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

21 Goal The overall aim of EDCTP2 will remain focused on reducing the burden of PRDs and improving the health of people in developing countries by making the most of Europe's research potential and national investments in this field. This shall be achieved by accelerating the development of new clinical interventions to diagnose and fight HIV/AIDS, tuberculosis, malaria and other NIDs through cooperative clinical research as well as by providing a critical mass of resources through a more efficient and effective use of European research capacities. This will be done through networking and integration of European national programmes and investments and by maintaining and reinforcing the partnership with sub-saharan Africa and like-minded organisations. EDCTP2 will strengthen capacity to undertake research in those countries most affected by these diseases. It will bring together stakeholders from Europe, other parts of the world and sub-saharan Africa to identify the state of product development worldwide and to ensure the timely implementation of clinical trials on key products. The programme will require flexibility to respond to a constantly changing pipeline and landscape of potential interventions and to ensure that the activities contribute effectively to global efforts to control infectious diseases. This is an ambitious undertaking, which cannot be delivered through a series of centrally managed research calls alone, but must build on the work that is already being carried out at national level. By joining EDCTP2, PSs are committing themselves to its vision of aligning and coordinating their national programmes to better achieve the objectives of the partnership. To achieve this, EDCTP2 will be established on the basis of Article 185 of the Treaty on the Functioning of the European Union (TFEU). Scope The EDCTP1 programme has created a very important niche in research and development of new or improved tools in combating PRDs. Because of the programme, there are several developments in this field that are taking place that would have not happened if EDCTP was not present. These include: Encouraging PSs to work in a joint programme with a centralised evaluation, administration and funding of research and development to combat disease in sub- Saharan Africa Creating a pull and push mechanism to move along the development pipeline the generally neglected intervention products for fighting PRD Conducting clinical trials to establish safety and efficacy of medicinal products among special groups such as pregnant mothers, infants, malnourished children and HIV infected individuals Evaluation of special formulations or treatments such as fixed drug combinations for children with HIV/AIDS or individuals with HIV/AIDS and tuberculosis co-infections Simplification of treatment regimens of registered drugs such as for severe malaria in children and tuberculosis Exploration of new regimens to replace failing treatment modalities due to the emergence of resistant organisms. Following an extensive consultative process on the future strategy for EDCTP, involving all stakeholders, the following has been agreed on EDCTP2: The programme will continue to focus on the clinical development of new products for treatment and prevention (i.e. diagnostics, drugs, vaccines, and microbicides) for the three target diseases identified in EDCTP1 (HIV/AIDS, tuberculosis and malaria), but expand to include NIDs Priority should continue to be on sub-saharan Africa, where the needs are greatest and most urgent, but collaboration with other developing countries will exceptionally be allowed when such collaboration is the best way to deliver the objectives of EDCTP2 All stages of clinical trials shall be included, from phase I to IV, though the main focus will be on phase II and III clinical trials Research will include implementation research on optimisation of health services. 21

22 Objectives The main objective of EDCTP2 will be to accelerate the development of new or improved tools (drugs, microbicides, diagnostics and vaccines) against PRDs (HIV/AIDS, tuberculosis, malaria and NIDs) in partnership with sub-saharan Africa, by provision of a critical mass of resources to support clinical trials, including a more efficient and effective use of Europe's research capacities and the networking and integration of European national programmes and investments. 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 platform for clinical and intervention trials (including diagnostics and health service delivery) against HIV/AIDS, tuberculosis, malaria and other NIDs EDCTP will have a governance and management structure in which the African coownership and the Africa-European partnership is fully embodied Contributions to EDCTP for research and capacity building by European and African partner countries as well as third parties will be accounted for in a transparent system that guarantees compliance with cofunding rules and promotion of integration of national programmes. Specific objectives: 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 effectively work in synergy and in mutual partnership with sub-saharan African stakeholders in conducting relevant clinical trials for the development of the tools to fight HIV/AIDS, tuberculosis, malaria and NIDs To develop and strengthen the capacities in sub-saharan Africa to ensure that the relevant clinical trials are conducted using best practice To develop closer partnerships with the pharmaceutical industry and other third parties to more effectively deliver the objectives of the programme. The primary focus of EDCTP2 will be to support phase II and III randomised controlled trials that add substantially to moving forward the field in the respective area. Priority will particularly be given to multicentre trials that are beyond the resource of a single funding agency, but smaller trials including phase I and small phase II will be supported where these provide development of products that are not being funded from elsewhere, but have potential to make an impact on the goals of EDCTP2. The core activities will focus on phase II and III clinical trials in sub-saharan Africa and the development of research capacity 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 effectively developed for implementation within national or regional health strategies. When necessary, research may be supported outside sub-saharan Africa through collaboration. Common Approaches (joint programming) The application of Article 185 implies a national (European) commitment by each European PS to mobilise their publicly funded organisations active in the field of the EDCTP to maintain the levels of support to this field at minimally equal levels throughout the programme and to provide an annual up-front minimum funding commitment over its lifetime. Membership criteria will be specified in the EDCTP2-IS statutes. This will enable EDCTP to facilitate coordination of the European PSs national programmes to carry out essential research and competence building programmes, and to gain from the diverse and complementary aspects covered by the programmes. This will include Integrated Activities, PSIA and Joint Activities. Integrated Activities These activities will be administered and funded by the EDCTP-IS from the cash contributions of the PSs, EU and other partners. EU contribution shall be allocated primarily to these 22

23 activities and the Horizon 2020 Rules of Participation shall apply with the applicable derogation. Participating States Initiated Activities (PSIA) These activities will include ones that are selected, funded and managed by the PSs. They will require being approved and included in the EDCTP annual workplans with the agreement of the EU. The aim of EU cofunding to such activities will be to increase impact or expand access to researchers from other PSs. PSs Rules of Participation will apply, with a minimal set of rules provided by the EC/EDCTP. Joint Activities These will be activities that are undertaken by EDCTP-IS or any PS together with other countries or third parties. This scheme will be desirable, for instance, in the case of an expensive undertaking, such as large phase III clinical trials, where multiple funders may need to setup a consortium of funders to support such a project. Joint rules of participation will be established, but in principle EDCTP will require to be involved early and have joint planning and running of the project with the involved partners. Moreover, transparent processes such as a robust peer review and appraisal by the EDCTP SAC will be mandatory. Developing a joint programme requires a committed political process by the PSs. European research on these target diseases now increasingly operates as common programmes with pooling of resources from a number of European PSs within a single project and so maximising the research benefit. Sustaining and further developing this approach requires political will at the national, institutional and project levels. People involved in the politics of research, development aid, national funding bodies and the research and development communities will be charged to participate in these processes. Therefore, EDCTP should also be viewed as an instrument to enhance the collaborative efforts and thus to maximise the potential to develop new interventions. 23

24 PROGRAMME MANAGEMENT AND STRATEGY European countries participating in EDCTP2 The 16 states participating in EDCTP1 have all expressed an interest in continuing with EDCTP2 depending on the agreement that is reached with the EU over the basis for assessing contributions to the common programme and the reporting requirements. In addition, Latvia, Poland, Slovakia and Finland have been actively following the programme. Latvia has acted as an observer with the intention of joining when circumstances allow. For the purposes of the business plan it has been assumed that the EC s legislative proposals for EDCTP2, as well as the Delegation Agreement, will be acceptable to all European PSs and that all current members, plus Latvia, will join the new programme. All European PSs have acknowledged the value of EDCTP in developing their own national programme of intervention studies to develop new products to fight HIV/AIDS, tuberculosis and malaria. Moreover, the programme has been one of the only international initiatives to have developed real partnership with African scientists, giving ownership and leadership to those on the ground in disease-endemic countries. PSs have noted that the public consultation on EDCTP and the impact assessments have strongly supported the work of EDCTP and its continuation. This has reassured funding bodies within all countries that the programme is well received and making an impact, even though it is too early to assess the outputs and the outcomes of the individual projects that have been funded. During EDCTP1, over 90% of funding came from just nine PSs. This reflects the differences in research activities in different countries, the size of national research budgets, the size of national research communities and the ability to redirect national programmes towards the common objectives. With the broader remit of activities under EDCTP2, the overall balance of funding may shift, with some of the countries who have made smaller contributions to EDCTP1 increasing their participation through inclusion of a wider cadre of researchers. The 16 countries willing to proceed with EDCTP2 are: Austria, Belgium, Denmark, France, Germany, Greece, Ireland, Italy, Luxembourg, Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and United Kingdom. Among the newer EU MSs, Latvia has also expressed strong interest in the EDCTP Programme. Governance and Management Structures Currently EDCTP-EEIG (based in The Hague) is the legal governing, executive and representative body of the EDCTP programme. EDCTP is exploring other forms of implementation structures, including that of an Association, which will allow the EU, its PSs and countries associated with the EU's Framework Programme on Science and Research to be eligible to join the EDCTP2-IS as full members. Unlike EDCTP1, it will not be possible to join as an associate member. However, countries eligible to join, but who have not made a decision to join, may be invited to attend meetings of the GA as observers, to inform the decision making process and to familiarise them with the activities of EDCTP. A new set of statutes will be drawn up for EDCTP2 which will clarify membership criteria and voting rights. It is anticipated that there will be one vote for each EDCTP full member. EDCTP2 will have a streamlined governance structure. It will be made up of a GA and the SEC. The EDCTP advisory body will be the SAC. The supreme body of EDCTP will be the GA, in which all members are represented. It is the ultimate and exclusive decision making body of the EDCTP-IS. Its principal responsibility is to ensure that all necessary activities are undertaken to achieve the statutory objectives of the programme, and that its resources are properly and efficiently managed. The GA takes responsibility for the provision of PSs matching financial contribution to EDCTP. GA members must have a mandate from the State which they represent to enable them to facilitate a direct decision making process leading to the allocation of funding from the national budgets for the 24

25 EDCTP programme. European PSs on the GA will have legal liability for the management of the programme. The GA will be supported by the SEC. The SEC is the executive body that implements the EDCTP programme, assures the day-today management of EDCTP and provides support to the other EDCTP bodies. The SEC will be fully responsible for the execution of the EDCTP2 programme and will be accountable to the GA. The key executive position on the SEC will be the Executive Director, assisted by the Director of Finance and Administration (DFA), Director of North-North Cooperation (DNNC) and Director of South-South Cooperation (DSSC, see Annex I). The SEC will have two offices, one in Europe and the other in Africa. Notwithstanding its dual location, the SEC will be one, with the Executive Director charged with managing both offices and the DSSC acting also as Head of the Africa Office. The Europe Office will serve as the main administrative, legal and financial centre serving EDCTP as a whole and act as a focal point for EDCTP1 in Europe, with a key role in promoting PS coordination and integration. The Africa Office will serve as a focal point for EDCTP in Africa, with a key role in promoting South-South networking activities, and for the coordination of capacity building activities. The SEC shall be staffed sufficiently to deliver the programme over ten years, including evaluating the impact of trials that are completed. To support its advocacy role, the SEC shall include a High Representative capable of representing the programme at the highest diplomatic levels. The strategic direction of EDCTP2 shall be supported by advice from an expert SAC, which replaces the former PB and DCCC. Unlike EDCTP1, there will not be additional groups representing European national programmes, nor will there be a DCCC. The work of the DCCC was invaluable during the early days of EDCTP, but its activities will be subsumed in EDCTP2 within the broader SAC and GA. The SAC will have representation from North and South, particularly European and African scientists, across the relevant disease areas, including NIDs and health systems research, health economics and planning as required to deliver the strategic research agenda. New terms of reference for the SAC will be prepared and these will permit specialist working groups to be established under the auspices of the SAC with additional experts co-opted for specific projects. A key role of the SAC will be to assess the state of global product development pathways and the critical paths for future product development. The SAC will work with the SEC to identify opportunities to coordinate calls in specific fields as products become available or to hold initiatives to broker activities based on the state of the field. On an annual basis, the SAC will prepare an SRA which will form the basis for the SEC to propose the annual work programme of the following year to the GA for approval. The EDCTP programme as such takes place in, and belongs indeed to, the African partner countries. Apart from the considerable input from sub-saharan African institutions, communities and ministries, the ultimate authority over the activities befall to the governments representing the populations which take part in the research and who should benefit from its results. In line with the Paris-Accra principles and the EU's Strategic European Framework for International Science and Technology Cooperation, EDCTP2 will further develop a governance and management structure that respects the African co-ownership as well as the European partnership and input. By 2020, EDCTP will be governed by a legal structure in which the African ownership as well as the European partnership is fully embodied. In the short-term it would streamline its governance and management, and optimise within current legal boundaries the representation of African partners and the EC in the GA. After several consultations and discussions on the future strategy for EDCTP, the PSs and partners from the developing countries have agreed that for EDCTP2: All European PSs will be represented at the GA, with a minimum of four African representatives to start with. This may be changed where deemed appropriate, but will start with representatives from the following: African Union WHO Regional Health Ministers Regional Economic Communities (membership will rotate in alphabetical order) and 25

