The CEO of the Danish Cancer Society, Arne Rolighed; Dean Søren Mogensen and Research Director of the Research Unit for General Practice, Professor Frede Olesen and a number of researchers associated with CaP. From the official start of CaP. The founders (from the left): Frede Olesen, Arne Rolighed, Peter Vedsted, Birgitte Nauntofte, Søren Mogensen and Gert Almind. Organisation of CaP CaP was associated as a centre at Aarhus University and with the Research Unit for General Practice as mother organisation. CaP is led by Professor, PhD, assistant research director, Peter Vedsted. He is the daily scientific leader of the centre with an own budget and scientific responsibility. He had been the scientific leader of the current research on the topic. The centre has its own scientific staff and furthermore gains maximum support from the Research Unit for General Practice. In collaboration with Aarhus University, the Research Unit provides office facilities and normal university IT infrastructure, and the CaP centre is fully supported by the dean at the Faculty of Health Sciences. CaP is regarded as a university based research centre and Health, Aarhus University, has supported CaP with nine 1/3 PhD scholarships. CaP is independent of the university as the accounts are kept, together with those of the Research Unit for General Practice, at Danish Regions central office in Copenhagen. Danish Regions is the mother organisation of the Research Unit for General Practice. A research organiser with particular skills within the specific research area heads each research line (see later). This researcher is responsible for linking together activities across projects. Thus, there are research organisers within the field of epidemiology, data management, psychology, anthropology and public health. 5

8 Part of the study focusing on symptoms was physically placed at the University of Southern Denmark as one of the ways to seek national collaboration. To ensure progress Peter Vedsted has appointed a specific person there to be responsible for the outcome (Dorte Jarbøl, see also project A.1., symptoms in the public). CaP has a national and an international advisory board (see appendix for members) to ensure high relevance of its research and high quality and efficient use of its funding. The board members have also acted as experts resolving any project uncertainties and as peers reviewing the protocols. The national advisory board meets twice a year with a specific agenda. Professor Frede Olesen is the chairman. As Frede Olesen is now former research director, the new director, Flemming Bro, has been included as member of the advisory board. At the meetings Peter Vedsted summarise the research results since the previous meeting and the implications for possible actions, feedback and further studies are discussed. Then the plans for the next period is presented and discussed. The research plan is approved by the end of the meeting. New ideas, trends and additional inputs are taken into the plans for CaP. The international advisory board meets at the Ca PRI congress where most of the members attend. The group meets for about an hour in connection with the executive meeting. The agenda includes a summary and feedback from the group. The main issue is to translate the CaP activities into an international context. The members are contacted during the year for input and reviews. Core function of the centre This section shortly introduces the core functions of the centre and then, in the following sections, the output of CaP is specified. The main function of CaP is to perform and complete the studies agreed upon in the final agreement supplied with spin off studies and studies arising from new research themes. In the next section is a description of the studies that CaP is doing or plans to carry out including new studies. In brief, CaP has managed to start nearly all the planned studies and a fine range of additional studies. The additional activity with new studies adds another core function of supporting further external funding. The continuous application for further funding has been a relatively successful process where we have raised additional funding. This amounts to approx million DKK. depending on what is included. In the next section, the research team is described. Many of the research questions addressed require an interdisciplinary approach and a critical research mass. Therefore, CaP has provided a framework for this while still ensuring a clear focus on the use of the results; on clinical work and on the improvement of the population s access to relevant clinical care and on providing efficient health service. By having a medically educated staff supplemented by psychologists, anthropologists and public health experts and other relevant competences, focus is ensured, and the research is done using relevant methodology and theory. The section after, describes how CaP has focused on solving the task of providing new knowledge in national and international settings. This has been done trough scientific publishing, conference presentations and through education and participation in government working groups. CaP has been a link between research and education and the development in health care systems nationally and internationally. CaP has initiated studies to ensure that Denmark participates in international studies. 6

9 CaP has focused on creating an infrastructure that supports an innovative and highly skilled group of researchers. In the section about infrastructure it is described how CaP now has an advanced database (CAPS) for studying primary cancer diagnosis. This database is one of the first in Denmark to combine all health databases and social data with national samples of cancer patients. CaP has been deeply engaged in PhD education and in establishing specific PhD courses (GIS, Use of medical questionnaires and Cancer related Health Services Research). CaP has participated in official working groups and has had more impact than expected in this role. The close collaboration with institutions for medical education and quality assurance throughout the health care system has indeed put focus on the importance of the research from CaP. A full section is dedicated to describing this part of the work at CaP. Studies at the CaP centre CaP hosts a series of studies within the original research agenda established in collaboration with the assessment committee during the application process and studies developed as new ideas. The latter have been driven by further development of research needs. The overall idea of the research centre is to focus Figure 1 The CaP project with the individual branches of research areas and the specific projects on three research lines: A. The patient: knowledge about symptoms, symptom interpretation and health care seeking behaviour. B. Clinical investigations: meeting with the patient, clinical symptoms, paraclinical investigations. C. Organisation and function: cooperation, structure and resources. 7

10 The original application thus included a series of studies briefly summarized here. Within each research line is also a presentation of the spin off studies and further developments of the studies in the application. They have emerged from the research field and from the international collaboration. These studies add to the knowledge pool in relation to the three research aims of CaP. A. Patients aspect The projects in this line of research seek to understand and identify specific processes, mechanisms in and around people with possible signs and symptoms of cancer and in groups of people who may be at particular risk of long waiting times, especially due to patient delay. The projects in this group are: A.1. Epidemiological studies of symptoms of cancer and health care seeking behaviour in the population. This study is further described on page 19 as The public health approach in CaP. The study is a large survey on symptoms in the public where 100,000 randomly identified adults are surveyed about current symptom experiences, their interpretation and action. The study is based on standardised questionnaires and forms the basis for a prospective sampling of non patients with symptoms that could be cancer (see also project D.3.). Dorte Jarbøl, University of Southern Denmark has now been appointed as PI for the study as this is one of our collaborative studies. The PI has been able to gather a group of young researchers. A.2. Epidemiological study of knowledge about cancer and symptoms (cancer awareness). How the public reacts to signs and symptoms may also depend on the knowledge about cancer and cancer symptoms. This study has been performed in cooperation with an international group (International Cancer Benchmark Partnership ICBP). The data collection has been completed; a report has been sent to the Danish Health and Medicines Authority and is used as the basis for an awareness campaign in Denmark during the spring of At this moment, three papers are under preparation within the framework of a PhD study (Line Hvidberg), two papers are submitted in collaboration with the international group and further 3 4 papers are being planned at CaP and in cooperation with Sweden and Norway as part of a Scandinavian initiative. A.3. Validation and operationalisation of patient delay. This part of the project was launched very early to make sure that the theory, models and measurements of patient delay were founded on a valid and carefully evaluated basis. It has primarily been led by Rikke Sand Andersen, anthropologist, post.doc., with substantial input from medical psychology and international partners. As part of the work in the international consensus working group, CaP has developed an international consensus on how to define milestones and intervals. This was published in a report and a paper in Br J Cancer and was called the Aarhus Statement named after the hometown of CaP. Furthermore, the project involves the anthropological work on understanding the process of experiencing symptoms, health care seeking and the psychological approach to understanding what is going on in patients minds when they experience symptoms. Thus, this study is in the centre of CaP s interdisciplinary research, building on and developing this area on an international level. The project is ongoing and will be for years. The definition and measure of patient delay has been a large research area with different input from different research directions, and CaP will continue trying to gather these inputs and produce evidence and new ideas for the international research on patient delay in serious diseases. 8

11 A.4. Psychological causes of patient delay. A central research theme in understanding and intervening in relation to the patient interval is to understand the psychological issues related to symptoms and health care seeking. Anette Fischer Pedersen, medical psychologist, post.doc, has led this medical psychology research line. Based on psychological theory and empiricism we have based new studies on the CAP1 cohort. A PhD study has been started on the interaction between attachment style and patient and doctor intervals (Christina Maar Andersen). Using the comprehensive data in the CAPS database we analyse the specific effects of psychological variables and traits on patient interval, adjusting for a number of confounding and modifying variables. A.5. Triggers of medical help seeking. It has often been asked whether there are specific triggers for patients help seeking. A better knowledge of these would enhance our understanding of how medical help seeking is formed. At the moment, these triggers are researched in several ways by one post.doc. (Rikke Sand Andersen) and two PhD fellows (Camilla Merrild and Sara Hebsgaard) and by an international branch from which we are applying for funding (collaboration with Jo Ellins and Chris Ham, The King s Fund, London). It has also been combined with study B.3. about the meeting between patient and doctor. A.6. From signs to symptoms decisions about health care seeking. It seems that some people react very promptly when they experience symptoms whereas others do not. Some research indicates that the social context is important together with psychological factors. This study is started as a PhD study (Sara Marie Hebsgaard) as part of the anthropological research line. The aim is to understand how symptoms are experienced and acted upon in different households. Focus is on network and interaction in the family and with the surrounding health care system. A.7. Investigation of the influence of patient modesty on patient delay and the importance of factors associated with the doctor patient relationship. Some psychological aspects of the patient s reaction to symptoms and health care seeking behaviour may originate from psychological and psychosocial aspects. They can be about the patient getting embarrassed (e.g. blood in stools), attachment style (secure or unsecure) and aspects relating to fear, coping, willingness to take a risk, cancer beliefs and health behaviour. This part of the study is conducted by a post.doc. (Anette Fischer Pedersen) and a PhD student (Christina Maar Andersen). A.8. Design and evaluation of intervention programmes aimed at reducing patient delay. This study is a natural extension of the studies presented above including symptoms in the public, awareness and beliefs, psychosocial and anthropological factors. Based on the results of these the study should develop a complex intervention to reduce time to presenting cancer symptoms. Therefore, this work has not yet been incorporated in a specific research project, but is one of the planned intervention studies in the next part of the project period. The study will be based on the MRC complex intervention method. Although not yet initiated, parts of the knowledge from the previous studies have already been tested and implemented in the Danish awareness campaign on cancer symptoms. This campaign was described in the Danish Cancer Plan III based on the knowledge from CaP. We will try to make it possible to evaluate this campaign in cooperation with the Danish Health and Medicines Authority who is responsible for the campaign. 9

