Clinical trials and operational research studies to optimise the use of products for poverty-related diseases in mothers, newborns, children and/or adolescents
This call aims to support actions on preventive and therapeutic clinical interventions of post-registration products, as well as related behavioural studies, aimed at optimising use of new or improved products or combination of products for mothers, newborns, children and/or adolescents.
Every year, more than 300 000 women die as a result of pregnancy, childbirth or postpartum complications and more than 6 million children die under the age of five, mostly from preventable diseases, according to WHO. The majority of these deaths occur in developing countries and represent the biggest global health inequity today. While substantial progress has been made in reducing maternal and child morbidity and mortality, many countries, particularly in sub-Saharan Africa, have failed to reach the Millennium Development Goal 4 and 5 targets of reducing under-5 mortality by two-thirds and maternal mortality by 75% by 2015 from the 1990-baseline.
In countries in sub-Saharan Africa, poverty-related diseases (PRDs) remain the leading causes of morbidity and mortality, especially during pregnancy and childhood. The importance of PRDs for maternal and neonatal deaths is often poorly-recognised because of the limited evidence on the contribution of these diseases to maternal and neonatal mortality, over and above direct, obstetric causes of pregnancy-related mortality. Adolescents are subject to particular health risks that need to be targeted specifically, such as early pregnancies, and infections such as HIV, diarrhoeal diseases, lower respiratory infections and meningitis, which are important causes of death in this age group. Adolescents (10-19 years of age) are now included as a target for the updated UN Global Strategy for Women’s, Children’s and Adolescents’ Health for 2016-2030, a platform to accelerate the new Sustainable Development Goals.
Roll-out of HIV treatment in large public health programmes has resulted in substantial reductions in HIV-related mortality across all ages, although ART coverage among children below 15 years of age, and especially below five years of age, is lagging behind coverage among adults. This is partly due to failure to timely diagnose vertically-acquired HIV infection in infants, but also due to children and adolescents not being seen in the healthcare system until late in the course of disease. Whereas prevention of mother-to-child transmission (PMTCT) programmes have largely been effective, a substantial number of HIV-infected pregnant women do not access PMTCT and are thus not benefitting from HIV treatment and care and continue to be at risk of morbidity and mortality for themselves and transmission and mortality for their offspring. Adolescents are often excluded from prevention of HIV infection public health efforts, because they are difficult to reach, are vulnerable at this time of their lives, and find it difficult to access healthcare systems to ask for the necessary prevention support.
Concerted efforts are needed to increase equitable access to potentially life-saving cost-effective interventions to treat PRDs in pregnant women, children, and adolescents. This is especially important in light of the frequent exclusion of both pregnant women and young infants and children from clinical trials and the paucity of available products that target these groups of the population. In this regard, little information is available on the pharmacokinetics and efficacy of drugs in late pregnancy and during breastfeeding. Adolescents are a difficult-to-reach group, not only for the prevention of PRDs such as HIV, but also for their treatment, and approaches dedicated to this age group need urgently to be developed. Few drugs for use in PRDs are optimised for use in children, as small children need age/weight-appropriate formulations, and expansion of drug choice for children in sub-Saharan Africa is urgently required.
There has been considerable success in HIV treatment and in PMTCT but little is known about the long-term adverse effects of lifelong treatment, both when treatment is started in pregnancy, in women who are not HIV-symptomatic and in their uninfected children who may be exposed to antiretroviral drugs for possibly two years in foetal and early life. Post-registration research on the long-term effects of life-long drugs is required, especially when started in pregnancy, early childhood or adolescence, but is often outside the scope and capacity of existing public health systems.
Challenges associated with continued high risk of maternal, neonatal, child, and adolescent morbidity and mortality are related to failure in (timely) accessing the health care system for prevention and/or treatment, as well as health system failures in providing quality care and the existing tools. Understanding these barriers, which include health system and behavioural factors, is urgently needed to improve the effectiveness of new or improved products. Importantly, the high burden of disease and death among these groups of the population in low income countries also relates to the paucity of interventions such as effective vaccines and efficacious drugs for prevention and case management of infectious diseases.