26 Ministers of Finance/Science and Technology/Higher Education as deemed appropriate. To ensure scientific excellence and the co-ownership of the African constituency, EDCTP2 will appoint an expert SAC with representation from North and South. The SAC may form sub-committees on different diseases and interventions and to assess African needs and priorities. While research might, in some circumstances, be performed in other developing countries outside sub-saharan Africa, there will be no representation from other geographical regions on the GA during EDCTP2. Strategic Roadmap (milestones) EDCTP2 will pursue its objectives in a step-wise approach over a period of ten years, consisting of the programme implementation phase (2014 to 2020) plus the phasing out and conclusion of the grant management processes ( ). EDCTP2 will be divided into terms of three to four years. The strategic vision will be translated into a logical framework that will guide actions, monitoring and evaluation. The Agreement between the EU and EDCTP will be concluded for 2014 to The continuation of EDCTP1 will overlap partially with EDCTP2. However, the two programmes will remain separated in financial and administrative terms, but coordinated in terms of operations and strategy. In a still tentative time frame, anticipated and preliminary milestones include: 2012: Developing and finalising the Strategic Business Plan for EDCTP2 and strategy for enhancing engagement with the private sector Mapping of national programmes and research activities on HIV/AIDS, tuberculosis, malaria and NIDs Holding thematic stakeholder meetings in preparation for EDCTP2 involving key players including the private sector Signing of Memorandum of Understanding with EFPIA to launch a fellowship scheme to support clinical research fellows in the research centres of European based Pharmaceutical companies Agreement to explore 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. 2013: Co-decision on EDCTP2 Definitive agreement on upfront commitments Preparation of programme details and delegation agreement between the Commission and the EDCTP2-IS Preparation of annual activity plans 2014: Launch of EDCTP2 (first term) Extension to NIDs, diagnostics and phase I-IV 2015: EDCTP2 up and running as successor to EDCTP1 African contribution and representation proposed 2016: African contribution and representation agreed, adapted legal format investigated Negotiation of alliances for intervention research First term internal assessment 2017: Beginning of EDCTP2 term II African representation finalised, possibly with an adapted legal format 2019: Second term internal evaluation External mid-term evaluation 26

27 2022: End of term review/impact assessment 2023: Renewal of EDCTP programme 2024: Closure of EDCTP2. In preparation for this transition during 2012 and 2013, EDCTP, through a FP7 Coordination and Support Action grant, will conduct a mapping of the landscape in PSs to determine ongoing activities and capacities, including those related to NIDs. EDCTP will also organise a series of stakeholder meetings to define and prioritise activities for EDCTP2 and subsequently draft an operational business plan by the fourth quarter of To facilitate these activities, EDCTP will phase out the current scientific and capacity-building advisory roles of the present PB and DCCC by May 2013 and replace them with a SAC with relevant expertise required for EDCTP2, including that for NIDs. EDCTP PSs have reviewed the co-decision that led to the establishment of EDCTP and other Article 185 TFEU as well as the rules for participation for Horizon 2020 to contribute their inputs on the ordinary legislative process for EDCTP2. These were discussed at the GA meeting of May 2012 in Copenhagen and further discussed at the GA meeting in Cape Town in November In addition, in preparation for EDCTP2 and taking into account the anticipated expanded scope and membership, PSs will also review the current statutes and propose any necessary changes for drafting applicable statutes by the second quarter of The current EEIG statutes registration is valid till 31 December Strategic Programming and Financial Planning The PSs propose that the new EDCTP programme should cover a ten-year period with a budget of up to 2 billion, of which a half will come from the PSs working in collaboration with African Countries and third parties (industry, private sector, charities, philanthropic donors, PDPs etc.) in cash and in-kind, whereas the remain half from EU. It is important to stress that the overall EDCTP programme, and the commitment to it under Article 185, is more than a single common pot with new cash to support a series of calls. It includes the coordination and integration of research or capacity building programmes, carried out under national programmes and including funding from at least two European PSs. The programme is thus broader than just the projects funded directly through the SEC. During EDCTP1 experience has shown that between 2006 and the present time the average total contribution of the European PSs has been fairly consistent at the level of around 64 million per annum, which may translate to 640 million over ten years. Moreover, current projections show that between 2012 and April 2015 at the end of EDCTP1 PSs have estimated to continue contributing around 38.4 million per annum during a time when no major clinical trial calls are expected to be launched as the programme comes to an end, thus emphasising their strong commitment to the programme. 45 However, this does not take into account the contributions that will arise from extending the scope to include NIDs. Cofunding arrangements for EDCTP2 Apart from the EU funding, the resources of EDCTP consist mainly of: 1) Unrestricted cash contributions of European PSs to the EDCTP common pot 2) Restricted cash contributions of European PSs directly managed by the SEC 3) Cash and in-kind contributions of national programme activities linked to EDCTP, managed by the European PSs 4) Cash and in-kind contributions of African PSs to EDCTP 5) Contributions from third parties. Resource types 1-3 were, and remain, the most important in political and legal terms, as they constitute the PSs cofunding conditional to the EU cofunding. EDCTP2 will establish a transparent and predictable cofunding system. For accounting purposes only, the funds that 45 SEC.(2010). Interim Technical Report, Annex 12 A6.EDCTP. 27

28 are channelled to the SEC to be centrally used without any restriction will be counted as cash contribution and the rest as in-kind contribution. This is summarised in the chart below: MANAGED BY EDCTP SECRETARIAT MANAGED BY PARTICIPATING STATES COMMON POT IN-KIND IN-KIND IN-KIND 1. EU cash contribution 2. Participating states unrestricted cash contribution Participating States restricted cash contribution Participating States restricted cash contribution Participating States in-kind contribution In addition, development aid agencies at national and community level could contribute to capacity strengthening, while science agencies should mainly cover the research per se. Furthermore, EDCTP will proactively seek to generate resources from African and external partners (type 4 and 5) and ensure that such resources are made more visible. During EDCTP1, the acquisition, certification and management of national cofunding was assured on a project-by-project and member-by-member basis. This approach is complex and cumbersome for all stakeholders, especially the scientists and African partners. Whereas conditional cofunding in EDCTP2 will remain inherent to the Article 185 principles, the system will become more transparent, predictable and manageable. The first prerequisite will be binding and substantial upfront, auditable commitment from at least a number of PSs to the Joint Programme. Only those PSs who comply with this requirement will have the status of Full Membership, whereby their programmatic cofunding will exempt them from project-by-project cofunding. Other PSs must provide a credible indication of additional resources on a year-byyear, call-by-call or project-by-project basis. They will have the status of Observer Membership, and will still have to ensure cofunding on a project basis. PSs commitments may be in-kind or cash to a virtual or a true common pot, for research and/or for capacity strengthening. However, minimal requirements will be determined for upfront, cash and true common pot contributions, for the PSs as a group and individually. The common and individual cofunding efforts will be monitored and audited annually, and consistent shortfalls may be penalised. Whereas many trials funded by PSs are now cofunded by EDCTP, the more ambitious aim of EDCTP2 will be the integration of national programmes and projects into one strategically coherent "Joint Programme". During EDCTP1, this objective remained challenging not least because of different understandings of the principles of integration and the various constraints on national funding. However, the majority of members are committed and able to accelerate integration of existing national programmes in EDCTP2 and to increase their contributions, including unrestricted or restricted cash contributions. In-kind contributions that are under national administration are eligible as cofunding only if the national activity they relate to is explicitly framed within the EDCTP Joint Programme. Contributions from PSs and third parties will be possible as either cash contributions or in-kind contributions. All such contributions may themselves attract matched funding from the EU and contribute to cofunded activities. For the purpose of EDCTP2, cofunding will be defined as the contribution in cash or in-kind that is raised by parties other than the EU to support the EDCTP programme. Cofunding may come from the European PSs, African partner countries or third parties. Third parties include all other funders, private sector, like-minded organisations, PDPs or any other organisation that may participate in the EDCTP programme. In EDCTP2, matched contributions will be assessed over the whole of the programme and not on a project-byproject basis. There will thus not be a need to apportion cofunding to each individual project. For accounting purposes, in-kind contributions will be defined as contributions, other than unrestricted cash, that directly make it possible for a clinical trial, networking or capacity development activity, or other activities that are within the scope of EDCTP to be performed 28

29 when undertaken with cash funding from the EC. It may include provision of goods or services that are required to undertake or enhance the EDCTP programme. Cash contributions may be allocated to the SEC to administer centrally or directly to a project. Cash administered centrally without restrictions may be referred to as a common pot. Individual cash contributions may have restrictions on use (e.g. limited to specific calls or nationals). It must, however, be emphasised that, although a common pot approach is desirable, the complex, multifaceted nature of the EDCTP programme does not make this a necessity or a prerequisite. 29

