Canadian HIV Vaccine Initiative

Consultation on CHVI Funding Programs

Clinical Trial Capacity Building and Networks

Global Context

Two international experts made presentations on the global context for HIV vaccine clinical trial capacity building and networks. Dr. Michael Keefer provided an overview of current, recent and future trials through the US NIAID-supported HIV Vaccine Clinical Trials Network (HVTN).  Dr. Neil Andersson outlined the challenges of developing countries in clinical trial capacity building and networks.

Dr. Keefer provided an overview of clinical trials conducted by the HVTN over the past decade where HIV vaccines focused on T cells.  From 1988 to 2007, trial activity, including phase IIB and phase III trials were conducted on a range of candidate vaccines.

The HIV vaccine field is at a crossroads.  This is because initial definitive results of the Step Trial, halted prematurely at 33 months, indicated that a greater number of infections resulted in the vaccine than in the placebo.  Since then there has been renewed focus on discovery science as a result. Focusing on immunology and improving the understanding of the precise events of HIV transmission are essential. Critical points to consider include the following:

• Establish a balance between early phase research and efficacy trial capabilities;
• Relationship between non-human primate research program and clinical research program;
• Challenge of working with mucosal specimens; and
• Community engagement/acceptance is critical and requires considerable attention.

The HVTN is committed to continue to conduct collaborative clinical research in the spirit of the Global HIV Vaccine Enterprise. Michael Keefer’s presentation

Dr. Neil Andersson’s presentation outlined the challenges of clinical trial capacity building and networks in developing countries. Most trial capacity is located where the trials happen; this is not in Africa where the clinical trials will be conducted. Vaccine clinical trials will need conditions that are specific to Africa to be able to prove their efficacy. They will also need the capacity to measure biological outcomes and to conduct follow-up of HIV status for individuals who have been vaccinated and to determine the “real life” relevance of a vaccine.
Every trial faces specific content issues, such as:

• Side effects and downstream effects;
• Adaptive responses of beneficiaries;
• Synergies (and conflicts) with traditional medicine; and
• The missing population (choice disabled).

The African Development of AIDS Prevention Trial Capacity (ADAPT) Program aims to develop a cohort of African trialists through a partnership among nine universities; four research NGOs and eight governments. The eight-week program covers all the components in a clinical trial. The objective of the ADAPT program is to turn 270 communities in 10 countries into a framework for controlled trials with a baseline of 45,000 adults and 100,000 youth aged 10-16 years. In each of the 10 countries, researchers and field teams, logistical systems, working relations with ethical review boards will have the capacity to conduct clinical trials. The focus of the work is to develop in-country scientific capacity for explanatory trials and pragmatic “real life” trials. Trial content will be related to vaccines and research will be conducted on vaccine implementation. In the end, the ADAPT sites will be part of integrated AIDS prevention that includes a vaccine. Neil Andersson’s presentation

CHVI’s Clinical Trial Capacity Building and Networks Funding Objectives

Louise Holt, Director, Canadian International Development Agency, and Co-Chair, Canadian HIV Vaccine Initiative’s Steering Committee, outlined the clinical trials capacity building and networks component of the CHVI. Its focus is to fill a globally-recognized gap in HIV vaccine clinical trial capability as identified by the Global HIV Vaccine Enterprise, particularly in low-and-middle-income countries where trials are ongoing or planned and build on the Global Health Research Initiative (GHRI) Canada-Africa HIV Prevention Trials Capacity Building Program.
In keeping with the CHVI guiding principles, the key objectives of the component are as follows:

• Strengthen individual and institutional capacity in low-and-middle-income countries for the conduct of clinical trials related to new innovations in HIV prevention, particularly HIV vaccines;
• Support partnerships (new or established) between Canadian and low-and-middle-income country researchers and research institutions; and
• Support collaboration and networking, and increase involvement of Canadian and low-and-middle-income country researchers and institutions in global HIV vaccine clinical trials efforts.

The planned funding program and requirements are for grants for teams co-led by Canadian and low-and-middle-income country researchers.  Funding will support initiatives aiming to build capacity in trials related to new innovations in HIV prevention and demonstrated commitment to CHVI principles.
The next steps for this funding stream are to develop and launch the RFA with input from this consultation. Louise Holt's presentation

Priorities for Clinical Trial Capacity and Networks

Those participants representing international clinical trial networks stressed the point that overcapacity was an important issue in the current environment given the dearth of products in the pipeline ready to be tested. Strategies to retain their existing staff included broadening the focus of their clinical trial sites to prevention and other diseases, particularly tuberculosis and malaria. Given the stream’s focus and the international situation, the discussion explored the options available to CHVI for moving forward. General points of discussion included the following:

• Enhancing capacity building options (e.g. training, career path development);
• Aligning activities with national HIV plans;
• Coordinating activities within CHVI both within CHVI and globally including encouraging networking among CHVI and international clinical trial activities; and
• Encouraging integration with the other CHVI streams (discovery and social research and policy and community engagement) under an overarching strategy.

Asked to select the most important themes from the discussion, the group focused on the following four areas:

1. Conduct gap analysis of existing clinical trial capacities

Even with a good representation from international organizations, there was little agreement on what specific capacities were missing in the existing clinical trial sites which led to the suggestion that an international gap analysis of current capabilities be undertaken. CHVI activities would not wait for this scan, but endeavour to incorporate the findings as they became available. It was broadly agreed that this kind of environmental scan would benefit each of the organizations represented.

2. Capacity Building for HIV Prevention Trials

Given the current climate over clinical trial capacity caused by a lack of products ready to be tested, the participants with existing clinical trial sites all stressed the need to focus the concept of capacity building more broadly to include HIV prevention trials to ensure that work could continue even without a specific product to test. Examples included offering educational courses and undertaking prevention-related activities, such as vaccine preparedness (epidemiology) studies to identify areas with adequate incidence levels and address Ministry of Health issues, community work, etc.

3. Ensure Sustainable Capacity

Recognizing the generally accepted 10-year timeframe to find an effective HIV vaccine, and ensuring ongoing, long-term capacity to continue the work was a recurring theme. With the most heavily affected areas all located in low-and-middle-income countries, developing and retaining capacity in these areas will be critical. One suggestion was to make smaller grants available to young researchers to enable them to run smaller trials as a practical means to learn to run larger ones.

4. Create and Encourage Linkages

Internationally, the movement is to create networks within areas of specializations as well as those with specializations that are directly related. With the primary objective of creating mutually value-added partnerships, this trend recognizes the inherent interdependencies among all areas of HIV vaccine activities within Canada and with the international community.