Final Report Summary - PATIENTPARTNER (Identifying the Needs for Patients Partnering in Clinical Research)
PATIENTPARTNER was a three year Seventh Framework Programme (FP7) funded that ran from May 2008 to May 2011. The main objectives of the project were the identification of patients' needs for partnership in the clinical trials context as well as development of a sustainable communication platform and guidelines, to enable the collaboration between patient organisations, sponsors and investigators in the development, conduct and implementation of clinical research. Based on an inventory of the views, needs, practices and experiences of patient organisations on their involvement in clinical research-a series of Europe-wide and regional workshops were organised. When patient organisations, sponsors and investigators met at the start-up workshop held in Brussels on 11 June 2009 they had a simple but ambitious target: to start a Europe-wide dialogue on how patient organisations can become partners in clinical research. The discussions at this first workshop revealed that partnership is not only desirable, it is also achievable. However, the concern was raised that there might be potential regional differences in patients' attitude, interest and level of involvement in clinical research. Three regional workshops followed-with the same thread of discussion and work in small groups rather than listening to formal presentations. The joint stakeholders present at the regional workshops - patient representatives, clinical researchers from academia and from industry- discussed the content and value of the role of patient organisations in clinical research as well as innovative ways on how to facilitate the building of partnerships between patient organisations, sponsors and investigators in clinical research.
Although the recommendations differed slightly in their formulation the three regional workshops identified similar core needs to be fulfilled:
-The need for raising awareness on the importance and value of patient partnership in clinical research amongst all European clinical research stakeholders.
-The need for a portal or match-making database for all stakeholders in clinical research, with the principle aim of enabling stakeholders to find the right partners.
-The need for adequate training on clinical research to be made accessible to patient organisations to enable successful engagement and equal partnerships with sponsors and investigators in clinical research.
Based on the outcomes of the regional workshop a final workshop was held in December 2010 aiming to obtain the joint stakeholders' input into ways to best deal with the identified needs. This resulted in three breakout sessions each covering one of the three ways to deal with the identified needs;
A. How to establish an ethically sound basis for collaboration between the stakeholders in clinical research; based on the document Ethical principles of partnership
B. How to build bridges to partnership.
C. How to build a partnering communication environment.
The key messages from the final workshop were:
-Patient involvement should be present in all clinical research, in every single clinical trial, and from the earliest possible moment on.
- Resources should be devoted to ensure that the findings of PATIENTPARTNER are taken up and built on by other organisations and projects throughout the EU.
- The draft ethical guide has a great deal of support. It needs to be revised by consultation of the stakeholders and then be used.
- Further work is needed to develop a 'match-making' database enabling interested partners to find each other.
Overall, the PATIENTPARTNER project demonstrated a wide consensus between all stakeholders in clinical research - patient organisations, sponsors and investigators - on the need and proven value of incorporation of the patients' perspectives into clinical trials and clinical research. The resulting, developed guidance documents and policy recommendations can be downloaded from the PATIENTPARTNER website: http://www.patientpartner-europe.eu
Project context and objectives:
Although patient organisations have become increasingly professional, their expertise still isn't used systematically by pharmaceutical and biotechnology companies and academic investigators in the start-up, execution, dissemination and implementation of clinical research. This has been suggested to be due to a lack of awareness of the potential benefits of collaborating with patient organisations. Moreover, the lack of information needed to decide upon the most suitable patient organisation, and the lack of any formal obligation to involve patients both contribute to the limited structural involvement of patients. Other causes have been identified as a general lack of awareness of patient organisations themselves being aware of the benefits of being active in the field of clinical research, or inadequate infrastructure and knowledge within the organisation.
Main objectives
The PATIENTPARTNER project is based on the premise that early, active involvement of patient organisations in clinical research will not only contribute to therapies that are better adapted to the needs of the patients, but also to the cost-effectiveness of the clinical trials conducted in the European Union (EU). The main objectives of this project thus are:
- to identify best practices of patient organisation's active involvement in clinical research in Europe
- to facilitate the dialogue between all involved stakeholders in clinical research as to how to establish active patient involvement and integral part of clinical research
- to develop and disseminate guidance material to be used by all stakeholders in order to facilitate the future partnerships in clinical research between patient organisations, sponsors and investigators
- to develop and disseminate policy recommendations to the European Commission (EC) and Member states on how to facilitate partnership between patient organisations, sponsors and investigators in clinical research in Europe.
Context
In the context of our main objectives, we underscribe the work that has been performed-during the course of the PATIENTPARTNER project- in several other FP7-funded projects as well as several policy developments at the EC that have acknowledged the value of the patient perspective in health related topics. Amongst them:
- The VALUE+ project 'promoting patients' involvement in EU supported health related projects' which conclusions were that 'meaningful patient involvement' means that patients take an active role in activities or decisions that will have consequences for the patient community, because their specific knowledge and relevant experience as patient. The involvement must be planned, appropriately resourced, carried out, and evaluated, according to the values of:
- the participating patients or patient organisations
- other participating organisations and funding bodies
- the quality of their experiences during the involvement activity
- the FP7 funded project RESPECT who have looked into ways to improve the participation of children in clinical trials through understanding their needs and possible routes to empowerment
- the FP 7 funded project BBMRI who have drafted a document on the basic principles of patient participation in biobanking activities
- the FP7 Cooperation Work Programme: Health-2011 reiterating that 'the early involvement of patients and their advocacy group in the planning, implementation and monitoring of a clinical trial is considered so that patients' needs are appropriately considered. This may also increase the rate of enrolment of trial participants and can have a positive effect on the performance of a clinical trial. All studies must carefully consider the ethical and regulatory framework at European and national level for the conduct of clinical trials'.
- other examples of the growing acknowledgement can be found by the consideration that at this moment there are several working committees at the European Medicines Agency that actively involves European patient organisations in a range of activities at the agency, including:
- being members of its scientific committees and management board;
- responding to specific requests from the agency's scientific committees, working parties and scientific advisory groups e.g. PCWP, COMP % - reviewing information on medicines prepared by the agency;
- being involved in the preparation of guidelines;
- regularly taking part in agency conferences and workshops.
- as a result of the growing interaction between patient organisation and members of pharmaceutical industry the European Federation of Pharmaceutical Industry Associations (EFPIA) has revisited their EFPIA code on working with patient organisations to regulate a safe and unbiased collaboration between the two stakeholders in their new role as partner in clinical research.
- the most recent remarkable involvement of patient organisations that needs to be mentioned is in the recent public consultations on the clinical trial Directive. Several of the national patient organisations, e.g. grouped in the European Patient Forum (EPF), have provided their comments to the EC on how to address the active involvement of patient organisations in this regulatory document as well as in the ethical review of clinical trials.
- finally a sign of the change in momentum in the European clinical research arena in which the value of the patient perspective in clinical research and the need for patient involvement has been recognised, has been in the third call of the Innovative Medicines Initiative (IMI) who issued a call on 'raising the awareness of patients in pharmaceutical research and development in Europe' hoping to inform and educate patients throughout Europe to the mutual benefit of both patients -treatments that better represent their needs- as well as pharmaceutical industry- a better understanding of the wider public audience can contribute to faster and easier patient recruitment thus leading to better cost effectiveness of clinical research.
Project results:
When we think of the role of patients in clinical research, this might be limited to the thought of a patient being a 'subject' in a clinical trial. However, patients and patient organisations may have much more to offer. By using their experiential knowledge, patients have a potential role as partners in clinical research. A partnership between patients and patient organisations and the other stakeholders e.g. pharmaceutical companies and clinical researchers, will create new paradigms from which not only the patient will benefit, but also the quality, quantity and effectiveness of clinical research. In the end, such partnerships will contribute to better, patient-centred health care. The results described in this chapter represent the foreground that has been generated by the project. As this project is based on dialogue all generated foreground -except for the personal and contact details of our workshop- is public. No exploitable foreground has resulted from this project due to the nature of the project being a coordination and support action rather than a research project.
The inventory
The PATIENTPARTNER project conducted an inventory to identify existing best practices of partnership as well as the needs, barriers and benefit of this new partnership in clinical research. The inventory consisted of:
- literature search
- inventory of best practices
- interviews.
The literature search
The literature search conducted between May 2008 and February 2009 recovered numerous interesting studies and articles on patient involvement in clinical and fundamental research, however due to the specific definitions that are involved when describing patient involvement in clinical trials, we were only able to identify a small number of studies that had described the involvement of patients and/or patient organisations in clinical trials as something other than just as research subjects in the clinical trial. To avoid further definition confusion-patient participation meaning the involvement of a patient as a research subject in a clinical trial to the major stakeholder groups of sponsors and investigators - we use the term patient involvement when describing a partnership between patient organisations, sponsors and investigators which objective is to incorporate the experiential knowledge of patient organisations into the clinical research process.