12 A.9. Cancer patients' use of general practice with particular focus on the time before diagnosis. There was a strong need for detailed information on health care seeking among cancer patients compared with matched people without cancer. This study has been part of the epidemiological studies at CaP and led by Karina Christensen, post.doc. The idea was to map the use of general practice to see whether patients actually seek care in the time before diagnosis. Furthermore, this study also has a great impact on the next group of studies on the diagnostic aspects as these studies provide very precise national data on the services provided by GPs and hospitals up to the date of diagnosis and in the period after the diagnosis. The first paper has been published and several are in preparation. Further collaborative studies on this issue have been started with international partners in the UK and The Netherlands. A PhD study (Anette Hvenegaard) will look at a more detailed description of the period just before the cancer diagnosis by combining the CAP cohort with detailed clinical information and the CAPS register. In this way, we will obtain information on in between consultation periods and how these are modified by other factors. A. Additional studies Cancer patients' experiences and assessment of health care (Henry Jensen) (in collaboration with the Danish Cancer Society): The study will investigate patients' experiences in relation to their primary cancer pathway and their assessment. In this project, we have used the sampling frame developed by CaP including 7,153 persons. Participation in mammography screening (Line F. Jensen): Based on the first screening round, this PhD study examines factors affecting participation in screening for breast cancer among women living in Central Denmark Region. The primary focus is socio demographic, psychosocial and health related factors. The study is primarily a register based study. B. Diagnostic aspect These studies focus on the clinical diagnosis from the patient s first presentation. B.1. Description of and knowledge about symptoms of cancer in general practice. This study was planned to provide a description of what symptoms of cancer GPs see AND their knowledge about what symptoms and signs to look for. However, very soon it became clear that there was very little research knowledge about symptoms seen in primary care, which meant that the second part of the study would be impracticable at that time. The description of symptoms led to one of the most significant papers from the project so far (In Danish). It described the variety of symptoms reported by GPs in cancer patients seen in general practice and especially it reported that only 50% had presented with alarm symptoms. Thus, the paper implied that the Danish health care authorities acknowledged that fast track for alarm symptoms was not enough to provide appropriate diagnostic support to general practice. The knowledge part of this study is now turned into an intervention study with a stepped wedge design where all 840 GPs in Central Denmark Region are given a 3 hour CME session on early cancer diagnosis in general practice (Berit Skjødeberg Toftegaard). 10

13 Another PhD study within this field (Henry Jensen) investigates the use of 'fast track' referrals and the GPs symptom interpretation and the effect on time to diagnosis and tumour stage. Data include three cohorts of newly diagnosed cancer patients from the years 2004, 2007/08 and 2010 (the CAP cohorts). The study will document GPs symptom interpretation, use of fast track referrals and time to diagnosis. The study will document changes in tumour stage during major organizational changes in Denmark. B.2. Uncharacteristic and atypical symptoms of cancer in general practice. GPs see a variety of symptoms in clinical practice, and some of them are signs of serious disease. However, we showed that half of the cancer patients had presented with vague or uncharacteristic symptoms. This PhD study (Mads Lind Ingeman) describes the use of fast track investigation of patients with unspecific, serious symptoms in general practice and their clinical characteristics and the diagnosis. B.3. The meeting between patient and doctor. How the practice performs and responds to patients help seeking behaviour for cancer symptoms. Some of the first results from our qualitative research showed that the doctor patient relationship had a surprisingly large impact on the health care seeking behaviour and the way people reacted and interpreted their symptoms that later turned out to be cancer symptoms. Therefore, this study sets out to investigate in detail what happens in the practice and in the doctor patient relationship when cancer symptoms are presented. The study is a post.doc. study (Rikke Sand Andersen); the field study ended in 2012 and the analyses are ongoing. B.4. Clinical audit of the diagnostic pathway focusing on long delay and critical events in general practice. In general, it has been shown that GPs regard the primary care interval as short, lasting only a few days. However, in some 10% of the patients, the time interval is reported longer by the GP and critical events may occur for these patients. This PhD study (Mona Lisa Kise) scrutinises the tail, i.e. the longest primary care intervals, using a special questionnaire. Based on the response from GPs and medical records these are audited by a panel of clinical experts. The study focuses on lung and colorectal cancer. The study will be completed in Part of the study is made in connection with a collaboration with the quality department at the Danish Cancer Society where the 2010 CAP cohort is investigated with respect to critical events in general practice as measured by the GP and the patient (Henry Jensen). B.5. From symptom to treatment in childhood cancer. Many health care professionals regard the diagnostic pathway for childhood cancer as seamless and well planned. However, from clinical general practice it is known that also childhood cancer often presents with unspecific and vague symptoms and that some cases have a prolonged diagnostic pathway. This study was completed with a PhD thesis (Jette Møller Ahrensberg) in B. Additional studies The effect of waiting time on cancer patients' survival (Marie Louise Tørring): Results for colorectal cancer has been published in the Br J Cancer (BJC 2011;104: ) and in the J Clinical Epidemiology. Results for colorectal, lung, melanoma, breast or prostate cancer have been published in the form of a PhD thesis (defended in March 2011). The project continues as a proposal for a PhD project with special focus on lung cancer (Lotte Linnemann Rønfeldt). 11

14 Quality issues along the diagnostic pathway for Danish cancer patients (Henry Jensen): The project will investigate the prevalence and type of suboptimal (critical) events during the diagnostic process of cancer patients in Denmark. In addition, the study will examine associations between the events and time to diagnosis. The study will also look at the patient reported events and the correlation between patient and GP. Patients are identified in the CAP2010 cohort (n= 7996). The ProCaRis study information about the risk of prostate cancer on the basis of a genetic test (Pia Kirkegaard): The project will develop and test a method to disseminate information about genetic risk for prostate cancer in patients who have a normal PSA level. It will assess whether it is possible for patients with normal PSA levels and low genetic risk to refrain from unsystematic screening with PSA tests, and for patients with normal PSA levels and high genetic risk to follow a systematic screening programme. The study is a randomized controlled trial of 5,600 patients. Effect of access to fast CT scan as part of early diagnosis of lung cancer in general practice. A randomised, controlled trial (Louise Mahncke): Only 35% of lung cancer patients survive the first year, and the prognosis is highly dependent on stage at diagnosis. Symptoms of lung cancer have a low positive predictive value, and this study investigates whether access to direct CT scan from general practice has an effect on the time to diagnosis and treatment, TNM stage, and 1 year mortality. Ongoing PhD study. Abdominal symptoms and cancer in general practice (Morten Bondo Christensen): A Norwegian based (PI: Professor Knut Holtedahl) multinational project aiming to examine the prospective association between abdominal symptoms and the development of cancer. C. Care management aspect The projects in this group focus on the organisation, structure and coordination of the diagnostic pathway. C.1. Audit of the cancer pathway focusing on system delay and optimising the pathway. This part of the project has two steps: 1) to acquire knowledge about the system delay in relation to the time from first presentation until treatment start and 2) to set up an audit procedure that will enable a more optimal pathway. Regarding the first part, several CaP projects aim to investigate system intervals. Thus, projects are looking at the time from referral to diagnosis in e.g. patients with unspecific symptoms (Mads Lind Ingeman) and lung cancer (Louise Mahnche), and in patients in general using register data (Karina Christensen and Marie Louise Tørring). The second part of the study has not yet been initiated, as this part needs support from the national clinical databases and, therefore, integration of data from primary care. CaP is working on establishing this possibility. C.2. The need for and use of imaging and endoscopic diagnostics in general practice for suspected cancer. The use of imaging and endoscopic procedures in the time before a cancer diagnosis is, in many instances, important for en earlier diagnosis. It has also been claimed that some cancers are diagnosed late due to poor access to and use of these investigations. This study measures the use and timing of such procedures for different cancers. At the moment, a post.doc. (Karina Garnier Christensen) and a PhD study (Louise Mahncke, lung cancer) are investigating this. Two young physicians are preparing projects within this area on the use of colonoscopy, gastroscopy and cystoscopy (for additional external funding). 12

15 In relation to the use of diagnostic procedures, a PhD study (Peter Hjertholm) investigates the variation between general practices in the use of diagnostic procedures and the association with cancer outcome. C.3. Patient and GP supported follow up of abnormal test response in cervical cancer screening. It was reported that a relatively large proportion of women with an abnormal smear test did not get a follow up within the required period. This study is a PhD study (Bettina Kjær Kristiansen) that in a natural experiment and in a cluster randomised trial evaluates the effect of providing the GP with a reminder for women who did not have a follow up and the effect of sending a letter directly to the women with the test result. C. Additional studies Shared care model for follow up in prostate cancer (Flemming Bro): The project aims to develop a model of cooperation on treatment and follow up of patients with prostate cancer and to implement the model at Aarhus University Hospital, Skejby, Viborg Hospital and the Regional Hospital Holstebro. The effect of a case manager in the cancer process (Christian Wulff): This project evaluated the effect of introducing case managers in the early stage(s) of the cancer pathway. In a randomized design, 280 patients with colorectal cancer allocated to either routine or case manager intervention were included. Efficacy was assessed by comparing the two patient groups evaluations, quality of life and health care contacts as well as the GPs evaluations. PhD defended in Impact of ICT supported cancer process in general practice (Thomas Mukai): The project investigated whether ICT enhanced the GP's advice and ensured continuity in the diagnostic process for patients diagnosed with breast cancer and prostate cancer. ICT was delivered as a link in medical records and test results to offer relevant information to the GP. PhD thesis under assessment. D. Projects across all three aspects These projects deal with the use of specific methods for sampling of patients and specific cases, for collection of clinical data and the use of register data. These projects are partly the foundation for several of the projects and an investment in future studies. D.1. Definition and operationalisation of delay throughout the cancer pathway. This part of the project was essential to the research field. It has been and is an issue both within CaP s research group and in the international collaborative work. As also mentioned in study A.3., the work has focused on the theory, models and measurements of milestones and time intervals on a valid and carefully evaluated basis. It has involved the senior researchers and has primarily led to international consensus work with a report financed by Cancer Research UK and the Aarhus Statement on measuring time intervals in the primary cancer pathway (Br J Cancer). The work is an ongoing process, and now CaP is working with extensive register data to try to set registerbased milestones and intervals at least for some cancers. We have developed a register based identification of newly diagnosed cancer patients which has now been implemented as a standard sampling instrument. We work together with a UK group on validating the core milestones in the diagnostic pathway. 13

16 D.2. Use of databases and registries in the study and monitoring of cancer diagnostics and establishment of continuous audit of the process from first contact to treatment of cancer. This part of the project has been extensively researched and developed through the project period. First, we established the three CAP cohorts (see later). We have also established CAPS, which is one of the most comprehensive databases on this research in Denmark (see later). Finally, we are now working on developing the following procedures: For every cancer patient diagnosed, the GP will be sent an online pop up questionnaire using a Data Capture feature asking about data relevant to primary care (symptoms, milestones, critical events etc.). These data will be used for auditing and monitoring. A complete registration of all referrals from general practice to investigation for cancer (fast track). These data will be used to monitor the diagnostic process, the effect of fast track and for audit purposes. D.3. Prospective data collection of people with emerging symptoms. One drawback of nearly all research within early cancer diagnosis is that it samples cases when the cancer diagnosis is already established. Thus, we will never be able to get real time and unbiased estimates of a large number of aspects. However, including persons prospectively will mean that we will have to approach thousands of people to be able to include an appropriate number of cancer patients. Therefore, CaP uses the possibility to sample, prospectively, people who report symptoms of various types during the national survey described in A.1. The sampling will be done based on specific algorithms testing the predictive values and likelihoods of these symptoms and symptom groups in relation to cancer. This will further be adjusted for a number of register based variables on health care seeking, socio economic status and co morbidity. D. Additional studies The importance of diagnostic variation in Danish general practice for cancer patients' prognosis (Peter Hjertholm): This project will develop a method for comparing diagnostic activity, such as referral rates, number of blood tests etc. in general practice and then use these data to investigate the effect on cancer outcome (prognosis and stage). Diagnostic delay for cancer patients in Central Denmark Region and the Region of Southern Denmark (Mette Bach Larsen): This study described and analysed cancer patients' diagnostic pathway before and after the national introduction of fast track referral for cancer. Focus was on: 1) Change in the time interval from GP referral of the patient to secondary care until treatment, 2) Changes in patients' sense of cohesion and 3) change in GPs' assessment of the pathway. Completed with a PhD thesis in