The objective of this call is to optimise the use, delivery and access to PRD(1) medicinal products in sub-Saharan Africa for mothers, newborns, children and/or adolescents. Supported projects should contribute to a better understanding of the role of PRDs in maternal, neonatal, child, and adolescent mortality and morbidity, as well as the barriers for the optimal effectiveness of health products, such as existing drugs or vaccines against these diseases in sub-Saharan Africa. This call aims to support actions on preventive and therapeutic clinical interventions of post-registration products, as well as related behavioural studies, aimed at optimising use of new or improved products or combination of products for mothers, newborns, children and/or adolescents. The scope of this call is limited to clinical trials and operational studies with a product focus. Activities may include: studies on product (drugs, vaccines, microbicides and diagnostics) development, delivery, uptake and adherence; and strategies for equitable and full-scale access to diagnostics, prevention and treatment interventions. This includes community-based interventions/approaches and qualitative studies.
Assessment of behaviour of those who would benefit from such products (or interventions) in terms of access to the health care system and uptake of the product/intervention, with adherence to product use, is within scope of this call.
EDCTP considers that proposals of between 36 and 60 months duration would allow this specific challenge to be addressed appropriately. Nonetheless, this does not preclude submission and selection of proposals of a different duration.
Actions funded under this Call for Proposals should contribute significantly to improving maternal, neonatal, child, and adolescent health in the world’s region with the lowest health indicators in these populations. The EDCTP is currently among the most visible initiatives that could contribute to improve these outcomes through evaluation of new approaches in rigorously conducted clinical trials in sub-Saharan Africa.
Consortia comprising a minimum of three independent legal entities are eligible to apply. Two of the legal entities must be established in two different European Participating States(2) of the EDCTP Association and one of the legal entities must be established in a sub-Saharan African country(3).All three legal entities shall be independent of each other.
‘Sole participants’ formed by several legal entities (e.g. European Research Infrastructure Consortia, European Groupings of Territorial Cooperation, central purchasing bodies) are eligible if the above-mentioned minimum conditions are satisfied by the legal entities forming together the sole participant.
- For the purpose of this call, PRDs include: HIV, malaria, tuberculosis, and also the following neglected infectious diseases (NIDs): dengue/severe dengue; rabies; human African trypanosomiasis (sleeping sickness); Leishmaniases; cysticercosis/taeniasis; dracunculiasis (guinea-worm disease); echinococcosis; foodborne trematodiases; lymphatic filariasis; onchocerciasis (river blindness); schistosomiasis; soil-transmitted helminthiases; Buruli ulcer; leprosy (Hansen disease); trachoma; yaws; diarrhoeal infections; lower respiratory infections; as well as emerging infectious diseases of particular relevance for Africa, such as yellow fever. Ebola Virus Disease vaccine development is specifically excluded from this call since it has already been extensively funded by other parts of the Horizon 2020 programme.
- Legal entities in the following European countries: Austria, Denmark, Finland, France, Germany, Ireland, Italy, Luxembourg, the Netherlands, Norway, Portugal, Spain, Sweden, and the United Kingdom.
- Legal entities in the following sub-Saharan African countries are eligible to apply: Angola, Benin, Botswana, Burkina Faso, Burundi, Cameroon, Cape Verde, Central African Republic, Chad, Comoros, Democratic Republic of Congo, Republic of Congo, Djibouti, Equatorial Guinea, Eritrea, Ethiopia, Gabon, The Gambia, Ghana, Guinea, Guinea-Bissau, Ivory Coast, Kenya, Lesotho, Liberia, Madagascar, Malawi, Mali, Mauritania, Mauritius, Mozambique, Namibia, Niger, Nigeria, Rwanda, São Tomé & Príncipe, Senegal, Seychelles, Sierra Leone, Somalia, South Sudan, South Africa, Sudan, Swaziland, Tanzania, Togo, Uganda, Zambia and Zimbabwe.
Procedure and application process
This is a two-stage application procedure. For the first stage, a letter of intent must be submitted by 29 September 2016 via EDCTPgrants. Applicants will be notified of the first-stage outcome before 22 December 2016. Successful applicants in the first stage will be invited to submit a full proposal. The indicative deadline for submission of full proposals is 2 March 2017.
Evaluation criteria, scoring and thresholds
Following an admissibility and eligibility check, letters of intent and full proposals are evaluated by external, independent experts. Proposals are evaluated according to the criteria Excellence, Impact and Implementation. Each criterion is scored between 0 and 5.