Inventory of best practices
With the conclusion in mind that examples of patient involvement in clinical research were few and hard to come by, a strategy was needed to identify best practices of patient involvement in clinical research in Europe in another way. The taskforce decided to carry out a survey to identify current practice and roles of patient organisations in clinical research. To structure this inventory we identified five levels of active involvement of patient organisations in clinical trials ranging from being an information provider to being the driving force behind a clinical trial have been identified:
1. as a research subject
2. as an information provider
3. as an advisor
4. as an reviewer
5. as a co-researcher
6. as the driving force.
These six levels make up the PATIENTPARTNER ladder of active patient involvement in clinical research. The survey held under patient organisations was sent by email to 12 000 regional, national and European patient groups. 205 individual patient organisations from around Europe responded to the survey, representing patient groups from 31 European countries; 58 % from the North-western European region (23 % from the Southern European region, 12 % from the Central European Region, 2 % from outside Europe and 5 % of the respondents chose not to reveal their region. The responding organisations represented the common (47 %) and rare (51 %) diseases in an equal number.11 % of all respondents have had no experience in being involved, on any level or otherwise, in clinical trials and research. Whilst 10 % of all respondents had experience in being actively involved on a single level in clinical research, 79 % of all respondents showed to be involved on more than one level. Finally 24 % of all respondents were involved on all of the described levels of patient involvement. In more detail the survey showed that a third of all respondents have been a research subject themselves or know of members of their patient organisation that have taken part in a clinical trial. The majority of the responding patient organisations are actively involved in the providing of information on the possibilities to take part in a clinical trial to their members as well as nearly half of the respondents providing disease specific information on their member base to different stakeholders for the use in clinical trials. Simultaneously there was a broad range of involvement in the other identified levels e.g. reviewing clinical trial protocols and lobbying for clinical trials. Finally several good practices of patient's representatives in e.g. ethical review, protocol development and improving the informed consent process have been identified.
In addition to the performed survey under patient organisations and Europe a small survey was also performed under several members of the pharmaceutical industry. An interesting finding of this study was that the pharmaceutical industry reported to rarely involve patient organisations, while patient organisations reported being involved quite often. This is probably due to the different view of the contact the two parties might have. Patient organisations might have provided information or advised companies, but the information has been perceived as informal and not been taken into consideration by the company. Another main finding was that the pharmaceutical industry appeared to be hesitant towards patient involvement and only grants patient organisations lower levels of involvement; for recruitment, providing of information. Pharmaceutical companies want the input from patient organisations but still want to be able to decide whether or not they use this input.
The interviews
In addition to the literature review and the survey we conducted 20 interviews with patient organisation representatives to identify barriers, opinions, experiences and recommendations on the topic of active patient involvement in clinical research. These interviews revealed that in general the public knowledge of clinical trials is absent and that patient organisations are in need of up to date information on where the opportunities are for their members to take part in clinical trials and for them to get actively involved in getting clinical trials to meet the real needs of the individual patients. The interviews identified barriers as well as benefits to a possible partnership with clinical researchers as well as defining the 'ideal' partnership as being involved from the very first step of a clinical trials including setting the agenda, but within the capacity of the organisation.
The dialogues between stakeholders
Based on the inventory PATIENTPARTNER held five European workshops with the aim of starting a dialogue between all stakeholders in clinical research- patient organisations, sponsors and investigators-on how to establish a model for partnership in which the patient perspective is integrated into clinical research by the collaboration of patient organisations and the other stakeholders.
Start-up central workshop
The start-up central workshop was held on June 2009 with 75 participants attending:
- patient organisations
- academic clinical researchers
- members of industry
- regulatory authority representative, representatives EC, others.
The aim of the workshop was setting the agenda of the upcoming planned regional European workshops. When patient organisations, researchers and companies from across Europe met in Brussels that day, they had a simple yet ambitious target: to start a Europe-wide dialogue on how patients can become partners in clinical trials. The conclusion of the workshop: partnership is not only desirable, it is also achievable. But there are a number of challenges to be met, including poor public perceptions, reluctance on the part of some - but by no means all - companies, the difficulty of recruiting patients to clinical trials, increasing regulation and the need for training.'Is patient involvement the answer to everything?
Maybe not, but we think it will help provide an answer,' Cor Oosterwijk, project coordinator, told the workshop. 'Partnership is not a goal in itself but a move towards more and better clinical trials, with more and better therapies.' The workshop began with an overview of best practices in the involvement of patients in clinical trials, introduced by a presentation of the results of PATIENTPARTNER's comprehensive survey of the views, needs, practices and experiences of patients and patient organisations in Europe. It was followed by a breakout session in which the stakeholders- representing a particular European Region-North-West, Central and Eastern or Southern- Europe- discussed the many obstacles to partnership.
The start-up workshop also heard of a number of successful models of partnership, with patients young and old, as well as plans to extend partnership. It ended with a series of agreed priorities for the regional workshops that will follow, of which two were deemed a major priority by the stakeholders of all represented regions:
- possibilities and hurdles for partnership between patient organisations and other stakeholders in clinical trial and drug development;
- training of and/or providing information to patient organisations on clinical trials and drug development.
Other identified priorities:
- accessibility (to take part as a research subject) to clinical trials, prioritised by Southern Europe
- how to define partnership between patient organisations and other stakeholders in clinical trials and drug development (prioritised by Central and Eastern Europe group);
- role of national and European governments in partnerships between stakeholders in clinical trials and drug development (prioritised by Central and Eastern Europe group)
- active involvement of patient organisations in the ethical decision-making process and/or ethics committees related to clinical trials (prioritised by North and Western Europe Group)
- accessibility to biobanks and patient registries (prioritised by Central and Eastern Europe group)
- active involvement of patient organisation in clinical trials with children (prioritised by Central and Eastern Europe and Southern group).
Regional European workshops
After the start up workshop an agenda was set for the three regional European workshops:
- PATIENTPARTNER North-Western European Workshop, 12 and 13 October 2009, London, United Kingdom (Austria, Belgium, Denmark, Finland, Germany, Ireland, Luxembourg, Sweden, the Netherlands, United Kingdom, Iceland, Liechtenstein, Norway, Switzerland)
- PATIENTPARTNER Central and Eastern European Workshop, 7 and 8 December 2009, Budapest, Hungary (Bulgaria, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia, Slovenia, Albania, Belarus, Bosnia Herzegovina, Croatia, Macedonia, Moldova, Serbia)
- PATIENTPARTNER Southern European Workshop, 24 and 25 March 2010, Athens, Greece (Cyprus, France, Greece, Italy, Malta, Portugal, Spain, Andorra, Gibraltar, Monaco, San Marino, Turkey, Vatican).
PATIENTPARTNER had decided to host three regional workshops based on the concern that was raised that there might be potential for regional differences in patients' attitude, interest and level of involvement in clinical research. Three regional workshops followed with the same thread of discussion and work in small groups rather than listening to formal presentations. The joint stakeholders present at the regional workshops - patient representatives, clinical researchers from academia and from industry- discussed:
- What role the patient organisations want to play and the areas in which Industry and Investigators find patient organisation participation desirable.
- What would need to be done in order for patient organisations and other clinical trial stakeholders to become partners.
- What the ideal world would be concerning a partnership in clinical trials, taking into consideration regionally different expectations, and what the partners are willing to do in order to achieve this.
North-Western European workshop
The North-Western European workshop was a true workshop: the bulk of the time was spent working in small groups on particular questions and problems, rather than listening to formal presentations. Eighty one participants attended the North Western European workshop:
- 31 patient organisations
- 11 academic clinical researchers
- 18 members of industry
- 1 regulatory authority representative, two representatives EC, 18 others.
This was the first regional workshop, so it was too early to tell what the regional variations might be. But the first lesson to emerge in London was of the sheer variety of patient organisations. Some are large, some small, some federations, some focused on individual genetic diseases, the list of differences goes on. So it was no surprise that the recommendations from the workshop took this variety very much into account. The question was not 'What is the ideal form of partnership?' but 'What form of partnership are individual patient organisations prepared and able to engage in?'
That led to the first key message: patient organisations need different models of engagement with clinical research so that they can choose which works best for them.