17 The interdisciplinary research team The research questions addressed by CaP require an interdisciplinary approach. From the beginning, it was important to ensure an interdisciplinary research group. This means a group that, with the overall aim of the project and the context in mind, can research ideas using the most appropriate theory, model and method. The research environment that has been established is therefore presented. The medical psychological approach in CaP Early cancer diagnosis in primary care will often be a matter of patients timely help seeking. Patients postponement of help seeking seems to be explained by a mixture of psychological factors such as low awareness of cancer symptoms, low social support, high levels of fear combined with low levels of selfefficacy and inappropriate coping responses. However, many of the studies conducted so far have included only a small number of patients. The GP s interpretation of the patients symptoms is determined by complex reasoning processes. These appear to be based on both biomedical logic and the psychology of the doctor patient relationship of which the last mentioned has only been investigated to a limited extent and never with a specific focus on cancer diagnosis. The first psychological studies performed by CaP followed the traditional approach to patient delay in cancer research and used retrospectively reported quantitative data from patients diagnosed with cancer. This approach has revealed new aspects of associations between psychological factors and patient delay, including gender differences in the influence of social support, and a dual process coping model suggesting that patients use both avoidance and approach coping strategies when experiencing symptoms. Moreover, we have shown that colorectal cancer patients with rectal bleeding have delayed help seeking more often and have had more cancer worries in the patient interval than patients without colorectal bleeding. These results are interesting as previous assumptions was that the long patient delays observed among colorectal cancer patients with rectal bleeding should be explained by patients assigning the symptom to benign causes. To gain more insight into the effect of psychological factors on help seeking while overcoming the problem of recall bias, three PhD projects have been launched. These projects are population based and focus on: 1. Cancer awareness and beliefs in the Danish population (Project A.2.) 2. Non participation in the Danish national breast cancer screening programme (Additional project) 3. Symptom perception and health worries in individuals experiencing a possible cancer symptom (Project A.1.) The Awareness and Beliefs about Cancer (ABC) instrument used in study 1 was developed based on psychological theories such as the Health Belief Model. The design of study 3 is guided by Leventhal s commonsense model of self regulation, which describes how individuals identify whether they are ill and what they do to get better. Together, the three projects will reveal important knowledge concerning healthy individuals awareness and beliefs about cancer symptoms. With the unique civil registration numbers of the participants in studies 1 and 3, we will examine whether the psychological factors assessed in the studies predict future outcomes (using the CAPS database). As a new tool to gain knowledge about the influence of the doctor patient relationship in the diagnostic cancer processes, we created the GP profile survey (see later) among all GPs in Central Denmark Region. 15

18 The GPs filled out The Physician Profile Questionnaire that among other things assesses the level of burnout symptoms, physician empathy, physician attitudes about uncertainty and risk taking, and attachment style. A PhD study is examining how patient and GP delay are influenced by patients and GP s attachment styles and the possible match/mismatch between the attachment styles. Based on this project, collaboration with Jonathan Hunter and Bob Maunder, Mount Sinai Hospital, Toronto, Canada has been established. Figure: Psychological theories and concepts of relevance on the general population level, the pre patient level, and the medical consultation level During the next two years, a series of manuscripts will be submitted based on the described studies focusing on: Burnout in GPs and its influence of diagnostic activities GPs willingness to take a risk and their use of diagnostic activities GPs attachment style and length of GP delay Patients attachment style and length of patient delay Mismatch of GPs and patients attachment styles and length of GP and patient delay Associations between positive cancer beliefs and anticipated delay Socioeconomic factors and awareness and beliefs about cancer Psychosocial factors and non participation in breast cancer screening 16

19 The psychological projects launched so far have some unique opportunities and qualities. To date, no studies have prospectively examined how psychological processes influence the decision making process associated with help seeking. Data obtained from the GP Profile provide us with the unique possibilities to combine self reported data with register based data. The knowledge gained from these studies can be used to design interventions aimed at reducing delays in cancer diagnostics on various levels. The medical anthropological approach in CaP The first anthropological research carried out at CaP explored reasons for patient delay in cancer and followed a traditional patient delay framework based on retrospectively conducted interviews with cancer patients. We integrated theoretical frameworks on symptom experiences and health seeking decisions which had not previously been applied in the patient delay literature. In that way, we were able to bring forth a series of new insights on the dynamic relationship between clinical practice and health seeking, the role that culture and social relations play in defining what bodily sensations count as symptoms, and how health seeking decisions are socially legitimated. A series of studies on patient delay has e.g. suggested that lack of awareness of potentially malignant symptoms is the main patient mediated factor causing late helpseeking among cancer patients. However, the literature only provides sparse information on the cultural and social embeddedness of bodily experiences and what people consider as symptoms. The results from the anthropological studies have been influential in the development of a standard framework for the exploration of delay in cancer (The Aarhus Statement). To gain more insight into these aspects, we are currently conducting three research projects based on traditional anthropological fieldwork methods (studies A.5., A.6. and B.3.). These projects are supplemented by a nationwide survey and register based studies on the prevalence of symptom experiences and health seeking in the background population (Study A.1.): 1. The embodiment of social inequality. A comparative anthropological study of social group and health seeking. PhD project, by Camilla Hoffman Merrild. 2. From bodily sensation to symptoms in need of health care. An anthropological study exploring the relations between symptom experiences and health seeking. PhD project, by Sara Hebsgaard. 3. When should I see the doctor? An anthropological study exploring the interrelatedness of patients health seeking decisions and general practice settings. Post.doc. study, by Rikke Sand Andersen. 4. Symptom presentations, social networks and health seeking decisions. PhD project, by Sandra Elnegaard. Anthropological studies on illness and health related behaviour have mainly been concerned with illness experience and responses to this in different treatment settings and clinical encounters. Thus, we have insight into what it means to be 'a patient' and how patients experience their contact with various forms of healthcare. By contrast, we know very little about how bodily changes or early symptoms of ill health are managed in the course of everyday life outside the clinical setting and how health seeking decisions are established before people become patients. We will now be able to provide these insights. Project one is guided by Paul Farmer s concept of structural violence, and more recent writings on the embodiment of inequality that describes how social, political and cultural forces put certain groups of people at risk of disease. Study 2 is based on the concept of local biology and more recent writings on the body, 17

20 describing how the interpretation and management of the body is perceived as culturally and socially informed. It will be explored how people define symptoms, and in particular how symptom experiences are associated with help seeking decisions. These projects are carried out in close partnership with Mette Bech Risør, PhD, MA, Anthropologist, Tromsø University. The third research project further explores the relationship between clinical practice and health seeking decisions. This project is heuristically influenced by a series of sociological and anthropological theories on congruence and the social organisation of work. The fourth project will provide us with insight into the prevalence of symptom experiences in the background population. Based on their civil registration number and registry data, we will have a unique opportunity to examine a series of social factors and how they may be associated with the reporting of symptoms, the role of social networks and health seeking decisions. During the next two years, a series of manuscripts will be submitted based on these studies. The manuscripts will explore: A comparative analysis of two different social groups, exploring the relationship between access to social and educational resources and health seeking decisions. A comparative analysis of two different social groups, exploring the relationship between bodily experiences, processes of meaning attribution and health seeking decisions. The process of distinguishing normal bodily sensations from symptoms of illness. Exploring the role of 1) gender, 2) cultural knowledge, 3) social sanctioning. The economy of time in Danish general practice settings and its socialising effects on peoples health seeking decisions. Healthcare decision making and morality. Clinical sanctioning of peoples health seeking decisions. The role of front desk staff in providing access to the consultation room. Exploring the relationship between visitation and health seeking decisions. We are in the process of broadening the anthropological research strategy at CaP to include research within the clinical setting, both to learn more about how patients experience recently introduced cancer treatments and screening regimes and how we may decrease time until diagnosis (system interval). 1. An anthropological study exploring daily clinical practice and clinical encounters in fast track diagnostic programmes. PhD project, by Rikke Aarhus. 2. Assessing risk of cancer: interpretations and negotiations among patients and their families about high genetic risk of prostate cancer. Post.doc. project, by Pia Kirkegaard. 3. Reframing cancer as an acute condition. Post.doc. project, by Marie Louise Tørring. 4. A comparative study of patients experiences of cancer care in England, Denmark, the Netherlands and Sweden. A possible PhD project in collaboration with The King s Fund, London. 18

21 Within the Danish health care system, rational diagnostics such as fast track referrals and techniques for improving opportunistic screening are increasingly considered important. However, little is known about the implications these changes may have on daily clinical practice and the clinical encounter between patient and healthcare providers. Projects 1 and 2 will explore these changes, particularly with focus on how they may influence the patient role. Project 3 sets out to explore the reframing of cancer as an acute condition in Denmark. Awareness of cancer is contagious ; it spreads through experiences with the health care system, through interactions with family and acquaintances and through the media; and it is linked to the bodily encounters with diagnostic equipment. The project is carried out in close collaboration with Centre for Cultural Epidemics (EPICENTER), which is under the strategic leadership of Professor Lotte Meinert and Associate professor, Jens Seeberg, Institute for Culture and Society, Aarhus University. Project 4 is an international, comparative interview study of 240 cancer patients carried out in close collaboration with researchers from England, Denmark, The Netherlands and Sweden. Prof. Chris Ham (The King s Fund) and Dr Jo Ellins (University of Birmingham) will share strategic leadership of the research project. The public health approach in CaP This research sets out to establish comprehensive epidemiological knowledge of the relation between symptoms and health care seeking in the Danish population. Bodily sensations, signs and symptoms may be caused by cancer at different stages. Our knowledge about cancer symptoms is largely based on cancer patients. We know little about the symptoms in the population, what importance the population attaches to the individual symptoms, and not least what leads to a visit to a doctor. This part of the CaP initiative describes the prevalence of early symptoms and possible warning signs of cancer disease in the population with special focus on symptom interpretation and help seeking behaviour among a large, randomly selected group of adults with varying socioeconomic status, comorbidity, health perception, network etc. We obtain knowledge about the significance of the specific characteristics of the symptoms and investigate factors of importance for health care contacts. The study will contribute with an assessment of the prognostic value of the symptoms and create the possibility of sampling of selected populations with recently developed symptoms. Extensive work has been carried out on the development and testing of a questionnaire to investigate symptoms, symptom interpretation, health perception and visits to the GP. A total of 100,000 Danish citizens aged 20 years or more have been randomly sampled from the Civil Registration System. They are mailed a written invitation to participate in an electronic questionnaire study. The data collection is ongoing and expected to be completed at the end of The study is carried out in close collaboration between the Research Units for General Practice in Odense and Aarhus. The project group has been established with Dr. Dorte Jarbøl, PhD, Deputy Head of Research, Senior Researcher (Research Unit of General Practice in Odense) as PI (responsible to Professor Peter Vedsted). Furthermore, the research group consist of three PhD fellows, a project coordinator and an associated statistician (see also later). The following studies have been established: 19

