E-Rare: Era-Net for Research Programmes on Rare Diseases

Transcription

1 E-Rare: Era-Net for Research Programmes on Rare Diseases Survey and Strategic Analysis on Future Themes and Needs for Rare Diseases Research Funding Posada M *, Ramírez A *, Carroquino MJ *, Messlich H, Schuster R, van Weely S, Lievens J, Koutouzov S, De Andrés R #, on behalf of E-Rare Consortium *Rare Diseases Research Institute and # Funds Research for Health, Instituto de Salud Carlos III, Madrid, Spain; Programme Management Agency in the German Aerospace Centre, Bonn, Germany; The Netherlands Organisation for Health Research and Development, The Hague, The Netherlands; GIS-Institut des Maladies Rares/INSERM, Paris, France E Rare ERA Net for Research Programmes on Rare Diseases European Commission 6 th Framework Program ERANET/CA No

2 EXECUTIVE SUMMARY BACKGROUND In the European Council recommendation on rare diseases (RD), Member States are advised on the one hand to identify needs and priorities for basic, clinical, translational and social research in the field of rare diseases, and, on the other hand, to identify ongoing research and research resources in the national and Community frameworks in order to improve coordination, assess the research context and establish the state of the art of rare disease research. This overlaps with the aims of the ERA-Net E-Rare consortium of national research funding bodies to influence research policies at both national and European level by providing information to fill the current gaps in this field and develop a strategic research agenda. To produce this kind of information, E-Rare has performed a survey about priorities for research on RD and an analysis of the potential bottlenecks that could have a negative impact on the development of the rare diseases research activities. The survey results were presented and discussed with experts from the field at the E-Rare workshop Future Themes and Needs of Rare Disease Research Funding held in Brussels on July 1st RESULTS Survey participation More than 1500 stakeholders (researchers, clinicians, funding agencies, patients associations, policy makers, etc.) were invited to participate in this survey. About 400 responses were received, yielding a response rate of 24.2%. Basic research and clinical scientists accounted for more than 85% of all respondents. Identification of high priority areas Across the nine priority areas offered for rating, research in genetics and pathophysiology (e.g. gene identification and elucidation of molecular mechanisms of disease) was rated with the highest interest among respondents with >85%. This was followed by therapeutic research (e.g. development of new therapeutic tools), preclinical therapeutic research and epidemiology / natural history of disease research which achieved similar scores of app. 65% of high interest. Similarly, the funding of tools to accelerate research on rare diseases (e.g. funding to establish transnational research co-operations) was seen as a major priority. Naturally, the distribution of priority areas and topics differed among the contributing groups of basic researchers, clinical scientists and physicians. Major bottlenecks for research The areas for which the most bottlenecks were identified are highly correspondent to the priorities. The study of epidemiology and natural history of disease was 2

3 perceived to be the most difficult one, named by over a third of the respondents as a bottleneck. This was followed by research in genetics and pathophysiology and therapeutic / pre-therapeutic research. The major bottleneck mentioned for all areas is the scarcity of funding, especially for transnational co-operations. Additionally, the difficulty to obtain funding to perform studies over a longer period of time, which is essential for natural history studies and therapeutic research, was often mentioned. In all three areas, researchers encounter bottlenecks in methodology, different in nature whether the research is focused in pathophysiology (-omics, animal models, etc.) or in epidemiology (registries, databases, etc.). Not surprisingly, policy and cooperation (private/public partnerships) issues are seen as major bottlenecks for researchers involved in therapeutic research. Criteria for prioritising When asked about the criteria used by participants for selecting priorities, respondents mainly pointed out the importance of improving scientific knowledge in several fields and strengthening top-level research, while at the same time taking into account the importance of morbidity/mortality and deficiencies in health care. OUTLOOK It is expected that the results of the survey and subsequent workshop will be taken into account by national and EU research policy makers when designing future programmes or other incentives for rare disease research. The strategy of E-Rare-2, which will start its work by the end of 2010, has taken up input from the survey and workshop and aims at addressing some of the issues raised, especially concerning the increase of transnational cooperation, by o o o o o deepening the knowledge of the state-of the-art of rare disease research funding in Europe and worldwide continuation of open calls for transnational research projects with the intention to increase budget and number of countries involved introduction of focused calls to address additional topics of strategic importance development of a common strategic rare disease research policy among the participating funding agencies in close communication with the EC increasing the dissemination of knowledge gained from the projects funded by E-Rare 3

4 Index 1. Aim and objectives p Methods p Results p Priority areas p Analysis by Priority Areas p Analysis by stakeholder interest p Analysis by topics p Criteria for prioritising p Analysis of Bottlenecks for research p Workshop Future Themes and Needs of Rare Disease Research Funding p Discussion p References p Annex p.26 4