The second lesson was that it can be difficult for stakeholders and potential stakeholders to know what is happening in their areas of interest. For patient organisations, what trials are being done, and by whom? Which researchers are interested in their disease areas?
For companies looking to run trials across Europe, where are interested patient organisations? Are they able to help in protocol design, or in trial recruitment?
Hence the second key message: that a Europe-wide internet-based 'dating agency' needs to be set up where patient organisations, companies and academic researchers can find potential partners. That will cost money, and there were differing views on whether the European Union should fund such a project - although its 'moral support' would be important.
The portal should also have details of ongoing clinical trials in Europe, or at the very least a link to somewhere that does have those details. In principle, information on these trials was expected to be publicly available on the EudraCT database as of summer 2010, but in practice, as several people from patient organisations pointed out, that database is not seen as 'patient-friendly'. So there was a clear proposal to ask EudraCT to have an additional field that would explain in simple language what a trial is about.
The third key message was that academia and pharmaceutical industry need to provide information on their areas of research and clinical trials understandable to patient organisations by using plain language. Fourth, all stakeholders need to have clear points of contact and clear internal procedures. 'It's great that pharma is here around the table,' said one patient representative, 'but we really need to know whom to talk to in pharma'. And vice-versa, too.
A final message was that for patients and their organisations training becomes paramount to becoming partners in clinical trials and a number of suggestions were made. Priority should be given to those who have or want to have direct contact with partnership organisations. Again, funding will be an issue to be dealt with.
Central and Eastern European regional workshop
The Central and Eastern European regional workshop was the second regional workshop, the discussions followed the same thread as the North-Western Europe workshop and also here the bulk of the time was spent working in small groups on particular questions and problems, rather than listening to formal presentations. The workshop was attended by 45 participants:
- 24 patient organisations
- 5 academic clinical researchers
- 8 members of Industry
- 1 regulatory authority representative, two representatives EC, five others.
The Budapest meeting came up with four clear core proposals:
- To conduct a mapping exercise to identify patient organisations in Europe.
- On the basis of the mapping exercise, to encourage the establishment of national umbrella bodies of patient organisations.
- To leverage those umbrella bodies to create channels of education and training to further the involvement of patients as partners in clinical trials in Europe.
- To raise awareness about the importance of patient partnership in clinical research among stakeholders and the general public through the creation of an annual European Clinical Research Day.
Southern European regional workshop
As with the two earlier regional workshops, the Southern European Regional workshop was spent working in small groups on particular questions and problems, rather than listening to formal presentations and the discussions followed the same thread as the two previous workshops. Forty four participants attended the workshop:
- 25 patient organisations
- 9 academic clinical researchers
- 6 members of industry
- 4 others.
The Athens meeting came up with four clear core proposals:
- To create a database for all stakeholders in clinical trials, with the principal aim of enabling stakeholders to find the right partners.
- To write to the EC to encourage a renewed emphasis on patient partnership, in particular urging it to support the database, training and education, moves to widen early access to treatments, the development of a code of conduct for partnership in clinical trials, and the development of guidelines on privacy and confidentiality for all stakeholders.
- To encourage the formation of umbrella patient organisations nationally and regionally, both at the level of individual indications and more generally.
- To enhance communication among patient organisations through workshops, a newsletter and the European Network for Patients Partnering in Clinical Research (EN-PCR).
Final workshop
The final workshop represented a coming-together of patients, clinical, academic and industry representatives from all over Europe to draw together the threads from the three regional workshops and to seek consensus on plans for policies and for action. One hundred and two stakeholders participated:
- 60 patient organisations
10 academic clinical researchers
- 18 members of industry
- 2 regulatory authority representative, 1 representatives EC, 12 others.
After a welcome from project coordinator Cor Oosterwijk (Dutch Genetic Alliance, VSOP), the workshop began with a report back on the three regional workshops from Kim Wever (also from VSOP). Delegates then heard a timely reminder of the history of patient involvement in clinical trials from veteran UK patient activist Hazel Thornton.
This was followed by three breakout sessions considering:
- 'Ethical principles involved in partnerships'
- 'Building bridges to partnership'
- 'Building a partnering communication environment'.
Ethical principles of involved in partnerships
The final workshop provided an opportunity for broad discussion of the document, 'Ethical principles of partnership', and it formed the topic for the first set of breakout groups. The tasks for the breakout groups were set as to discuss the following questions:
- Are there any important principles missing?
- Would the document be useful in practice - and if so, why and when?
- Select the most important two principles, and then think about how you might handle any breaches of them in a partnership (given the absence of legal measures).
- Any suggestions for changing it?
- And finally, would your organisation be likely to endorse the document?
As well as responding to the tasks they were set, the groups raised other issues that were picked up in discussion, in particular around two questions: conflict of interest, and whether the principles in the document could or should be legally enforceable.
Building bridges to partnership
In this breakout session the stakeholders had the task of addressing the following questions:
- Who should cooperate - which patient organisation, which functions in industry, who in academia?
- When - what are the ideal points in time for establishing requirements for clinical trials?
- Which regulatory or legal framework would optimally support cooperation between patient organisations, academic researchers and industry?
- How can patient organisations, academia and industry work together optimally?
- 'How do we ensure that everyone in the partnership understands the principles?'
The consensus reached in this breakout session was that the objective of developing a new framework for partnership is to ensure that every clinical trial protocol has had patient involvement. The consensus was that-'It's not easy to formalise how the collaboration will work' but that it is necessary to collaborate. The general conclusion of the breakout session; 'Just do it!'
Building a partnering communication environment
One of the key themes to emerge from the regional workshops was the need to make connections: some kind of network, website, database, a central resource so that patient organisations, academics and industry can find their partners. All the workshops, independently, came up with the idea of a central database - but the idea is at once instantly appealing yet hard to pin down. How exactly would it work, what information would it hold, and how would it be funded?
The third and final group of breakout sessions were set the task of fleshing out the dream, with a focus on four questions:
- What data should be in the database?
- How to get the system up and running.
- How to 'govern' this database.
- How to get this database from theory to practice, and what do we need to do have in place to keep networking and communicating when we do not have a database?
The breakout groups were consistent in their approach coming to these main action points on how to establish the communication platform:
- The platform could be started by filling a database with simple information - a short description and contact information of all stakeholders
- It should be a useful tool not just for patient organisations but also industry and researchers.
- The information that goes into the database should be kitemarked, assuring the quality of information in the database.
- Money should be found to upkeep the database.
- The databases should stimulate communication between all stakeholders, incorporate a networking function.
Final discussion and key messages of the final workshop
A final panel discussion considered how to build on the results of the PATIENTPARTNER project. The key messages agreed on during the final workshop were these:
- The draft ethical document had a great deal of support. It needed to be rapidly revised, sent out to stakeholders for consultation - and then used in practice.
- The project must now shift to an emphasis on dissemination of its findings within and beyond the stakeholders' communities, though this should not be left to the project alone: stakeholders must help, too.
- Patient partnership should be present in all clinical research and in every single clinical trial, and from the earliest possible moment. Some countries are further along this road than others, and the sharing of best practice can help to encourage others.
- In the current situation partnership agreements and memoranda of understanding are preferred to attempts to create legal frameworks enforcing patient involvement.
- Resources should be devoted to ensuring that the findings of PATIENTPARTNER are taken up by other organisations and projects, including EU research programmes and Europe-wide networks, and built on.
- Further work is needed to develop the idea of a 'matchmaking' database to enable the right partners to meet each other. It should start with holding simple information, and should use linking to take advantage of information held in other databases.
From dialogue to the development of tools for partnership
To work out the results from the inventory and the consensus resulting from held dialogue between stakeholders in the Workshops we developed guidance documents for both patient organisations and clinical research professionals, ethical principles of partnership, a memorandum of understanding as well as recommendations for policy makers and regulators.
Guidance documents for patient involvement in clinical research
Two guidance documents were developed in the course of the project:
- Patient involvement in clinical research; a guide for patient organisations and patient representatives
- Patient involvement in clinical research; a guide for sponsors and investigators.
The guidance document for patient organisations covers potential blockages and bottlenecks that patient organisations may experience on their way to being actively involved in clinical research and advises how to deal with this.
The guidance document for sponsors and investigators is aimed at organisers / sponsors of clinical trials, from both biopharmaceutical industry and academic research, to help them to work and partner with patient organisations in clinical research.