22 Epidemiological studies of gastrointestinal symptoms and cancer alarm symptoms in Denmark A population based study (by Sanne Preus Hatting, PhD Student) Gynaecological alarm symptoms in a general population prevalence, determinants and consequences (by Kirubakaran Balasubramaniam, PhD Student) Symptom registration, experience and interpretation. Factors of importance for visits to the GP? (by Sandra Elnegaard, Research Fellow) The results from the pilot questionnaire have been presented at The Cancer and Primary Care Research International Network (Ca PRI) Conference, Cleveland, Ohio, USA, 5 7 June 2012, for all sub studies. During the next two years, we will obtain new knowledge about early symptoms and warning signals of possible cancer disease in the population. For both respondents and non respondents data form e.g. Statistics Denmark, the National Patient Registry, the National Cancer Registry etc.) will be linked to provide a unique opportunity for investigation of person characteristics, disease development and comorbidity as well as the possibility of analysing relationships between symptom prevalence and health care seeking behaviour among the respondents. Epidemiology and data management at CaP To provide valid, statistically precise and highly internationally relevant results, we have established a comprehensive data infrastructure. This will support epidemiological research and health services research. The three CAP cohorts CaP has established three cohorts of newly diagnosed cancer patients; one in where approx. 3,000 cancer patients were included; in a cohort including 12,000 incident cancer patients was established and, most recently, in 2010 the third cohort with about 10,000 patients was established. We plan a 2012/13 cohort. These patients are described using questionnaire data from their GP and from the patient when possible. The data include, e.g. time intervals, symptoms, evaluations, assessment of the patient etc. All questionnaire data are transferred to Statistics Denmark and connected with the complete CAPS database (see later). Therefore, we now have three cohorts with approx. 25,000 cancer patients combined with all Danish registry data. CAPS Existing studies regarding cancer patients, their background, use of health services and prescriptions, use of general practice before, during and after the disease are often based on questionnaires and are thus relatively small studies. The use of the unique civil registration number at each contact with the Danish health care system together with linking this to a number of registries makes it possible to use these data for research. In this way we will obtain results based on app. 30,000 new cases of cancer each year in Denmark. The CAPS database is used by CaP researchers in a number of projects. It is possible to describe the cancer patients use of general practice, practising specialists, hospitalisations, outpatient treatments, psychiatric hospitals, prescription of drugs as well as cause and date of death. Furthermore, the available register data allow investigating whether cancer patients change GPs, and we can describe the characteristics of medical care and compare these with the performance of the cancer patients, etc. Finally, the CAPS database con 20

23 tains a number of variables from Statistics Denmark, which makes it possible to describe patient characteristics, e.g. origin, family situation, education, occupation, income and habitation. The CAPS database links more than 10 registries and contains information about all cancer patients in Denmark from the creation of the Danish Cancer Registry in 1943 to date with approx. 30,000 new cancers per year. We have a complete list of all cancers in Denmark, as the completeness of the Danish Cancer Registry is extremely high with an underreporting of 0.9%. The CAPS database contains over 200 variables in all from the registers (see figure). Moreover, the CAPS database holds information regarding the background population so that we, for each research question, can compare the cancer patients with people without cancer. Three local interdisciplinary groups (task forces) are working to collect and share knowledge in the field of registry based research and produce high quality data and algorithms. The aim is to make guidelines regarding the use of register data in three domains: socio economy and socio demography, health services utilisation and for measuring comorbidity. The guidelines will describe existing methods, variables together with Stata commands. Sampling of incident cancer patients To be able to make a timely and valid identification of cancer patients we developed a new sampling method of incident cancer patients in Denmark via the National Patient Register (NPR). As the Cancer Registry is about one year behind, we needed such a sampling frame to make e.g. questionnaire studies. By comparison with previously used sampling methods and the Cancer Registry we have validated the completeness and timeliness of the sampling. An article on this method is now under publication. 21

24 Variation In relation to the register data we have established a special epidemiological theme about the effect of variation on cancer outcome. This is done in a PhD study (Peer Hjertholm) where we have included senior statisticians, epidemiologists and clinicians in a specific research team on variation. This team develops standardised, high quality data for characterising general practice according to their activity. Afterwards the data are used for measuring the association with outcome. The rates are adjusted for numerous confounding variables and the statistical modelling forms the basis for PhD studies at the Section for Biostatistics, Aarhus University. The GP profile To support the health services research agenda we started the GP profile survey. This was also done to provide data for the study of psychological aspects among GPs and diagnostic activity. In this way, we would get unique data that have not been investigated before. In January 2012, all GPs in Central Denmark Region received a questionnaire package assessing several psychological factors and satisfaction with working conditions ( The Physician Profile Questionnaire ). A total of 601 GPs (72%) completed and returned the questionnaire assessing among other things level of burnout symptoms, physician empathy, physician attitudes about uncertainty and risk taking and attachment style. This is one of the largest databases in the world on these issues and provides unique scientific possibilities. Data capture from general practice Since 2006, general practice has developed an electronic data capture module that can be implemented into all GPs electronic patient record systems. In 2014, all GPs must implement this data capture module and all registered clinical data will be available for research. Therefore, CaP has started defining these datasets and including them into CAPS. However, there is a fundamental need for validating the data and providing further evidence for their use in science. CaP works very closely with national parties on these issues. CaP in relation to the national and international parties The pre hospital diagnosis of cancer rapidly attracted increasing interest. From the very start, CaP experienced interest in exchange of knowledge, ideas and developments from the national and international community. Nationally The Danish Cancer Society has been of great and important support and acquired the new knowledge to be incorporated in their work. The national collaboration of the multidisciplinary cancer groups (DMCG.DK) very early became interested in the work from CaP and soon started to include the new knowledge in their work. CaP has close cooperation with relevant institutes and faculties from which the various professions involved are educated, especially anthropology, psychology, clinical epidemiology and biostatistics. An example is the study of cancer investigation within an infectious analytical framework for understanding how the suspicion of cancer spreads from patient to doctor and from the primary to the secondary sector. This project is part of a new AUFF Pilot Centre for Cultural Epidemics. 22

25 CaP has a close connection to different clinical settings in primary care and in hospitals. CaP is deeply involved in the development of diagnostic centres based on the research results showing the need for this. Especially Silkeborg and Vejle Hospitals have been closely connected to CaP, and now further hospital units are involved in this work. In relation to oncology and diagnostic specialities (radiology and laboratory medicine) CaP is in close collaborative contact with departments at different hospitals and especially at Aarhus University Hospital. Collaborative clinical work is also established with the department for colorectal surgery as well as internal medicine and lung specialists at Aarhus University Hospital. In relation to developing new ideas and translating the biomedical research into clinical practice in relation to cancer diagnosis, CaP has an extremely interesting cooperation with MOMA, Molecular Medicine, at Aarhus University Hospital, Skejby (Professor Torben Ørntoft). The ProCaRis (Prostate Cancer Risk Assessment in General Practice) project is carried out in collaboration with MOMA. The centre has close cooperation with the Central Denmark Region and the initiative Cancer in General Practice'. This centre has special competences in the implementation, organisation and training in cancer related issues. Thus, CaP is an important partner in health care interventions. CaP has participated in the foundation of a regional group on research in cancer diagnosis with a collaborative network of five hospitals. This is also seen on a national level where CaP has been involved in the development of Danish Regions initiatives on e.g. fast track for unspecific, serious symptoms, the establishment of Diagnostic Centres and the integration of primary care based and hospital based cancer research to provide optimal cancer care in Denmark ( Kræftforskningsforum ). The Danish Health and Medicines Authority very early asked CaP to be closely connected so that new knowledge and international knowledge could easily be transferred into recommendations. In this way, CaP has had central positions in defining national Cancer Plan III for CME in general practice, the cancer awareness campaign and the development of diagnostic centres and the fast track referral for unspecific but serous symptoms. CaP and The Danish Health and Medicines Authority work closely together on the International Cancer Benchmark Partnership (ICBP). CaP has been a close partner in Barometerundersøgelsen (Cancer patients evaluate the cancer pathway) conducted by the Danish Cancer Society. The survey is planned to be a continuous part of the monitoring of cancer care in Denmark. On several occasions, researchers from CaP have been invited to be members of government working groups and advisory boards. CaP has made several presentations in different settings, including clinical, political and public. Internationally The Research Unit for General Practice has a long tradition for contact with leading primary care research centres abroad. Therefore, CaP was also well integrated into the international research environment from the beginning. CaP has been an active part of international research networks in the area and has produced a number of international scientific publications. CaP has established a strong international position together with several international partners; Edinburgh University (Professor David Weller), Cancer Institute UK (Professor Mike Richards, National Cancer Director, Department of Health, UK), Durham University and 23

