STRATEGIC BUSINESS PLAN

Transcription

1 STRATEGIC BUSINESS PLAN for the second phase of the European & Developing Countries Clinical Trials Partnership programme (EDCTP2, ) undertaken by several Member States under Article 185 of the Treaty on the Functioning of the European Union (EU) Version 22.1 (18 October 2013)

2 Table of Contents Preface...4 Executive Summary...5 Background Current Context and Challenges Ahead The Global Health Case HIV/AIDS Malaria Tuberculosis NIDs Political context, challenges and choices Goal, Scope and Objectives EDCTP by Lessons learnt from EDCTP Goal Scope Objectives Common Approaches (joint programming) Integrated Activities Participating States Initiated Activities (PSIA) Joint Activities Programme Management and Strategy European countries participating in EDCTP Governance and Management Structures Strategic Roadmap (milestones) Strategic Programming and Financial Planning Cofunding arrangements for EDCTP Programme Implementation and Activities Actions for achieving the objectives including: Key Principles Activities Criteria for prioritisation of Integrated Activities Funding instruments and activities National Programmes Integration of Participating States Research Programmes through EDCTP Existing integration activities Integration of Funding Integration activities for EDCTP Engaging with African Networks of Excellence Network of EDCTP Centres in Europe and Africa Joint Training Programmes Continuation of Existing Integration Activities Joint Funding Notes to table outlining PSs indicative commitments to EDCTP Further Commitments Provisional Planning of Funding Activities Evolution of the SEC Programme Monitoring and Evaluation Scientific outcome and strategic impact Operational performance Definitions Acronyms Annex I: Organisation, structure and management of the EDCTP Secretariat (SEC) Organogram of the EDCTP Secretariat Location and role of the SEC Role of offices Financial system

3 Internal control and accountability Per Diems and Travel Expenses Staff Regulations Risk Management Programme management Document management and video conferencing systems

4 PREFACE This document is a proposal for a second phase of the European & Developing Countries Clinical Trials Partnership (EDCTP2). It outlines the scope, objectives, strategy and implementation of the multiannual EDCTP2 joint programme by the Participating States and its Dedicated Implementation Structure, the EDCTP2-IS. It has been drafted by the Members of the EDCTP General Assembly (GA) with the support of the EDCTP Secretariat (SEC). While intensive consultations with the African and scientific stakeholders have preceded the drafting, in particular with the former Developing Countries Coordinating Committee (DCCC) and Partnership Board (PB), and the African representatives in the EDCTP GA, it should be noted that the Strategic Business Plan of EDCTP2 is part of an intra-european political process. The intended result is an EU decision providing the legal and financial framework for the European contribution to the EDCTP "Joint Programme" that will be implemented, of course, in close collaboration with the African partners and the scientific community. The Strategic Business Plan describes the Participating States (PSs) common ambitions for further integration and alignment of their efforts in joint activities and investments in clinical research on poverty-related diseases in developing countries, in particular in sub-saharan Africa, based on what has been set up and achieved in the first phase of EDCTP since It shall serve as a foundation for the European Commission (EC) to prepare the legislative proposals for the financial participation by the EU in EDCTP2 provided by the next multiannual framework programme for research and innovation, Horizon 2020, the Framework Programme for Research and Innovation, and based on Article 185 of the Treaty on the Functioning of the European Union (TFEU). The Strategic Business Plan complements the PSs' expressed political will and dedicated commitment to launch and support the implementation of a second phase of EDCTP, as well as their intention to provide the resources both cash and in-kind as described in the financial planning hereunder. 1 The Strategic Business Plan was first approved by the EDCTP GA on 25 August 2011 on behalf of the relevant national authority having the political responsibility for the country's participation in EDCTP and now incorporates subsequent amendments agreed by the PSs. The current version has been updated to incorporate decisions that were made since then at various meetings including the meeting between Member States (MSs), Associated countries and EU and the May 2013 GA meeting held in Brussels. 1 As set out in the FP7 decision [DECISION No 1982/2006/EC, 18 December 2006, OJ L412/1), implementing Article 185 [169] implies that the participating EU Member States integrate their research efforts by defining and committing themselves to a joint research programme. In implementing Article 185 [169] initiatives, the EU goes beyond simply coordinating research programmes, in that it participates actively in the voluntary integration of scientific, managerial and financial aspects. The EU provides substantial financial support to the joint implementation of the national research programmes involved, based on a joint programme, the setting-up of a dedicated implementation structure and a financing plan based on formal commitments from competent national authorities. The lessons learnt from EDCTP helped to set up clear selection criteria for new Art. 185 [169] initiatives under FP7. These criteria are: relevance to Community objectives; the clear definition of the objective to be pursued and its relevance to the objectives of this Framework Programme; presence of a pre-existing basis (existing or envisaged research programmes); European added value; critical mass, with regard to the size and the number of programmes involved and the similarity of activities they cover; efficiency of Article 185 [169] as the most appropriate means for achieving the objectives. 4

5 EXECUTIVE SUMMARY The European & Developing Countries Clinical Trials Partnership (EDCTP) was established by the EU in 2003 in response to the global health crisis caused by the major three povertyrelated diseases (PRDs) HIV/AIDS, tuberculosis and malaria, and the EU's commitment to achieving the Millennium Development Goals (MDGs) by EDCTP supports clinical trials against these diseases in sub-saharan Africa, in partnership with their African counterparts and like-minded organisations, and facilitates cooperation and integration of corresponding European national research programmes and activities. EDCTP is the first initiative based on Article 185 of the Treaty on the Functioning of the EU (ex-art. 169), which allows the EU's participation in research programmes undertaken by several EU and Associated MSs. The current EDCTP programme (EDCTP1) is funded with 400 million by the EU and 14 EU MSs (and 2 associated European countries). 2 It came to an end on 14 September However, the EC agreed to an extension with no additional Community funding until May 2015 to allow for the conclusion of the EDCTP-funded activities with the phasing out of the corresponding EDCTP1 grant management and project review. The EDCTP programme thus brings together the combined strengths of the PSs together with those of their sub-saharan African counterparts and interested third parties, in order to address the global challenge of fighting PRDs, which is beyond the capacity of individual countries. This facilitates cross-border research in Europe and sub-saharan Africa which supports the completion of the European Research Area (ERA). The programme also promotes sustainability and establishment of a level playing field by supporting capacity building in sub- Saharan African countries. Through EDCTP, European countries have a coherent and coordinated voice internationally and a common strategy in the fight against PRDs. During the current programme from 2003 to 2012, EDCTP has funded 241 projects in 30 different countries. These included 88 clinical trials of which 31 were on HIV/AIDS, 25 on tuberculosis and 32 on malaria. The trials were on treatment drugs, vaccines, microbicides and diagnostics. This has led to the registration of one paediatric formulation of an antiretroviral product (Pedimune) in several African countries; informing national and international policies such as the World Health Organisation (WHO) policy on the prevention of maternal to child transmission (PMTCT) of HIV 3 ; and the coordination and integration of national research programmes in conducting these clinical trials. During this first phase, EDCTP provided professional training to more than 400 African scientists and medical doctors (all schemes put together) including 55 Career and Senior Fellows who almost without exception have remained in their own countries to date as well as more than 320 Masters and PhD students. The co-operation and networking of European national programmes and activities under EDCTP1 have resulted in the launch of the first African Regional Networks of Excellence for clinical trials 4,5 ; strengthening and in some cases establishment of National Regulatory Authorities and ethics review capacities in many African countries; and the establishment of the Pan-African Clinical Trials Registry 6 (PACTR) as an African initiative funded by EDCTP, which is now officially recognised as a WHO Primary Clinical Trials Registry. Overall, EDCTP has succeeded in paving the way for conducting sound clinical trials in sub-saharan African countries and succeeded in building a true partnership between Europe and Africa and 2 The EDCTP1 program involved the following 16 European countries: Austria, Belgium, Denmark, France, Germany, Greece, Ireland, Italy, Luxembourg, Netherlands, Norway, Portugal, Spain, Sweden, Switzerland, United Kingdom. 3 The Kesho Bora Study Group. (2011). Triple antiretroviral compared with zidovudine and single-dose nevirapine prophylaxis during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV-1 (Kesho Bora study): a randomized controlled trial. Lancet Infect Dis, 11(3), See also EDCTP Annual Reports at 5 WANETAM The West Africa NoE for TB, AIDS and Malaria (WANETAM) builds capacity to prepare West African sites for clinical trials on HIV, TB and malaria. The network started its activities on 31 July 2009 and is coordinated by Professor Souleymane Mboup. - EACCR The East Africa Consortium for Clinical Research (EACCR) strengthens clinical trial sites in Eastern Africa. The Network started 14 May 2009 and is coordinated by Dr Pontiano Kaleebu. - CANTAM In Central Africa, the Central African Network on TB, HIV/AIDS and malaria (CANTAM) joins institutions involved in clinical trials. The Network started its activities on 19 December 2008 and is coordinated by Dr Francine Ntoumi. - TESA The Trials of Excellence for Southern Africa (TESA) Network focuses on the Southern African region. It started on 23 November 2009 and is coordinated by Dr Alexander Pym