5 1. Aims and objectives A major aim of E-Rare consortium in the area of research funding is to influence research policies at both national and European level with the production of information to fill the current gaps in this field. To fulfil this aim and due to the great diversity of stakeholders and different type of actions developed by European institutions, E-Rare WP4 has considered to perform a survey about priorities for research on RD and an analysis of the potential bottlenecks that could have a negative impact on the development of the rare diseases research activities. This effort will be useful for developing some preliminary strategic analyses for shaping future research programmes at both European and national levels. This aim is in line with those stated in the Council Recommendations report approved in June 2009 by the European Council and the Parliament. In this Recommendation, Member States are advised on the one hand to identify needs and priorities for basic, clinical, translational and social research in the field of rare diseases, and, on the other hand, to identify ongoing research and research resources in the national and Community frameworks in order to improve coordination, assess the research context and establish the state of the art of rare disease research. To design a strategy for achieving this aim we initiated a long consultation process, which started with four thematic workshops, some of them organized in collaboration with other WPs, where clinicians and scientists were asked about their long term perspectives and goals in rare diseases research for the next years, the new approaches and techniques as well as possible ethical and legal problems and how they might be overcome. The E-Rare External Advisory Board also played an important active role in this consultation process. A survey was considered as an essential tool to gather additional knowledge and views on the priorities for future funding in all fields of research on rare diseases, which was sent to all stakeholders: researchers, clinicians, funding agencies, patients associations, policy makers, etc. Finally, the survey results were presented and discussed with experts from the field at the E-Rare workshop Future Themes and Needs of Rare Disease Research Funding held in Brussels on July 1st 2009 This survey and the ensuing strategic analysis paper on future themes and needs of RD research funding represent the sum of all work carried out in the work package. 2. Methods A first draft of a questionnaire used to collect data for this survey was prepared based on the existing literature on the topic of research funding priorities. This first draft was distributed among all E-Rare partners for feedback and corrections. A second updated draft version was then re-distributed among the E-Rare partners who provided final suggestions and modifications for the preparation of the final version of the questionnaire (Annex 1). Once the final version was ready, the questionnaire was sent to the potential responders together with a presentation and invitation letter. A reminder was sent after three weeks to the non-respondents. 5

6 The questionnaire aimed at assessing the interests and views of the rare diseases community (researchers, clinicians, funders, patients, private companies ) on the priorities for future funding among a number of proposed topics. The questionnaire was anonymous and at the time of processing the answers each questionnaire was given a random number by a software application with no link to the received . The only personal information collected was the professional category and the type of institution of the respondent. All participants were asked to provide this information (Annex 1). The questionnaire was divided into three different sections: an introductory section, a section on the priority areas analysis and a section on the criteria for prioritization. The first section (introductory) consisted of one table divided into nine (priority) research areas that cover the spectrum of research in rare diseases. For each of the nine areas respondents had to declare what they considered to be a priority area by rating their general interest with No interest,, low, and responses. Only those declaring any of the two high interest options would be offered to continue answering the corresponding priority area table (Figure 1). The questionnaire was done on paper and there was no automatic mechanism to control this step. Figure 1. Priority areas and type of answers This choice was designed to allow respondents to provide answers only in those areas where they had an interest (or knowledge/expertise) while at the same time reducing their work load and time needed to complete the questionnaire. However, we are aware that this strategic choice may have introduced a bias as a higher response rate in a specific area would result in a high interest in the items included in that particular priority areas. 6

7 The next section of the questionnaire consisted of nine different tables corresponding to each of the nine priority areas defined in the introductory table (Figure 1). Each of the table was broken into specific items pertaining to the particular area. The response options had the five categories described above from no interest to high interest plus an extra option designed only for funding agencies (Figure 2). Figure 2. Example of a detailed priority area: Health systems research The third section of the questionnaire focused on a number of aspects (criteria) to take into account at the time of establishing priorities in research programmes in rare diseases, as for example, the number of people affected (prevalence), morbidity/mortality, obvious gaps in health care, etc (Figure 3). 7

8 Figure 3. Criteria for establishing priorities in research programmes In all tables, a space was dedicated for the respondents to provide comments or identify bottlenecks corresponding to a particular issue from the particular priority area or from the priority areas in general. As this space was not limited, this created some burden for the analysis of this information as in some cases long and multiple comments were provided for the same statement. 3. Results A total of 1898 stakeholders corresponding to 19 Europe-wide contact groups provided by E-RARE partners were invited to participate in this survey. Since some of the participants belonged to more than one of these contact groups, 1568 people were actually contacted. Four hundred and one (401) responses were received yielding a response rate of 24.2% (Figure 4) However, it is to note that applicants to the two E-Rare 2009 and in 2007 joint transnational calls (JTC) represented a large fraction of the participants (as well as the responders) to the survey. Conversely, it is clear that some of the groups were underrepresented making their opinions not representative for their whole group (Figure 4). 8