Stage 1: Letters of Intent
For the evaluation of the first stage (Letters of Intent), only the criteria Excellence and Impact are evaluated. Within these criteria, only the aspects in bold will be considered. The threshold for both individual criteria will be 4. The overall threshold, applying to the sum of the two individual scores, will be set at the level such that the total requested budget of proposals admitted to stage 2 is as close as possible to three times the available budget. The actual level will therefore depend on the volume of proposals and funding request per proposal received. The threshold is expected to normally be set at 8 or 8.5. Successful applicants will be invited to submit a full proposal in the second stage.
Stage 2: Full proposals
For the evaluation of the second stage (Full Proposals), evaluation scores will be awarded for the criteria Excellence, Impact and Implementation. Each criterion is scored between 0 and 5. The threshold for individual criteria is 3 and the overall threshold for the sum of the three individual scores is 10. Applicants have the opportunity to submit a written response to the expert reviewers’ comments prior to an expert review committee meeting convened by EDCTP to finalise the funding recommendations.
The following aspects are considered under the evaluation criteria:
- Fit with the scope and objectives of the EDCTP2 programme and the call topic description.
- Importance, relevance/pertinence and clarity of the objectives.
- Soundness of the concept and credibility of the proposed approach/methodology.
- Importance of the question being addressed and the rationale/need for the proposed clinical trial(s) now.
- Excellence and appropriateness of the clinical trial design, including the proposed location(s) of the trial.
- Extent that the proposed trial will advance the field. In particular, how it differs from or complements any relevant planned, ongoing or recently completed trials internationally.
- Appropriate consideration of interdisciplinary approaches, and where relevant, use of stakeholder knowledge
- The extent to which the outputs of the proposed work would contribute, at the European, African and/or International level, to each of the expected impacts listed in the work plan under the relevant topic.
- Likelihood to result in major advances for the field.
- Advancing the clinical development of new and improved products.
- Generalisability of the trial/study results beyond the immediate research setting in a way that will maximise the impact of the results.
- Contribution to improved disease management and prevention through changes in policy, with the ultimate goal of improving public health.
- Contribution to strengthening the capacity in sub-Saharan Africa to conduct clinical trials.
- Effectiveness and quality of the proposed measures to exploit and disseminate the project results (including management of IPR) to communicate the project activities to different target audiences, and to manage research data where relevan
3. Quality and efficiency of the implementation
- Quality and effectiveness of the work plan, including extent to which the resources assigned to work packages are in line with their objectives and deliverables.
- Appropriateness of the management structures and procedures, including risk and innovation management, and how responsibilities for research data quality and sharing, and security will be met.
- Complementarity of the participants within the consortium, and the extent to which the consortium as whole brings together the necessary expertise.
- Appropriateness of the allocation of tasks and resources, ensuring that all participants have a valid role and adequate resources in the project to fulfil that role.
- Feasibility and appropriateness of the methods and project management to achieve the objectives within the timeframe of the grant.
- Compliance with national and international standards of research, Good Clinical Practice, ethics and safety related issues.
- Participants have the operational capacity, to carry out the proposed work, based on the competence and experience of the individual participant(s).
- Competence of the participants and their investigators in conducting trials according to international standards of Good Clinical Practice (ICH-GCP).
- Involvement of sub-Saharan African researchers in the scientific leadership of the clinical trial.
- Arrangements and plans to take forward clinical development of the products under evaluation (where applicable).
For the evaluation of letters of intent only the criteria Excellence and Impact will be evaluated. Within these criteria, only the aspects highlighted above in bold will be considered.
For all applications involving human participants, and/or human tissues, cells or personal data, the evaluation process will include an assessment of ethical issues.
The call budget is 10 million EUR.
The requested EDCTP contribution per action should not exceed 3 million EUR. The funding level is 100% of eligible costs.
The Coordinator is required to sign a grant agreement with EDCTP (EDCTP2 multi-beneficiary grant agreement) within three months of receipt of the conditional award letter. All participants in the project must sign a consortium agreement.
Documents and more information
- EDCTP2 annual work plan 2016 (PDF)
- Template of application form – Letter of Intent (Word)
- Template of application form – Full Application (Word)
- Annex: Essential information for clinical trials applications (PDF)
- For questions related to this call for proposals, please contact: Dr Christy Comeaux, at comeaux[at]edctp.org
- For questions and issues about EDCTPgrants and the online application submission please contact EDCTP via edctpgrants[at]edctp.org or +31 (0) 70 344 08 80.
- For guidance on online application procedure, please refer to the Guidance for applicants.
- For more information about EDCTP2 procedures, please refer to the EDCTP2 Grants Manual and EDCTP2 FAQs
- Call-specific FAQs (PDF)