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The European and Developing Countries Clinical Trials Partnership

22 Jul 2008

Tatum Anderson

Source: TropIKA

The European and Developing Countries Clinical Trials Partnership (EDCTP) has had a very bumpy ride during its short life.

Formally launched in 2003, it brings together 16 European and 46 sub-Saharan countries in a joint mission to accelerate the development of new or improved vaccines, drugs and diagnostics against HIV/AIDS, malaria and tuberculosis. A huge project and the first of its kind, EDCTP’s core aim is to fund phase II and III clinical trials in sub-Saharan Africa using the European Commission’s research budget, with matching funds from individual European countries and other donations.

However, EDCTP has seen four executive directors in four years, and European member states have failed to provide the level of funds expected when it launched.

Last July, an independent External Review Panel – comprising five high-level experts including Adetokunbo Lucas, professor of international health at Harvard University and ex-director of TDR and Wim Van Velzen of US law firm Covington Burley – released a scathing report on the problems at EDCTP. It said that results were slow to materialise, EDCTP was not working enough with the pharmaceutical industry and public-private development partnerships (PPDPs), and that it was operating bureaucratically and allocating funds too slowly. Indeed the panel said that unless wholesale changes were made, critical future European Union funding – so called FP7 – might not be given to EDCTP.

With EDCTP’s future in the balance, Executive Director Charles Mgone, has instituted a turnaround with a team that includes EDCTP’s High Representative, Pascoal Mocumbi, ex-prime minister of Mozambique.

A Tanzanian paediatrician, with expertise in genetics, malaria and HIV/AIDS, and ex-network director of the African Malaria Network Trust (AMANET), Mgone remains quietly optimistic about the future of the organisation. He describes EDCTP as a huge project with ambitious aims that has experienced teething problems – both at the EU and within the organisation.

‘When you have a huge project like this, it takes a time to bed in’, he says. ‘To garner support from member states takes time because every member state has their own funding mechanism and philosophy. It took a while for them to adapt to the new ways of working together. We have learned from that’.

EDCTP is trying to institute large-scale changes to the way in which research is done today. The European Commission and individual countries have conducted research on these diseases for years; individual countries each have national research programmes dedicated to AIDS, TB and malaria.

Developing a common strategy

EDCTP has been tasked with producing a coherent, common research strategy for HIV/AIDS, TB and malaria in all European member states. The idea is to work together in a co-ordinated way to prevent duplication of research projects.

The challenges are not really scientific but political, says Mgone. There are very strong bilateral ties between institutions in Europe and sub-Saharan Africa – usually with colonial roots. There must be the political will for an EU country to change and work for the first time with countries where a historical connection is lacking.

Fernand Sauer, the independent panel’s rapporteur – who is also an honorary director-general of the European commission and member of the French High Council for Public Health – agrees. ‘Countries like the UK, France, Spain and Belgium have a tradition of bilateral ties with certain African countries, but seem reluctant to share them with other member states’, he says. ‘In our report, we stressed that these prerequisites should have been checked more carefully before embarking on such a complex enterprise.’

Sauer adds that some European countries with voting rights within EDCTP do not even run national programmes for poverty diseases for instance. He told TropiKA.net, ‘Their role and interest should have been questioned from the start.’

But things are starting to change, says Mgone. Almost all the member states are starting to provide funds now and increasing numbers are working together. ‘When we started we had two or three member states working together; now several European states are working with up to seven African countries’, he says.

For example, last year, multi-country research funded by EDCTP ensured that a paediatric fixed-dose combination anti-retroviral drug, Triomune Baby and Junior, received approval from the US Federal Drugs Regulatory Authority (FDA). The pharmacokinetic study was undertaken by the University Teaching Hospital in Zambia with research collaborators from Netherlands, San Francisco and the UK-based Medical Research Council (MRC) Clinical Trials Unit.

And in the coming months EDCTP hopes to fund one of the largest TB drug trials in recent years. It will bring together researchers from several countries, PPDPs and pharmaceutical companies.

Two drugs that might be used to shorten the existing TB regimen from six months to four are being trialled. They could help increase the number of people completing a full course of treatment, and prevent more potentially deadly drug-resistant TB strains from appearing.

Currently an existing South African trial, called REMoxTB, is testing one of the drugs, moxifloxacin, in place of drugs usually given to TB sufferers. It is run by the PPDP Global TB Alliance, with University College London and German pharmaceutical company Bayer HealthCare, which originally developed moxifloxacin.