6 fostering African leadership in research, with over 70% of all EDCTP-funded activities led by African researchers. Despite these significant achievements of EDCTP1, the burden of PRDs still remains a major problem in developing countries, particularly those in sub-saharan Africa. New medical interventions are urgently needed. Developing new drugs, vaccines or microbicides is costly, especially the clinical trials required to evaluate their safety and efficacy. Related research efforts in Europe are still fragmented and thus inefficient, whereas the research capacities and investments in developing countries are inadequate. Building on the progress made under EDCTP1, intensifying the work on the current focus (including large-scale phase-iii trials), and extending to related domains (including other Neglected Infectious Diseases [NIDs]), implementation research on health services optimisation), will maximise returns on investment as well as the impact on health and healthcare. Extension to other geographical areas is not being considered in the medium term as it would require a different political framework and vast additional resources. The inclusion of new EU MSs into EDCTP is actively sought and would greatly enhance political cohesion and scientific power. The EDCTP2 joint programme will operate on an extended mandate and duration. It may also involve an increased partnership, with additional European countries joining. Based on the achievements of EDCTP1, the vision of EDCTP2 ( ) is to support 150 new clinical trials (paying special attention to larger and more costly phase III trials where products are available); to strengthen Africa's capacities for clinical research; and to train 600 African researchers and doctors. To this end, a budget of up to 2 billion may be required. 14 EU MSs, with Norway and Switzerland 7, have expressed their political will to support the EDCTP2 programme and have, to date, committed over 1 billion, while expecting an equal amount of cofunding from the EU. Latvia and Finland have also expressed a strong interest in joining. Additional contributions by PSs over and above this commitment may also be matched by funding from the EU up to a total of 1 billion. Thus this business plan envisages an initial commitment of 1 billion between PSs and the EU, with potential to realise a budget of up to 2 billion through additional matched funding. Fresh EU funding requires a co-decision of the European Parliament and the Council on a new EDCTP programme (EDCTP2). Continuation has been recommended by an Independent Expert Review and an Impact Assessment that included a public consultation. These assessments point to an innovative and strong partnership with Africa and a greatly improved programme over the years, with remaining challenges regarding full integration of national programmes and transparent cofunding. To facilitate this, PSs have agreed to adopt a common scientific research strategy and goal, together with a centralised or common administration including scientific review and funding. The joint funding will include both new EU and national money to a common pot for direct funding of Integrated Activities through the EDCTP2-IS, as well as in-kind contribution from PSs. The in-kind contribution from PSs will include, among other things, a sustained corefunding of activities within the EDCTP scope, both in Europe and sub-saharan Africa, such as support for clinical trial centres, conduct of cohort studies and site preparation and maintenance. PSs will continue to participate in Joint Activities, including Calls for Proposals, common review and evaluation and joint training. To facilitate this, the cofunding from PSs will be described in advance through annual workplans. Moreover, African PSs and third parties, including industry and other funders, will be proactively sought to jointly participate in the projects. The context of the programme is the persistent impact of infectious diseases in many developing countries despite the resources dedicated globally to develop new products to prevent, diagnose or treat these diseases. The EU remains committed to supporting a concerted effort to fight PRDs, particularly HIV/AIDS, malaria, tuberculosis and NIDs and to ensuring that the expertise and investments of the EU and its MSs can be used synergistically 7 The following 16 European countries expressed their political will to provide financial support to the EDCTP programme: Austria, Belgium, Denmark, France, Germany, Greece, Ireland, Italy, Luxembourg, Netherlands, Norway, Portugal, Spain, Sweden and Switzerland, United Kingdom. 6

7 to make a significant impact on health inequalities. By combating these diseases, EDCTP jointly targets the three MDGs related to health that aim to reduce childhood mortality, improve maternal health and to combat malaria, HIV/AIDS and other diseases, as well as to fight poverty. EDCTP2 will retain much of the core mission of EDCTP1, but will build on an extended and more flexible mandate in order to valorise the clinical capacities established and reinforced by EDCTP1: to encompass a wider range of PRDs, to support the clinical testing of new products and the appropriate use and delivery in the health systems context. The programme will explore a wider range of mechanisms to integrate national activities; ensure greater commitment to implementation of products in clinical practice through the support of postmarketing studies (broadly referred to here as phase IV studies); support development of new diagnostics; engage industry; and ensure the timely development of new products in the global pipeline. This is consistent with option 4 of the EC s draft Impact Assessment for EDCTP2, the expanded scope scenario. This option has the support of the expert group advising the impact assessment and is consistent with the majority view of the public consultation on EDCTP2. Furthermore, the approach will address a broader innovation cycle (value chain) and accelerate better the translation of products and services to address global health needs in keeping with the Europe 2020 strategy. The goal of EDCTP2 will remain to reduce the burden of poverty related diseases by accelerating the development of new or improved tools to address them. In addition, the proposal is directed towards a future vision of EDCTP, in which by 2020 the following strategic objectives should be realised: EDCTP will be a common European platform for clinical and intervention trials against HIV/AIDS, malaria, tuberculosis and other NIDs, coordinating national efforts and implementing joint/common additional activities EDCTP will have a governance and management structure in which the African coownership as well as the Africa-European partnership is fully embodied Contributions to EDCTP for research and capacity building by European PSs and African partner countries as well as third parties will be accounted for in a transparent system that guarantees compliance with cofunding rules and promotes alignment and integration of national programmes and activities. The specific objectives are: To accelerate research and development of new or improved diagnostics, drugs, microbicides and vaccines against HIV/AIDS, tuberculosis, malaria and NIDs To coordinate the European national programmes to work effectively in synergy and in mutual partnership with sub-saharan stakeholders to conduct relevant clinical trials for the development of the tools to fight HIV/AIDS, tuberculosis, malaria and NIDs To develop and strengthen the capacity for conducting clinical trials in sub-saharan Africa and in European PSs using best practice. The primary focus of EDCTP2 will be the support of phase II and III randomised controlled trials that add substantially to advancing the field in each area. In particular, multicentre multinational trials that are beyond the resources of a single funding agency will be given priority. Smaller trials, including phase I and small phase II, will be supported, where there is an absence of funding alternatives, and where the product under investigation has the potential to make an impact on the objectives of EDCTP2. Nevertheless, the core activities will focus on phase II and III clinical trials in sub-saharan Africa, including the development of research capacities to deliver these. There will, however, be an increasing investment in phase IV studies to ensure that products that have shown promise in phase III trials can be developed effectively for implementation within national or regional health strategies. Where it is necessary, collaborative research may be supported outside sub-saharan Africa. The successful implementation of EDCTP1 has led European PSs and the EC to conclude that a second EDCTP programme should be established for a longer period. This would demonstrate a 7