Development of the guides
The guides were based on the identified bottlenecks, solutions and needs for information on how to come to partnerships between patient organisations, sponsors and investigators in clinical research. Both documents were piloted via a survey focused on validation and quality assurance of the lay language regarding the definitions to be used in the guidance documents. The finalised content of the guides were also distributed to stakeholders who were consulted on their content, changes were made as necessary and deemed appropriate. This was a multi-phased grounded process which was driven by the views and opinions of the stakeholders who are the intended audience and beneficiaries of the guiding documents. Once the content was finalised following development, evaluation and validation, the guides were formatted accordingly. Individual case studies were also included in the documents. Finally, after thorough development, refinement and quality assurance, the two guide documents were printed and distributed.
Ethical principles of partnership and the memorandum of understanding
From the dialogue and discussion at the regional workshops it became evident that some kind of ethical guidance would be appreciated by the joint stakeholders on how partnerships between patient organisations, sponsors and investigators can be set up and maintained.
A document was drafted outlining the major ethical principles that all participants in a partnership should adhere to called 'The ethical principles of partnership between patient organisations, sponsors and investigators in clinical research'.
The document was drafted by the PATIENTPARTNER ethics committee (four ethicists, two patient representatives) and presented at the final workshop to the joint stakeholders for consultation.
The document is based on the following convictions:
- The perspective of patients is unique in its kind and therefore should be valued as specialist knowledge that is different from the professional knowledge of medical specialists, clinical researchers, members of ethics committees and members of pharmaceutical industry.
- The perspective of patients is represented by patient organisations who combine the experience of their members and disseminate this information in order to serve their members in a way that contributes to a better quality of life with their condition or disease. Incorporating the patient perspective into the clinical research (development) process will lead to clinical research and treatments that are more adapted to the real needs of patients.
- The perspective of patients can be represented by different categories of patient advocates; in this document we focus on patient organisations and their representatives without defining the 'ideal' patient representative to be actively involved in clinical research.
- A partnership between patient organisations and other sponsors and investigators can generate benefits for all parties involved as described in the PATIENTPARTNER guides on patient involvement in clinical research.
- The integrity, credibility and independence of all involved partners, as well as the constraints and obligations under which all stakeholder operate, should be respected at all times when negotiating the terms of any partnership.
- In order to assure a partnership in which the integrity of all parties concerned is upheld, adherence to the ethical principles of partnership as described in this document is a prerequisite.
The principles described in the document:
- mutual respect
- trust
-reliability
- transparency
- accountability
- acknowledgement
- sustainability.
There was strong - almost unanimous - support for the principles described in the draft document, although endorsement was not always unanimous. For all to endorse, the document the PATIENTPARTNER taskforce agreed on a round of additional consultation for review of the document by the workshop participants after the workshop. With the review of the document based on the workshop and the consultation round and with the addition of a memorandum of understanding the document was finalised.
Policy recommendations
The policy recommendations drafted by the PATIENTPARTNER project are addressed to European and national policy makers. However, all other involved stakeholders in clinical research - patient organisations, investigators and sponsors- have a key role to play in grounding patient involvement into the clinical research development, execution and implementation. The recommendations reflect the need for the facilitation and support of the project's outcomes by national and European policy makers.
The policy recommendations have been based on four categories each with corresponding recommendations:
1. The public's perception of clinical research
As an important result of the multi-stakeholder dialogue held during the PATIENTPARTNER project the joint stakeholders reiterated the need for an improved understanding of clinical research by the public at large in Europe.
We recommend that the EC's DG SANCO, DG Research and DG Enterprise as well as the ministries of health of the European Member States join forces in developing a harmonised approach to inform the public at large about clinical research and its benefits to the individual patient. By raising awareness on clinical research, patients, when confronted with the question whether or not to be a clinical trial participant or to be more actively involved in clinical research trough their patient organisation will know where to find the support and the tools to do so. In return this will stimulate the conduct of clinical trials in the European member states, thus benefiting the European patients.
2. Capacity building
In order to enable patient organisations to successfully collaborate with sponsors and investigators-with the objective of providing the patient perspective to the development, conduct and implementation of clinical research- the joint stakeholders agreed that patient representatives' knowledge of clinical research needs to be increased.
We recommend that the EC's DG SANCO, DG Research, DG Enterprise and the European the Member States develop a pan-European approach to the establishment of an adequate training programme for patient organisations in order to increase the capacity of patient representatives to be knowledgeable in clinical research and thus enabled to take over partnering roles with industry and academia
In addition to the provision of training we recommend that the EC's DG SANCO, DG Research and the ministries of health of the Member States increase access to resources for patient organisations in order for them to build the required capacity they need to fulfil their new role as partner in clinical research.
3. Building partnerships
In line with increasing the knowledgebase of patient organisations through the provision of training an infrastructure for building the necessary partnerships between sponsors, investigators and patient organisations is essential for the incorporation of the patient's perspective in clinical research.
We recommend that the EC's DG SANCO,DG Research and DG Enterprise establish communication channels e.g. via the National Contact Points in the Member States to inform sponsors and investigators on the value of collaboration with patient organisations in clinical research as stated in the 2011 FP7 Work Programme -Health.
- We recommend that the EC's DG SANCO , DG Research and DG Enterprise combine forced to provide the funds for setting-up a European portal or communication platform contact point for active involvement of patient organisations in clinical research. The European Member States are called upon to fund the building of inventories of patient organisations, sponsors and investigators in their countries and provide the contact details of these stakeholders as well as their areas of indication and kind of interest in research to this portal.
4. Addressing patient involvement in clinical research legislative and regulatory documents
The active involvement of patient organisations is essential to the development of the legal infrastructure for developing new treatments that are fitted to the patient's needs.
We recommend that the EC's DG SANCO ,DG Research and DG Enterprise address the value of active involvement of patient organisations in the new clinical trials legislation as well as involving patients in the development of regulatory and other main policy documents - in order to stimulate the incorporation of the patients' perspective into the clinical research process- with particular emphasis on the informed consent procedure and ethical review.
PATIENTPARTNER network
In order to develop a sustainable platform for discussion on the active involvement of patient organisations in clinical research and the resulting partnerships between all stakeholders in clinical research we have started two LinkedIn groups - the PATIENTPARTNER network - for all combined stakeholders and the PATIENTPARTNER patient organisation network, for patient organisations and patient representatives. These two online discussion groups will be the platform where the dialogue started during the PATIENTPARTNER workshops can continue.
In addition, the online discussion groups PATIENTPARTNER has dedicated a page on the thematic website where stakeholders can publish their contact details as well as their interest in collaborating with the other stakeholders in clinical research.
Potential impact:
- A broader awareness on clinical research amongst the general European public trough patient organisations that are well informed and involved in clinical research; facilitating the recruitment of patients to clinical trials.
- Patient involvement in clinical research as integral part of clinical research; in all steps and from the earliest moment possible leading to clinical research that is based upon the patients' needs.
- Patient organisations that are better equipped to function as partners in all aspects of clinical research facilitating the incorporation of the patient perspective into clinical research; strengthening their role as major stakeholder in the health arena.
- Pharmaceutical and academic researchers that are knowledgeable about, and equipped to partner with patient organisations.
- The formation of ethically sound partnerships in clinical research respecting the integrity, credibility and independence of all involved partners, as well as the constraints and obligations under which all stakeholder operate.
- Patient organisations that are better equipped to involve and empower their membership in clinical research by information and education.
- The involvement of patient organisations in the development of policy and regulatory documents and guidelines concerning clinical research.
- Improved cost effectiveness of clinical research.
Main dissemination activities
The main dissemination of the project's outcomes consisted of presentation on the project's outcomes and progress during the five organised European workshops. Over 300 stakeholder representatives took part in the workshops representing-patient organisations, sponsors, investigators and regulatory bodies-across the majority of countries represented in the Europe.
In addition several presentations were given at National and European conferences on the project its aims, progress and the resulting tools and recommendations over the course of the three years of the project. In the year after the project, the project coordinator and project officer will actively reach out to the stakeholder groups to identify suitable conferences, workshops, newsletters, journals etc to disseminate the project's final outcomes.
The guidance documents that were developed during the project have been spread to over 2000 stakeholders by the end of the project and the spreading of these materials will continue by all consortium members when possible at upcoming national and European wide events where any of the stakeholders in clinical research are present.
The policy recommendations that have been developed in the project will be send to relevant members of the EC, European Parliament and via the national patient organisations to policy makers in the member states. Collaboration will be sought with members of our advisory and dissemination committee to facilitate the reach out to the policy environment.