30 PROGRAMME IMPLEMENTATION AND ACTIVITIES Actions for achieving the objectives including: The EDCTP programme goals will be realised through PS joint programmes with a common research administration and funding. This will include a common peer-review, co-financing, projects oversight, and monitoring and evaluation. The action will be implemented through calls launched by the SEC in consultation with PSs. PSs will jointly fund clinical trials through cash donations to EDCTP or to projects, as well as provide in-kind contributions, thereby making available to the projects the research laboratories, clinical trial sites and training programmes that they fund through their national programmes. PSs will also launch their own initiated activities. These will be described first in the annual workplan agreed by the GA and will support the objectives of EDCTP for the integration of national programmes. Subject to the conditions of cofunding of EDCTP2 activities, the EU may agree to match funds of PSIA in order to increase the impact or expand access to researchers from other PSs. The programme will achieve its objectives by supporting clinical trials of the appropriate products. This will require strengthening of the capacities and enabling environment in sub- Saharan Africa to enable the conduct of clinical trials using best practice. This will include: Funding of clinical trials through open calls and brokering Supporting of ethical review and regulatory framework Training of personnel (short- and long-term courses) Infrastructure upgrades (laboratory, clinical trials sites, trial recruitment facilities, etc.) Networking, including continuing support to the Regional Networks of Excellence Senior Fellowships and post-doctoral training. Based on this strategic business plan, the SAC will prepare an SRA to assist in the preparation of three-year workplans that will include annual activities and estimated budgets. The PSs will be asked to give upfront annual, or where possible multi-annual, contributions to cover for the running of the activities. The contributions may be in-kind or cash. Annual workplans and budgets will be drawn up by the SEC, in consultation with the SAC, for review by the IRP and subsequent approval of the GA six months in advance of each calendar year. This will take into account the state-of-the-art, prevailing status of the landscape of diseases of poverty and product development pipeline, as well as other requirements, such as capacity needs, based on consultation with all partners and stakeholders through stakeholder meetings. Experience from EDCTP1 has shown that stakeholder meetings involving all potential players, including partner PSs from the North and South, funders, scientists, SMEs, pharmaceutical industry and likeminded organisations, are very useful for deciding on research areas for funding, fostering joint ownership of projects and stimulating working in partnership. This will also take into account the need to be flexible as new issues emerge and the landscape changes. This, for instance, may include teaming up with other partners to facilitate registration of promising candidate products through phase III clinical trials. Key Principles Flexibility to allow to react and adapt to the changing landscape in terms of needs resulting from new threatening challenges or promising opportunities Improved integration of national activities through existing or novel innovative funding schemes and funding mechanisms at individual, project, institution and programme level Ensuring leadership and ownership of EDCTP-funded clinical research and related capacity building activities by sub-saharan African countries Increased third party funding and industry participation Assured availability, accessibility and delivery of medical products that have been proven to be efficacious through strategic partnerships and coordination with relevant partners Alignment and integration of scientific activities and resources 30

31 Sound operational funding strategy that includes thematic and upfront financial commitment of partners on an annual or tri-annual basis Transparency, planning security, accountability and visibility of the programme. Activities To pursue its mission, the activities of EDCTP2 will be built on its four main pillars: Promoting networking, coordination, alignment, cooperation and integration of national research programmes and activities on HIV/AIDS, tuberculosis, malaria and NIDs at scientific, management and financial level (common strategic research agenda, joint/coordinated calls for proposals, joint evaluation criteria and peer review, mapping/inventory of national programmes, activities and stakeholders) Supporting clinical trials research activities on the diagnosis, treatment, prevention and health services/optimisation of these diseases, involving collaboration between European and African institutions and scientists, and partnerships with industry, PPPs, the charitable sector and development agencies (stakeholder meetings, Networks of Excellence) Fostering capacity development for clinical trials and clinical research in developing countries (Junior/Senior Fellowships for career development, mobility grants, staff exchange grants, research training networks, strengthening ethics and regulatory bodies, mentoring and partnerships at individual/institutional level) Assuring sustainable political, societal and financial support of the EDCTP programme and its activities through advocacy and communications. In order to enhance the alignment, coordination and cooperation between PSs, it is proposed that during the preparatory phase of EDCTP2, under the EDCTP-Plus Coordination and Support Action grant, EDCTP will map the national research programmes within the scope of the EDCTP2 to develop a strategy for developing intervention against these diseases. This will augment and fill gaps in the information that is currently being collected by PSs through the annual A certificates. European countries have developed expertise, interest and long-term commitments in all these areas, though the activities have most often been uncoordinated and directed to individual African nations. Increased coordination is important to optimise these efforts. Although EDCTP will not fund activities in pre-clinical development phases, it will encourage R&D through interaction with PSs, private and not-for-profit sectors and other upstream programmes, including those financed by the EC such as the African Network for Drugs and Diagnostics Innovation (ANDI) and research funded from previous Framework Programmes. More importantly, it will promote and support development by offering a platform that can absorb new products for further development through the EDCTP programme. EDCTP views the process as a chain of events that transform candidate products into adapted interventions and brings them into the hands of the healthcare service providers and the people they serve. EDCTP adheres to the principle that the process must be viewed as one. The ultimate aim of development is to produce information that is most relevant to the use of a new product in practice by the end-users and control programmes in developing countries. The process has complex political, economic and social dimensions whose relative contributions may be difficult to disentangle. However, this is a critical phase if EDCTP wants research results to be taken up and translated into policy and practice (see also Decision No 1209/2003/EC of the European Parliament and of the Council, specifically (among others) recitals nr. 11 and 16). In EDCTP1, experience with private sector has resulted in collaborative projects in clinical trials with various private entities, primarily PDPs and philanthropic organisations, but also with pharmaceutical companies and Small- and Medium-sized Enterprises (SMEs). EDCTP2 will expand and structure its engagement with the private sector through an active dialogue, especially through the DNNC. A working group to expand the participation and mobilisation of funds from the private sector during EDCTP2 has been set up. An agreement has been signed between EDCTP and EFPIA to develop a joint fellowship programme. 31

32 In addition to the proposed fellowship scheme, EDCTP and EFPIA have recognised the need and demand for 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. This would also provide an opportunity to strengthen links between the research communities in the North and South as well as building capacity and delivering training on site. EDCTP could eventually play a role in facilitating such exchanges though will initially focus on developing the fellowship scheme. To achieve its goal, EDCTP will not only fund research projects, but will also build and enhance capacities and overall capabilities for clinical trials in developing countries; create synergies across programme (especially in Europe and in the South); act as a broker for more research into product development; and encourage research that will inform policy. In EDCTP2, thematic stakeholder meetings will be held before the launch of new clinical trial calls. The experience with the stakeholder meetings has enabled all interested parties including industry to play an important role in identifying current research issues in the field and to ensure that calls remain focused on the most pressing research needs and the most promising opportunities. They will continue to be catalysts to focus on pressing needs and to show the importance of EDCTP involvement not only in relation to the PRDs, HIV/AIDS, tuberculosis, malaria and NIDs, but also in the promotion and integration of national programmes of EDCTP European PSs and in strengthening a true partnership with African researchers. Criteria for prioritisation of Integrated Activities Experience from EDCTP1 has shown that Calls for Proposals that are narrow and target specific topic areas may be restrictive and limit wider participation. It is therefore proposed that in EDCTP2 calls should cover a broader scope to attract a wider and high quality of research applications. The importance of partnering with other funders to support large trials, especially taking into account the need to support more phase III clinical trials and expansion of the remit to include phase IV trials is strongly emphasised. Regarding implementation research, the remit will be limited to research that will optimise delivery and increase access to products, but not the full spectrum of health systems research. Prioritisation of Integrated Activities will take into account the following: 1. Disease burden and need for appropriate interventions As an example, in HIV the scaling up of treatment has expanded very rapidly and on an immense scale to an extent that it has now created a growing and urgent need for optimisation of HIV care. In contrast, HIV prevention interventions have received less attention compared to the scale up in treatment and hence the need for prioritisation 2. Emerging opportunities EDCTP will 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 3. Balance between immediate and long-term priorities and in clinical trial phase This is important not only to ensure that the development pipeline remains robust, but also to allow a steady flow of products. ACTIVITY AREA 1: Disease-specific priorities for clinical trials and health services/optimisation research EDCTP will build on its core portfolio of the previously funded early phase trials and other studies to focus on the larger efficacy trials in EDCTP2, particularly phase IIb and III. The ideas for these studies will emerge from current EDCTP-funded and other ongoing research, including discussions with industry on the co-design of projects. New studies will take advantage of the infrastructure, human capacity, improved ethics review and national regulatory framework and investigator networks that EDCTP has supported. The extension to health services optimisation research is designed to inform strategies that may increase effective access to new interventions to ensure that their impact is maximised in the African 32

33 setting. Many of these studies will be large-scale randomised trials in order to provide a strong evidence base to inform policy. Some randomised trials can be very expensive, costing 50 million or more. Such trials are likely to be done in consortia, which EDCTP2 will be best placed to facilitate and provide the necessary direction and leadership given the extensive previous experience of fostering such groups gained in EDCTP1. Malaria In the next ten years, a number of new malaria vaccines are likely to emerge from the discovery pipeline and be ready for evaluation. Our aim will be to test new vaccines. Vaccines for evaluation will include those which might protect young children and pregnant women and which will be delivered through existing mechanisms such as the Expanded Programme on Immunisation (EPI) or through other novel mechanisms. Trials of such vaccines are likely to be large, complex, and expensive undertakings that will need to be done in partnership. A large array of anti-malaria drugs is also going to enter the development pipeline. Building on EDCTP1, we plan to lead the evaluation of new drugs or drug combinations (including combinations of new and existing drugs) with a particular focus on children and pregnant women and on tackling uncomplicated malaria, which has a massive burden. Treatments for severe malaria which can act rapidly and against resistant strains will also be evaluated. There have been recent advances in malaria diagnostics. EDCTP2 will support the evaluation of new diagnostic tools which are accurate, easy to use and are less invasive than those available currently. It is essential to optimise the effectiveness of products in the real world after efficacy has been demonstrated in controlled trials. Thus, EDCTP2 will support the evaluation of different strategies for delivering and scaling up access to drugs, vaccines and diagnostics, including evaluation of different delivery schedules of drugs and vaccines that might be more optimal in the African setting. Malaria has declined in some settings across sub-saharan Africa, raising exciting questions of malaria elimination/eradication. Whether and how elimination might be feasible will require research, which EDCTP2 plans to support. This will include testing of potential malaria elimination strategies for example, evaluating the impact of drugs in combination with various vector control strategies and surveillance strategies. Research will tackle the different forms of human malaria prevalent in Africa, but with a particular focus on Plasmodium falciparum. Research on tools for tackling the human and vector infectious reservoirs including transmission blocking drugs and vaccines will also be undertaken. Prioritisation of Call for Proposals for malaria projects i. Treatment Malaria treatment Call for Proposals will be given immediate priority. This will be on drugs in combination with various vector control strategies ii. Diagnostics This will be given immediate priority, planned to take place in the first period. This will include both the evaluation of novel tools and innovative use of existing technologies in the malaria control iii. Prevention Evaluation of novel vaccines targeting different populations such as infants and pregnant mothers will be done in partnership with other funders. Taking into account of the changing diseases landscape and the declining in the incidence of malaria, feasibility studies will be given priority. These activities are planned to take place in the early period of the programme iv. Implementation research This will be included in workplans for the second or third period. It will comprise work on drugs in combination with various vector control and surveillance strategies; 33