8 long-term commitment to tackling these diseases and ensure that there is sustainable investment within the countries that are most affected. The extended programme would allow partners to build on the experience of delivering trials in sub-saharan Africa and to extend the programme to the most neglected infectious diseases disproportionately affecting African countries. The programme of support for NIDs will develop over time as PSs countries align and integrate their national programmes and activities in this area. The activities of EDCTP2 will broadly fall into the following main categories: Promoting networking, coordination and alignment of national research programmes and activities Supporting clinical trials involving collaboration between European and African partners and other relevant stakeholders Fostering capacity development/strengthening in developing countries Assuring sustainable political, societal and financial support of the EDCTP programme Closer working with the pharmaceutical industry and other third parties to more effectively deliver the objectives of the programme. The current set of funding modalities will be applied further, adapted according to the lessons learned, or new ones will be designed which are more appropriate to novel needs and opportunities in order to implement the joint programme. These will fall into the following categories: Integrated Activities Participating States Initiated Activities (PSIA) Joint Activities The Integrated Activities will be administrated by the SEC using centrally managed funds from the EU and PSs and follow the applicable Horizon 2020 rules for participation. The PSIA will, on the other hand, include projects that are proposed by the PSs and brought to EDCTP for extra funding to add value and facilitate integration, whereas Joint Activities will involve working in partnership with third parties or other participating members, especially where such partnerships will facilitate consortium model of financing, such as for large and expensive phase III clinical trials. The EDCTP2-IS will be the legal entity for EDCTP and the recipient of the financial contribution from the EU. The legal entity is currently a European Economic Interest Group (EEIG), but plans are underway to change this to a new entity that will allow full membership participation of Associate and sub-saharan African countries. The EDCTP2-IS will be governed by the GA, in which all European PSs are represented. In addition to the European PSs, the African interests in EDCTP will be represented. In accordance with Article 185 of the Treaty, it will be up to the EU to decide on its adhesion or not to the EDCTP2-IS, to reflect its contribution to the programme. The statutes of the EDCTP-IS will be drafted to define the legal obligations of members, including membership criteria. It is expected that within the GA there will be one vote per participating country. The executive body of the EDCTP2-IS will be the SEC, which assures the day-to-day management and implementation of the programme and provides support to the other EDCTP bodies. The High Representative will operate as a member of the SEC, but with a diplomatic role to promote EDCTP2 at the highest level. The EDCTP scientific and strategic advisory body will be the Strategic Advisory Committee (SAC). The Chair and Vice chair(s) of the SAC will hold permanent, but non-voting seats on the GA. The SAC will prepare an annual Strategic Research Agenda (SRA). This SRA underpins and forms the basis for the Secretariat to propose the annual work programme of the following year to the GA for approval. The SAC will comprise representation from African and European scientists who are experts in the target diseases and delivery of clinical trials. Membership will include expertise in broader areas, such as health economics, planners and behavioural scientists to ensure a multidisciplinary approach to developing the SRA. The SAC may operate as a single forum and as specialist subgroups to develop strategy and to advise on 8

9 implementation plans. The SAC will be supported by the SEC and will report to the GA. The SAC will encompass the activities previously undertaken by the DCCC and the PB in EDCTP1. This new committee will provide a streamlined group that will ensure EDCTP2 develops its plans fully in the context of global activities, taking into account the dynamic state of product development pipelines, annual workplans, and African needs and priorities. The SAC will not be involved in peer-review in the project evaluation process, as each Call for Proposals will have its own specific external panel of evaluation. The role and operations of each body will be determined in the EDCTP2-IS statutes and Internal Regulations. The strategic planning and programming of EDCTP2 will be divided into three-year periods, each with specific objectives, deliverables and milestones. As a preliminary estimate, total funding would amount to 2 billion for , of which up to 1 billion may be contributed by the European PSs working in partnership with African PSs, non-pss and third parties such as industry, private sector, charities, philanthropic donors and Product Development Partnerships (PDPs). This is expected to be matched by an EU contribution of up to 1 billion. The operational and organisational planning will be prepared annually by the SEC in a workplan for the following year, on the basis of the recommendations of the SAC and the PSs upfront commitment for that year. Prior to approval by the GA, the annual workplans will be reviewed by an Independent Review Panel, which will comprise a range of broad-minded individuals external to EDCTP, with a remit to conduct a (non-scientific) review of the relevance of activities to the scope of EDCTP2 and of their added value to the programme. Prioritisation criteria for carrying out these activities will be based on the disease burden and need for appropriate interventions, available opportunities, and take into account the balance between immediate- and long-term activities. A balanced prioritisation of immediate- and long-term activities is necessary to ensure that the development pipeline remains robust and that a steady flow of products for clinical trials is maintained. Regarding the burden of disease and needs for instance in the case of HIV, the scaling up of treatment has expanded very rapidly and on an immense scale that it has now created a growing and urgent need for optimisation of HIV care. In contrast, HIV prevention has received less attention compared to the scale up in treatment and therefore requires immediate prioritisation. EDCTP will also take advantage of product development opportunities in respect to the expanded remit that will include NIDs and post registration programmes including effectiveness studies and pharmacovigilance. Based on the outputs of EDCTP1, the continuing support of EDCTP2 is expected to increase the number of clinical trials supported to at least 150, with a focus on large phase III trials to accelerate the development of new clinical interventions to fight HIV/AIDS, malaria, tuberculosis and NIDs. The intention is to evaluate 25 new or improved therapeutic approaches, 20 preventive approaches, five new or improved diagnostics and to contribute to the registration of up to five new products. The programme is expected to support up to 30 new European coordinated and integration initiatives and to support the training of over 600 African scientists, including Career and Senior Fellows, Masters and PhD students. 9