The ethical principles of partnership will be send by email to over 550 stakeholder representatives who in some shape or form have been involved in the PATIENTPARTNER project. The principles have also been mentioned in the developed guidance document, increasing its dissemination rate significantly.
In addition to the project's produced deliverables, when possible, members of the taskforce and steering committee have participated in working groups on the topic of partnerships between patient organisations and other stakeholder groups in clinical research; e.g. EFPIA Thinkthank, Patient and Consumers Working Party, Joint Operation Group of the EUdraCT Taskforce at EMA (TIG).
As follow up to the project's outcomes the consortium will explore possibilities to imbed the outcomes of the project in new European project's in order to build on the work and dialogue preformed in the project.
Project website: http://www.patientpartner-europe.eu
Although the recommendations differed slightly in their formulation the three regional workshops identified similar core needs to be fulfilled:
-The need for raising awareness on the importance and value of patient partnership in clinical research amongst all European clinical research stakeholders.
-The need for a portal or match-making database for all stakeholders in clinical research, with the principle aim of enabling stakeholders to find the right partners.
-The need for adequate training on clinical research to be made accessible to patient organisations to enable successful engagement and equal partnerships with sponsors and investigators in clinical research.
Based on the outcomes of the regional workshop a final workshop was held in December 2010 aiming to obtain the joint stakeholders' input into ways to best deal with the identified needs. This resulted in three breakout sessions each covering one of the three ways to deal with the identified needs;
A. How to establish an ethically sound basis for collaboration between the stakeholders in clinical research; based on the document Ethical principles of partnership
B. How to build bridges to partnership.
C. How to build a partnering communication environment.
The key messages from the final workshop were:
-Patient involvement should be present in all clinical research, in every single clinical trial, and from the earliest possible moment on.
- Resources should be devoted to ensure that the findings of PATIENTPARTNER are taken up and built on by other organisations and projects throughout the EU.
- The draft ethical guide has a great deal of support. It needs to be revised by consultation of the stakeholders and then be used.
- Further work is needed to develop a 'match-making' database enabling interested partners to find each other.
Overall, the PATIENTPARTNER project demonstrated a wide consensus between all stakeholders in clinical research - patient organisations, sponsors and investigators - on the need and proven value of incorporation of the patients' perspectives into clinical trials and clinical research. The resulting, developed guidance documents and policy recommendations can be downloaded from the PATIENTPARTNER website: http://www.patientpartner-europe.eu
Project context and objectives:
Although patient organisations have become increasingly professional, their expertise still isn't used systematically by pharmaceutical and biotechnology companies and academic investigators in the start-up, execution, dissemination and implementation of clinical research. This has been suggested to be due to a lack of awareness of the potential benefits of collaborating with patient organisations. Moreover, the lack of information needed to decide upon the most suitable patient organisation, and the lack of any formal obligation to involve patients both contribute to the limited structural involvement of patients. Other causes have been identified as a general lack of awareness of patient organisations themselves being aware of the benefits of being active in the field of clinical research, or inadequate infrastructure and knowledge within the organisation.
Main objectives
The PATIENTPARTNER project is based on the premise that early, active involvement of patient organisations in clinical research will not only contribute to therapies that are better adapted to the needs of the patients, but also to the cost-effectiveness of the clinical trials conducted in the European Union (EU). The main objectives of this project thus are:
- to identify best practices of patient organisation's active involvement in clinical research in Europe
- to facilitate the dialogue between all involved stakeholders in clinical research as to how to establish active patient involvement and integral part of clinical research
- to develop and disseminate guidance material to be used by all stakeholders in order to facilitate the future partnerships in clinical research between patient organisations, sponsors and investigators
- to develop and disseminate policy recommendations to the European Commission (EC) and Member states on how to facilitate partnership between patient organisations, sponsors and investigators in clinical research in Europe.
Context
In the context of our main objectives, we underscribe the work that has been performed-during the course of the PATIENTPARTNER project- in several other FP7-funded projects as well as several policy developments at the EC that have acknowledged the value of the patient perspective in health related topics. Amongst them:
- The VALUE+ project 'promoting patients' involvement in EU supported health related projects' which conclusions were that 'meaningful patient involvement' means that patients take an active role in activities or decisions that will have consequences for the patient community, because their specific knowledge and relevant experience as patient. The involvement must be planned, appropriately resourced, carried out, and evaluated, according to the values of:
- the participating patients or patient organisations
- other participating organisations and funding bodies
- the quality of their experiences during the involvement activity
- the FP7 funded project RESPECT who have looked into ways to improve the participation of children in clinical trials through understanding their needs and possible routes to empowerment
- the FP 7 funded project BBMRI who have drafted a document on the basic principles of patient participation in biobanking activities
- the FP7 Cooperation Work Programme: Health-2011 reiterating that 'the early involvement of patients and their advocacy group in the planning, implementation and monitoring of a clinical trial is considered so that patients' needs are appropriately considered. This may also increase the rate of enrolment of trial participants and can have a positive effect on the performance of a clinical trial. All studies must carefully consider the ethical and regulatory framework at European and national level for the conduct of clinical trials'.
- other examples of the growing acknowledgement can be found by the consideration that at this moment there are several working committees at the European Medicines Agency that actively involves European patient organisations in a range of activities at the agency, including:
- being members of its scientific committees and management board;
- responding to specific requests from the agency's scientific committees, working parties and scientific advisory groups e.g. PCWP, COMP % - reviewing information on medicines prepared by the agency;
- being involved in the preparation of guidelines;
- regularly taking part in agency conferences and workshops.
- as a result of the growing interaction between patient organisation and members of pharmaceutical industry the European Federation of Pharmaceutical Industry Associations (EFPIA) has revisited their EFPIA code on working with patient organisations to regulate a safe and unbiased collaboration between the two stakeholders in their new role as partner in clinical research.
- the most recent remarkable involvement of patient organisations that needs to be mentioned is in the recent public consultations on the clinical trial Directive. Several of the national patient organisations, e.g. grouped in the European Patient Forum (EPF), have provided their comments to the EC on how to address the active involvement of patient organisations in this regulatory document as well as in the ethical review of clinical trials.
- finally a sign of the change in momentum in the European clinical research arena in which the value of the patient perspective in clinical research and the need for patient involvement has been recognised, has been in the third call of the Innovative Medicines Initiative (IMI) who issued a call on 'raising the awareness of patients in pharmaceutical research and development in Europe' hoping to inform and educate patients throughout Europe to the mutual benefit of both patients -treatments that better represent their needs- as well as pharmaceutical industry- a better understanding of the wider public audience can contribute to faster and easier patient recruitment thus leading to better cost effectiveness of clinical research.
Project results:
When we think of the role of patients in clinical research, this might be limited to the thought of a patient being a 'subject' in a clinical trial. However, patients and patient organisations may have much more to offer. By using their experiential knowledge, patients have a potential role as partners in clinical research. A partnership between patients and patient organisations and the other stakeholders e.g. pharmaceutical companies and clinical researchers, will create new paradigms from which not only the patient will benefit, but also the quality, quantity and effectiveness of clinical research. In the end, such partnerships will contribute to better, patient-centred health care. The results described in this chapter represent the foreground that has been generated by the project. As this project is based on dialogue all generated foreground -except for the personal and contact details of our workshop- is public. No exploitable foreground has resulted from this project due to the nature of the project being a coordination and support action rather than a research project.
The inventory
The PATIENTPARTNER project conducted an inventory to identify existing best practices of partnership as well as the needs, barriers and benefit of this new partnership in clinical research. The inventory consisted of:
- literature search
- inventory of best practices
- interviews.
The literature search
The literature search conducted between May 2008 and February 2009 recovered numerous interesting studies and articles on patient involvement in clinical and fundamental research, however due to the specific definitions that are involved when describing patient involvement in clinical trials, we were only able to identify a small number of studies that had described the involvement of patients and/or patient organisations in clinical trials as something other than just as research subjects in the clinical trial. To avoid further definition confusion-patient participation meaning the involvement of a patient as a research subject in a clinical trial to the major stakeholder groups of sponsors and investigators - we use the term patient involvement when describing a partnership between patient organisations, sponsors and investigators which objective is to incorporate the experiential knowledge of patient organisations into the clinical research process.
Inventory of best practices
With the conclusion in mind that examples of patient involvement in clinical research were few and hard to come by, a strategy was needed to identify best practices of patient involvement in clinical research in Europe in another way. The taskforce decided to carry out a survey to identify current practice and roles of patient organisations in clinical research. To structure this inventory we identified five levels of active involvement of patient organisations in clinical trials ranging from being an information provider to being the driving force behind a clinical trial have been identified:
1. as a research subject
2. as an information provider
3. as an advisor
4. as an reviewer
5. as a co-researcher
6. as the driving force.