9 E-Rare JTC 2009 coordinators were not included in the survey because the 2009 call had not been resolved at the time of this survey. This is why, only E-Rare JTC 2007 coordinators appear in the figure 4. Figure 4. Stakeholders participation in the survey As seen in Figure 5, basic research and clinical scientists accounted for more than 85% of all respondents; thus, the scientist/researcher category was the major contributor to the general conclusions drawn from this survey. Figure 5. Distribution of response rates across stakeholders* 9

10 As illustrated in Figure 6, 3 main types of institution accounted for more than 85% of all respondents; the public sector government institutions, public research institutes and hospitals. Figure 6. Distribution of response rates across contacted institutions The list of contacts for the distribution of the questionnaires was elaborated using lists of persons provided by different contact institutions. It should be noted that one person may have been included in more than one of these groups (Figure 6). For example one person may have been part of the RD Task Force and of the Research Institution category. In order to elaborate the response rates for each contact institution, the denominator used consisted of the total number of persons originally included in each of them. By combining responses from institutions and type of stakeholders, this first analysis shows that basic research scientists from public/government institutions (94 out of 401) and public research institutes (68 out of 401) as well as clinical scientists from hospitals (77 out 401) were the main participants in this survey Priority areas scored from top to bottom As mentioned previously, the second section of the questionnaire was devoted to the assessment of a number of previously identified (in the first section) priority areas for research in rare diseases. Across the nine priority areas offered for rating, research in genetics and pathophysiology scored the highest among respondents with >85% of high interest. Therapeutic research, epidemiology research, research tools development and preclinical therapeutic research gathered similar scores with approximately 65% of high interest among respondents. The other priority areas fell from 45% of high interest 10

11 (for research platforms/infrastructures) down to 20% (for human and social science research) (Figure 7). Figure 7. Declared interest in the different research areas 3.2. Priority Areas: from highest to smallest interest: who responded and how? Table 1 shows the percentage of stakeholder participants who responded to have a and/or interest in each specific priority area. Basic research scientists, clinical scientists and physicians were unanimous (for approximately 90% of them) in pointing research in Genetics and Pathophysiology as their first priority area. Most of these respondents were highly interested in gene identification and molecular mechanisms. These 3 groups of scientists, again, also showed the same high interest in pre-clinical therapeutic research (for approximately 70% of them). 11

12 Table 1. Stakeholder interests by areas: Percentage of responses and The Pre-clinical Therapeutic Research priority area and the Therapeutic Research priority area were covering aspects from clinical research to implementation of the preclinical advancements. Interest in these areas was rather high with 70% participation rate. It is noticeable that patients and patient organizations, although with low numbers of respondents, were highly interested in these areas. Items within these areas that received the highest values were therapeutic target identification, biotechnological research (such as enzyme therapy or monoclonal antibodies) and proof-of-concept studies. In general, basic research scientists were much more interested in pre-clinical research (71%), and their interest dropped quite significantly for therapeutic research (55%). The topics that attracted the biggest interest in the therapeutic research area were phase I/II clinical trials and epidemiological/clinical/therapeutic investigations. On the other side, transplants and assessment of surgery procedures were found as areas of very low interest in this field. Not surprisingly, research in Epidemiology and Natural history of diseases gathered a much higher interest from the clinical scientists and physicians ( 90%) than from the basic research scientists ( 55%). Among the proposed topics within these areas, genotype/phenotype correlations and biomarkers for diagnosis, prognosis and severity were the areas that gathered the biggest interest. Remarkably, the area on Development and Availability of tools needed to accelerate research on Rare Diseases reached 76% of participants, one of the highest of all considered areas. It is also to note that this area scored high across all categories of respondents. Indeed, the need for Development and Availability of tools to accelerate research on Rare Diseases is perceived as very high across the rare disease community, no matter it concerned research networks, transnational calls for funding and transnational research consortiums. 12