10 BACKGROUND EDCTP was the first and, under FP6, the only Article 185 Programme of the EU. This article of the Treaty on the Functioning of the European Union (TFEU) - previously Article 169 of the EC Treaty - enables the EU to participate in research programmes undertaken jointly by several PSs, including cofunding and participation in the structures created for the execution of the joint research programme. 8 The EU participation in EDCTP was approved in 2003 by codecision of the European Parliament and of the Council. 9 EDCTP was established in response to the global health crisis caused by HIV/AIDS, tuberculosis and malaria and aimed at establishing a "research and development programme for the development of new or improved clinical interventions to combat HIV/AIDS, tuberculosis and malaria through a long-term partnership between Europe and developing countries". It was to be part of a European accelerated and coordinated response to HIV/AIDS, tuberculosis and malaria in developing countries, involving the EC's Directorates for Research, Development and Trade. The specific objective was to integrate and cofund PSs' national programmes for clinical trials of new and improved products against these diseases, in collaboration with their African counterparts and like-minded organisations. All the MSs of the EU at that time, except Finland, co-founded EDCTP, i.e. Austria, Belgium, Denmark, France, Germany, Greece, Ireland, Italy, Luxembourg, the Netherlands, Portugal, Spain, Sweden, the United Kingdom, and Norway joined in. Given the uncharted territory, the EC played a major role in the start-up of the organisation. In 2005, Switzerland joined as an associated member. Over the past few years, consultations have taken place with the new EU MSs, the majority of which expressed scientific and political interest in joining EDCTP, including Latvia which has already joined as an observer. The first phase of EDCTP (EDCTP1) started on 15 December 2003 with a European Economic Interest Group (EDCTP-EEIG) 10 based in The Hague (Netherlands), as dedicated implementation structure. It is governed by a GA in which the PSs are legally represented by ministries, government agencies or institutions. Other EDCTP bodies include a SEC, as well as the former PB and DCCC. To enhance efficiency, the DCCC and PB have, since January 2013, been amalgamated to form an interim Strategic Advisory Committee (isac). The EDCTP-EEIG concluded a grant agreement with the EC for a maximum EU contribution of 200 million, to be matched by an equal amount of PS contributions to a "Joint Programme" over the lifetime of the project, initially 1 January December In 2006, the parties agreed to a no-cost extension for the ongoing programme until the 14 September 2010, which in 2010 was extended further to 14 May 2015, in order to allow for the conclusion of the EDCTP-funded activities with the phasing out of the corresponding EDCTP1 grant management and project review. The co-operation and networking of European national programmes and activities under EDCTP1 have resulted in: the launch of 88 clinical trials 11 ; training and support of more than 400 African scientists and medical doctors; launch of the first African Networks of Excellence for clinical trials 12 ; establishment and strengthening of National Regulatory Authorities and 8 "In implementing the multiannual framework programme, the Union may make provision, in agreement with the Participating States concerned, for participation in research and development programmes undertaken by several Member States, including participation in the structures created for the execution of those programmes." Article 185 of the Treaty on the Functioning of the European Union (TFEU). 9 Decision No 1209/2003/EC of the European Parliament and of the Council of 16 June 2003 on Community participation in a research and development programme aimed at developing new clinical interventions to combat HIV/AIDS, tuberculosis and malaria through a long-term partnership between Europe and developing countries, undertaken by several Member States (OJ L 169, , p. 1). 10 The EDCTP-EEIG was founded in 2003 on the basis of the Council Regulation (EEC) No. 2137/85 of 25 July 1985 on the European Economic Interest Grouping (EEIG) (OJ L 199, , p. 1). 11 See also EDCTP Annual Reports at 12 WANETAM The West AfricaNoE for TB, AIDS and Malaria (WANETAM) builds capacity to prepare West African sites for clinical trials on HIV, TB and malaria. The network started its activities on 31 July 2009 and is coordinated by Professor SouleymaneMboup. - EACCR The East Africa Consortium for Clinical Research (EACCR) strengthens clinical trial sites in Eastern Africa. The Network started 14 May 2009 and is coordinated by Dr Pontiano Kaleebu. - CANTAM In Central Africa, the Central African Network on TB, HIV/AIDS and 10

11 ethics review capacities in many African countries; establishment of the Pan-African Clinical Trials Registry 13 (PACTR) as an African initiative funded by EDCTP, which is now officially recognised as a WHO Primary Clinical Trials Registry; and approval of an antiretroviral formulation (Pedimune) for treatment of HIV in children in Africa. More broadly, EDCTP activities have contributed to the development of capacity and infrastructure which have enabled clinical trials to be conducted in sub-saharan African countries in accordance with internationally recognised standards and in partnership with both European individual researchers and institutions. In addition to contributing to product registration and new treatment guidelines, these trials have also contributed through the generation of information and publications to inform future research and healthcare. That notwithstanding, PRDs continue to weaken health systems and affect societies across sub-saharan Africa, and European research policies and activities remain weakened by fragmentation and inefficiencies. EU funding of a new EDCTP programme (EDCTP2) requires a decision of the European Parliament and the Council. 14 Continuation has been recommended by an Independent Expert Evaluation 15 and the draft Impact Assessment, which included a public consultation 16. The assessments point to an innovative and strong partnership with Africa and a greatly improved programme over the years, with remaining challenges regarding full integration of PSs programmes and transparent cofunding. Based on the conclusions from a PSs meeting in September , the Belgian EU Council Presidency proposed to the Competitiveness Council on 26 November 2010 the launch of the second phase of EDCTP under Article 185 with duration of at least ten years. malaria (CANTAM) joins institutions involved in clinical trials. The Network started its activities on 19 December 2008 and is coordinated by Dr Francine Ntoumi. - TESA The Trials of Excellence for Southern Africa (TESA) Network focuses on the Southern African region. It started on 23 November 2009 and is coordinated by Dr Alexander Pym In particular Articles , 185 and 188 of the Treaty on the Functioning of the European Union (TFEU). 15 Independent External Evaluation Report of the EDCTP ( ), EDCTP1EE Panel chaired by Wim Van Velzen, see also Independent External Review Report of the European and Developing Countries Clinical Trials Partnership ( ) 16 Public consultation regarding a future proposal for a new European & Developing Countries Clinical Trials Partnership (EDCTP), 17 Consensus meeting on a proposal for a second phase of the European & Developing Countries Clinical Trial Partnership (EDCTP), 11