These six levels make up the PATIENTPARTNER ladder of active patient involvement in clinical research. The survey held under patient organisations was sent by email to 12 000 regional, national and European patient groups. 205 individual patient organisations from around Europe responded to the survey, representing patient groups from 31 European countries; 58 % from the North-western European region (23 % from the Southern European region, 12 % from the Central European Region, 2 % from outside Europe and 5 % of the respondents chose not to reveal their region. The responding organisations represented the common (47 %) and rare (51 %) diseases in an equal number.11 % of all respondents have had no experience in being involved, on any level or otherwise, in clinical trials and research. Whilst 10 % of all respondents had experience in being actively involved on a single level in clinical research, 79 % of all respondents showed to be involved on more than one level. Finally 24 % of all respondents were involved on all of the described levels of patient involvement. In more detail the survey showed that a third of all respondents have been a research subject themselves or know of members of their patient organisation that have taken part in a clinical trial. The majority of the responding patient organisations are actively involved in the providing of information on the possibilities to take part in a clinical trial to their members as well as nearly half of the respondents providing disease specific information on their member base to different stakeholders for the use in clinical trials. Simultaneously there was a broad range of involvement in the other identified levels e.g. reviewing clinical trial protocols and lobbying for clinical trials. Finally several good practices of patient's representatives in e.g. ethical review, protocol development and improving the informed consent process have been identified.
In addition to the performed survey under patient organisations and Europe a small survey was also performed under several members of the pharmaceutical industry. An interesting finding of this study was that the pharmaceutical industry reported to rarely involve patient organisations, while patient organisations reported being involved quite often. This is probably due to the different view of the contact the two parties might have. Patient organisations might have provided information or advised companies, but the information has been perceived as informal and not been taken into consideration by the company. Another main finding was that the pharmaceutical industry appeared to be hesitant towards patient involvement and only grants patient organisations lower levels of involvement; for recruitment, providing of information. Pharmaceutical companies want the input from patient organisations but still want to be able to decide whether or not they use this input.
The interviews
In addition to the literature review and the survey we conducted 20 interviews with patient organisation representatives to identify barriers, opinions, experiences and recommendations on the topic of active patient involvement in clinical research. These interviews revealed that in general the public knowledge of clinical trials is absent and that patient organisations are in need of up to date information on where the opportunities are for their members to take part in clinical trials and for them to get actively involved in getting clinical trials to meet the real needs of the individual patients. The interviews identified barriers as well as benefits to a possible partnership with clinical researchers as well as defining the 'ideal' partnership as being involved from the very first step of a clinical trials including setting the agenda, but within the capacity of the organisation.
The dialogues between stakeholders
Based on the inventory PATIENTPARTNER held five European workshops with the aim of starting a dialogue between all stakeholders in clinical research- patient organisations, sponsors and investigators-on how to establish a model for partnership in which the patient perspective is integrated into clinical research by the collaboration of patient organisations and the other stakeholders.
Start-up central workshop
The start-up central workshop was held on June 2009 with 75 participants attending:
- patient organisations
- academic clinical researchers
- members of industry
- regulatory authority representative, representatives EC, others.
The aim of the workshop was setting the agenda of the upcoming planned regional European workshops. When patient organisations, researchers and companies from across Europe met in Brussels that day, they had a simple yet ambitious target: to start a Europe-wide dialogue on how patients can become partners in clinical trials. The conclusion of the workshop: partnership is not only desirable, it is also achievable. But there are a number of challenges to be met, including poor public perceptions, reluctance on the part of some - but by no means all - companies, the difficulty of recruiting patients to clinical trials, increasing regulation and the need for training.'Is patient involvement the answer to everything?
Maybe not, but we think it will help provide an answer,' Cor Oosterwijk, project coordinator, told the workshop. 'Partnership is not a goal in itself but a move towards more and better clinical trials, with more and better therapies.' The workshop began with an overview of best practices in the involvement of patients in clinical trials, introduced by a presentation of the results of PATIENTPARTNER's comprehensive survey of the views, needs, practices and experiences of patients and patient organisations in Europe. It was followed by a breakout session in which the stakeholders- representing a particular European Region-North-West, Central and Eastern or Southern- Europe- discussed the many obstacles to partnership.
The start-up workshop also heard of a number of successful models of partnership, with patients young and old, as well as plans to extend partnership. It ended with a series of agreed priorities for the regional workshops that will follow, of which two were deemed a major priority by the stakeholders of all represented regions:
- possibilities and hurdles for partnership between patient organisations and other stakeholders in clinical trial and drug development;
- training of and/or providing information to patient organisations on clinical trials and drug development.
Other identified priorities:
- accessibility (to take part as a research subject) to clinical trials, prioritised by Southern Europe
- how to define partnership between patient organisations and other stakeholders in clinical trials and drug development (prioritised by Central and Eastern Europe group);
- role of national and European governments in partnerships between stakeholders in clinical trials and drug development (prioritised by Central and Eastern Europe group)
- active involvement of patient organisations in the ethical decision-making process and/or ethics committees related to clinical trials (prioritised by North and Western Europe Group)
- accessibility to biobanks and patient registries (prioritised by Central and Eastern Europe group)
- active involvement of patient organisation in clinical trials with children (prioritised by Central and Eastern Europe and Southern group).
Regional European workshops
After the start up workshop an agenda was set for the three regional European workshops:
- PATIENTPARTNER North-Western European Workshop, 12 and 13 October 2009, London, United Kingdom (Austria, Belgium, Denmark, Finland, Germany, Ireland, Luxembourg, Sweden, the Netherlands, United Kingdom, Iceland, Liechtenstein, Norway, Switzerland)
- PATIENTPARTNER Central and Eastern European Workshop, 7 and 8 December 2009, Budapest, Hungary (Bulgaria, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia, Slovenia, Albania, Belarus, Bosnia Herzegovina, Croatia, Macedonia, Moldova, Serbia)
- PATIENTPARTNER Southern European Workshop, 24 and 25 March 2010, Athens, Greece (Cyprus, France, Greece, Italy, Malta, Portugal, Spain, Andorra, Gibraltar, Monaco, San Marino, Turkey, Vatican).
PATIENTPARTNER had decided to host three regional workshops based on the concern that was raised that there might be potential for regional differences in patients' attitude, interest and level of involvement in clinical research. Three regional workshops followed with the same thread of discussion and work in small groups rather than listening to formal presentations. The joint stakeholders present at the regional workshops - patient representatives, clinical researchers from academia and from industry- discussed:
- What role the patient organisations want to play and the areas in which Industry and Investigators find patient organisation participation desirable.
- What would need to be done in order for patient organisations and other clinical trial stakeholders to become partners.
- What the ideal world would be concerning a partnership in clinical trials, taking into consideration regionally different expectations, and what the partners are willing to do in order to achieve this.
North-Western European workshop
The North-Western European workshop was a true workshop: the bulk of the time was spent working in small groups on particular questions and problems, rather than listening to formal presentations. Eighty one participants attended the North Western European workshop:
- 31 patient organisations
- 11 academic clinical researchers
- 18 members of industry
- 1 regulatory authority representative, two representatives EC, 18 others.
This was the first regional workshop, so it was too early to tell what the regional variations might be. But the first lesson to emerge in London was of the sheer variety of patient organisations. Some are large, some small, some federations, some focused on individual genetic diseases, the list of differences goes on. So it was no surprise that the recommendations from the workshop took this variety very much into account. The question was not 'What is the ideal form of partnership?' but 'What form of partnership are individual patient organisations prepared and able to engage in?'
That led to the first key message: patient organisations need different models of engagement with clinical research so that they can choose which works best for them.
The second lesson was that it can be difficult for stakeholders and potential stakeholders to know what is happening in their areas of interest. For patient organisations, what trials are being done, and by whom? Which researchers are interested in their disease areas?
For companies looking to run trials across Europe, where are interested patient organisations? Are they able to help in protocol design, or in trial recruitment?
Hence the second key message: that a Europe-wide internet-based 'dating agency' needs to be set up where patient organisations, companies and academic researchers can find potential partners. That will cost money, and there were differing views on whether the European Union should fund such a project - although its 'moral support' would be important.