26 the National Audit of Cancer Diagnosis in Primary Care, UK (Professor Greg Rubin), Exeter University (Professor William Hamilton), Cardiff University (Professor Richard Neal), Frankfurt University (Martin Bayer), Melbourne University, Australia (Jon Emery), Cambridge University (Fiona Walter), Oxford University (Peter Rose), Tromsoe University, Norway (Knut Holtedal), Karolinska Institute, Stockholm, Sweden (Carol Tisherman), Toronto University, Canada (Eva Grunfeld). Unfortunately, our Dutch partners with whom we had a very fine cooperation have changed jobs and we are now looking for new partners. In addition to these close partners we have several other connections to researchers within this field. As CaP is a one of the few research institution for early diagnosis of cancer in the world, we have a strong and very inspiring network throughout the world. One of the stimulating circumstances is the yearly conference in the international Ca PRI network. Peter Vedsted and Frede Olesen have been members of a small group creating this international network of researchers (see pri.com). We arranged the second conference for the group in Copenhagen in April 2009 with some 80 participants from leading countries in Europe, the US, Canada and Australia. Peter Vedsted is a member of the executive committee and is one of the organisers each year. A core function of CaP is to facilitate exchange of researchers. Rikke Sand Andersen and Line Jensen have spent some months at Toronto University and New Jersey University, respectively. Furthermore, we have had visits from Richard Neal, Greg Rubin, Mike Richards and the Consensus Working Group to discuss delay in cancer diagnosis. In the summer of 2012, it was a pleasure for CaP to be able to attach Professor Henrik Møller, King s College University, London, as part time professor at Aarhus University and CaP. Henrik Møller is one of the world s leading cancer epidemiologists and has been very interested in the research at CaP. CaP will try to secure funding for professor Møller and is in the process of establishing a research portfolio. CaP researchers are increasingly invited as speakers to give lectures and symposia at relevant international conferences (see later for activities). Part of the strong international work has led to an international Consensus Working Group on Early Cancer Diagnosis in Primary Care that produced The Aarhus Statement, an international guideline on measuring milestones and time intervals in cancer diagnosis. This has been published in Br J Cancer. In addition The Aarhus Checklist has been produced, which is a guideline for research in the area and for writing papers on this. CaP hosted the third and final meeting of this working group. On this occasion, the group concluded its discussions of the various definitions. CaP has, in cooperation with the Danish Health and Medicines Authority, been leading the Danish part of the International Cancer Benchmarking Partnership (ICBP) modules 2, 3 and 4 ( info/spotcancerearly/icbp/index.htm). Peter Vedsted is the international co chair of module 4 and the national lead for modules 2, 3 and 4. Responsible for each of these modules are Line Hvidberg (module 2), Berit Toftegaard (module 3) and Henry Jensen (module 4). The ICBP work includes very close international collaborative work, and the Scandinavian ICBP countries (Sweden, Norway and Denmark) work very closely together to obtain specific results for these countries with further analyses and knowledge about cancer awareness, primary care organisation and waiting time. 24

27 In collaboration with Tromsoe University, Knut Holtedal and his group, CaP is responsible for the Danish branch of an international study on the predictive value of abdominal symptoms and later cancer. Peter Hjertholm has been the Danish lead and the analyses are ongoing. In Norway and Sweden CaP has had very close contacts in relation to dissemination of knowledge and development of the area of early cancer diagnosis. The Norwegian organisation Within 24 hours has visited CaP twice. In Sweden, we collaborate with a group in southern Sweden (Lund/Malmoe) to develop a diagnostic centre. Research will be started during the next years. The members of the Consensus Working Group on Early Cancer Diagnosis in Primary Care: Back row from the left: David Weller, Richard Neal, Eric van Rijswijk, Peter Vedsted, William Hamilton, Greg Rubin. Front row from the left: Rikke Sand Andersen, Suzanne Scott, Sara Hiom, Peter Rose, Fiona Walter, Christine Campbell, Christiane Muth, Martin Beyer. From the Ca PRI network, CaP has taken responsibility for the international colorectal cancer diagnosis group. This collaborative project aims to measure primary care intervals in colorectal cancer based on a number of existing observational studies. The aim is to further investigate the association between diagnostic interval and tumour stage. Data are collected from England, Holland, Spain, Canada, Scotland and Denmark. Marie Louise Tørring is the coordinator. Building the largest database on GPs psychological characteristics made it possible for CaP to start close collaboration with Jonathan Hunter and Bob Maunder, Mount Sinai Hospital, Toronto, Canada, about psychological issues in relation to cancer diagnosis. This research is cutting edge and very new and we can expect interesting results with international impact. 25

28 The director of CaP, Peter Vedsted, has been appointed as chairman of the Discovery II group in the UK, led by Willie Hamilton, with a research budget of 20 million DKK (2.2 million ). Peter Vedsted has been appointed as the international liaison of the Canadian project Can IMPACT, led by Eva Grunfeld. A UK study funded by the NAEDI initiative, the ASTRID project, led by David Weller and Christine Campbell, Edinburgh, has been associated with CaP. Its aim is to validate the Aarhus Statement and develop a generic questionnaire. Impact on research environment The formation of CaP has had several important consequences not only for the local research environment but also for the national and international research environment. These can be divided into four main effects: 1. Academic impact. CaP entered the national research scene at an extremely convenient point of time. There was a growing need for knowledge and development on the diagnosis of serious diseases in the health care system, and there was a need for increased research competences in relation to theory, models, methods and interpretation. CaP therefore introduced an environment for these activities at the right time. This indicates that there is now a research and competence centre in Denmark with specific knowledge on the three main aspects of the diagnosis of serious diseases. Locally, CaP has had an important impact on the academic level, which is illustrated with increased international research quality and pre and postgraduate teaching. Thus, earlier diagnosis of serious disease with cancer has now been included in the medical curriculum at Aarhus University, as a specific learning task for the special training in family medicine and as a part of the continuous medical education for family medicine. The formation of an interdisciplinary research team has made it possible to utilise and manage quite advanced quantitative and qualitative theory and analyses. The formation of CaP has not only heightened the level of research within early diagnosis but also within all research areas at the Research Unit for General Practice in Aarhus and contiguous research areas. CaP now has, in collaboration with many partners, one of the most extensive and best developed interdisciplinary research groups at Aarhus University. This ensures synergy, available expertise and perfect interaction. As an example, the collaborative work is signified by the fact that both our anthropology and psychology researchers are employed as assistant professors at their respective institutes and both have planned a career within their research and teaching. The widespread use of research methods in quantitative and qualitative research has led to the creation of PhD courses in questionnaire research, qualitative research and GIS research. All researchers at CaP have a mandatory obligation to teach at pre graduate and/or PhD level. 2. Research output. The research group at the Research Unit for General Practice in Aarhus has been one of the leading research groups in Denmark with an impact internationally. In recent years, however, focus has been on the central position of primary care within treatment and follow up for people with chronic diseases, prevention of lifestyle diseases and the need for a much more cost efficient health care system. 26

29 These factors have increased the need for research and development in primary care and have led to increased funding of several research centres, especially in Europe and North America. Therefore, the CaPinitiative was extremely well timed supporting further research output and being a centre with a unique and highly relevant research agenda. Thus, the research output from the environment has been amplified as part of the funding. 3. Attracting competences. An intensive and competitive research environment will raise the need for better methods, performance and impact, and consequently, this will attract further national and international competences in the field. CaP s research environment has led to the extensive collaborative work with different research centres. A number of International researchers have been visiting CaP and have contributed to the research environment. CaP has played a significant role in e.g. the ICBP and in the development of projects within the Ca PRI group. Eventually, CaP has started to associate highly experienced researchers and has therefore been able to associate Professor Henrik Møller, King s College London, to the scientific staff beginning from CaP will continue to attract and associate highly competent researchers within the financial ability. The methods used at CaP have resulted in several research collaborations on statistical methods, qualitative methods and data management. In relation to a further increase of the relevant competences, CaP has succeeded in implementing new statistical methods and data relating to the extensive data built up by researchers at CaP. As an example, we are now among the first in the world to work with GIS (Geographic Information System) for an entire population. Addresses and distances/travel time for every citizen in Denmark (5.6 mill inhabitants) from home to their own GP, to hospital, to diagnostics etc. have been registered. And this is combined with individual data on socio economy (e.g. EOCD adjusted income, education, number of cars in the household, use of health services, medicine, screening participation, cancer survival etc.). 4. Infrastructure and funding. The critical mass of researchers and the need for a seamless and highquality based data infrastructure has made it possible for CaP to employ highly qualified data manager and statistician. We have built up a large register (CAPS) which contains data on all citizens in Denmark based on information from numerous registers. At the moment we are expanding the CAPS data with clinical data from the Danish General Practice Database (DAMD), and these efforts will then result in the first Danish database with a full description of a patient s pathway through the health care system including social and ad hoc data (e.g. our three CAP cohorts with 25,000 newly diagnosed cancer patients). Furthermore, data on practice, GPs and the health care system are being included. As a tremendous opportunity, the formation of the CaP centre has made it possible to attract more funding for some of the proposed research projects, but more importantly, for associated projects like the screening projects. This funding has made it possible to create introductory scholarships for young talented researchers who will be able to attract more funding to their projects. Being part of a large research group with a well established infrastructure has therefore attracted further projects and funding. 27

30 Impact on state of the art and health care development in early cancer diagnosis The following section presents some of the main impacts on the state of the art where CaP has contributed considerably with new knowledge and by collecting international research results. CaP introduced and supported the need for research in the diagnosis of serious diseases in general practice and has added to the general insight in the need for such initiatives to support an effective health care in a modern health care system. CaP is now an integrated research centre in the field and has an extensive international network. The formation of a highly efficient interdisciplinary research team such as CaP, a team with great expertise in the necessary research methods, has set new standards for research interaction within this field. CaP has published science on long waiting times and has specified some of their origins and where in the cancer diagnostic pathway the waiting times can be seen and altered. As the first in the world, CaP has documented the prognostic significance of the diagnostic interval and increased mortality. This has lead to a change in the theories and knowledge of the interaction between the importance of clinical assessments, the waiting time paradox and the statistical modelling. Today we know that time from first symptom presentation to diagnosis matters. CaP was the first to publish a paper that documented that the alarm symptom approach was not sufficient for improving primary cancer diagnosis. Based on studies of presenting symptoms, we were able to split these into alarm symptoms, unspecific symptoms, serious symptoms and uncharacteristic symptoms. This division supports that a rational and effective primary cancer diagnostic strategy should consist of at least three main pathways: one for alarm symptoms, a second with a multidisciplinary approach for unspecific, serious symptoms, and a third with easy access to relevant diagnostic procedures from general practice. This was also proposed by the Danish Cancer Society. CaP has created a clinical database for unspecific, serious symptoms at Silkeborg Hospital, from which we find results on how to optimise the clinical diagnosis of cancer. CaP established one of the CAP cohorts during the period when the fast track referral was introduced in Denmark. We showed that fast track referral had a major impact on the diagnostic time interval for patients with alarm symptoms, but not for patients with nonspecific symptoms. We are currently analysing the effect on stage and survival. CaP has shown that patient evaluation of the health care system is highly associated with the diagnostic pathway and the experience of e.g. time to diagnosis, critical events etc. We have shown that the trust in the system gets lower when the diagnostic time interval increases. CaP has shown that the health care system and the interaction with people and patients have a measurable effect on time to diagnosis. Thus, the interaction with the GP seems to be able to introduce patient delay ( doctor induced patient delay ). This decreases the access to medical advice about symptoms. In the same way, CaP documented the contradictory effect of a strong primary care on the cancer survival. Countries with a system where the GP acts as gatekeeper, a list system or a general practice as the first point of contact, had significantly lower cancer survival than countries without the GP as gatekeeper. This 28