12 CURRENT CONTEXT AND CHALLENGES AHEAD Common European Research Platform for Clinical Research on PRDs in Developing Countries Since its inception in 2000, the European Research Area (ERA) 18 has been the guiding vision for shaping EU policy on research and innovation and for driving activities to this end, in particular that "the European research area should be an area where the scientific capacity and material resources in Participating States can be put to best use and where national and European policies can be implemented more coherently". 19 Health research played a major and pioneering role in the design and experimentation of joint programming approaches since then. The multi-annual framework programmes 20,21 and other legal provisions in the EU treaty were used and tested to structure and integrate European health research capacities and activities in specific fields, such as the EDCTP based on Art 185 (Ex Art. 169, 2003), the Joint Technology Initiative IMI (Innovative Medicines Initiative) based on Art 187 (2007), the Joint Programming Initiative on Neurodegenerative Diseases and other life science topics based on Art 181 (2010), the Pilot European Innovation Partnership on Active and Healthy Ageing (2011), and the many ERA-NET and ERA-NET Plus projects that were initiated under FP6 and FP7 by PSs research and funding organisations since Today, the joint programming approach is the EU's key strategy to consolidate and restructure its fragmented research systems and make the most of its resources and competencies. Before the first EDCTP programme was established, many EU PSs and their partners in the developing countries were already engaged in substantial collaborative research activities in this field. Unfortunately, these programmes were often fragmented and uncoordinated. Many of these programmes were also underfunded and lacked capacity in the field. New and specific requirements, such as the need for multicentre protocols, a demanding regulatory environment and universal ethical standards are additional reasons why a well-coordinated, intensified effort in a genuine and innovative partnership with the developing countries was needed. The EDCTP programme has had a significant impact in this area by funding integrated clinical trials that brought together researchers and funding from a number of European and African countries, with as many as seven European PSs contributing funds to a single project. EDCTP2 will build on the successful work of EDCTP1 to further develop and expand this integration of European national research programmes and to complement the activities specifically funded through EDCTP projects. In recognition of the EU's significant, but still fragmented research efforts on PRDs and the lack of adequate resources and capacities to conduct clinical trials in developing countries, particularly in sub-saharan Africa, EDCTP was launched to combat HIV/AIDS, tuberculosis and malaria by aligning and integrating national efforts and establishing a genuine partnership with African partner countries. However, the PSs' national activities, funding streams and research systems for clinical research on PRDs (in the scope of EDCTP) present a very heterogeneous picture, which prevents the design of a simple one-size-fits-all strategy to reduce fragmentation and maximise the efficiency and effectiveness of Europe's capacities, competences and investments in this field. Also the Independent Evaluation Expert Group highlighted this drawback and realised that: "Some countries (e.g. Germany, Switzerland, etc.) have projects, but not a national programme related to the three diseases targeted by EDCTP. Other countries namely Belgium, France, the U.K. have one or several national programmes. However, countries like Germany and Switzerland perceive EDCTP's integration efforts as positive because it provides an international platform for their research institutes. On the other hand, Member States with national programmes report integration difficulties because their research institutes act independently and define their own research agenda and priorities" Commission Green Paper "From Challenges to Opportunities: Towards a Common Strategic Framework for EU Research and Innovation funding", , COM(2011)48 19 Commission Communication "Towards a European Research Area", COM(2000) 6 final, January FP6 decision: 21 FP7 decision: 22 Mapping ERA-NETs across Europe: overview of the ERA-NET scheme and its results, European Commission, Independent External Evaluation Panel Report on EDCTP, Brussels 2009: 12

13 Mapping of national programmes, activities and actors, such as publicly-funded institutions, projects and researchers addressing clinical research on PRDs in developing countries, particularly in sub-saharan Africa, will be performed before the start of the EDCTP2 programme. Based on this, a structured approach will be developed and tailor-made joint programming measures and tools addressing the commonalities of the different countries' research activities, funding streams and actors will be determined under the common umbrella of the EDCTP Joint Programme and strategy. Prior to EDCTP there was a risk of new tools for the prevention and treatment of infectious diseases being stuck in the development pipeline. This is because restricted market opportunities have reduced the incentives for the pharmaceutical industry to undertake the necessary investment risks on its own. There is a lack of private investment; local capacity in developing countries; and suitable patients in Europe. Developing new drugs, vaccines or microbicides is costly with the major proportion of the costs being associated with clinical trials. Undertaking these clinical trials in a reasonable timeframe and for a reasonable budget is only possible with access to a sufficient number of patients, hence the need for these to be undertaken in disease endemic regions. The only economical way to undertake such trials is by establishing local capacity to perform them locally. Efficient development of new interventions can only happen if EDCTP2 is given the flexibility to take forward products as and when they are available for trialling. The rate of advancement of any new product along its critical development path is difficult to predict. To ensure success, EDCTP2 will require flexibility to respond to emerging opportunities around new products. It will therefore not set out a rigid plan for Calls for Proposals in advance, but develop a strategically informed itinerary at intervals throughout the programme. A common European Research platform in matters of global health should by definition engage all MSs. The inclusion of new EU MSs in EDCTP2 is vital for its political cohesion and scientific power, particularly since several of them have considerable experience especially with the clinical management of HIV and tuberculosis. Preliminary consultations with newer MSs have indicated substantial scientific and political interest. EDCTP is now indeed one of the most visible global health research initiatives emanating from Europe: a vital element of its research programme for PRDs and one of its strongest instruments for fostering cooperation with Africa. The partnership model of EDCTP could be extended progressively to broader clinical and intervention research on a wider range of PRDs. The Global Health Case Every year, infectious diseases are responsible for the deaths of 9.5 million people and the loss of 302 million disability adjusted life years. 24 The vast majority of the deaths occur in developing countries, in particular Africa where the burden of infectious disease is highest and exceeds that of non-communicable diseases. Furthermore, the most common infectious diseases, including HIV and tuberculosis, predominantly affect young and middle-aged adults in the prime of life while other big killers such as malaria, pneumonia and diarrhoeal diseases cause a very high death toll among children. As a consequence, infectious diseases are the major cause of poverty among African people. Not only does Africa have the highest burden of infectious diseases, it also has the weakest health systems. The continent lacks the infrastructure to deliver known preventive and therapeutic interventions effectively. Africa also has limited research capacity and has the lowest continental research output, lower than most individual countries in Western Europe. 25 Consequently the evidence-base on new cost-effective clinical interventions and health service strategy, for example on how to optimise the delivery of existing interventions is limited. We have long known that evidence-based health policy saves costs for the health services; thus the low level of research in Africa ultimately results in higher health care costs for a setting 24 WHO.(2008). Deaths and DALYs Retrieved May 4, 2011, from Adams, J et al. (2010, April). Global Research Report: Africa. Retrieved May 4, 2011, from Thomson Reuters Evidence: 13