13 The Platforms/Infrastructures Development area included aspects such as population registries, biobanks and GMP platforms and their exploitation for research purposes. In general terms, this priority area created a rather low interest with a participation of 57% of the total participants, and not surprisingly, with a higher interest from scientists ( 60%) than from physicians ( 50%) Keeping in mind the low participation in this priority area, the issues that raised the highest interest were the long-term cohort study designs, biobanking research and development of genomic and proteomic platforms. The Health System Research priority area elicited more interest from clinical scientists (53%) than from basic scientists (37%) or clinicians (44%). The area that raised the highest interest was the development of new technologies such as new diagnostics tests or population screening programmes. In the Human and Social Sciences area, availability of orphan drugs, the need of patient awareness and RD research and innovation (public/private partnership, role of patient organizations ) were the highest scored topics. The Human Resources priority area had the lowest participation rate (43%). This area was covering aspects such as rotational positions for both clinicians and researchers and specific training in RD and bioinformatics. It could be highlighted that both clinical scientists and physicians working in hospitals were more interested in this issue than basic research scientists (50 vs. 35%). This indicates that these professionals, especially those working in hospitals are the ones with a higher interest in rotation and/or protected time for research. The Human and Social research area is the one where the gap between scientists/clinicians and patients is the most visible: 100% of patients rated this area as highly interesting while only 35 % of the scientists and clinicians altogether showed a high interest in this area. Priority areas seen from the institutions/organizations point of views show a similar distribution of interests than the ones shown by the different stakeholder groups. This is due to the existence of certain degree of correlation between the type of stakeholders and the institution from where he/she is partipating. In general, areas like epidemiology, genetics and therapeutic research concentrate the highest interest (Table 2). The number of responders in the patient s organization group does not match with the number of patients who responded. This is because each respondent marked their own classification as the organization to which they belonged and as a stakeholder group. Some patient s organizations responses were not filled out always by patients but by their representatives, such as scientist, medical doctors and others. 13

14 Table 2 Institutional interests by areas: Percentage of responses and 3.3. Analysis by stakeholder interest The next step in the analysis of this survey was to go deeper in the interests expressed by the respondents by focusing only on particular groups. For this, we considered the three main categories of stakeholders identified previously as they are the only ones with large enough number of respondents to allow drawing conclusions. Basic Research Scientists showed high or rather high interest in areas related with genetic issues, new technologies facilities development as well as therapeutic tools. Conversely, they showed a very low interest in topics like public health, social and economical issues and e-health (Figures 8 and 9). 14

15 Figure 8. Most interesting topics according to Basic Research Scientists (Percentage of Basic Research Scientists rating topics as of high or rather high interest) Figure 9. Least interesting topics according to Basic Research Scientists (Percentage of Basic Research Scientists rating topics as of very low interest) In general, clinical scientists and basic researchers showed a high interest in a lot of similar topics. Both groups are very interested in topics related to genetics and pathophysiology. However, clinical scientists showed a particular interest in research areas dealing with diagnosis and therapeutics while basic scientists show more interest for tools (technology platforms/animal models) crucial for the study of physiopathology mechanisms (Figure 10). Also, clinical scientists showed a high and more uniformly distributed degree of interest in almost all the areas than the group of basic 15

16 researchers, who concentrated their interest in the genetic identification and molecular mechanisms research. Figure 10. Most interesting topics according to Clinical Scientists (Percentage of Clinical Scientists rating topics as of high or rather high interest) It is also interesting to see the low interest expressed by clinical scientist in topics like e-health, training of bioinformatics, social and public health and in general translational issues (Figure 11). Figure 11. Least interesting topics according to Clinical Scientists (Percentage of Clinical Scientists rating topics as of very low interest) The interests shown by the physicians are quite different as compared to the other two main groups. For them, the most interesting topics are diagnosis methods, therapeutic research, registries, cohorts, biomarkers and in general issues providing direct results to their patients (Figure 12). 16

17 Figure 12. Most interesting topics according to Physicians (Percentage of physicians rating topics as of high or rather high interest) Conversely, they did not show so much interest basic research areas and new technologies (Figure 13). Figure 13. Least interesting topics according to Physicians (Percentage of physicians rating topics as of very low interest) 3.4. Analysis by topics The next step in the analysis of this survey was focused on determining which topics within the priority areas were the most or the least interesting. 17

18 Not surprisingly, the topics that attracted the highest interest were the genetics and pathophysiology area and the development and availability of tools needed to accelerate research priority areas. For these topics, around 300 hundred and more participants expressed a high interest (Figure 14). Figure 14. The five most interesting topics ( interest) The less interesting topics are shown in Figure 15. Figure 15. The least interesting topics ( interest) A methodological question can confound the interpretation of this ranking. The response rate to each item was used as a measure of the interest in that particular item. The rate was calculated using the number of respondents showing higher interest to this particular item as the numerator and the total number of respondents to all 18