34 evaluation of novel and existing delivery programmes; and scale-up of access to drugs, vaccines and diagnostics. Key short- and medium-term priorities: Emphasis will be on supporting of a product and building partnerships with stakeholders to advance the development of the product to the delivery stage. In the event that no suitable product is identified, a call will be published on the other listed priorities. Tuberculosis EDCTP1 has made a significant investment in TB vaccine research. EDCTP2 will build on this and evaluate novel TB vaccines, including those which might be effective in populations with a high burden of HIV, in whom TB risk is very high, and vaccines which might be effective in latently infected individuals. Innovative new drug regimens which might target latent TBinfection will also be a priority. Opportunities will be sought to identify surrogate markers of response and immune mediated protection in such research studies. Some of this research will be done in centres where EDCTP1 has contributed to the establishment of state-of-the-art TB clinical and diagnostic laboratory infrastructure which will expedite the research and build capacity further. EDCTP2 will also prioritise evaluation of new drugs and drug regimens which might be efficacious in the treatment of both drug-sensitive and drug-resistant TB or which could be used for a shorter duration. Opportunities will be sought to identify surrogate markers of treatment response from these trials. The programme will also support evaluation of practical accurate diagnostics tools as these are critical for the timely detection of infection and response to treatment. Furthermore, research to identify novel second-line treatment for children with tuberculosis will be a high priority. Research on the use of diagnostics and drugs after they have been tested successfully will be essential to optimise the impact of the products and prevent drug resistance and other complications. EDCTP2 will support the evaluation of different strategies for delivering and scaling-up diagnostics, vaccines and treatments for tuberculosis as well as research to maximise the synergies in HIV/TB control including strategies for delivering services for both infections. Prioritisation of Call for Proposals for tuberculosis projects i. Treatment This will be included in the immediate- and long-term plans during the entire period of EDCTP2. Call for Proposals will be on the evaluation of new drugs and regimens; treatment shortening and/or simplification using new regimens or existing drugs in different formulations, especially in childhood tuberculosis, and depending on the outcome of the stakeholder meeting, this may also include evaluation of novel products for detection, prevention and treatment of MDR-TB. ii. Prevention This will include development of vaccines in partnership with others as determined at the stakeholder meetings. TB vaccine research and development will span through the entire EDCTP2 programme iii. Epidemiology This is of immediate importance, but such studies should be done when there is a product in mind that will be subsequently evaluated iv. Diagnostics Work on diagnostics will be included in the mid- to long-term periods and will include evaluation of new products, particularly at the point-of-care. This will include existing and new diagnostics in different populations v. Implementation research Activities on implementation research will be planned throughout the entire period of the EDCTP2 programme starting from the mid-period. Priority will be on delivery methods and research on the use of diagnostics and drugs after they have been tested successfully. This will also include the integration of HIV/TB treatments and services, 34

35 innovative use of existing strategies to diagnose and manage TB, MDR-TB and TB/HIV co-infections. Key short- and medium-term priorities: Support the evaluation of products e.g. vaccines and new point-of-care diagnostics in an advanced clinical stage in partnership with other stakeholders linked to relevant epidemiological studies. In the absence of suitable products, emphasis will be on health systems research. HIV/AIDS Following on its previous investments in large-scale HIV prevention trials and the recent findings that an antiretroviral-based microbicide could prevent HIV-infection, EDCTP plans to prioritise research in future microbicides, including those which use combinations of antiretrovirals to curb the development of resistance. EDCTP will continue to support HIV vaccines research and maintain an interest in other prevention strategies, including pre- and post-exposure prophylaxis, by evaluating promising products when they become available. Since such trials will be very expensive, they should be undertaken with other partners to share costs. EDCTP1 has supported a number of trials on the use of antiretroviral therapy in Africa. EDCTP2 will aim to build on this research portfolio and support future trials on the improvement of treatments, as well as address other clinical questions which might become pertinent with the use of newer regimens in Africa. EDCTP1 successfully conducted policy-relevant research on the prevention of mother-to-child HIV transmission. This will be improved upon with the use of newer combination antiretroviral therapy. Opportunities will be sought to support research on the evolution and impact of resistance to antiretrovirals. EDCTP2 will continue to support research to identify simpler formulations for children and also monitor for other emerging priorities, such as the use of treatment for prevention in selected populations should feasibility studies provide positive findings. Delivery of HIV treatment services is particularly challenging because HIV requires continuous care. Similarly, adherence to microbicides and other prophylaxis measures is sub-optimal because these interventions need regular application. To optimise the scale-up and effectiveness of interventions against HIV in real-life, EDCTP will support research to identify models of delivery which increase coverage of interventions safely, effectively and equitably. This research may extend to studies evaluating strategies for detecting co-infection, getting people into care and retaining them in care. Prioritisation of Calls for proposals for HIV/AIDS projects i. Therapeutics and diagnostics A Call for Proposals on treatment/diagnostics will be launched during the first period of EDCTP2. This may include clinical management within priority areas such as paediatric ARV formulations to complement previously funded EDCTP CHAPAS trials; novel therapeutics and novel use of existing therapeutics (e.g. to prevent the evolution and/or impact of resistance); evaluations of drugs for second and third-line regimens and drug-drug interactions. Co-morbidities, including cryptococcal meningitis and communicable diseases (NCDs) such as diabetes, hypertension and others, would not be prioritised in the first Call for Proposals ii. Implementation research to optimise impact of interventions A Call for Proposals will be launched immediately during the first period. This may cover evaluation of novel strategies for linkages to care (e.g. professional support interventions to enhance quality of care and in improving retention and adherence in care); evaluation of models of delivery which safely increase coverage of interventions e.g. option B+ and effect on infants (this is also part of other funders main strategies for future partnerships); evaluation of existing combination prevention methods iii. Prevention This will be part of a long-term undertaking planned to start in the second period of EDCTP2. Area of coverage will include novel biomedical prevention; new combination prevention strategies currently in the development stage and well-funded by other international development partners; and new PrEP/microbicides. 35

36 Key short- and medium-term priorities: The first call will be general and planned to cover novel use of existing therapies or diagnostics to improve treatment and/or prevention of HIV. Partners and opportunities will be sought for calls involving new products. This will, however, unlikely be in the first call since the product pipeline is currently unclear. NIDs Although NIDs are new to EDCTP's portfolio, NID research has been supported through successive EU Framework and national programmes. While the group of NIDs is highly diverse in medical and geographical terms, the priority setting for diseases and research needs will draw on the experience and results acquired through the Framework, PS national programmes, and other stakeholders. There is opportunity for a bottom-up approach in which the existing collaborating centres and researchers supported through the Framework Programmes could contribute to a region-wide survey of needs and capacities to be integrated and included by the new SAC. Potential priorities that are currently apparent will include phase II and III trials for new drugs for helminths and protozoan diseases, as well as for new drug combinations against different diseases such as trypanosomiasis, leishmaniasis, Buruli ulcer, filariasis and helminths. Treatment and prevention strategies for co-morbidities will be supported. EDCTP2 will also support research to inform strategies for scaling up new drugs, diagnostics and vaccines. Prioritisation of Calls for Proposals for NID projects i. Treatment The evaluation of novel drugs and drug combinations in advanced clinical stages in partnership with relevant stakeholders will be given priority to start in the first period. A mechanism will be put in the Call for Proposals to facilitate partnerships for the evaluation of the selected products ii. Diagnostics Evaluation of diagnostic products will be given priority to start during the first period iii. Prevention Candidate vaccines will be evaluated as they become available. This will be prioritised to start from the first period through the entire EDCTP2 programme. It will take place in collaboration with other partners and stakeholders iv. Implementation research Studies will be on the optimisation and integration of the management of co-infections with PRD; evaluation of the different disease burden (regional vs localised); effect of mass drug administration (MDA) including drug delivery, uptake and adherence; and strategies for accessing treatment. These activities are planned to take place from the second period. Key short- and medium-term priorities: the stakeholder meetings will guide the key priority areas. However, as with other disease areas, the main priority is to evaluate the advanced products via a Call for Proposals in which partnership will be a requirement. 36

37 ACTIVITY AREA 2: Capacity building in developing countries EDCTP s guiding principle is to invest in research capacity to support national health objectives towards needs-based and field-relevant outcomes. The programme will strive to achieve sustainable capacity building deliverables. In particular, EDCTP will be looking for evidence that proposed investments consider factors necessary to attract and retain scientific leadership for conducting clinical trials in Africa beyond EDCTP s involvement. Thus, EDCTP values: An emphasis of training and mentorship in Africa The training of trainers approach Training conducted in the context of institutions, with consideration of infrastructure requirements The use of research fellowships to build individual scientific leadership capacity Training through using real working experience - learn while you work Partnerships with industry to develop an industry/edctp fellowship/scholarship scheme. EDCTP-supported centres are expected to assist with capacity development at other institutions or host individuals supported by EDCTP capacity building initiatives. The capacity building contributions will generally be part of the product evaluation projects that the programme is funding. This may either be through direct investments or through respective, existing dedicated initiatives. EDCTP will promote the strengthening of health systems in developing countries through the indirect benefits of developing clinical trial capacity, but will be careful not to compromise health service delivery through the conduct of the clinical trials. Thus, applicants for EDCTP funding should reassure that activities in support of clinical trials will not divert resources away from health systems, but strengthen them. Operational links and a defined scope of work with disease control programmes will therefore be encouraged and activities contributing to components such as disease control programme management; disease and resistance surveillance; reference laboratories; improved quality control; and clinical care and diagnostic laboratory capacities will be taken into account. EDCTP will encourage specific clinical trial capacity building initiatives through the national programmes of PSs and increase funding allocation towards infrastructural development of host institutions in EDCTP1 integrated and related grants, particularly for weak institutions. Strategy EDCTP will pursue the following capacity strengthening objectives: Upgrading of sites including training for specific staff. Capacity building grants will continue to support the training of staff working on clinical trial sites such as IT staff, clinical monitors, financial managers, project managers, personnel involved with patients or patient material, community representatives and laboratory personnel, etc. The training component should cover aspects such as training facilities and equipment; training workshop costs (including transport and accommodation for trainees); or shortterm attachments of staff from capacity development sites Training of Masters and PhD students as well as Postdoctoral and Senior Fellows. EDCTP may support Postdoctoral fellowships and Senior Fellowships linked to or independent of clinical trial grants Recognising the difficulty in obtaining specific training during normal academic study or employment, EDCTP has agreed on a joint fellowship scheme to enable researchers from sub-saharan Africa to acquire skills related to the design, conduct or analysis of trials within the research centres of European based pharmaceutical firms. Retention of a critical mass of highly skilled, senior scientists in developing countries and encouraging the return of those in the Diaspora to their countries of origin i.e. reversing the so-called brain drain Improving compliance with internationally accepted standards for ethical review Improving the performance of drug regulatory authorities. EDCTP may support coordination of regulatory activities at a regional level through collaboration with WHO initiatives Support for Networks of Excellence, some of them regional ones Supporting proposal development and site characterisation studies Ensuring sustained capacity once trials have started and preparing for the expansion of the clinical trials network. 37

38 ACTIVITY AREA 3: Networking of European and African Programmes North-North networking The objectives for national programme networking and coordination at the European level are: Coordination of research objectives, strategies and activities in the European PSs Cooperation to promote efficiency, complementarities and avoid duplication Creation of synergies and added value Collaboration and brokering between national programmes Collaboration with industry. To initiate and promote the European networking, the SEC will work closely with PSs, primarily through the European members of the GA, in order to identify and update national programmes and priorities and develop opportunities for collaborations between PSs and their researchers. All PSs will identify national contact points to represent and coordinate their participation in the networking and coordination activities. The national contact points will support the GA member in: Mapping and updating the inventory of relevant national activities and partnerships relevant to EDCTP Identification of gaps, overlaps and potential synergies between the national programmes Analysing and comparing national funding mechanisms and developing proposals that will facilitate joint funding of research projects Developing proposals for European networking strategies and action plans, including tools, consortia, incentives and possibly the allocation of funding. National contact points involved in European networking will be provided with organisational support from the SEC. Funding European networking EDCTP will continue to facilitate European networking by providing guidance, logistical and financial support. The intention is not to control, but to promote synergies and create leverage in the national programmes and funding. The EDCTP funds for this component will focus on providing incentives for actors at the different levels to engage in joint, transnational activities, such as: Enabling national funding mechanisms to overcome institutional or national constraints to joint calls Brokering coordination and exchange between national programmes, e.g. workshops on specific diseases or sub-regions, joint strategy development and benchmarking Facilitating creation of and support to consortia Supplementing budgets of trans-national collaborative projects to improve coordination and exploit synergies. EDCTP funding for European networking will aim at achieving a benefit to existing national or European mechanisms and promote greater integration as a means of accelerating product development. Funding may be made available through competitive, peer-reviewed calls for proposals. North-South networking Currently there are many interactions between European and African scientists and institutions. These collaborations tend to be determined by a joint history, institutional affiliations and personal relations, or based on national agendas and national aid and foreign policies. Scientists from different EU countries, in some cases, still collaborate independently with the same African scientists or institutions with little or no coordination between groups. Moreover, resources are concentrated in relatively few, but strong or attractive institutions while paying little attention to the less developed centres. EDCTP will continue to break these barriers. 38