EDCPT – which has funded REMoxTB – plans to fund the expansion of these trials to other countries. More importantly it plans to test another promising TB drug developed by US company Sequella as part of the trial in a similar way to moxifloxacin. This series of distinct but complementary trials will bring together researchers from several European and African countries such as the UK, Tanzania, South Africa, Zambia and Gabon.

Potential collaborations on the horizon

Mgone is trying to involve European development agencies in EDCTP projects because he sees staffing such clinical sites as a development issue.

There is a fear that staff on trial sites will have been poached from already-drained health service delivery systems. Therefore, it is imperative that training must be funded, not just from research funds but from development money he says.

He also wants African countries to contribute ideas and research priorities for the drugs, vaccines and diagnostics they need. He says: ‘To me, one of the clear outcomes we want is that ideas and priorities and capacity development should come from African countries.’ Encouragingly, the majority of these researchers responding to calls for research grants are now coming from Africa, according to Mgone.

But while Mgone agrees that EU countries should decide how to spend their own money, he wants to look at additional mechanisms to involve more African policymakers in those decisions. He is now talking to regional political groupings within the African Union. However, increasing collaborations with countries, companies and PDPs is not the only way to accelerate trials, says Mgone.

The problem is a shortage of trial sites with the right level of staff or equipment to cope with the huge influx of new malaria, TB and HIV trials expected to come to Africa for trials in coming years.

EDCTP says it is trying to put in place resources needed to cope with such trials. That includes funding the establishment of ethics committees and regulatory agencies necessary to vet the quality of such trials. The main focus, however, are the clinical trial sites themselves. EDCTP is funding laboratories and medical staff training.

There are, of course, many well-established and reputable sites that have conducted drug trials for decades. However, others are less mature, understaffed and have far less infrastructure. That is why EDCTP is setting up an ambitious project to link trial sites across Africa. It has divided the continent into several regions – such as South, East, and Central – and asked groups of clinical trial sites to work together within these regions.

The idea is that the best and most mature sites will help less mature regional neighbours to reach international standards. That way, they will be able eventually to bid and carry out multi-country research projects as a group. Drug developers will then have access to the large and diverse cohorts of patients necessary to carry out large-scale multi-country phase III trials.

Different sites will have different strengths. One might specialise in data analysis, one in malaria and another specialise in analysing samples. It is a model that is being used by several organisations including the Drugs for Neglected Diseases Initiative (DNDi).

EDCTP is currently organising the funding of these so-called Regional Centres of Excellence. Each region will be expected to establish a five-year plan detailing exactly what gaps in infrastructure, staff or expertise they need to fill and how.

However, balancing the priorities – conducting clinical trials and getting sites up and running – is difficult, says Mgone. That is because EDCTP has not set aside funding specifically for so-called capacity building projects and, because training is a longer-term game, the results take longer to materialise. ‘That is the tricky part. You’re building capacity at the same time as conducting clinical trials’, says Mgone.

But whether EDCTP’s frenetic activities, vision and strategy will provide the visible and measureable output and results, expected by Europe is unclear. The organisation is expected to be reviewed again at the end of the year with a view to checking its progress since the panel report. For his part, Mgone is confident that EDCTP will receive FP7 funding.

Encouragingly, Sauer says: ‘In my view, the new Executive Director and key people such as the Chair and vice-Chairs of the Board, as well as the High Representative have been able to turn things around during the last 18 months.’

Key Questions

Briefly, what are the priority concerns of your organisation?

To accelerate the development of new or improved vaccines, drugs and diagnostics against HIV/AIDS, malaria and tuberculosis.
And, more precisely, what goals have you set?

To integrate European member states’ national programmes for HIV/AIDS, TB and malaria.
What is it about your organisation’s approach to these issues that distinguishes you from others in this field?

Cooperation between African and European countries as a relationship of equals.
What progress has been made so far?

Sixty-nine grants were issued by July 2007, Euro 60million committed to end of 2007; 30.9% spent on management costs, 44.5% on clinical trials and capacity building. Projects in 26 different sub-Saharan countries involving 123 institutions and almost all 16 participating European member states.
What are the main challenges outstanding?

To further integrate European member states’ national programmes for HIV/AIDS, TB and malaria, develop capacity to conduct clinical trials across the continent and enable African countries to help set ideas and research priorities.
Which other organisations will you be working with most closely?

European states (14 EU members plus Switzerland and Norway) and 46 African countries, PDPs, industry, academic institutions.