19 priority areas as the denominator including those who did not marked that priority area to which the item belonged. It has to be emphasized that what is important for the entire group of responders could be of a different importance for the different sub-groups. This is the case for instance for the patients: for them the most important or interesting topic is the Phase I/II clinical trials while for the entire population study this topic is in middle area of interest. Also, patients have a great interest in the assessment of surgery procedures which is a topic that rated very low interest for the entire population of respondents Criteria for prioritising The third section of this survey focused on getting to know the criteria used by participants for selecting priorities. Respondents mainly pointed out the importance of improving scientific knowledge in several fields and strengthening top-level research while at the same time taking into account the importance of morbidity/mortality, and deficiencies in health care (Figure 16). Figure 16.- Criteria for prioritising analysis 3.6. Analysis of Bottlenecks for research Participants were asked to provide information about identified bottlenecks in their research. For the priority areas a total of 172 bottlenecks were identified. The bottlenecks were classified in an operative way. It should be noted that the bottlenecks were provided in a free text format with no space limits. Some bottlenecks were concise and appropriate but a number of them were too vague, inappropriate or illegible. For this, the classification of the bottlenecks was a very important task for the present analysis. The distribution is shown in figure

20 Figure 17. Distribution of bottlenecks along the research areas Clearly, the priority area with the greatest number of bottlenecks is the epidemiology and natural history of diseases. This area refers to topics such as registries, cohort study designs, biomarkers and databases for epidemiology studies, among others. The great number of bottlenecks indicates that the research community encounters a great number of issues when dealing with this area of expertise or the instruments used such as registries. The bottlenecks were classified into the following categories: funding, policy, research inequalities, ethics, methodology, cooperation, other issues and not informative bottlenecks (i.e, Identification new entities ) or just comments such as criticisms to the questionnaire. Attending to this classification the distribution is shown in Figure 18. The most common bottlenecks are related to funding issues (45%). These issues are normally related to the scarcity of funding and the difficulties researchers face to apply and obtain funding. Other important categories of bottlenecks concern methodology and cooperation. It is important to note that cooperation is also related to funding issues, as it relates to transnational research funding and international research funding. Figure 18. Distribution of bottlenecks by the operative classification 20

21 Looking more closely at the priority areas with the largest number of bottlenecks (e.g. Epidemiology and natural history of diseases, Fig 19A; Genetic and Physiopathology, Fig 19B; Therapeutic research, Fig 19C), we can observe that funding is the predominant issue for the first two areas and still a major issue for the last area. In all shown areas researchers encounter bottlenecks in methodology, different in nature whether the research is focused in pathophysiology (omics, animal models, etc.) or in Epidemiology (registries, databases, etc.) Not surprisingly, policy and cooperation (private/public partnerships) are seen as major bottlenecks for researchers involved in therapeutic research. Figure 19. Bottlenecks in specific areas of research on rare diseases A - Epidemiology/Natural History of diseases B - Genetics and Physiopathology C - Therapeutic research 4. Workshop Future Themes and Needs of Rare Disease Research Funding The objective of the E-Rare workshop Future Themes and Needs of Rare Disease Research Funding held in Brussels on July 1 st 2009 was to present the preliminary results from the survey. Also, invited speakers presented their experience in rare diseases research with a special focus on the bottlenecks they have found. It started with a short introduction to the E-Rare ERA-Net project by the E-Rare coordinator with main achievements and present situation. It continued with the presentation of the 21

22 results of the WP4 survey on rare diseases (RD) research priorities, followed by presentations of invited speakers (scientists, EC, EURORDIS) on RD research bottlenecks. At the end, conclusions and recommendations that were highlighted during the day were further discussed and summarized. 4.1 Recommendations addressed to EU Commission Increase funding Need for a common (Member States, EU) roadmap: E-Rare could act as a working group to develop this roadmap (take into account EU communication & EU Council communication as well as Europlan project) Promote rare diseases as a model for common diseases Promote mobility of clinicians ("protected time") Decrease discontinuity of funding different elements of the (translational) research continuum. Existing administrative restrictions for fixed funding periods should be overcome. Funding for proof-of-concept is especially important Be active in promoting rare diseases interests (interact with stakeholders, EU Council and EU parliament) Promote international collaboration beyond EU borders Promote (the build-up and maintenance of) a database of EU funded research projects on rare diseases (DG Research, DG Sanco, etc.) Address current gaps in research on policies & ethical regulations Address inequalities (neglected rare diseases) 4.2 Recommendations addressed to E-Rare Increase funding Maintain open calls, i.e. no restrictions in terms of disease and type of projects Reconsider the procedures of E-Rare in order to allow success for less well developed research consortia Develop/support decentralized technology platforms (e.g. bioinformatics), with some leading centres that develop the progress Maximize collaborative output: focus on biobanks, registries, patients, etc. (interact with other activities such as BMS ESFRI) Promote interdisciplinary interactions and social & human science (QoL, psychological aspects, societal burden, health services research, etc?) projects because policy developers need this kind of information (e.g. costs of untreated rare diseases) Focus on support for those projects that promise fast translational progress into clinical practice Funding for proof-of-concept is especially important Necessity of rare disease research funding in different programmes should be well explained, e.g (1) anchored in common diseases programmes and (2) rare diseases specific funding programmes 22