14 that has the least sources. The end result is a vicious cycle: ill health leads to poverty; poverty leads to ill health. HIV/AIDS 26 A total of 33 million people were living with HIV-infection globally in Africa is the least populous continent and has by far the highest burden a staggering 23 million people (or 1 in 20 of the adult population) are living with HIV-infection. The burden is highest in East and Southern Africa, where about 6 and 20% of adults respectively, are living with HIV-infection. In several countries, including South Africa, Nigeria, Malawi, Zambia, and Swaziland, life expectancy has fallen below 50 years as a direct consequence of HIV/AIDS. HIV/AIDS predominately affects young and middle aged adults in the prime of their working lives. Thus, the infection has had a devastating social and economic impact in Africa, driving countries into deeper poverty and deeper hardship. HIV incidence peaked in 1997 and recently there have been reported declines in several settings in East and Southern Africa including in South Africa, Zimbabwe and Zambia. This has led to complacency about the severity of the epidemic and optimism about its future course. The incidence, however, has fallen only marginally since Last year 1.3 million people were newly infected in Africa accounting for 50% of the 2.6 million global new cases. A major impediment to the future success of antiretroviral programmes will be this staggering year-onyear escalation in the number needing treatment. Although there are currently around 4 million HIV-infected people on antiretroviral therapy (ART) in Africa, these represent only 37% of patients in need of therapy. It is however, unclear how improved access to ART will increase much above this current level of uptake. Also unclear and requiring research is how African health services can sustain the delivery of chronic care optimally to such large numbers bearing in mind the prevailing constraints in infrastructure. Research is also needed in Africa on the efficacy of locally appropriate therapeutic interventions including better paediatric management of HIV, prevention of mother to child transmission, and management of co-morbidities, in particular hypertension, diabetes, tuberculosis and malaria and with other infectious diseases. HIV has also led to a huge rise in tuberculosis (people living with HIV have a 10% per year risk of developing tuberculosis compared to a 10% lifetime risk in those who are HIV negative). 27 Furthermore, a link has also been shown between HIV and malaria. Thus, HIV has both a direct and indirect effect on families and populations and on health services. Preventing HIV transmission therefore remains a very high priority. Male circumcision, HIV voluntary counselling and male condom use are the main interventions used in controlling the infection, but their coverage is low and in the case of male circumcision, the effectiveness of the intervention outside of the clinical trial setting is unclear. A newer generation of microbicide (containing an antiretroviral drug tenofovir) has been shown to be around 40% effective in one trial conducted in South Africa, but recent results have been disappointing and further evidence is needed before this product can be considered for registration. 28 How effective this intervention will be in the real world is unclear. What is clear is that more research is needed on microbicide agents and ultimately we need a vaccine although that seems a long way off. Malaria Sub-Saharan Africa continues to be plagued by malaria, despite some success in reducing infection rates in countries such as Ethiopia, Kenya and The Gambia. The reasons behind these pockets of success or whether they will be sustained are unclear, but they have led some to ponder the possibility of malaria elimination and possibly eventual eradication. 26 UNAIDS. (2010). Global report: UNAIDS report on the global AIDS epidemic Geneva: WHO 27 WHO.(2010). Global tuberculosis control. Geneva: WHO. 28 Quarraisha K, et al. (2010). Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the Prevention of HIV Infection in Women. Science, 329, 1168 and 14

15 Accurate estimates of the current clinical and cost burden of malaria are difficult to make due to the variation in methods used to diagnose malaria and to the variability of the available data. Many cases of malaria are defined based on fever, which lacks specificity; many do not present to health services and national reporting of deaths is variable and often incomplete; there are poor data on absenteeism and it is difficult to capture risk mitigation strategies that households may take. The WHO estimates that there were 225 million malaria cases (defined as fever probably due to malaria) globally in 2009, though this number is probably an underestimate. 78% of these were in Africa. WHO has estimated that globally malaria directly caused 863,000 deaths in 2008 and 781,000 in About 90% of these deaths were estimated to have occurred in Africa and 85% were among children below five years of age. 29 In Africa, the cost to the health service due to malaria is large despite many cases not seeking care. The African Leaders Malaria Alliance estimated that malaria costs the African continent approximately $12 billion a year. 30 WHO estimates that malaria accounts for 25 35% of all outpatient visits, 20 45% of hospital admissions and 15 35% of hospital deaths in endemic African countries each year. The financial burden on households is enormous since, in malaria endemic countries, many households have multiple episodes of malaria each year. 31 Widespread resistance to the most common antimalarial drugs is a major challenge. There are already reports of emergence of resistant malarial parasites to recently introduced combination therapies which include artemisinin. The effectiveness of insecticides is also waning with increasing resistance. Thus, there is also a need to develop new interventions for malaria control and to contribute to research towards malaria elimination efforts. Malaria genome mapping has raised hopes that effective vaccines will be forthcoming but it may be many years before products are available assuming that there will be resources to distribute them amongst the most at risk populations. EDCTP1 has supported two major phase II clinical trials of candidate malaria vaccines and has enhanced capacity to conduct such trials. There is a need to build on these investments and efforts. Tuberculosis Tuberculosis is a disease of poverty that affects mostly young adults in their most productive years. In 2009 there were around 9.4 million TB cases and 1.7 million deaths globally. In 2009 there were 2.8 million TB cases and nearly a half a million deaths in Africa. These rates of tuberculosis cases and death are higher in Africa than in any other continent. HIV has a major detrimental impact on TB control. About 15% of TB cases occur in HIVpositive individuals and tuberculosis is the leading cause of death among people with HIV. However, despite this association only about 50% of TB-infected patients are tested for HIVinfection in Africa and reciprocally less than 50% of HIV-infected subjects are tested for tuberculosis. Among those who agree testing, diagnosis of TB among HIV-infected subjects lacks accuracy. This calls for improved diagnostic tools preferably at the point of care. Multi-drug resistant tuberculosis (MDR-TB) is particularly difficult and expensive to treat and has a high case-fatality rate. In 2008, there were 440,000 new cases of MDR-TB and 150,000 deaths. In 2010, over 3% of new TB cases were MDR-TB and in some settings 1 in 4 of new cases were MDR-TB. Fifty eight countries (5.4% of all MDR-TB) have reported extensively drug resistance (XDR-TB), where resistance occurs in second-line drugs and which can take two or more years to treat and has a particularly high case-fatality rate. The incidence of XDR-TB is thought to be a staggering 25,000 cases a year. Research is urgently needed to identify more effective treatment regimens for tuberculosis, particularly shorter course and simpler regimens as well as more sensitive and specific TB diagnostics in both HIV and non-hiv-infected patients. It is also important to determine how these interventions should be delivered to communities to maximise the detection of TB and 29 WHO.(2010). World Malaria Report. Geneva: WHO. 30 ALMA. About Malaria. Retrieved May 4, 2011, from African Leaders Malaria Alliance: 31 WHO.(2010). World Malaria Report. Geneva: WHO. 15