39 Experience from EDCTP1 has shown that coordination of European research and collaborations in Africa is of great benefit to all partners, and strengthens the visibility and the impact of the European contribution. EDCTP will continue to stimulate and encourage multi-site activities, ensuring closer collaboration between national programmes in the north and the establishment of new North-South collaborations where appropriate. The respective inventories of European and African national programmes will be linked to identify and analyse the existing links, promote synergies, discourage duplication and broker new opportunities. A biennial EDCTP forum will provide a platform for scientists from Europe and Africa to share information and views, and to create and strengthen collaborative links. The EDCTP-funded regional networks will also encourage collaborative research and training activities involving partners from Europe. South-South networking Objectives and activities of African (South-South) networking are to: Improve and promote interaction between scientists, institutions, national disease control programmes and health policy makers Leverage support for the already established regional networks to encourage growth and sustainability Work very closely with regional bodies and national health research focal persons to create a database of national health research expenditures Analyse gaps, overlaps and potential synergies (opportunities) in health research in Africa Organise media training for scientists and training for scientific journalists in Africa Improve the capacity of African reviewers and journal editors Improve capacity for Institutional Review Boards (IRBs), National Ethics Committees (NECs), regulatory and legal agencies dealing with clinical trials Organise regular scientific forums for dissemination of research findings Proliferate capacity and create a critical mass to ensure sustainability Assess, monitor and evaluate clinical trial sites, reference laboratories and training institutes within regional Networks of Excellence. Strategy for implementation To achieve the above stated objectives, different approaches are envisaged. SAC members will work closely with regional bodies, national health research focal points and networks of excellence to advocate for participation in EDCTP activities and provide strategic planning advice The SAC will advise the SEC on the organisation of regional meetings where regional bodies, national health research focal points and representatives of networks will be requested to provide relevant information. Such information will be provided to the African GA members for their use at that level. This strategy will also be used to analyse the gaps and existing synergies The SAC will advise the SEC on supporting Networks of Excellence in activities such as meetings, workshops, exchange visits and mentorship programmes, dedicated websites, resource sharing and the biennial EDCTP forums The SEC will organise biennial meetings for all four Networks of Excellence which will be linked with the biennial EDCTP forums Support media training for scientists and journalists regionally Provide opportunities for training journal editors and reviewers Maintain and increase grant funds of calls for IRBs, NECs, capacity building and support to initiatives that build national and regional regulatory capacities in Africa Encourage SAC, Networks of Excellence and grantees to advocate for EDCTP1 in international meetings The African GA representatives, High Representative, the SEC and with the support of SAC members, will strive to gain the support of national, regional and international authorities The EDCTP High Representative will play a crucial role in promoting and facilitating African networking, particularly at the level of governments, and regional and subregional organisations 39

40 The Africa Office will also serve as a focal point for African networking and provide support to the SAC in this effort The Africa Office will continue to be the link of collaboration with other initiatives and networks in Africa, such as ANDi, INDEPTH, ASLM, NEPAD and Regional Economic Communities and their health arms. ACTIVITY AREA 4: Advocacy and resource mobilisation Goal and general objectives EDCTP aims to secure sustainable support through the following objectives: Creating awareness and visibility for EDCTP and its mission and goals Generating a sense of ownership and partnership amongst stakeholders in pursuing the EDCTP mission Developing new and more flexible mechanisms to increase and sustain funding for EDCTP s mission. Strategy on advocacy EDCTP1 is a niche player with a clear focus. The research it supports may be complex; in particular clinical trials are often associated with perceptions, many of which are not valid. Proper visibility and clarity of the EDCTP mandate and modus operandi is required to achieve the mission and goals, and to avoid inappropriate perceptions. Clarifying EDCTP s philosophy, principles, ethics and other characteristics will be just as important as stating what EDCTP will or will not do. Demonstrating how EDCTP will go beyond political statements of intents and contribute to sustainable development (i.e. evidence-based monitoring and evaluation) will also be necessary to get the kind of support EDCTP wants. Communication messages and strategies will need a combination of scientific, political and developmental input. EDCTP s overall message should be that it seeks to provide a platform which facilitates and ensures that, through direct engagement of partners, appropriate clinical trials are conducted under the best possible conditions and for the benefit of the populations concerned. Strategy on engaging with private sector EDCTP1 is working in an arena where multiple actors are already involved in activities, both upstream and downstream of the clinical trials stage. Public relations efforts will be deployed with all potential partners to ensure a cooperative rather than competitive working relationship. To a large extent, both the North-North/North-South and the South-South coordination and networking activities will rely mainly on public relations activities in so far as EDCTP will not be able to exercise sufficient influence through funding relationships. This will include enhancement of EDCTP s engagement with the private sector through the following: Increasing EDCTP s understanding of issues related to private sector engagement to allow a suitable decision-making process Definition of a clear case for support and engagement with EDCTP message to the private sector and inclusion of realistic goals about the type and size of the private sector involvement Provision of an overview of potential private partners and their needs and wishes to lay the foundation for a network of potential private partners Development of a policy comprising a principal set of unambiguous and transparent rules on how EDCTP will engage with the private sector Development of a strategic and operational proposal to maintain a private sector network and intensify partnerships. Strategy on resource mobilisation The main activities will be organised around three main themes: External relationship to enhance awareness of EDCTP Brokerage between different initiatives and programmes to mobilise additional resources Development of innovative mechanisms for encouraging synergy and collaborative projects in Africa. 40

41 Activities of the High Representative The High Representative s role will be to raise visibility and political support of EDCTP globally and particularly in Africa. This will include achieving full recognition of EDCTP by African leadership. Specifically, the High Representative s tasks are: Informing national leaders and national bodies about the EDCTP mission and objectives Getting government views and inputs that can help the EDCTP meet the needs of African countries Ensuring coherence of the EDCTP1 initiatives with African Union policy for improving health and fighting PRDs. Additionally, the High Representative will entertain regular contacts with EU institutions and national programmes to promote better understanding of the needs of the African partners in the EDCTP and ensure that coordination of European national programmes leads to a longterm partnership. The role will also include brokering of new partnerships and supporting ongoing partnerships as needed for EDCTP with governments in the North and in developing countries, like-minded organisations, private sector and civil society. It is necessary to identify bottlenecks to the use of new tools and provide information to policy makers on the new products that are being developed for application in the control of diseases, and seek complementarities to ensure their accessibility and affordability in developing countries. Funding instruments and activities Each year, the SAC will work to develop a SRA to guide EDCTP s activities for the following year. This will take into account the state of the field and any opportunities for taking forward specific products to clinical trial. The SRA will define the programme of calls that the SEC will launch and will take account of ongoing national programmes. The SAC will endeavour to ensure that all diseases and their associated activities are covered during each three-year period, but priority will be given to calls that are timely for the critical pathway for that disease. For example, calls for studies on TB vaccines may be delayed if there are no strong candidates ready for study at a time when there are strong vaccines against HIV or NIDs. The research agenda must therefore remain flexible, but will be prepared in sufficient detail to ensure that there is a range of activities that can be taken forward each year. Once the SRA has been agreed by the GA, European PSs will be able to identify whether they propose to allocate new cash to the common pot to support these calls and whether there will be any restrictions on the use of funds. As the agenda will have taken into account on-going national programmes, EDCTP will be able to maintain a comprehensive rolling programme of activities. The core calls that the SEC will develop to implement the SRA will fall into the following categories: Integrated Projects Training Fellowships Ethics and Regulatory Projects Networks of Excellence Participating States Initiated Activities Joint calls. Integrated Projects on HIV/AIDS, tuberculosis, malaria and NIDs Integrated Projects will be the largest of all EDCTP grant schemes in terms of budget and complexity. They will have multi-centre, multi-national clinical trials as the core activity. To ensure successful outcomes and sustainability, all supported clinical trials will be integrated with project management, networking and capacity development components. Consequently, an Integrated Project will usually consist of the following components: Clinical trials Networking and coordination of European national research and development programmes Networking and coordination of African national programmes 41

42 Strengthening African capacity through baseline epidemiological studies, site infrastructure upgrading, short-term training, MSc studentships, PhD scholarships and Postdoctoral fellowships. Training Fellowships and Mentorship Programmes As scientific capacity can be limited by the lack of suitably qualified researchers, EDCTP s strategy is to support researchers at different stages of their careers. Fellowship calls will identify and support researchers capable of building and leading research groups at sub- Saharan African institutions that will be internationally competitive and capable of winning grants from international funding bodies. The objectives of the fellowship programme are to: Develop capacity for research in sub-saharan African institutions Promote the career development of sub-saharan African researchers by encouraging them to upgrade their profile and/or return or continue to work in Africa Strengthen the capacity to undertake clinical trials of interventions on any of the EDCTP1 infectious diseases in Africa conducted using best practices. Ethics and Regulatory Support EDCTP wishes to strike a balance between the public health interest, the interests of the innovative pharmaceutical industry, those of the generic pharmaceutical industry, and ethical values. Currently, many African countries lack sound ethical review mechanisms and some even lack regulatory bodies. In order to strengthen local capacity in both ethical review and the national regulatory framework in Africa, EDCTP will provide support in the following areas: Establishment and strengthening of both institutional and national ethics committees Ethics training in Africa through courses and seminars An African coordinating office that oversees activities in clinical trials and related research ethics Strengthening of the national regulatory frame work in Africa through collaboration with the WHO. Networks of Excellence EDCTP will continue to support institutions in sub-saharan Africa to set-up regional networks to conduct the following: Organise mentorship programmes and training of staff members working at African institutions where clinical trials will be conducted Conduct epidemiological and demographic studies that facilitate the planning of trials Support less established institutions by providing additional expertise to enable them to participate in multi-centre clinical trials. Such expertise shall include design of trials, data management, financial management, administration, quality assurance and required laboratory techniques. Currently these networks are organised on regional basis namely Eastern, Western, Southern and Central regions of sub-saharan Africa. This allows institutions to work together in accordance with African regional economic communities or sub-regions. Similarly, all the regional networks are encouraged to network at a Pan-African level. PSIA European PSs often independently fund projects that fall within the remit of EDCTP. The purpose of this grant will be for EDCTP to provide funding and added value to these initiatives by acting as the locus of integration for various projects and programmes that have been independently initiated and/or funded by PSs. This scheme facilitates the integration of European PSs to work jointly with partners from developing countries. In order to fulfil the requirements for this call, participants in a proposal must be from at least two publicly-funded institutions from the PSs and at least one publiclyfunded institution from participating African countries. 42