31 suggests that the rationing effect of general practice may have serious side effects in some health care systems. CaP was the first to document the diagnostic pathway for childhood cancer and to discover that a relatively large group of children experienced long diagnostic intervals and that the presenting symptoms had very low predictive values. Further, it was shown that these children tended to increase the number of contacts to general practice months before the diagnosis. CaP played an important part in the formation of the Consensus Working Group, which in 2012 published their first international statement concerning guidelines for research in cancer diagnosis: The Aarhus Statement. This was combined with the The Aarhus Checklist to support researchers within this field. CaP has provided comprehensive scientific input on the patient interval and its complexity. Results have proven that knowledge about symptoms, thoughts of symptoms and cancer, the social environment (network) and access to medical advice play an important role. Patients with alarm symptoms may postpone health care seeking and the association with psychological aspects of this has been documented. Psychological factors play a perhaps previously overlooked importance. CaP has revealed extensive new knowledge about the Danish population s knowledge and attitudes towards cancer. These results showed a large variation between gender and socio economic groups. Further, aspects of fatalism and barriers to health care seeking were pronounced in Denmark. CaP has created, and is still creating research based input to the formation of the Danish Fast Track Pathways in relation to updated positive and negative predictive values of presenting symptoms in general practice. Part of the previous knowledge was built on hospital based data, it was considered obsolete or relevant knowledge was non existent. CaP has shown that there are social inequalities in time to diagnosis and people with lower socio economic position have a longer diagnostic interval. This may be an explanation to parts of the social gradient in cancer survival. In the same way, CaP has shown a huge social gradient in women s participation in breast cancer screening. In 2011, the third Danish cancer plan (Cancer Plan III) was launched and CaP made several knowledgebased inputs to the work in the Danish National Health Board. These included: Defining the content and clinical pathways for establishing diagnostic centres in each region in Denmark. This included clinical assessment including lab tests and imaging. CaP is doing research on the effect of these centres. A revision of the fast track pathways in cancer diagnostics. The purpose and idea behind an awareness campaign have been described and will be the subject of a national campaign in 2012/13. This was based on CaP research and will be followed up by CaP, if it is made possible by the National Board of Health. A national CME for GPs on earlier cancer diagnosis. The purpose is to implement a national training programme for GPs. CaP has launched an intervention study in the field. 29

32 CaP has initiated the development of regional audits on cancer diagnosis where general practice is presented to a standardised electronic questionnaire about each newly diagnosed cancer patient. CaP is in close collaborative contact with the work in DMCG on data for the pre diagnostic phase of clinical databases. This is included in the new plans for these registers. CaP has developed the standardised forms for collecting valid and useful data. The latest scientific calculations of the cancer survival trend in Denmark suggest an increased 1 year relative survival rate and thus an improvement (Storm HH, Kejs AM, Engholm G. Improved survival of Danish cancer patients compared with earlier periods. Dan Med Bul 2011;58:A4346). Infrastructure, location at and cooperation with Aarhus University Location and infrastructure were crucial for CaP to become a success. Therefore, we used a substantial part of the initial recourses to get location and infrastructure from the University. There was huge support from the faculty, and we now have two large rooms with eight and six PhD desks, respectively, and some smaller rooms at the Research Unit for General Practice with four desks. We are part of the standard infrastructure meaning that our PhD students have the same rights as the university based PhDs. There is a very warm and supporting interest from the Dean, Alan Flyvbjerg. He supports and encourages further initiatives within the context of early diagnosis of serious disease that can form the basis for a superior health care system taking responsibility for such diagnostic pathways. The Research Unit for General Practice has been extremely generous and exceptional in supporting with additional infrastructure, administration and other important resources. From the beginning, CaP established the website It is targeted at a Danish academic audience and has an English section for an international audience. Please also consult this web page to see more We arranged with the Danish Cancer Society and the Danish Health and Medicines Authority that we would provide new knowledge for their readers. Perspectives of the remaining project period ( ) CaP s first years have focused on the establishment of a well consolidated research institution with a mission and impact both nationally and internationally. The following section describes how the coming 2½ years could be applied and thus the second half of the project period. Section 1 and 2 are in line with the proposed research plan and section 3 5 and new studies proposed in section 2 will need further funding for larger parts of the studies. 1. Continue the launched studies. As mentioned above, several studies are running and several studies are in progress. These studies will continue and the results will be published further on. 2. Observational clinical and register studies. CaP will initiate studies on prognosis based on the CaPcohorts combined with CAPS. In these studies, stage and mortality will be outcome. Further studies on psychological issues will be launched including the GP Profile Database. 30

33 Based on our extensive register data, CaP will begin specific clinical epidemiological studies on variation and the effect of using different diagnostic strategies in clinical practice. This will include innovative statistical procedures in collaboration with the Department of Biostatistics (lead, professor Erik Parner) and Clinical Epidemiology (lead, professor Mogens Vestergaard), both situated at Aarhus University. The preparation of some of these studies is well underway and further funding will be applied for. 3. Intervention research. We will initiate evidence driven intervention studies in close collaboration with the Central Denmark Region and other interested parties if possible. The planned studies are: 1) a randomised study of population interventions in relation to knowledge about symptoms and medical health care seeking consultation. This will be preceded by a description of a complex intervention to diminish patient interval. 2) Trial of CME of training GPs in investigation strategies, including use of diagnostic imaging and blood tests. This study will be based on relevant CaP studies describing symptom presentation, predictive value, diagnostic strategies and how to organise an effective diagnostic pathway. 3) Randomised trials of diagnostic imaging, endoscopies and blood tests when diagnosing specific cancers to bring down the system interval. This project s final part depends on the collaboration with the specific departments doing this kind of research and will need further funding to finance e.g. research assistants (agreements with the mentioned departments have been entered). 4. Imaging and biomarker research. Based on observational research, CaP will initiate investigations on the efficacy and effectiveness of diagnostic imaging and laboratory procedures, using e.g. low dose spiral CT and cancer relevant biomarkers as a diagnostic aid in frontline care. This research will be conducted in collaboration with imaging departments and biochemical and human biology departments. Finally, this study will present the value of these tests and new ways of organising general practice in diagnosing cancer. It is the hope that we will be able to extend the collaboration with Professor Torben Ørntoft, MOMA, on establishing a research Centre for Translational Clinical Cancer Research. 5. Implementation into clinical practice and health policy. CaP will continue to work on the implementation of the knowledge base into practice. This will include audits together with frequent monitoring and surveillance. With appropriate intervals, CaP will conduct surveys on diagnostic intervals in Denmark. The surveys will be made in close collaboration with relevant parties, e.g. the Danish National Board of Health, Danish Regions and the Danish Cancer Society. The surveys will then identify successes and failures and give input to further efforts to improve the diagnostic intervals. A method to run these surveys has already been established. CaP will continue to establish education and special training and to spread knowledge to other medical specialities, especially imaging, surgery and internal medicine and oncology. CaP will establish national courses, which focus on specific areas relevant to development, new research topics and presentations of international knowledge. These courses are planned to take place at least once a year and often there will be several courses, especially in the decentralised education of GPs. The ambition is to create a foundation for continuous updating of health care professionals in the area with ongoing training activities. CaP would like to apply to host the 2015 International Ca PRI conference in Aarhus or Copenhagen. 31

34 6. Funding. Based on the funding received through the CaP initiative by the Novo Nordisk Foundation and the Danish Cancer Society, senior researchers at CaP will continue to apply for further funding. However, these activities can be rather time consuming and we will therefore primarily apply for substantial funds in the coming years. CaP will also seek a further synergetic collaboration with the clinical epidemiology group at the Research Unit for General Practice in Aarhus (professor Mogens Vestergaard) in order to provide comprehensive data and analyses, thus increasing the critical mass of competences even more. Perspectives beyond the project period CaP may be regarded as an innovative initiative in two ways. First, as a research initiative on primary cancer diagnosis. Second, as a case of how to organise research in the diagnostics of serious diseases in the healthcare system. When CaP s project period ends in 2014, there will still be a need for further knowledge of cancer diagnostics. The number of citizens with cancer will increase by 20% over the next 10 years, and the need for efficient and knowledge based strategies will rise dramatically. Therefore, more intervention studies within the cancer area will be needed. Even more important, we will need a huge number of translational studies where we can test the appropriateness of new methods to diagnose, including biomarkers and molecular medicine in particular. In relation to this we have started exploring the possibility to start a research Centre for Translational Clinical Cancer Research in collaboration with professor Torben Ørntoft, MOMA, with a focus on the use of biomarkers in the pre diagnostic face. CaP is also getting more involved in early diagnosis of relapses and the follow up of cancer survivors. It is becoming more and more evident that diagnosis of recurrent tumours and metastases need another approach than regular follow up and scans. Thus, there is a huge need for exactly the research CaP has performed in primary diagnosis in this area too. As a further perspective, the creation of a Centre for Research in Primary Diagnosis where focus is on rational diagnostic strategies of serious and important diseases will be of huge importance. How the health care system chooses to arrange diagnostic strategies will have huge impact on the medical outcome, the patient evaluation, and the economic efficiency of our health care system. An example is the increasing use of high resolution image processing. This could be of high value in high prevalence diagnostics but could also be less efficient and perhaps even give serious side effects in low prevalence areas (general practice). We need to focus much more on these strategies in order to inform how we can develop the future healthcare sector in relation to diagnosis. The Danish Cancer Society has indicated that there is a need for a long term strategic initiative in the field of early diagnosis and has expressed its willingness to support the topic for at least 10 years. The donation of 30 million DKK by the Novo Nordisk Foundation and the Danish Cancer Society has resulted in a dedicated strategic centre with unique opportunities. The formation of such a research centre will attract more international researchers to positions where the prominent Danish data can be explored. In the years following the project period, a large knowledge base for clinical, randomised intervention studies is available. Consequently, there will be a need for further clinical epidemiology to evaluate diagnosis and the effects of treatment, follow up and prognosis. New research including molecular medicine, bio 32

35 markers and translational research will be much needed as several new laboratory aids for the diagnosis of cancer will be available in the near future. The need for appropriate effectiveness studies will therefore become obvious. The increasing acknowledgment of health services research in a cost efficient health care system necessitates a more well defined commitment to this research. Hence, a future research line in this field is hugely needed. In the long run, the CaP centre could be seen as the initiative that will bring early diagnosis of a serious disease in primary health care back into focus of the core activities of a well performing and efficient health care system. Concluding remarks and self evaluation CaP has been established in an international and competitive research environment. CaP has consolidated its position in three main areas: population and patients, clinicians and diagnostic procedures, and health care service. CaP was founded at a time when innovative research centres were particularly needed and has from its start experienced a tremendous professional and public interest in its aims and outcomes. The formation of CaP had a very important implication; primary care research may only difficultly accomplished the research presented here, had the CaP initiative not been funded. Primary care research needs such initiatives to reach critical mass and to collect enough data to make precise and valid scientific conclusions to provide the best health care of high quality. What has also been evident is that many hospital department and especially the paraclinical, has used the research performed at CaP too. Thus, the research in early diagnosis is valued and important in a well performing health care system. CaP has delivered satisfactory scientific output to the scientific literature and for implementation in daily clinical work within the three main areas. CaP is consolidating its activities and has become an important international research centre within this field. It seems that the research results are contributing to the increasing survival rates after cancer diagnosis, better patient evaluation, better evaluation by the health care professionals, and a more efficient diagnostic strategy. CaP has had a fantastic support from the practicing GPs and the college and the trade union for GPs. CaP is grateful to all these hard working people. The barriers have been surprisingly few when CaP was first established. There has been a brilliant support from Health, Aarhus University. The Research Unit for General Practice has been extremely willing to house and develop the project and support with staff and funding. Further, a large number of national parties have wished to be involved and have taken up the new knowledge. As head of research, I have never experienced that the free initiative to set up studies and to publish results has been questioned or challenged. Being head of research at CaP, it is my unambiguous assessment that the CaP initiative is a successful innovation and has proven its worth with the clear knowledge breakthroughs which have led to visible changes for cancer patients in Denmark. It is my wish that the second half of the project will perform as well with the same mission in mind. Moreover, that we will be able to attract additional funding for the necessary studies and to retain talented researchers, including when CaP manages to attract and associate foreign professors. In the next years, I hope CaP will be able to initiate randomised intervention studies on early cancer diagnosis. 33