16 increase the effectiveness of treatment. Moreover, top priority should also be given to research to find a more effective vaccine against tuberculosis than the one in current use. 32 NIDs NIDs (also known as Tropical Neglected Diseases or Neglected Infections of Poverty) have normally received low priority in national and international health agendas. Together they are responsible for a significant, though hidden and often silent suffering, with an estimated 1.2 billion people affected and 500,000 deaths occurring each year. However, the greatest impact of NIDs is the severe physical disability that is inflicted, resulting in 57 million disability adjusted life years. NIDs include onchocerciasis and trachoma, which are major causes of blindness; leprosy and lymphatic filariasis causing deformities that hinder economic productivity and prevent normal social life; Buruli ulcer, which may lead to amputations; human African trypanosomiasis (sleeping sickness), which severely debilitates and almost invariably leads to death when untreated; rabies which is always fatal; leishmaniasis, which causes deformities and in its most severe form, attacks internal organs and is rapidly fatal if untreated; schistosomiasis, which contributes to poor school attendance, malnutrition and impaired cognitive development of children; guinea-worm disease causing debilitating pain sometimes for extended periods and often coinciding with the peak agricultural season; and dengue, a leading cause of hospital admissions in several countries. This is far from being an exhaustive list of NIDs, but it includes some of the most common diseases that contribute to their heavy burden, especially in sub-saharan Africa. 33 Political context, challenges and choices The international health landscape has changed considerably since the initiation of EDCTP. Research and aid budgets for international health development have increased substantially, although are still inadequate to meet all needs, and may come under new strain from the current financial crisis. Many Global Health Initiatives and Public Private Partnerships (PPPs) are active in or related to the field of the EDCTP scope. 34 In recent years, emerging economies such as China, Brazil, India and others are also claiming an important role in global health in terms of aid, research and trade. The EU is arguably the largest donor and strongest player in international health aid and research, but due to fragmentation, its visibility is not proportional and still compromises its influence and impact. Over the past years, a number of policy statements and collaborative agreements have laid the foundation for a stronger position of the EU. Recently, the Commission Communication 35 and Council Conclusions 36 on the Role of Europe in Global Health (2010) have established a conceptual framework, with emphasis on strengthening national health systems, maternal health and the continued fight against HIV/AIDS, tuberculosis and malaria. The 2007 EU Programme for Action 37 and its 2009 Progress Report highlighted the key role of EDCTP1 in its own right and as a catalyst model for other programmes aiming at coordinated international collaboration. EDCTP1 is now one of the most visible global health initiatives emanating from Europe, a vital element of its research programme for PRDs, and one of its strongest instruments for fostering cooperation with Africa. 38 Regarding aid policies, EDCTP1 is one of the few international research initiatives that explicitly pursues the principles of the Declaration of Paris on Aid Effectiveness (2005) and the Accra 32 WHO.(2010). Global tuberculosis control. Geneva: WHO. 33 Hotez, P et al. (2007). Control of neglected tropical diseases. N Engl J Med, 357, WHO Special Programme for Research and Training in Tropical Diseases (TDR); African Network for Drug and Diagnostics innovation (ANDi); Bill and Melinda Gates Foundation (BMGF); Foundation for Innovative Diagnostics (FIND); Drugs for Neglected Diseases initiative (DNDi); Global Fund to fight AIDS, Malaria and Tuberculosis (GFAMT); Medicines for Malaria Venture (MMV); International Aids Vaccine Initiative (IAVI); Global Alliance for TB Drug Development (TB-Alliance); Global TB Vaccine Foundation (AERAS). 35 Commission communication on "The EU Role in Global Health", COM(2010)128 final, Council conclusions on "The EU role in Global Health", 3011 th Foreign Affairs Council meeting, May Commission Communication "A European Programme for Action to Confront HIV/AIDS, Malaria and Tuberculosis through External Action" ( ), COM(2005) 179 final. 38 EU conference on poverty-related diseases research, Lancet Infectious Diseases 2009, 9:

17 Agenda for Action (2008) 39, by fostering country ownership and integrating donor programmes. These OECD principles are at the very heart of EU's international partnerships, especially with Africa. Several recent policy declarations, programmes and reports highlight the key role of EDCTP as an effective model for other programmes aiming at coordinated international collaboration. The Africa-EU Strategic Partnership, emanating from the 2007 Lisbon Declaration 40 and reemphasised in the Europe 2020 Strategy 41, identifies EDCTP as an important actor in its first Action Plan for Implementation 42 especially, in the Eight Partnerships on Science, Information Society and Space. In order to maintain the European effectiveness, visibility and coherence in international health research, there can be no reservation about the consolidation of EDCTP, or continued support from PSs and the EC. In addition, its partnership model could in the long term be extended to broader clinical and intervention research to all poverty-related infectious diseases. EDCTP can evolve to a common platform for conducting clinical trials contributing to a ERA, as envisaged for EU's international science and technology cooperation programmes 43. In September 2010, the United Nations took stock of the MDGs, with five years to go until the 2015 deadline. In terms of health (MDG 4, 5, 6), important but uneven progress has been made. In sub-saharan Africa, enormous challenges are still to be overcome including the fight against HIV/AIDS, tuberculosis and malaria. Therefore, the current geographic focus of EDCTP still reflects the greatest urgency. Sub-Saharan Africa also remains in great need of capacity strengthening for clinical research and regulatory mechanisms. A geographical extension to other continents would be of great interest, but would require a different political framework and considerable resources. Apart from weak health delivery systems and inadequate prevention, major hurdles in the fight against HIV/AIDS, tuberculosis and malaria remain the lack of affordable, efficacious and safe drugs. Not only new compounds, but also simpler formulations such as single-dose and/or fixed combination therapies are greatly needed to increase efficacy, lower the burden on health systems and avoid the emergency of resistant strains. Significant progress has been made in the development of vaccines and microbicides, but preventive trials - especially Phase III - require enormous investments, capacity and tenacity. Improved case detection is crucial for the rational use of drugs; an extension of EDCTP to diagnostics would therefore be highly consistent with its mission and expertise. In the past years, the international community has woken up again to the fact that functional health systems are key to the efficiency and sustainability of disease control. The social, economic and qualitative disciplines of health systems research are not within EDCTP's scope. However, within its product-oriented objectives and competencies, it can extend its portfolio to operational research on delivery and uptake of medical products, including post-marketing (phase IV) trials and collection of safety data that may inform pharmacovigilance and controlled community-based interventions. This extension would increase the direct relevance of EDCTP for health services and development agencies, as highlighted in the conference "Connecting the Chain-II" held in June African health services have to deal not only with HIV/AIDS, tuberculosis and malaria, but also with many other NIDs for which no adequate diagnostics, drugs or vaccines are available, such as sleeping sickness, leishmaniasis, helminths, leprosy and Buruli ulcer. Comorbidities are the rule rather than the exception. The capacities needed for clinical research on NIDs are similar to those for HIV/AIDS, tuberculosis and malaria. An extension of EDCTP to NIDs will boost its relevance, efficiency and credibility. Moreover, it would broaden substantially the opportunities for collaboration and cofunding. 39 The Paris Declaration on Aid Effectiveness and the Accra Agenda for Action, OECD 2005 and Lisbon Declaration EU-Africa Summit, December Commission Communication "Europe 2020: A strategy for smart, sustainable inclusive growth", March 2010 COM(2010) 2020 final. 42 First Action Plan ( ) for the Implementation of the Africa-EU Strategic Partnership, September 2007, 43 Commission Communication "A Strategic European Framework for International Science and Technology Cooperation", COM (2008)588, and the subsequent Council Conclusions. 17