23 Promote rare diseases as a model for common diseases Involve patient organisations for research policy development (e.g. by a survey on patient organisations opinions; see "roadmap") Promote mobility of clinicians ("protected time") Decrease discontinuity of funding different elements of the (translational) research continuum. Existing administrative restrictions for fixed funding periods should be overcome. Consider the implementation of funding schemes which enhance the efficient use of available funds. Address methodology bottlenecks (detected by WP4 survey) Consider use of different definition for rare diseases to focus future calls (shift towards rarer diseases?) 5. Discussion The questionnaire has provided two types of information: the level of interest in a number of proposed priorities for research in rare diseases and the bottlenecks in the mentioned research areas. Some of the topics of most interest, as expressed by participants, were related to the transnational funding of research (creation of consortiums, common calls). If we analyze the bottlenecks we find a great number of issues dealing with the scarcity of funding which creates a high competition among researchers and limits cooperation. For this, it can be concluded that funding and especially transnational funding is a priority in rare disease research. This would not only provide more funding resources but would also help to diminish the effect of the scattering of both patients and resources among countries. Participants declared in various occasions that the process to participate or to create transnational research is complicated, with many policy and legal barriers. For this, it is important to consider that European countries open their calls and their funding for transnational collaboration. Research in genetics and physiopathology is an essential area for successful research in rare diseases, and it was also the most valued research area among respondents. The area also showed a large number of bottlenecks. From the bottlenecks highlighted by respondents, it is clear that funding continues to be an important issue. The study of epidemiology and natural history of disease was perceived to be the most difficult one, named by over a third of the respondents as a bottleneck. It must be pointed that many bottlenecks were related to the matching of human resources with the new technologies or tools needed for research in this area. In this sense, specific training or a specific curriculum in rare diseases research is seen as very important and it should be taken as a priority. For instance, capacity building related to bioinformatics and biostatistics is considered of vital importance for research in rare diseases even though they were not marked as a high priority topic by the respondents. Also, related to the work of the human resources in general, participants continuously repeated the need of protected time to conduct research as a clinician. 23

24 However, these are issues usually related to clinical research in general and are not specific for rare diseases. The workplan for E-Rare-2 has taken into account the input of the survey and workshop and is already addressing some of the issues raised i.e. o o o o o deepening the knowledge of the state-of the-art of rare disease research funding in Europe and worldwide continuation of open calls for transnational research projects with the intention to increase budget and number of countries involved introduction of focused calls to address additional topics of strategic importance development of a common strategic rare disease research policy among the participating funding agencies in close communication with the EC increasing the dissemination of knowledge gained from the projects funded by E-Rare 6. References th EURORDIS Position Paper on the Research Priorities for the 7 Programme Framework EURORDIS Position Paper on Research Priorities for Rare Diseases. NICE R&D Strategy. Amended in January Selection of research priorities method of critical Technologies. Karel Klusacek. Technology Centre of the Academy of Sciences CR Principles for allocation of scarce medical interventions. Govind Persad, Alan Wertheimer, Ezekiel J Emanuel. Lancet. Vol 373 January 31, 2009 Identifying and prioritising. HTA research. NIHR Health Technology Assessment programme. IMCI research priorities: Investigating methods to prevent and manage childhood illness. WHO/CHS/CAH/98.1I REV Commission of the European Communities. Communication from the Commisssion to the European Parliament, The Council, The European Economic and Social Committee and the The Committe of the Regions on Rare Diseases: Europe's challenges. Brussels, COM(2008) 679 final Council of the European Union. Council Recommendation on an action in the field of rare diseases. Brussels, 5 June 2009 Fleurence RL, Torgerson DJ. Setting priorities for research. Health Policy. 2004;69:1-10. Claxton K, Sculpher M, Drummond M. A rational framework for decision making by the National Institute for Clinical Excellence (NICE). Lancet. 2002;360:

25 Lionis C, Stoffers HE, Hummers-Pradier E, Griffiths F, Rotar- Pavlic D, Rethans JJ. Setting priorities and identifying barriers for general practice research in Europe. Results from an EGPRW meeting. Fam Pract. 2004;21: Lomas J, Fulop N, Gagnon D, Allen P. On being a good listener: setting priorities for applied health services research. Milbank Q. 2003;81: Detsky AS. Using cost-effectiveness analysis to improve the efficiency of allocating funds to clinical trials. Stat Med. 1990; 9: Annex Annex 1.- Questionnaire on Research Priorities 25