43 Joint Activities EDCTP-IS with or without PSs may fund projects with third parties through a joint call or a brokering process that ensures transparency. This may, for instance, include putting together a consortium of funders to finance phase III clinical trials, or a specific product development plan that has been openly peer-reviewed and vetted by the scientific research community. Prerequisites for these activities include: 1. Early involvement of EDCTP 2. Review and positive recommendation from the SAC 3. Participation of EDCTP in the selection and administrative processes of the joint activity. National Programmes Each country supports research within the remit of EDCTP through a variety of different methods. It is not the purpose of EDCTP2 to harmonise these methods, but to ensure that the programmes align to a common vision and complement the SRA. National programmes may develop joint calls with other national programmes and may focus on existing strengths or develop new strategic interests. Projects that are to be included as national cofunding contributions to EDCTP2 will need to be portrayed as being part of EDCTP and make reference to EDCTP in any communication or publicity. EDCTP will report on the approach and mechanisms taken to implement projects under national programmes so as to share best practice and for reporting purposes. Integration of Participating States Research Programmes through EDCTP1 A major goal of the EDCTP programme has been the integration of research programmes by EDCTP PSs. Early in the programme, European partners appointed national representatives (European Network Officers ENO) to network national programmes and to meet regularly in their own forum (European Network of National Programmes) in order to facilitate closer integrated working. The importance of integration was further emphasised in the EDCTP strategy and EDCTP roadmap of As outlined in the roadmap, the EDCTP partners envisaged integration at three levels: scientific, administrative and financial. However, it is important to stress that the commitment to work within EDCTP and to contribute resources to projects supported by the current programme is itself a major part of the process of integrating these three levels to deliver the objectives of EDCTP. The Joint Programme (JPA/JPB) is the technical document that outlines the integrated scientific programme. In EDCTP1, this was developed through consultation of experts on the PB and DCCC. In EDCTP2, the SAC, which amalgamates the scientific expertise of the PB and the DCCC, will continue to provide direction to the strategic integration of EDCTP science policy. The SEC is the mechanism through which Participating States integrate administrative activities such as the preparation of call specifications, peer review, grant negotiation, project management and monitoring and evaluation. The SEC is also the mechanism for promoting EDCTP and disseminating the results of EDCTP activities. The integration of funding is more complex and partners have developed a number of instruments to deliver this aspect of the strategy. Given the large scope and broad nature of EDCTP activities, there are a number of different modalities that will be used to achieve increased integration by PSs. EDCTP does not have a single focused objective, but covers clinical trials and capacity building for all facets of clinical trials, training and development of regulatory and ethical environment in relation to drugs, vaccines or microbicides to tackle HIV/AIDS, tuberculosis and malaria. Each combination of these activities may normally be carried out by different individuals and institutes. For example, expertise in developing anti-malarial drugs may not rest with those developing capacity for HIV vaccine trials. Integration of activities by PSs must therefore take into account that there is rarely a single national programme that covers all aspects, and so there has to be a range of activities that covers the spectrum of participants. By presenting a range of different modalities, the most appropriate one can be selected by individual programmes for closer integration. With this in mind, EDCTP PSs have already developed a portfolio of integrating measures and will develop further measures for EDCTP2. The following account describes some of the existing modalities and suggests others that may be taken forward. However, because of the diversity of the programme, it will not be possible to predict in 43

44 advance which programmes in which partner countries will follow any specific modality. Rather, PSs have agreed to commit to adopting the appropriate modality to integrate any specific programmes within the EDCTP2 remit. Existing integration activities The objective of integration is the alignment of national programmes such that their funding and research priorities meet common agreed priorities as developed through the EDCTP SRA. The agreement to support a common vision does not exclude national support for work outside that vision, but serves to focus and strengthen the effort within that vision. By working through the SEC, PSs have agreed to use a common peer review, monitoring and evaluation process that ensures that funding is aligned to EDCTP priorities. By using common processes, work that falls outside the EDCTP scope is not supported. EDCTP requires projects to include two or more partner countries, ensuring applicants work together to develop proposals. Based on the current programme, the minimum requirement is usually exceeded and, on average, three to four PSs both in Europe and sub-saharan Africa partner in clinical trials and, in some cases, the level of collaboration achieved is much higher. Such partnerships participate in cofunding of the project, either in cash or in-kind, through the SEC or directly to the project. Working in this way, the objectives of EDCTP are delivered more clearly than they could be if funding was left to individual funding agencies in the PSs. The agreement to use the SEC to monitor and evaluate trials also means that there is a more consistent integrated approach to developing best practice, disseminating results, building capacity in technical financial and managerial expertise and to coordinating the development of products to the delivery of new interventions. Additionally, this has enabled some European PSs that had not previously been engaged in clinical research in HIV/AIDS, tuberculosis and malaria in partnership with Africa to join forces with others to work in that area. PSs support EDCTP because the scale of the problem and the cost of large trials is not something that individual funders or countries can support on their own. Working together is a pragmatic solution to the complex problems that EDCTP addresses. By aligning national programmes and policies to those of EDCTP, countries are able to build a more effective critical mass of expertise and scientific progress. Rather than spreading resources thinly across a wider geographical area or disease portfolio, PSs are focusing their efforts on the poverty related diseases of sub-saharan Africa aligned with the EDCTP framework. This integration occurs not just for trials but also for capacity building, networking and infrastructure support. Out of the new partnership between institutions in the North and South, EDCTP has been able to broker more sustainable integration of skills and knowledge to deliver EDCTP objectives. For example, expertise in the North has been used to evaluate and reform financial management, audit process and accountability within institutions in the South that have not been used to handling and coordinating large research funds. Although there may not yet be formal accreditation of institutions that have enhanced their management systems though partnership with EDCTP, their explicit involvement with a prestigious programme of the EU increases their competitiveness for other international funding. Integration of Funding EDCTP established the principle of integrating funding for its programmes through a single common pot. Although not all PSs were able to contribute funds through this mechanism, the common pot is an important part of the mechanism for integrating national resources to deliver EDCTP activities. With a common pot funding mechanism in place, it is possible for scientists to find their own partners through a bottom-up approach without being constrained by national funding considerations. The system is uncomplicated and therefore easier to manage and deliver. PSs in Europe are generally unable to allow their national research funding to be used across European borders but the common pot approach has enabled many to use their funding directly to support research in sub-saharan Africa. This is useful for funders as it transfers the burden of assessing the financial probity of recipient institutions, and the concomitant financial liabilities in respect of trials sponsorship, to the EEIG and SEC. Ultimately there is joint responsibility for the trials supported and managed in this way. Following the Connecting the Chain-II meeting and the Consensus Meeting under the Belgium 44

45 Presidency of the EU, it was agreed to augment the common pot through Development Agencies, as some PSs are already implementing in the current EDCTP programme. This may also allow a two-track approach, as is done under the current EDCTP, where funds that cannot be administered through the common pot and need to be ear-marked may continue to be managed that way while un-earmarked funds are included in the common pot. PSs have also integrated their national processes by launching Participating States Initiated calls. These are projects that have been managed and assessed by national partners, but for which EDCTP funding is available to add value to these initiatives by acting as a locus of integration, bringing together centres supported by different national programmes. EDCTP therefore provides glue money for projects both prior to the award and for monitoring after the award and brings otherwise disparate projects into the EDCTP framework where they can be better integrated into all the other EDCTP activities. In this scheme, PSs agree to accept the peer review that will have already been conducted by the lead partners and to also accept the peer review of the glue activities undertaken by the SEC. Further integration has been achieved through the alignment of national calls, independent of any EDCTP funding. Such joint calls by PSs (designated Joint Call by the Member States (JCMS) scheme) are a potentially important way of aligning national programmes in the future. PSs may individually champion ideas for a funding call or work with their EDCTP partners in the development of the call. To qualify as a Joint Call ultimately more than one partner will be a partner to the call. All the funding comes from the PSs with no funding from central EDCTP funds (although in principle common pot funding could be used if agreement was reached with other EDCTP partners not participating in the call). The integration is achieved by an agreement that the call will be administered, and post awards process managed, by the SEC and by the agreement to shape the call to deliver EDCTP strategic objectives. Integration activities for EDCTP2 The mechanisms that EDCTP has already established for integrating research, management and funding will of course continue into EDCTP2. The lessons learnt so far will ensure that best practice is carried forward and that momentum is not lost in developing the programme to include NIDs and in strengthening operational research. The following are areas which will be specifically enhanced or initiated in EDCTP2. Engaging with African Networks of Excellence European PSs will participate and focus their efforts on Networks of Excellence in Africa in order to strengthen these networks further. The current regional Networks of Excellence will be expanded in scope and coverage. Where necessary new networks will be established and joined together into sub-regional or regional hubs. PSs may be able to direct core institutional support beyond clinical trials per se and make greater contributions through the networks in order to develop support in areas such as data management or financial management. European and African PSs will promote the establishment of African Regional and sub-regional Reference Laboratories. It is proposed that initially four Regional Reference Laboratories will be created, one per region. This will be undertaken as a concerted effort of PSs through strengthening the capacity of selected laboratories. The Networks of Excellence and African states will select national laboratories requiring such support from EDCTP, which will be done in partnership with the African Society of Laboratory Medicine (ASLM) and WHO through the Strengthening Laboratory Management Towards Accreditation (SLMTA) programme. Through this and other programmes, Participating States will jointly contribute funding towards infrastructure improvement and training whereby the designated laboratories will be taken through various stages of accreditation towards full International Organisation for Standardisation (ISO) certification. The process will be coordinated by the SEC which will evaluate and monitor the awards. Individual European institutions may additionally integrate the relevant parts of their institutional capacity building programmes into EDCTP Networks of Excellence, which form the 45

46 essential partners of excellence networks. Where EDCTP accreditation or affiliation is recognised in national programmes, such EDCTP affiliated institutions will also be able to form partnerships with the African networks. Network of EDCTP Centres in Europe and Africa PSs will fund a network of EDCTP Centres in Europe based along thematic lines. Collaborating institutions will contribute their expertise in specific areas such as vaccinology, biomarkers, immunoassays, drug development, pharmacovigilance etc. Some institutions will then play a leading role in spearheading partnerships with their Africa counterparts and opening up the African centres to specific resource excellence. Funding and management of these centres will be coordinated by the SEC. Over time these will establish a bi-directional flow of expertise as African centres feedback their expertise in tropical diseases and trials management on the ground. Joint Training Programmes Training forms an essential part of capacity building objectives of EDCTP. Many European institutions carry out training programmes but there is plenty of scope for more coherent integration of these programmes into a coordinated and internationally recognised EDCTP training package. Currently there are a number of individual schemes providing PhDs, Masters, Diplomas or other qualifications in areas such as clinical trials management, statistics, data management, health economics, etc. Under EDCTP2, institutions will be encouraged to allocate a proportion of the fellowships to EDCTP objectives. Universities and other institutions will join together to provide integrated training courses such as those run under the Erasmus Mundus schemes. African institutions will be brought into the programmes with a gradual transfer of training to Africa though a network of African Schools of Tropical Medicine. Continuation of Existing Integration Activities The experience of supporting institutional reform under the umbrella of EDCTP activities will be extended in EDCTP2. With greater representation of African institutions on the GA of EDCTP and a renewal of commitment from PSs and the EC to fund work in Africa through the EDCTP partnership, there will be greater incentives for African institutions to seek to raise standards in research management to facilitate clinical trials. This in turn will lead to increased networking at institutional level as well as amongst researchers. PSs will use different methodologies to support institutional reform depending on local needs and available expertise. Many of the trials being undertaken target different population groups. Microbicides designed for vaginal use are necessarily targeted at women while other studies may be particularly focused on pregnant women or children, whose clinical presentation or response to drugs may differ from adults. In general, there is a need to ensure that, across the spectrum of disorders, men and women are equally represented in clinical trials and that joint programmes enhance the participation of under-represented or minority groups. Mentorship programmes will also be developed to ensure that there is greater representation of women in the conduct and design of clinical trials, where possible working with local community groups to ensure appropriate empowerment and involvement. 46