The portal should also have details of ongoing clinical trials in Europe, or at the very least a link to somewhere that does have those details. In principle, information on these trials was expected to be publicly available on the EudraCT database as of summer 2010, but in practice, as several people from patient organisations pointed out, that database is not seen as 'patient-friendly'. So there was a clear proposal to ask EudraCT to have an additional field that would explain in simple language what a trial is about.
The third key message was that academia and pharmaceutical industry need to provide information on their areas of research and clinical trials understandable to patient organisations by using plain language. Fourth, all stakeholders need to have clear points of contact and clear internal procedures. 'It's great that pharma is here around the table,' said one patient representative, 'but we really need to know whom to talk to in pharma'. And vice-versa, too.
A final message was that for patients and their organisations training becomes paramount to becoming partners in clinical trials and a number of suggestions were made. Priority should be given to those who have or want to have direct contact with partnership organisations. Again, funding will be an issue to be dealt with.
Central and Eastern European regional workshop
The Central and Eastern European regional workshop was the second regional workshop, the discussions followed the same thread as the North-Western Europe workshop and also here the bulk of the time was spent working in small groups on particular questions and problems, rather than listening to formal presentations. The workshop was attended by 45 participants:
- 24 patient organisations
- 5 academic clinical researchers
- 8 members of Industry
- 1 regulatory authority representative, two representatives EC, five others.
The Budapest meeting came up with four clear core proposals:
- To conduct a mapping exercise to identify patient organisations in Europe.
- On the basis of the mapping exercise, to encourage the establishment of national umbrella bodies of patient organisations.
- To leverage those umbrella bodies to create channels of education and training to further the involvement of patients as partners in clinical trials in Europe.
- To raise awareness about the importance of patient partnership in clinical research among stakeholders and the general public through the creation of an annual European Clinical Research Day.
Southern European regional workshop
As with the two earlier regional workshops, the Southern European Regional workshop was spent working in small groups on particular questions and problems, rather than listening to formal presentations and the discussions followed the same thread as the two previous workshops. Forty four participants attended the workshop:
- 25 patient organisations
- 9 academic clinical researchers
- 6 members of industry
- 4 others.
The Athens meeting came up with four clear core proposals:
- To create a database for all stakeholders in clinical trials, with the principal aim of enabling stakeholders to find the right partners.
- To write to the EC to encourage a renewed emphasis on patient partnership, in particular urging it to support the database, training and education, moves to widen early access to treatments, the development of a code of conduct for partnership in clinical trials, and the development of guidelines on privacy and confidentiality for all stakeholders.
- To encourage the formation of umbrella patient organisations nationally and regionally, both at the level of individual indications and more generally.
- To enhance communication among patient organisations through workshops, a newsletter and the European Network for Patients Partnering in Clinical Research (EN-PCR).
Final workshop
The final workshop represented a coming-together of patients, clinical, academic and industry representatives from all over Europe to draw together the threads from the three regional workshops and to seek consensus on plans for policies and for action. One hundred and two stakeholders participated:
- 60 patient organisations
10 academic clinical researchers
- 18 members of industry
- 2 regulatory authority representative, 1 representatives EC, 12 others.
After a welcome from project coordinator Cor Oosterwijk (Dutch Genetic Alliance, VSOP), the workshop began with a report back on the three regional workshops from Kim Wever (also from VSOP). Delegates then heard a timely reminder of the history of patient involvement in clinical trials from veteran UK patient activist Hazel Thornton.
This was followed by three breakout sessions considering:
- 'Ethical principles involved in partnerships'
- 'Building bridges to partnership'
- 'Building a partnering communication environment'.
Ethical principles of involved in partnerships
The final workshop provided an opportunity for broad discussion of the document, 'Ethical principles of partnership', and it formed the topic for the first set of breakout groups. The tasks for the breakout groups were set as to discuss the following questions:
- Are there any important principles missing?
- Would the document be useful in practice - and if so, why and when?
- Select the most important two principles, and then think about how you might handle any breaches of them in a partnership (given the absence of legal measures).
- Any suggestions for changing it?
- And finally, would your organisation be likely to endorse the document?
As well as responding to the tasks they were set, the groups raised other issues that were picked up in discussion, in particular around two questions: conflict of interest, and whether the principles in the document could or should be legally enforceable.
Building bridges to partnership
In this breakout session the stakeholders had the task of addressing the following questions:
- Who should cooperate - which patient organisation, which functions in industry, who in academia?
- When - what are the ideal points in time for establishing requirements for clinical trials?
- Which regulatory or legal framework would optimally support cooperation between patient organisations, academic researchers and industry?
- How can patient organisations, academia and industry work together optimally?
- 'How do we ensure that everyone in the partnership understands the principles?'
The consensus reached in this breakout session was that the objective of developing a new framework for partnership is to ensure that every clinical trial protocol has had patient involvement. The consensus was that-'It's not easy to formalise how the collaboration will work' but that it is necessary to collaborate. The general conclusion of the breakout session; 'Just do it!'
Building a partnering communication environment
One of the key themes to emerge from the regional workshops was the need to make connections: some kind of network, website, database, a central resource so that patient organisations, academics and industry can find their partners. All the workshops, independently, came up with the idea of a central database - but the idea is at once instantly appealing yet hard to pin down. How exactly would it work, what information would it hold, and how would it be funded?
The third and final group of breakout sessions were set the task of fleshing out the dream, with a focus on four questions:
- What data should be in the database?
- How to get the system up and running.
- How to 'govern' this database.
- How to get this database from theory to practice, and what do we need to do have in place to keep networking and communicating when we do not have a database?
The breakout groups were consistent in their approach coming to these main action points on how to establish the communication platform:
- The platform could be started by filling a database with simple information - a short description and contact information of all stakeholders
- It should be a useful tool not just for patient organisations but also industry and researchers.
- The information that goes into the database should be kitemarked, assuring the quality of information in the database.
- Money should be found to upkeep the database.
- The databases should stimulate communication between all stakeholders, incorporate a networking function.
Final discussion and key messages of the final workshop
A final panel discussion considered how to build on the results of the PATIENTPARTNER project. The key messages agreed on during the final workshop were these:
- The draft ethical document had a great deal of support. It needed to be rapidly revised, sent out to stakeholders for consultation - and then used in practice.
- The project must now shift to an emphasis on dissemination of its findings within and beyond the stakeholders' communities, though this should not be left to the project alone: stakeholders must help, too.
- Patient partnership should be present in all clinical research and in every single clinical trial, and from the earliest possible moment. Some countries are further along this road than others, and the sharing of best practice can help to encourage others.
- In the current situation partnership agreements and memoranda of understanding are preferred to attempts to create legal frameworks enforcing patient involvement.
- Resources should be devoted to ensuring that the findings of PATIENTPARTNER are taken up by other organisations and projects, including EU research programmes and Europe-wide networks, and built on.
- Further work is needed to develop the idea of a 'matchmaking' database to enable the right partners to meet each other. It should start with holding simple information, and should use linking to take advantage of information held in other databases.
From dialogue to the development of tools for partnership
To work out the results from the inventory and the consensus resulting from held dialogue between stakeholders in the Workshops we developed guidance documents for both patient organisations and clinical research professionals, ethical principles of partnership, a memorandum of understanding as well as recommendations for policy makers and regulators.
Guidance documents for patient involvement in clinical research
Two guidance documents were developed in the course of the project:
- Patient involvement in clinical research; a guide for patient organisations and patient representatives
- Patient involvement in clinical research; a guide for sponsors and investigators.
The guidance document for patient organisations covers potential blockages and bottlenecks that patient organisations may experience on their way to being actively involved in clinical research and advises how to deal with this.
The guidance document for sponsors and investigators is aimed at organisers / sponsors of clinical trials, from both biopharmaceutical industry and academic research, to help them to work and partner with patient organisations in clinical research.
Development of the guides
The guides were based on the identified bottlenecks, solutions and needs for information on how to come to partnerships between patient organisations, sponsors and investigators in clinical research. Both documents were piloted via a survey focused on validation and quality assurance of the lay language regarding the definitions to be used in the guidance documents. The finalised content of the guides were also distributed to stakeholders who were consulted on their content, changes were made as necessary and deemed appropriate. This was a multi-phased grounded process which was driven by the views and opinions of the stakeholders who are the intended audience and beneficiaries of the guiding documents. Once the content was finalised following development, evaluation and validation, the guides were formatted accordingly. Individual case studies were also included in the documents. Finally, after thorough development, refinement and quality assurance, the two guide documents were printed and distributed.