36 Staff at CaP The following is an alphabetically ranked overview of the staff attached fully or partly to CaP during the period. For each person there is a short description of projects, tasks and role. Jette Møller Ahrensberg GP, PhD fellow until June 2012, post.doc from July Childhood cancer in primary care from symptom to treatment The study aims to understand why some children wait longer than others from the first symptom of disease to diagnosis and treatment. The study explores which symptoms are seen early in children with cancer and the factors that affect the length of the intervals from first symptom to treatment. PhD thesis defended June Jette Ahrensberg is involved in a partnership established with the Section for Epidemiology, Department of Public Health, Aarhus University in studies concerning cancer in children. Christina Maar Andersen Master of Science (MSc) in Psychology, PhD fellow from The influence of attachment style on delay in cancer investigation The aim is to examine whether already learned patterns of seeking and giving help (attachment style) are important for delay in the diagnostic process of cancer. Emphasis is on 1) the importance of the patients attachment style on patient delay, 2) the importance of the GPs attachment style on doctor delay, and 3) the importance of the interaction between GPs and patients attachment style for the overall delay in the cancer investigation. The study uses registry data and questionnaires and includes newly diagnosed cancer patients from the Central Denmark Region and their GPs. Rikke Sand Andersen Master of Science (MSc), Anthropology, PhD January 2011, post.doc from February From September 2011 also assistant professor at Anthropology, Arts, Aarhus University. Responsible for the medical anthropology research line. Approaching patient delay and cancer. Anthropological perspectives on concepts and causes Rikke has focused on patient delay and on how to better describe and understand what it means when we can see that some patients present to the doctor with symptoms of cancer at a later stage, and why it happens. The results include both methodological work and working with 30 patient interviews. 34

37 Help care seeking. An anthropological study of the interaction between general practice and health seeking behaviour The purpose of the study is to examine how general practice as an organisation sets the framework for the doctor patient interaction, and the resulting patient reflections on access to general practice. Supervisor for Sara Hebsgaard and Camilla Hoffmann Merrild. Kirubakaran Balasubramaniam GP, PhD fellow Gynaecological alarm symptoms in a general population prevalence and consequences The aim is to describe the public reporting of gynaecological symptoms with special focus on alarm symptoms and the prognosis in relation to health care seeking and cancer incidence. The study is part of the CaP symptom project at the Research Unit of General Practice, University of Southern Denmark. Flemming Bro Senior researcher until summer 2011, Research director from August 2011, GP, Professor, PhD, DrMedSc. Shared care model to follow up on prostate cancer patients The project aims to develop a cooperation model for the control and treatment of patients with prostate cancer and to implement the model at Aarhus University Hospital, Skejby, The Regional Hospital Viborg and the Regional Hospital Holstebro. The model includes the proper task assignment from the three departments of general practice, where finishing and advantage control can be performed. Supervisor for Mona Lisa Kise, Bettina Kjær Kristiansen and Thomas Mukai. Kristine Bundgaard Master of Arts (MA) in International Business Communication, PA for Peter Vedsted from December 2009 to March Kristine was PA for Peter Vedsted and greatly involved in the construction of CaP. Responsible for coordination, financial budgets, homepage and revision of manuscripts. Kristine started as PhD fellow at the Aarhus School of Business, April

38 Karina Garnier Christensen Post.doc, PhD Cancer patients' use of primary care and other health services in relation to early diagnosis This is an umbrella project for a number of epidemiological studies of cancer patients' use of primary care and other health services based on register data. The aim is to describe and analyse cancer patients' consultation patterns in general practice before cancer diagnosis. Moreover, to provide a basis for analysing use of diagnostic tests. The study includes all newly diagnosed cancer patients in Denmark from 1 January 2001 onwards. Morten Bondo Christensen Part time senior researcher, GP, PhD. Abdominal symptoms and cancer in general practice a prospective study A Norwegian lead multinational study investigating the prospective association between abdominal symptoms and later cancer. Supervisor for Mads Lind Ingeman and Peter Hjertholm. Sandra Elnegaard MD, research fellow Experience and interpretation of symptoms. Factors of importance for doctor visits This study aims to describe symptom perception and health worries in individuals experiencing a possible cancer symptom. This is one of the first projects ever to sample people before they become patients or even have been seeking help. The prospective investigation of symptoms will bring specific knowledge of how people react upon symptoms. The study is part of the CaP symptom project at the Research Unit of General Practice, University of Southern Denmark. 36

39 Kaare Rud Flarup Datamanager Kaare is responsible for the data part of CaP's research infrastructure, dealing with register data and questionnaire data as well as work on Statistics Denmark's servers. This feature is a major cross cutting function at CaP and includes nearly all projects. The work is documented in internal descriptions and in papers. Heidi Gram Project nurse Heidi is project nurse and coordinator of the symptom project (A.1.) at the Research Unit of General Practice, University of Southern Denmark. The study includes questionnaires to 100,000 random adults. Morten Fenger Grøn Statistician (started in 2012). Morten is responsible for the statistical supervision and the development of advanced statistical modelling. Responsible for the interaction with data management and the use of standardised data and analytical models in relation to e.g. use of health care services. Rikke Pilegaard Hansen Part time senior researcher, GP, PhD. Head of the regional institution: Cancer in Practice. Rikke is associated with CaP to ensure continuity in relation to the first CAP cohort and the start up of new research studies. Rikke has published articles on the CAP1 cohort. Supervisor for Mona Lisa Idriss Kise, Jette Møller Ahrensberg, Mette Bach Larsen and Anette Hvenegaard Kjeldgaard. 37

40 Sanne Preus Hatting MD, PhD fellow. Epidemiological study of gastrointestinal symptoms and alarm symptoms in Denmark A populationbased study The project aims to describe the incidence of GI symptoms in the population and with special focus on alarm symptoms. Further, the study analyse the association with health care utilisation and prognosis. The study is part of the CaP symptom project at the Research Unit of General Practice, University of Southern Denmark. Sara Marie Hebsgaard Master of Science (MSc) in Anthropology, applying for PhD fellowship (Oct. 2012). From bodily change to symptom. An anthropological study of help seeking behaviour. Based on an anthropological perspective on the body as 'embodied', the purpose of the study is to examine the processes which direct the interpretation of bodily signs as potentially requiring medical assessment or treatment. Peter Hjertholm MD, PhD fellow from October The effect of diagnostic variation in general practice The purpose is to develop a method for comparing diagnostic activity (e.g. referrals, blood tests etc.). The method is then used to investigate whether there is a correlation between the general practitioner's diagnostic activity and cancer prognosis. 38

41 Line Hvidberg Master of Science (MSc) in Public Health, PhD fellow from January The public knowledge and beliefs about cancer Based on 3,000 responses to the Danish version of 'Awareness and Beliefs about Cancer' (ABC), the aims are to validate ABC DK, to elucidate public knowledge and beliefs about cancer and to examine correlations with socio demographic characteristics. Furthermore, to compare the Danish population with the Swedish and Norwegian populations. Mads Lind Ingeman GP, PhD fellow from June Fast track for unspecific, serious symptoms use, effect and implementation The purpose is to explore general practitioners use of the fast track referral for unspecific symptoms and to examine who and why patients are referred and the effect of this. The study is based on questionnaires, register data and a clinical database at Silkeborg Hospital. Dorte Jarbøl MD, PhD, senior researcher, vice director. Responsible for the public health research line on symptoms in the public. Dorte is the PI for the symptom project placed at the Research Unit of General Practice, University of Southern Denmark. A large random sample of adults (100,000) are asked about symptoms and the pathway is then followed in different ways. Dorte has employed three PhD fellows. See also the description about the CaP symptom project earlier. 39

42 Henry Jensen Master of Health Science, PhD fellow from March Fast track referral in general practice Studies of symptom interpretation, time to diagnosis and tumour stages The aim is to describe the GPs interpretation of the patients symptoms, use of fast track referrals and analyse the influence on time intervals. Further, to describe the development in time intervals and tumour stage before, during and after the introduction of fast track in DK. The study builds on the three CAPcohorts of newly diagnosed cancer patients. Quality issues during the diagnostic pathway Danish cancer patients This study is performed in collaboration with Aase Nissen, the Danish Cancer Society, and aims to describe critical or suboptimal events in the primary cancer pathway as seen by the GP and later by the patient. A total of 7,996 patients are included. Sampling of incident cancer patients This is the study that develops and validates a new and more timely identification of newly diagnosed cancer patients. Cancer patients evaluation of the primary cancer pathway This study is made in collaboration with the Danish Cancer Society and aims to describe cancers patients evaluation of the diagnostic pathway. Line Flytkjær Jensen Master of Science (MSc) in Public Health, PhD fellow from October Participation in mammography screening for breast cancer Based on the first screening round for breast cancer, this PhD study investigates the factors affecting participation in screening for breast cancer among women living in Central Denmark Region. The primary focus is socio demographic, psychosocial and health related factors. 40

43 Jacob Reinholdt Jensen MD, research assistant Incidence of cancer symptoms in general practice and their prognosis The aim of this study is to describe the number of cancer symptoms seen in general practice, how often the GPs suspect cancer and activity in relation to this. The study involves the use of Data Capture in general practice and an electronic push pull system. The study is in preparation. Jacob Søgaard Juul Medical student, attached for 4 months, preparing MD PhD in Unspecific symptom in diagnosis of colorectal cancer This was a short literature study on knowledge on symptoms at presentation of colorectal cancer. Jacob is preparing a MD PhD study on the subject. Pia Kirkegaard Master of Science (MSc) in Anthropology, PhD fellow until Sept. 2011, post.doc from October ProCaRis information about risk of prostate cancer based on genetic test The purpose is to develop a method to disseminate information about genetic risk for prostate cancer in men who have a normal PSA level. It will be measured whether it is possible for patients with normal PSA level and low genetic risk to refrain from unsystematic screening with PSA tests, and for men with normal PSA level and high genetic risk to follow a systematic screening program. The study is a randomised controlled trial of 5,600 patients. 41