47 JOINT FUNDING Following a consultative process, PSs have come up with an indicative cofunding that will be matched by the EU funding over the life of the programme. This includes cash and in-kind projections as summarised in the following table: 47

48 Country Participating States Indicative Commitment to EDCTP2 (2013, subject to political and legislative approval) Managed by SEC: Cash (restricted and unrestricted) Managed by PS: Cash and In-kind including funding to PDPs Cash and Total Cash Total In- Kind In-kind Total Austria Belgium Denmark Finland France Germany Greece Ireland Italy Latvia Luxembourg Netherlands* Norway Portugal Spain Sweden Switzerland UK TOTAL Note: Some PSs have not yet reported their indicative commitment as they are still estimating cash and in-kind contribution to EDCTP2. 48

49 Notes to table outlining PSs indicative commitments to EDCTP2 Austria: Austria indicated their commitment and intended type of contribution in Belgium: The document received from Belgium in November 2011 outlined the prospective commitments to the programme for the relevant period until In June 2013, Belgium provided their estimated in-kind contribution for the period Belgium is currently calculating their indicative commitment for the period Denmark: Indicated contribution to EDCTP2 from Denmark was likely to be at least equivalent to EDCTP1. France : Expressed political support and indicated future contribution at least equivalent to EDCTP1. In July 2013, France provided their estimated in-kind contribution for EDCTP2. Germany: In a letter received in October 2011, Germany expressed political support, noting the direct contribution to the 'common pot' and projected in-kind contribution. In 2013, Germany indicated cash and in-kind commitments to EDCTP2. The cash contribution from Germany will be restricted. Ireland: Expressed political support for EDCTP2; in a letter received in November 2011 Ireland explained that the in-kind contribution is based on Ireland's current funding to PDPs. Cash contribution presented in the table is pending approval Italy: Expressed political support noting the changing political context in Italy. Amounts presented are based on an estimation for 2014, which is expected to continue throughout the EDCTP programme, subject to revision depending on the political situation. 93.4% of the contribution presented in the table represents cash to be managed by Italy. Latvia: Expressed interest and support; a letter received in November 2011 outlined possible ways in which Latvia could support future participation in EDCTP. Latvia indicated in 2013 that the contribution is expected to be 200,000/year in the form of in-kind contribution. Netherlands: Cash contribution included in the table represents the estimated VAT refunds; the amount of the in-kind contribution from The Netherlands does not include funding to PDPs. Norway: Political commitment and cash contribution to the common pot foreseen but subject to political processes and legislative approval. Portugal: Confirmed participation in EDCTP2 in Contribution of at least 200,000/ Spain: Sweden: year cash, in-kind or a mix of both foreseen. Political indicative commitment of 7M but no breakdown in contribution and subject to political and legislative approval. Due to the National Parliamentary elections held in Spain on November 20th, 2011, the Annual National Budget for 2012 has not been approved yet so there are no appropriations allocated for ISCIII to carry out the above mentioned activity. The new Parliament should be constituted by December 9th 2011, the new Government appointed by December 22nd The Annual National Budget for 2012 may be approved by the new Parliament of Spain during The documents submitted outlined the different forms of Swedish contribution and participation in EDCTP2 including cash contribution to the common pot. Switzerland: Expressed political support and contribution at least equivalent to EDCTP1, subject to political and legislative approval. The in-kind contribution only includes the expected contribution from Swiss TPH; other research institutes might provide additional support to EDCTP projects. The figures were converted from Swiss francs to Euros and there will be fluctuation in the rate. UK: The figures were converted from Pounds sterling to Euros and there will be fluctuation in the rate. The cash contribution from the UK will be restricted. 2.3 M for EDCTP has already been transferred from MRC to EDCTP bank accounts. 49

50 FURTHER COMMITMENTS Within the different modalities available to PSs to integrate their EDCTP participation, there will be a number of activities that will be specific to individual institutions or researchers. PSs will support specific integration measures that help support EDCTP objectives and which will be funded either through reallocation of existing resource or provision of new resource. Examples include: Raising the profile of EDCTP objectives as part of national strategy for funding Prioritising EDCTP relevant research within national programmes Accrediting work that contributes to EDCTP objectives and facilitating networking and coordination of EDCTP accredited researchers Allocating resource for training schemes (possibly as a minimal percentage) with greater visibility for the EDCTP brand within that allocation (i.e. specifically designating EDCTP fellows, students etc.) Working with Development Agencies to develop research capacity strengthening within an EDCTP context Aligning institutional capacity strengthening programmes with EDCTP programmes (e.g. networks, ethics boards, national regulatory bodies) Reformulating internal programme costing to explicitly reflect EDCTP commitments Promoting EDCTP as a model example of Africa-Europe partnership. Provisional Planning of Funding Activities Based on this EDCTP2 Strategic Business Plan, EDCTP will develop three-year operational and annual work plans. The plans will be prepared by building in flexibility, within the rules of Horizon 2020, to rapidly respond to disease conditions or interventions and by working in partnerships with other funding organisations and stakeholders in jointly supporting such trials, particularly the expensive phase III trials. Indicative EU matching of Participating States cofunding by activity area for EDCTP2 programme Area % of total expenditure by area ( ) Total expenditure per area ( ) Clinical Trials 80.73% (including integrated activities) HIV/AIDS 22.21% Malaria 22.21% TB 22.21% NIDs 14.08% Stand-alone capacity building activities Ethics, Regulatory and Registry Bodies 4.39% % Integration 8.88% and Networking MSI-Institutions 1.73% MSI-Projects 1.73% MSI- 1.73% Researchers NoEs 3.70% Administration costs 6.00% Total programme expenditure per year 100%

51 Please note that Clinical Trials includes integrated capacity building activities such as MSc, PhD and postdoctoral grants and infrastructure to enable conduct of clinical trials in accordance with Good Clinical Practice (GCP) & Good Laboratory Practice (GCLP). It is not possible, at the time of writing the business plan, to specify the indicative budgets that will be leveraged from African States and third parties. Evolution of the SEC The SEC will remain the executive body and carry out all day-to-day functions of the EDCTP2 programme. The SEC will be headed by the Executive Director, assisted by the DNNC and DSSC for operational matters and the DFA for financial and administrative matters. The Directors will in turn be assisted by the Operations Manager and North-North Networking Manager based in Europe, and a South-South Networking and Capacity Development Manager based in Africa. The Operations Manager will be responsible for all grants administration processes from the initiation and launch of calls; peer and internal review; follow-up; monitoring and evaluation; to project closure. The Networking Managers will be responsible for coordinating partner state and third party programmes, including industry, in the Northern and Southern PSs, working closely with Networking and Project Officers, who will specialise in different disease themes such as HIV/AIDS, tuberculosis, malaria and NIDs. The North-North Networking team will liaise with national focal persons to keep and update an inventory of PS activities and facilitate their coordination and joint programming. Similarly, the South-South networking team will identify national programmes in sub-saharan Africa, especially those of bilateral collaboration to facilitate their incorporation into networks. Prior to the start of EDCTP2, during the transition period between 2011 and 2013, the SEC will continue to engage with third parties, especially pharmaceutical companies, SMEs, PDPs, likeminded organisations and other funders to explore how best they can work together with EDCTP. This process is ongoing. Furthermore, the SEC with the help of national contact persons will set out to map PS national programmes within the scope of EDCTP with a view to establishing joint programmes. This will include seeking out such programmes among the newer European Union MSs and inviting them to join in. As EDCTP1 winds down and EDCTP2 takes off and continues, there will increasingly be a need for monitoring, evaluation and reporting of the ongoing and completed activities. Together with the potential need to deliver a programme of up to 2 billion, this will, in turn, require an expanded function of the SEC and therefore it will accordingly require more resources to grow to meet these needs. This will include recruitment to vacant positions. 51

52 PROGRAMME MONITORING AND EVALUATION Scientific outcome and strategic impact The most important evaluation criteria will be the ability of the EDCTP programme to develop new or improved products that will be used in clinical practice to improve the health and lives of people in the countries affected by HIV/AIDS, tuberculosis, malaria and NIDs. Individual projects will submit final reports on the outcomes of the study. These will form the basis of the assessment of project impact. It is in the nature of clinical trials that not all newly developed products will prove to be effective or necessarily safe for use, but it is important that studies have been designed to give clear definitive answers. EDCTP will not have succeeded if the results of projects are inconclusive. However, studies providing conclusive evidence, will demonstrate the effectiveness of the programme. Where studies have shown a positive effect, the immediacy of the impact on health will depend on the phase of the trial and how the results are taken forward. For phase III and IV trials the results may inform clinical practice directly, but for earlier phase trials, the results may identify the specific directions in which the field should develop. The programme may therefore be evaluated against a drug or vaccine development pathway. Indicators of success will therefore include: Successful completion of clinical trials Progress of products along the pipeline from early to later stage trials Introduction of new or improved products or regimens Introduction of new disease management policies. At the end of each three-year term, EDCTP will conduct an internal evaluation to assess the progress of the programme and determine its impact on health issues, such as its influence on health policies, healthcare, capacity strengthening, strengthening of partnerships and synergy with other programmes. EDCTP, via its outreach activities, will interact with likeminded research and development organisations to identify best practices for monitoring and evaluation of similar activities. In order to further develop the standards for the evaluation of impact of research activities, EDCTP will also work with these organisations. To this effect, for instance, EDCTP, together with other like-minded funding organisations, through the ESSENCE on health research initiative (Enhancing Support for Strengthening the Effectiveness of National Capacity Effectiveness), have developed a tool for monitoring and evaluation of capacity building projects. 46 This has been adapted by EDCTP and is currently being used to monitor and evaluate EDCTP-funded Networks of Excellence for conducting clinical trials and other capacity building activities. This will also be used to monitor and evaluate all capacity development activities under EDCTP2. Operational performance The implementation performance and the effectiveness of the programme will be monitored on a regular basis using Key Performance Indicators (KPIs) that give a clear picture of whether the programme is moving in the right direction and measures the progress towards planned goals: grant evaluation and processing procedures; effectiveness of North-North and North- South partnerships and networking; the degree of participation of developing countries; number, outcome and effectiveness of the projects; level of capacity attained; administrative costs; and other relevant outcomes. KPIs similar to those in current use will be developed and monitored internally on a monthly basis and updated quarterly on the EDCTP website, as is the current practice. These will include: Performance of the SEC in the processing of grants applications from the time the call is launched to the signing of contracts Successes in the organisation and outcomes of stakeholder meetings Timeliness in the launching of calls Degree of participation of third parties Degree of participation of PSs Contributions of PSs. 46 ESSENCE. Planning, Monitoring and Evaluation: Framework for Capacity Strengthening in Health Research Retrieved June 30, 2011, from WHO: 52