Ethical principles of partnership and the memorandum of understanding
From the dialogue and discussion at the regional workshops it became evident that some kind of ethical guidance would be appreciated by the joint stakeholders on how partnerships between patient organisations, sponsors and investigators can be set up and maintained.
A document was drafted outlining the major ethical principles that all participants in a partnership should adhere to called 'The ethical principles of partnership between patient organisations, sponsors and investigators in clinical research'.
The document was drafted by the PATIENTPARTNER ethics committee (four ethicists, two patient representatives) and presented at the final workshop to the joint stakeholders for consultation.
The document is based on the following convictions:
- The perspective of patients is unique in its kind and therefore should be valued as specialist knowledge that is different from the professional knowledge of medical specialists, clinical researchers, members of ethics committees and members of pharmaceutical industry.
- The perspective of patients is represented by patient organisations who combine the experience of their members and disseminate this information in order to serve their members in a way that contributes to a better quality of life with their condition or disease. Incorporating the patient perspective into the clinical research (development) process will lead to clinical research and treatments that are more adapted to the real needs of patients.
- The perspective of patients can be represented by different categories of patient advocates; in this document we focus on patient organisations and their representatives without defining the 'ideal' patient representative to be actively involved in clinical research.
- A partnership between patient organisations and other sponsors and investigators can generate benefits for all parties involved as described in the PATIENTPARTNER guides on patient involvement in clinical research.
- The integrity, credibility and independence of all involved partners, as well as the constraints and obligations under which all stakeholder operate, should be respected at all times when negotiating the terms of any partnership.
- In order to assure a partnership in which the integrity of all parties concerned is upheld, adherence to the ethical principles of partnership as described in this document is a prerequisite.
The principles described in the document:
- mutual respect
- trust
-reliability
- transparency
- accountability
- acknowledgement
- sustainability.
There was strong - almost unanimous - support for the principles described in the draft document, although endorsement was not always unanimous. For all to endorse, the document the PATIENTPARTNER taskforce agreed on a round of additional consultation for review of the document by the workshop participants after the workshop. With the review of the document based on the workshop and the consultation round and with the addition of a memorandum of understanding the document was finalised.
Policy recommendations
The policy recommendations drafted by the PATIENTPARTNER project are addressed to European and national policy makers. However, all other involved stakeholders in clinical research - patient organisations, investigators and sponsors- have a key role to play in grounding patient involvement into the clinical research development, execution and implementation. The recommendations reflect the need for the facilitation and support of the project's outcomes by national and European policy makers.
The policy recommendations have been based on four categories each with corresponding recommendations:
1. The public's perception of clinical research
As an important result of the multi-stakeholder dialogue held during the PATIENTPARTNER project the joint stakeholders reiterated the need for an improved understanding of clinical research by the public at large in Europe.
We recommend that the EC's DG SANCO, DG Research and DG Enterprise as well as the ministries of health of the European Member States join forces in developing a harmonised approach to inform the public at large about clinical research and its benefits to the individual patient. By raising awareness on clinical research, patients, when confronted with the question whether or not to be a clinical trial participant or to be more actively involved in clinical research trough their patient organisation will know where to find the support and the tools to do so. In return this will stimulate the conduct of clinical trials in the European member states, thus benefiting the European patients.
2. Capacity building
In order to enable patient organisations to successfully collaborate with sponsors and investigators-with the objective of providing the patient perspective to the development, conduct and implementation of clinical research- the joint stakeholders agreed that patient representatives' knowledge of clinical research needs to be increased.
We recommend that the EC's DG SANCO, DG Research, DG Enterprise and the European the Member States develop a pan-European approach to the establishment of an adequate training programme for patient organisations in order to increase the capacity of patient representatives to be knowledgeable in clinical research and thus enabled to take over partnering roles with industry and academia
In addition to the provision of training we recommend that the EC's DG SANCO, DG Research and the ministries of health of the Member States increase access to resources for patient organisations in order for them to build the required capacity they need to fulfil their new role as partner in clinical research.
3. Building partnerships
In line with increasing the knowledgebase of patient organisations through the provision of training an infrastructure for building the necessary partnerships between sponsors, investigators and patient organisations is essential for the incorporation of the patient's perspective in clinical research.
We recommend that the EC's DG SANCO,DG Research and DG Enterprise establish communication channels e.g. via the National Contact Points in the Member States to inform sponsors and investigators on the value of collaboration with patient organisations in clinical research as stated in the 2011 FP7 Work Programme -Health.
- We recommend that the EC's DG SANCO , DG Research and DG Enterprise combine forced to provide the funds for setting-up a European portal or communication platform contact point for active involvement of patient organisations in clinical research. The European Member States are called upon to fund the building of inventories of patient organisations, sponsors and investigators in their countries and provide the contact details of these stakeholders as well as their areas of indication and kind of interest in research to this portal.
4. Addressing patient involvement in clinical research legislative and regulatory documents
The active involvement of patient organisations is essential to the development of the legal infrastructure for developing new treatments that are fitted to the patient's needs.
We recommend that the EC's DG SANCO ,DG Research and DG Enterprise address the value of active involvement of patient organisations in the new clinical trials legislation as well as involving patients in the development of regulatory and other main policy documents - in order to stimulate the incorporation of the patients' perspective into the clinical research process- with particular emphasis on the informed consent procedure and ethical review.
PATIENTPARTNER network
In order to develop a sustainable platform for discussion on the active involvement of patient organisations in clinical research and the resulting partnerships between all stakeholders in clinical research we have started two LinkedIn groups - the PATIENTPARTNER network - for all combined stakeholders and the PATIENTPARTNER patient organisation network, for patient organisations and patient representatives. These two online discussion groups will be the platform where the dialogue started during the PATIENTPARTNER workshops can continue.
In addition, the online discussion groups PATIENTPARTNER has dedicated a page on the thematic website where stakeholders can publish their contact details as well as their interest in collaborating with the other stakeholders in clinical research.
Potential impact:
- A broader awareness on clinical research amongst the general European public trough patient organisations that are well informed and involved in clinical research; facilitating the recruitment of patients to clinical trials.
- Patient involvement in clinical research as integral part of clinical research; in all steps and from the earliest moment possible leading to clinical research that is based upon the patients' needs.
- Patient organisations that are better equipped to function as partners in all aspects of clinical research facilitating the incorporation of the patient perspective into clinical research; strengthening their role as major stakeholder in the health arena.
- Pharmaceutical and academic researchers that are knowledgeable about, and equipped to partner with patient organisations.
- The formation of ethically sound partnerships in clinical research respecting the integrity, credibility and independence of all involved partners, as well as the constraints and obligations under which all stakeholder operate.
- Patient organisations that are better equipped to involve and empower their membership in clinical research by information and education.
- The involvement of patient organisations in the development of policy and regulatory documents and guidelines concerning clinical research.
- Improved cost effectiveness of clinical research.
Main dissemination activities
The main dissemination of the project's outcomes consisted of presentation on the project's outcomes and progress during the five organised European workshops. Over 300 stakeholder representatives took part in the workshops representing-patient organisations, sponsors, investigators and regulatory bodies-across the majority of countries represented in the Europe.
In addition several presentations were given at National and European conferences on the project its aims, progress and the resulting tools and recommendations over the course of the three years of the project. In the year after the project, the project coordinator and project officer will actively reach out to the stakeholder groups to identify suitable conferences, workshops, newsletters, journals etc to disseminate the project's final outcomes.
The guidance documents that were developed during the project have been spread to over 2000 stakeholders by the end of the project and the spreading of these materials will continue by all consortium members when possible at upcoming national and European wide events where any of the stakeholders in clinical research are present.
The policy recommendations that have been developed in the project will be send to relevant members of the EC, European Parliament and via the national patient organisations to policy makers in the member states. Collaboration will be sought with members of our advisory and dissemination committee to facilitate the reach out to the policy environment.
The ethical principles of partnership will be send by email to over 550 stakeholder representatives who in some shape or form have been involved in the PATIENTPARTNER project. The principles have also been mentioned in the developed guidance document, increasing its dissemination rate significantly.
In addition to the project's produced deliverables, when possible, members of the taskforce and steering committee have participated in working groups on the topic of partnerships between patient organisations and other stakeholder groups in clinical research; e.g. EFPIA Thinkthank, Patient and Consumers Working Party, Joint Operation Group of the EUdraCT Taskforce at EMA (TIG).
As follow up to the project's outcomes the consortium will explore possibilities to imbed the outcomes of the project in new European project's in order to build on the work and dialogue preformed in the project.
Project website: http://www.patientpartner-europe.eu