18 GOAL, SCOPE AND OBJECTIVES EDCTP2 will provide a push and pull mechanism to facilitate new or improved tools for PRDs along the development pipeline from phase I to IV. This will facilitate their optimal development and deployment in developing countries. This is important since experience has shown that without such a purpose driven and target oriented mechanism, these products stagnate in the pipeline due to lack of commercial interest and motivation from the private sector. Furthermore, experiences from EDCTP1 have shown that in the mainstream of drug development, various special groups such as pregnant women, malnourished children or people living with HIV/AIDS and other underlying diseases are generally left out of clinical trials. EDCTP has funded several clinical trials that included these groups, which have generated safety information that will allow label expansion of drugs to include such groups. EDCTP2 will also continue to fund clinical trials that explore improvements of tools and regimens in current use. This is important because quite often regimes in use are not optimised for efficacy, tolerability and ease of use in resource-limited settings. Moreover, there is a great paucity of tailor-made products that proactively target these groups of populations (children, people living with HIV/AIDS and those living with HIV/AIDS-TB co-infection) that are disproportionately represented in sub-saharan Africa. This disparity and inequity in the availability of appropriate treatments can only be addressed by programmes such as EDCTP. By coordinating the national programmes of the PSs through a common EDCTP scientific administration and funding, PSs will cooperatively work with their sub-saharan African counterparts, in collaboration with like-minded organisations, to launch more than 200 projects during the lifespan of the EDCTP2. Among these will include 150 new clinical trials. During the ten-year period more than 600 African scientists will be trained in relevant areas within the scope of EDCTP. These will include Senior Fellows and Postdoctoral scientists, as well as Masters and PhD students, in various fields such as epidemiology, data management, parasitology, immunology, molecular biology and related disciplines. In preparation for EDCTP2, EDCTP has signed a Memorandum of Understanding with the European Federation of Pharmaceutical Industries and Associations (EFPIA), with the aim to establish a new EDCTP- EFPIA fellowship scheme providing training for between 6-10 clinical research fellows annually in European based pharmaceutical companies research centres. Opportunities to send or second European researchers from pharmaceutical companies to train for brief periods with African researchers in African research institutions and other relevant settings will be explored. EDCTP by 2020 Towards a common platform for clinical research and intervention trials Lessons learnt from EDCTP1 Prior to the inception of EDCTP, each of the European PSs in the programme had their own approach and guidelines in relation to PRDs and collaboration with sub-saharan African countries. Many of these countries also did not have national programmes and had limited activities, particularly regarding clinical trials on these diseases. Moreover, where such programmes or activities were present there were limited mechanisms for cross-border funding within Europe and as such each country undertook these activities as a bilateral agreement rather than in partnerships with other European MSs. This landscape contributed to EDCTP s initial challenges. Thus, although EDCTP developed a common scientific agenda and priorities together with a common administrative structure and processes through the SEC, the cofunding mechanism was disjointed at times. Some members had restrictions in the use of their funds as stipulated by national financial guidelines and, for instance, could not fund researchers from other countries. Furthermore, some countries also required a national review of applications in addition to that conducted by the SEC. These challenges have generally been surmounted and now most PSs accept a single review either via the SEC or, in the case of Member State Initiated (MSI) projects, through a lead country. During the course of the current EDCTP programme, some PSs have improved the cofunding mechanisms to the projects by the adoption of a two-track system that combines a virtual and a true common pot; the virtual through a restricted mechanism for example to particular groups of researchers and the true through an open mechanism accessible to all researchers participating in a project. Following these difficulties all PSs have agreed that for 18

19 EDCTP2 there will be both a common review mechanism and all the cofunding will be upfront. Upfront commitments will be made annually and set out in the annual workplan. The setting up of a common scientific strategy, peer review, single research administration and funding in EDCTP2, will go a long way towards achieving the goal of completion of the ERA. Through EDCTP, PSs have secured a common platform for conducting joint activities on clinical trials. This includes capacity building, networking and the actual undertaking of the trials. Working in partnership with EU PSs and with other partners, EDCTP has managed to broker and leverage for additional resources including funding, expertise and services. This has led to an increase in the number of PSs working in EDCTP projects, which on average comprise 3-4 European countries working in collaboration with 3 sub-saharan African counterparts per project, and in some cases exceed 6 European countries working with 4 African countries. The successes of the partnership motivated the aim of bringing together ongoing similar projects in which European Participating States were working independently with a sub-saharan African partner or partners where there was clear indication that joining such projects would add value to the network. This was the basis of the EDCTP MSI funding scheme. Under this scheme, European PSs were required to produce at least 75% of the budget. This concept was advanced in another funding scheme referred to as Joint Call by Member States, whereby PSs fully fund the calls in an area of mutual interest without any funding coming from EC. Although these partnerships have been largely successful and have resulted in 88 clinical trials, some of which will be moving to phase III, the funding has been on a project-by-project basis. In general, partners - including industry - have tended to join in the cofunding once projects had been selected through competition. This mechanism of project selection and then subsequent funding is not always a suitable approach with industry and where larger and more expensive trials that may require brokering and leverage of funds from other partners. The experience of EDCTP1 demonstrated that this approach is feasible and desirable where appropriate, as in the case of the Pan-African Consortium for the Evaluation of Anti- Tuberculosis Antibiotics (PanACEA) consortium, which aims to shorten and simplify tuberculosis treatment. PanACEA, which is funded by EDCTP member countries (including sub-saharan African countries and the EC), BMGF, Sequella (a pharmaceutical company) and TB Global Alliance (a PDP), comprises three networks involving 22 institutions; 11 in Africa, 10 in Europe and 1 in USA. 44 This experience suggests that funding in EDCTP2 should be flexible in order to accommodate such novel approaches to pressing clinical questions as well as the demands of larger phase III trials, which may require multi-partner funding to meet the resource requirements. Therefore EDCTP, as well as providing added European value in channelling common efforts to tackle the societal challenges of poverty related diseases, also provides a cost-effective mechanism where member countries may work with other stakeholders to share risks and benefits. The value of this mechanism is clearly pronounced with regards to the resource intensive pivotal phase III clinical trials. Finally, in terms of operational challenges, a number of factors can result in delays in clinical trials. This is particularly pronounced in developing countries where multiple factors such as lack of capacity among the clinical trial personnel, inadequate infrastructure including for ethical and regulatory review, and logistic challenges in the shipment of investigational products and samples may come into play. This requires that these factors be taken into consideration in planning to ensure sufficient time to allow completion of such projects. Together with the need for appropriate capacity development, this necessitates a long-term approach to the programme. This was clearly demonstrated in EDCTP1 and hence the need for longer timelines in EDCTP2. Clinical research for better drugs and vaccines remains crucial to strengthen and sustain the achievements already made in the fight against HIV/AIDS, tuberculosis and malaria. Moreover, extending EDCTP's remit to diagnostics, health services/optimisation research and NIDs, and expansion of its membership to new European MSs, provides great opportunities to increase its impact, efficiency and visibility. EDCTP2 will not be merely a continuation of EDCTP1, but will 44 Burkhi, T. (2012).PanACEA: a new approach to tuberculosis research. Lancet Infect Dis Mar;12(3):

20 have a bold ambition to create a broad, open and robust European research platform for clinical and operational trials against HIV/AIDS, tuberculosis, malaria and other NIDs. Therefore, the guiding vision for EDCTP2 shall be: By 2020, EDCTP will be an open and collaborative European research platform for clinical and intervention trials against HIV/AIDS, malaria, tuberculosis and NIDs. EDCTP would thus unite all "midstream" research by EU members and African partners against HIV/AIDS, malaria, tuberculosis and NIDs. It would encompass clinical trials of new or improved drug regimens, vaccines and diagnostics, as well as research on the application of these products in health services and disease control programmes. The evolution from EDCTP1 to EDCTP2 will follow a progressive, stepwise approach with clear commitments, responsibilities, timelines and deliverables in a transparent and realistic logical framework. The co-decision would be taken for the full period and budget of EDCTP2 ( ). However, the work programme would be divided over terms of three or four years, each with specific objectives and targets and a strategic and action plan. Progress will be monitored on a six-monthly basis and evaluated at the end of each term, (re)defining the logical framework and (co)funding provisions for the next term. 20