26 European Research Projects on Rare Diseases (E-RARE) Dear Colleagues, Questionnaire on Research Priorities Constituted by 8 European partner s countries (Belgium, France, Germany, Italy, Israel, Spain, The Netherlands, and Turkey), E-RARE is an action under the FP6 ERA-NET scheme for the coordination of national and regional research activities in Rare Diseases in Europe. The E-RARE research and development programme aims at coordinating existing programmes and preparing joint and strategic activities to overcome limitations imposed by scattered funding and fragmentation between national research programmes. The overall objective of E-Rare is to pave the way for a close networking of national/regional research programmes on rare diseases, and to implement a joint transnational research programme in European partner s countries. The major achievement of E-Rare programme has been the successful launching in 2007, and at the end of 2008, of two joint transnational calls for projects on research in rare diseases, which gathered hundreds of multi-disciplinary applications from more than 15 different countries, and covered all domains and themes of research in rare diseases. To go further in defining a global research policy development on rare diseases at national and European levels, E-Rare is seeking to gather from researchers, clinicians, funding agencies, patients associations and other stakeholders in the field of rare diseases their views on the priorities for future funding in all aspects of research on rare diseases. We now call upon your participation in this important task with the filling of the attached questionnaire. We count in your participation and the information you will provide in order to gain highly relevant and representative data. The data provided by you will be used together with additional data from national programmes and European Union agencies to elaborate a number of recommendations on research that will be presented to the European Commission in a strategy paper on Future themes and needs of rare disease research funding. The result of this work will represent a cornerstone for the shaping of future research programmes at both European and national level. We would like to thank you in advance for your help and your time. 26

27 Instructions for completing the questionnaire The following questionnaire comprises 11 tables: one introductory table, nine thematic tables and one final table on criteria for the prioritization of RD programmes. In the first table (Priority Areas) you will have to state your interest/knowledge on the particular areas/themes this questionnaire assesses. Only areas/themes where you declare an interest will be responded in the coming tables. This is, the areas where you respond high or interest will be the ones you will have to fill in. Please ignore the tables corresponding to areas where you declared no, low or rather low interest. In order to fill in the questionnaire, please tick only option per item and make sure you complete the table thoroughly. All tables display an option to answer Others. If this is your answer for certain items, please provide as much information as possible in the space provided for this purpose. Also, we would appreciate if you could give us information on the existing bottlenecks (if any) for the areas where you declared an interest. Once you complete the questionnaire, please save it and sent it back to any of the following s: Alejandro Ramirez The information you provide is very important for this vital area of rare diseases. The compiled information will be aggregated and treated in anonymous way. Once we receive your with the questionnaire the information will be placed in a database with no link to sender of the . The only personal information matched to the data extracted from the questionnaires would the position you hold (e.g. researcher, clinician, patient ) and the location where you are responding from or on behalf of (e.g. public administration, hospital, private company, patient association ). You are Researcher Responding on behalf of Public Administration 27

28 I. Priority Areas Priority Areas Priority No Interest 1. Health Systems Research 2. Human and Social Science Research 3. Epidemiology/Natural History of diseases 4. Research in Genetics and Pathophysiology 5. Pre-Clinical Therapeutic Research 6. Therapeutic Research 7. Research Platforms/Infrastructures 8. Human Resources 9. Development and availability of tools needed to accelerate research on rare diseases 10. Others* * If your answer is Others, please specify and provide information on why you think this is an important issue to take into consideration: Please, continue by filling in ONLY the specific sections that you have rated or 28

29 II. Areas and Topics 1. Health Systems Research Health Systems Research Priority No Interest Not Applicable (for Funding Agencies only) a. Research policy (e.g., guidelines development; national plans; health care resources) b. Cost analysis (e.g., guidelines implementation) c. New technologies (e.g., New diagnostic tests, population screening programmes) d. Health-Technology assessment of Orphan Drugs e. e-health activities f. Others* * If your answer is Others, please specify: For the answers rated or, do you identify bottlenecks? If yes, please, comment: 29

30 2. Human and Social Science Research Human and Social Science Research No Interest Priority Not Applicable (for Funding Agencies only) a. Society and RD (e.g., social perception, accessibility to care, ) b. RD, Research and Innovation (e.g., public/private cooperation, role of patients org,.) c. Care practises (selfmanagement, health education policy, ) d. Patients awareness (e.g., understanding genetic data, importance of animal models, ) e. Support for caregivers f. Public Heath and RD (e.g., health care policies, prospective public policies, ) g. Methods for social support to improve quality of life h. Services accessibility i. Orphan Drugs availability i. Methods to assess QoL k. Others* * If your answer is Others, please specify, For the answers rated or, do you identify bottlenecks? If yes, please, comment: 30