44 Mona Lisa Idriss Kise MD, PhD fellow from May Social gradient in delayed cancer diagnosis reasons and effect The project examines the importance of cancer patients socio economic status on the time to diagnosis divided into primary and secondary care intervals. A comprehensive audit is performed on a group of patients with long primary care intervals to elucidate whether social factors play a role in the mechanisms leading to investigations for lung and colorectal cancer. Anette Hvenegaard Kjeldgaard MD, PhD fellow from April 2011 (maternity leave followed by sick leave from March 2012). Cancer patients use of general practice and association with delay and co morbidity The aim is to examine cancer patients use of general practice in the period just before cancer diagnosis, to identify the group of cancer patients who at an early stage increases the use of general practice and examine the association with delay, co morbidity, cancer type and socio economic factors. Bettina Kjær Kristiansen Master of Health Science, PhD fellow from August Follow up after smear test with suspicion Effects of two interventions Annually, there are about 400,000 smear tests in the screening of cervical cancer. Approx. 10% of the tests are abnormal or inappropriate. However, new data show that 15 20% of these women delay or fail to attend follow up. This project tests two interventions on follow up. The results will feed directly into the national strategy on cervical cancer screening. 42

45 Mette Bach Larsen Master of Science (MSc) in Public Health, PhD fellow, PhD March New job at the Department for Screening, the Regional Hospital of Randers. Diagnostic interval for cancer patients before and after introducing fast track referrals The aim was to describe and analyse the diagnostic interval for cancer before and after the national introduction of fast track referrals. The focus was on change in the time interval, changes in patients evaluation and change in GPs assessment of the pathway. PhD thesis defended in Pia Veldt Larsen Statistician, PhD, part time associated with CaP. Pia is associated to the CaP symptom project at the Research Unit of General Practice, University of Southern Denmark. The data modelling will need huge methodological considerations in relation to non response and time to event. Louise Mahncke MD (oncology), PhD fellow from October The effect of direct referral for fast CT scan in early lung cancer detection in general practice clinical, randomised trial There is a need for knowledge on how to speed up the diagnosis of lung cancer so that we can hopefully get a larger proportion diagnosed in early stage. This study will provide evidence about the effect of direct access to CT scan from primary care, how to organise the fast track diagnostic pathway and whether this will bring down the time to diagnosis. 43

46 Camilla Hoffmann Merrild Master of Science (MSc) in Anthropology, PhD fellow from August The embodiment of social inequality. A comparative anthropological study of social position and health care seeking. Cancer is marked by social inequality and one reason could be differences in health behaviours. It has been suggested that people with low SEP are more hesitant in seeking medical care. This study will explore the significance of the socioeconomic context for processes leading to decisions surrounding health care. The object is the bodily experience of moving from being fine to being sick and subsequent decisions surrounding health care seeking. The study will use a mix of qualitative methods (participant observation, repeated semi structured interviews and health diaries). Thomas Mukai MD, PhD fellow with dissertation under assessment at the moment Effect of ICT supported cancer pathways in general practice The aim is to study the extent to which ICT can improve and support the general practitioners' counselling and a more seamless pathway regarding diagnosing. The patients in this study are women enrolled in a breast cancer screening initiative and men with a suspicion of prostate cancer. The intervention consists of the insertion of a link in the electronic test results, a link in e mails and letters to the GP. Also, a decision support web tool is constructed guiding the GP when ordering and using the test for prostate specific antigen (PSA). The PhD thesis is being assessed. Dorthe Toftdahl Nielsen BA, PA to Peter Vedsted from March Dorthe is secretary of CaP and PA to Peter Vedsted. Responsible for coordination of daily correspondence, revision of manuscripts, website and fund accounts. Dorthe participates in the coordinating in relation to standard infrastructure and ensures the structure for the researchers daily activities. 44

47 Frede Olesen Professor, DrMedSc., senior advisor. Research director of The Research Unit for General Practice in Aarhus until August Frede Olesen was, as the research director of the Research Unit for General Practice, overall responsible for CaP and as such contributed substantially to the activities of CaP. Is the supportive counsellor and resource person on the entire project. Frede is now associated with CaP and is chair of the scientific board. PhD supervisor for Christian Wulff, Thomas Mukai, Marie Louise Tørring, Jette Møller Ahrensberg, Mette Bach Larsen and Christina Maar Andersen. Anette Fischer Pedersen Master of Science (MSc) in Psychology, PhD, senior researcher. Responsible for the medical psychology research line. The importance of social support for patient delay The aim is to investigate the importance of social support for the duration of patient delay, including gender differences in the use of the social network. Papers are being published. The importance of coping strategies for patient delay The aim is to investigate the importance of coping strategies for the duration of patient delay. Papers are being published. Alarm symptoms and thoughts about cancer in patients with colorectal cancer The purpose is to investigate the relationship between alarm symptoms, thoughts of cancer and patient delay in patients with colorectal cancer. Papers are being published. Supervisor for Christina Maar Andersen, Line Hvidberg and Line Flytkjær Jensen. Lotte Linnemann Rønfeldt Master of Health Science, research assistant (preparing PhD). Epidemiological studies of the relationship between mortality and waiting time for lung cancer With the Danish cancer plans and fast track approach for lung cancer, it remains to be seen whether the waiting time in the process has the desired positive effect on survival. This study will investigate the association between delayed diagnosis and treatment of Danish lung cancer patients and their prognosis. In addition, draw the map of routes to diagnosis of lung cancer. The study is applying for funding. 45

48 Ineta Sokolowski Statistician until Ineta was responsible for the daily statistical supervision of CaP researchers. Ineta was replaced by Morten Fenger Grøn in the beginning of Lars Peter Sønderby Master of Science (MSc) in Anthropology, research assistant until April A qualitative anthropological study of case management The purpose is to study and analyse case management of cancer patients in an anthropological perspective with qualitative interviews, short field visits and interviews with case managers in an intervention at Aarhus University Hospital. In collaboration with Christian Wulff. Berit Skjødeberg Toftegaard GP, research assistant, applying for PhD fellowship (Oct. 2012). The effect of CME in cancer diagnosis on time to diagnosis and stage The aim is to describe the Danish general practitioners knowledge and awareness of cancer symptoms. This is also part of the International Cancer Benchmarking Partnership (ICBP) Module 3. Further, to identify barriers for referring patients and to implement new knowledge in general practice. Lastly, to investigate the effect of focused and multi faceted training in cancer diagnosis in general practice. 46

49 Marie Louise Tørring MA, PhD fellow until March 2011, post.doc from April From September 2011 also assistant professor at Anthropology, Arts, Aarhus University. What is the effect of diagnostic waiting time on cancer mortality This study made a valid assessment of the relationship between diagnostic waiting times and cancer mortality. The results have been published in the British Journal of Cancer, Journal of Clinical Epidemiology and in a PhD thesis. The project continued in 2012 as a PhD project under preparation (Lotte Linnemann Rønfeldt). Collaborative CAPRI project: Measuring primary care intervals in colorectal cancer A project that collects data from a number of existing observational studies for colorectal cancer patients in England, Holland, Spain, Canada, Scotland and Denmark. MLT has been appointed coordinator. 'Alarm symptoms' revisited in a nature culture discussion This study develops anthropological arguments in the debate of delayed doctor seeking for alarm symptoms by exploring recent medical anthropological literature of the relationship between nature and culture. Infectious suspected cancer The goal is to study cancer investigation in an infection analytical framework in order to understand how the suspicion of cancer spreads from patient to doctor and from the primary to the secondary sector. The project is part of a new AUFF Pilot Centre for Cultural Epidemics. Task force for the calculation of comorbidity The aim is to develop algorithms for assessing morbidity in specific patient populations. We discuss the advantages and disadvantages of using data from the National Patient Register, National Health Registry and the new data acquisition module in General Practice. MLT is the coordinator. Supervisor for Henry Jensen and Lotte Linnemann Rønfeldt. Peter Vedsted MD, Research director of CaP, assisting research director at The Research Unit for General Practice in Aarhus, Professor, PhD. Peter is research director at CaP. Is responsible for the daily activities at CaP. Supervisor for Mads Lind Ingeman, Mette Bach Larsen, Jette Møller Ahrensberg, Marie Louise Tørring, Mona Lisa Idriss Kise, Christian Wulff, Thomas Mukai, Anette Hvenegaard Kjeldgaard, Christina Maar Andersen, Line Hvidberg, Line Flytkjær Jensen, Louise Mahncke and Peter Hjertholm. 47

50 Mogens Vestergaard GP, Professor in primary care epidemiology, PhD. Mogens is professor in primary care epidemiology and attached to the epidemiological part of CaP. The development of the register based research and further development of comprehensive databases is done in close collaboration with Mogens Vestergaard. Supervisor for Peter Hjertholm. Christian Wulff MD, PhD fellow, PhD from August 2012, new job at Department of Oncology, Aarhus University Hospital Effect of case management in early cancer care pathways This study tested the use of case management in early cancer care pathways by means of a randomised trial. A total of 280 patients with colorectal cancer were included. Effect was assessed by comparing the two patient groups evaluations of diagnosis and treatment, quality of life, contacts to general practitioners and emergency. PhD thesis defended in Supervisor for Line Hvidberg. 48

51 CaP activities Selected events 2010: The Research Centre for Cancer Diagnosis in Primary Care officially opened on 8 January It was a very fine day with many interesting contributions from, among others, the Novo Nordisk Foundation Director Birgitte Nauntofte, the CEO of the Danish Cancer Society, Arne Rolighed, Dean at Health, Aarhus University, Søren Mogensen, the research director of the Research Unit for General Practice Frede Olesen and a number of researchers associated with CaP. Co organising the 3rd annual meeting of the Ca PRI Network, Toronto, Canada. June Meeting of the Research Methods Consensus Working Group, November The International Working Group Research Methods Consensus Working Group on Early Cancer Diagnosis in Primary Care had the third and final meeting in Aarhus. Visit by Professor Amanda Ramirez, King s College London, November. Lectures and discussion of research collaboration (ICBP). Mini Symposium, November CaP held a popular mini symposium on early diagnosis of cancer at Aarhus University. Four leading international researchers (David Weller, Fiona Walter, William Hamilton and Greg Rubin) gave presentations on early diagnosis of cancer in general practice. Subsequently, a number of researchers at CaP presented their research and the early results. Professor William Hamilton from Exeter and former research director Frede Olesen, The Research Unit for General Practice in Aarhus, at the mini symposium. 2011: Rikke Sand Andersen defended her PhD thesis with the title: Approaching Patient Delay and Cancer. Anthropological Perspectives on Concepts and Causes, 13 January Marie Louise Tørring defended her PhD thesis with the title: Time from first presentation of symptoms in primary care until diagnosis of cancer: Association with mortality, 25 March Visit by Professor Richard Neal, who held the presentation: A systematic literature review of studies on associations between time intervals in cancer diagnosis and outcome, March Co organising the 4th annual meeting of the Ca PRI Network, Holland. May