53 The monitoring will be a continuous process conducted on a quarterly basis and reviewed annually. This will evaluate strategy effectiveness and whether there is a need for a change in direction or modification. Views of other stakeholders will continue to be solicited through the stakeholder meetings and feedback at the biennial EDCTP forums. These have been found to be very useful during EDCTP1. During EDCTP1, with the assistance of the then Swiss Tropical Institute, EDCTP conducted an internal evaluation and developed a tool for this purpose which will be used for the future internal evaluations. Monitoring will also be done to see that there is no duplication of projects or waste and to ensure that all areas of research are covered, bearing in mind the changing needs as new discoveries are made and new problems emerge. Furthermore, at the mid-term and end of the programme, there will be an impact assessment to determine the effect of the programme on key health issues, as stated in the mission and objectives of EDCTP. Therefore, to realise these goals, multiple systems will be setup for monitoring and evaluation of the performance of both the programme and research output. The following targets and indicators used for this purpose will include: Number, quality and relevance of clinically tested new or improved medical interventions available against poverty-related and neglected diseases in sub-saharan African countries (number of clinical trials in different phases; number of medical interventions proceeding to further development; number of clinical trials integrated in guidelines or recommendations for improved clinical practice or submitted to regulators) Number of sub-saharan African countries participating in EDCTP and promotion of African leadership in clinical trials research (number of sub-saharan African countries participating in EDCTP; number of clinical trials projects lead by African researchers/institutions; number of African collaborators benefitting from EDCTP support; number of fellowships and studentships (MSc/PhD) for African researchers) Number of African researchers working in clinical trials research through the provision of training opportunities and fellowships (number of fellowships and studentships (MSc/PhD) for African researchers; number of African fellows trained at pharmaceutical companies) Number of new European coordination and integration initiatives or level of integration of European national research programmes Number of jointly-funded clinical trials and contribution of sub-saharan African countries and third parties. 53

54 DEFINITIONS Alignment of national programmes: the coordination of PSs programmes within the scope of EDCTP to complement and fit with each other, and with the needs of their sub-saharan counterparts. Cofunding: is the cash or in-kind contribution that is raised by parties other than the EU to support the activities of the EDCTP Programme. Common pot: unrestricted contribution that is centrally managed by the SEC. Coordination of national programme: The organisation and harmonisation of PSs activities and projects within the scope of EDCTP with developing countries into synergistic and efficient joint ventures with common scientific review, oversight and administration including monitoring and evaluation as part of common programming. EDCTP Participating States: any country that is a member of the EDCTP-IS. In-kind contribution: resources managed by the SEC or PSs that directly make it possible to undertake clinical trials, networking or other activities within the scope of EDCTP. It may include provision of restricted cash, good or services that are required to undertake or enhance the EDCTP programme. Integration of national programmes: is to bring together the European partner countries national programmes into a common programme under the umbrella of the EDCTP and directed to the objectives of the EDCTP. This is a long-term goal of EDCTP. National programmes: are country-based publicly funded activities within the scope of the EDCTP programme. These may be at individual, project, institutional or programme level. Restricted cash contribution: resources to which the contributing country may impose some limitations on how such funds can be spent. For instance, funds limited to researchers within the same country as the contributor. Unrestricted cash contribution: resources to which the contributing countries do not place limitations and which, therefore, can contribute to any part of the EDCTP programme. 54

55 ACRONYMS AMANET African Malaria Network Trust ARV Antiretroviral Treatment ASLM African Society for Laboratory Medicine AU African Union CSA Coordination and support actions DCCC Developing Countries Coordinating Committee DMS Document Management System DSMB Data and Safety Monitoring Board EAC East African Community EC European Commission ECOWAS Economic Community of West African States EDCTP European and Developing Countries Clinical Trials Partnership EDCTP1 First EDCTP programme ( ) EDCTP2 Second EDCTP programme ( ) EDCTP2-IS EDCTP2 Implementation Structure EEIG European Economic Interest Group ENNP European Network of National Programmes ENO European Networking Officer EPI ERA ESSENCE Expanded Immunisation Programme European Research Area Enhancing Support for Strengthening the Effectiveness of National Capacity Efforts EU European Union GA General Assembly of the EDCTP EEIG GCLP Good Clinical Laboratory Practice GCP Good Clinical Practice GMS Grant Management System IAS International Accounting Standards I(C)T Information (and Communication) Technology IPR Intellectual Property Rights IRB Institutional Review Board ISO MDG International Organisation for Standardisation Millennium Development Goal MMV Medicine for Malaria Venture MRC MS Medical Research Council (South African hosting organisation) Member State MTCT Mother to Child Transmission NEC National Ethics Community NEPAD New Partnership for Africa s Development NID Neglected Infectious Disease NIH National Institutes of Health (USA) NWO Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Dutch hosting organisation) PB PDP Partnership Board Product Development Partnership PI Principal Investigator PPP Public Private Partnership PR PRD PS PSIA R&D RCT SAC SADC SEC SOP SRA SRC TFEU Public Relations Poverty Related Disease Participating State Participating State Initiated Activity Research and Development Randomised Clinical Trials Strategic Advisory Committee Southern African Development Community EDCTP Secretariat Standard Operating Procedure Strategic Research Agenda Scientific Review Committee Treaty on the Functioning of the European Union 55

56 UN VCT WHO WHO/AFRO United Nations Voluntary Counselling and Testing World Health Organisation WHO Regional Office for Africa 56

57 ANNEX I: ORGANISATION, STRUCTURE AND MANAGEMENT OF THE EDCTP SECRETARIAT (SEC) The current SEC has two offices, one in Europe and the other in Africa. Notwithstanding its dual location, the SEC is managed as a single entity, with the Executive Director charged with managing both offices and the Director of South-South Cooperation (DSSC) acting also as Head of the Africa Office. The SEC currently comprises 26 staff, of whom 4 are based in the Africa office. Among these are two part-time staff members (Human Resource Advisor and Legal Advisor). In addition, EDCTP employs the High Representative based in Mozambique on a retainer contract basis. The roles and responsibilities of the SEC staff will be fully described in new Internal Regulations. Executive Director Leading EDCTP in fulfilling its objectives established under Article 185 (ex169) to achieve closer European integration of the PSs national projects in the field of scientific research into PRDs and demonstrating a solid and palpable improvement in European research networking by the end of the Action Ensuring compliance with legal, fiscal, administrative and financial obligations of EDCTP and reporting to EC on behalf of the GA, including the annual update of the workplans Leading negotiation teams for brokering partnerships for research and funding with governmental, non-governmental and private sector organisations Leading grant negotiation teams Developing an overall organisational scheme for the SEC Managing the SEC in The Hague and Cape Town Recruiting and staffing the SEC Negotiating contracts with consultants, experts, sub-contractors and third parties Assessing and limiting the risk to the members of the EDCTP. Director of Finance and Administration Controlling and managing the cash resources of the organisation Preparing annual budgets Producing annual audited accounts Implementing a strong system of internal controls Ad hoc financial reports and statements of expenditure for the constituencies and EC Financial monitoring of grantees Financial Standard Operating Procedures (SOPs) and staff policies. Director of North-North Cooperation Identifying and coordinating European PSs national programmes Supervising the North-North networking team Fostering close collaboration with the private sector Assisting the Executive Director in the management of scientific matters. Director of South-South Cooperation Head of the EDCTP Africa Office Fostering close relationships with the African scientific, policy making and political leadership Assisting the Executive Director in the management of scientific matters Advising on capacity development, South-South and North-South networking. 57

58 Organogram of the EDCTP Secretariat 58

59 Location and role of the SEC Role of offices The Europe Office will have the following principal functions: To serve as the main administrative, legal and financial centre serving EDCTP as a whole To be a focal point for EDCTP, with a key role in promoting PSs coordination and integration To liaise with the EC To organise meetings of constituencies To provide support to the GA, national points of contact, and the SAC To launch new calls and administer the review of proposals To liaise with grantees over new grants To ensure a proper follow-up of EDCTP-supported projects To serve as the focal point for advocacy and fundraising activities To create, maintain and update the databases of relevant MSs national programmes contributing to EDCTP. The Africa Office will have the following principal functions: To be a focal point for EDCTP in Africa, with a key role in promoting South-South networking activities To serve as a focal point for the coordination of capacity development activities To participate in preparing calls, advertisements, announcements of clinical trials To participate in the SEC s activities relating to the start of EDCTP-supported trials and to follow-up clinical trials in Africa To coordinate site visit activities in Africa To serve as a regional base for HR To create, maintain and update the African databases relevant to EDCTP activities To serve as the focal point for communication and advocacy, especially in Africa. Financial system During EDCTP1, the SEC had put in place an effective financial control and cash flow management system with an automated accounting system (Access accounts). This will continue to be used in EDCTP2. The purpose of the accounting system is manifold: To provide checks and balances which compose a crosscheck to the internal controls to prevent fraud and error of misstatement of expenditure To provide monthly management accounts relating actual expenditure to budget To ensure that cash flow management of the EDCTP liabilities over the course of the Action does not exceed funding parameters To provide a clear electronic audit trail linked to hard copy documentation, which can be used by the EC and external auditors in assessing the financial systems and controls To produce the annual EC financial statement To answer ad hoc financial questions and reports on expenditure, as requested by the constituencies To assist in the setting of the annual budget for the following year and latest estimates where required To ensure an objective system of accounting in-kind contributions. Internal control and accountability A robust system of internal controls is very important. The finance department has implemented systems and SOPs to minimise the risk of error and to comply with requirements of the EC and the EDCTP Internal Regulations. Annual accounts, which are independently audited by external auditors, are prepared for 59

60 presentation to the GA by the DFA within six months of the year-end. Reconciling statements are also produced to link the annual accounts to the EC financial statement. This system will continue to operate in EDCTP2. Per Diems and Travel Expenses In EDCTP2, efforts will be made to reduce travel costs and per diems by streamlining the governing and advisory bodies. Staff Regulations A full set of Staff Regulations were developed by EDCTP in 2008 and accepted by the GA in the meeting of November These regulations cover all employment terms and conditions for staff on EDCTP contracts and now all new contracts offered are EDCTP ones only, with no new seconded staff being taken on from the Hosting institutions. Risk Management The SEC has produced a risk management matrix to map the major risks effecting the organisation in its operations and to identify actions which can be taken to mitigate those risks, where possible. This matrix is monitored quarterly by the Management Team and updated. Programme management Implementation of the EDCTP programme will require development of and support for the activities of the SEC that are described in the chapter on management. Information management aims to support knowledge management and dissemination. This shall be done by establishing appropriate databases and making available relevant information to scientists and the public. In addition, EDCTP will support and strengthen African sites in their capacities and capabilities in respect of information management, through provision of funding in the clinical trials grants work packages. EDCTP has provided a grant for the establishment of a clinical trials database at the Cochrane Centre in South Africa, which provides details of all clinical trials being conducted in Africa and is publicly accessible on line. This has evolved to become a Pan-African Clinical Trials Registry (PACTR), with a WHO primary registration status. EDCTP will continue to support this important activity as well as coordinate and harmonise clinical trial registration with regulatory and ethics framework in sub-saharan Africa. Document management and video conferencing systems The SEC has implemented a Document Management System (DMS), which has been in use since This serves as the main document archive for electronic copies. The insufficient bandwidth between the two offices that had in the past resulted in the Africa Office having difficulty linking into the DMS has now been resolved. Additionally, an intranet has been set up using MS SharePoint, which gives access to constituency members via a web portal. The intranet contains management reporting information about the performance of EDCTP, as well as documentation for constituency meetings providing constituency members with access to much more information more easily and quickly. The EDCTP website has been developed to a high professional standard and is updated continually, including having RSS news feed through web browsers. This will continue to be improved during EDCTP2. The SEC has installed a video conferencing system over internet protocol (VOIP), which is in frequent use for meetings between the two offices. It is aimed to expand this during the EDCTP2 to reduce the costs of face-to-face meetings by providing a viable and effective alternative to travelling. However, a major restriction on this is the limited bandwidth in many parts of Africa. 60