31 3. Epidemiology/Natural History of diseases Epidemiology/Natural History of diseases No Interest Priority Not Applicable (for Funding Agencies only) a. Registries b. Databases/data management systems for epidemiology studies c. Cohorts d. Genotype/Phenotype correlations e. Biomarkers to assess diagnosis, prognosis and severity of diseases f. Diagnosis/prognosis methods (e.g., other than biomarkers) g. Identification of new entities h. Networks for ultra rare diseases i. Others* * If your answer is Others, please specify: For the answers rated or, do you identify bottlenecks? If yes, please, comment: 31

32 4. Research in Genetics and physiopathology Research in Genetics and physiopathology No interest Priority Not Applicable (for Funding Agencies only) a. Gene identification and Molecular Mechanisms b. New database method developments to be applied to omics research c. Biobanking research d. throughput genomics/sequencing e. New bioinformatic methods and developments f. New technologies (e.g., atomic microscopy ) g. Omics technology (e.g., proteo, metabolo..) h. Development of new animal models i. New Imaging/Microscopy methods j. Development of new therapeutic tools k. Others* * If your answer is Others, please specify: For the answers rated or, do you identify bottlenecks? If yes, please, comment: 32

33 5. Pre-clinical therapeutic research Pre-clinical therapeutic research No interest Priority Not Applicable (for Funding Agencies only) a. Proof-of-concept b. Drug libraries c. Search for active chemical compounds d. throughput drug screening e. Therapeutic target identification/validation (e.g.,. stem cells, systems biology) f. Cell therapy research (e.g., viral vectors ) g. Innovative biotechnological research (e.g., monoclonal antibodies, cell and gene therapy, enzyme therapy ) h. Drug toxicology/pharmacology i. Others* * If your answer is Others, please specify: For the answers rated or, do you identify bottlenecks? If yes, please, comment: 33

34 6. Therapeutic research Therapeutic research No interest Priority Not Applicable (for Funding Agencies only) a. Drug development b. Phase I/II Clinical Trials c. Bioproduction centres d. Epidemiological/clinical/ therapeutical investigations e. Medical devices f. Assesment of surgery procedures g. Transplants h. Pharma/academic partnerships i. Others* *If your answer is Others, please specify, For the answers rated or, do you identify bottlenecks? If yes, please, comment: 34

35 7. Platforms/ Infrastructures development Platforms/ Infrastructures development No interest Priority Not Applicable (for Funding Agencies only) a. Bioinformatics b. Pharmacogenomic diagnostic assays c. Population Registries d. Genetically-modified animal model repositories e. GMP platforms f. Biobanking g. Genomic and proteomic platforms h. Long-term cohort of patients studies i. throughput drug screening j. Others* * If your answer is Others, please specify, For the answers rated or, do you identify bottlenecks? If yes, please, comment: 35

36 8. Human Resources Human Resources No interest Priority Not Applicable (for Funding Agencies only) a. Rotational positions for clinicians b. Rotational positions for researchers c. Specific training in RD d. Training in bioinformatics e. Others* * If your answer is Others, please specify: For the answers rated or, do you identify bottlenecks? If yes, please, comment: 36

37 9. Development and availability of tools needed to accelerate research on rare diseases Development and availability of tools needed to accelerate research on rare diseases No interest Priority Not Applicable (for Funding Agencies only) a. Network development b. Creation of transnational research consortiums c. Transnational calls for projects funding d. Opening of national research programmes to international collaboration e. Transnational research infrastructures f. Development of an inventory/directory of databases of experts g. Transnational collection of funded RD research projects h. Others* * If your answer is Others, please specify: For the answers rated or, do you identify bottlenecks? If yes, please, comment: 37

38 III. Criteria for prioritising programmes Priority Criteria No interest Not Applicable (for Funding Agencies only) 1. Number of people affected (Prevalence) 2. MorbiMortality 3. Obvious gaps in health care 4. Economical and individual burden 5 Focus on particular groups of diseases 6. Social Burden of Diseases (DALY) 7. Clinical utility and applicability 8. Significance for the health care system (economical efficiency) 9. Potential for economic exploitation 10 Potential for scientific and technological innovations 11. Potential for strengthening top-level research 12. Bottom up approach Scientific excellence only 13. Others* * If your answer is Others or you suggest to exclude some groups of diseases, please specify: 38

39 For the answers rated or, do you identify bottlenecks? If yes, please, comment: On behalf of all E-Rare partners we would like to thank you for your precious time and participation in this important activity. Should you have any queries about this questionnaire, please don t hesitate in contacting any of the following: Sophie Koutouzov E-RARE Project Coordinator skoutouzov@gis-maladiesrares.net Alejandro Ramirez E-RARE WP4 Officer aramirez@isciii.es 39