What is INESS and what is new?

The INDEPTH Effectiveness and Safety Studies of Anti-malarial Drugs in Africa (INESS) is an exciting new platform that aims to enable African researchers to carry out a large Phase IV trials. This will result into systematic, evidence-based reviews of the comparative effectiveness and safety of malaria drugs in many widely used drug classes, and to apply the findings to inform public policy and related activities in local settings.

This kind of Phase IV studies for antimalarials has not previously taken place in Africa under the direction of African researchers. It will provide objective country-specific effectiveness and safety data to inform global and national policy and practice and will speed up access to evidence on treatment effectiveness and safety. INESS will also enhance African capacity to monitor local health systems in order to track the costs, effectiveness of coverage, and impact of newly registered antimalarial treatments. Overall, INESS aims to reduce the time gap between the licensing of a new drug and its introduction into health systems for use.

INESS goals and objectives

The INESS platform aims to provide national, regional and international health decision makers with independent and objective evidence on the safety and effectiveness of new antimalarial drugs as a basis for malaria treatment policy in Africa.

INESS seeks to enable decision making and not to make decisions on behalf of affected countries. The more particular objectives of INESS are to:

• develop and maintain a Phase IV effectiveness and safety studies platform in Africa;
• assess the effectiveness and safety of new malaria treatments – and the factors that determine effectiveness and safety – in real life settings in Africa; and
• undertake research in line with comprehensive pharmaco-vigilance in the context of African health systems.

How and where is INESS being implemented?

A standardised process for evaluating the real life safety and effectiveness of current and alternative antimalarial treatments will be developed and implemented.

During the initial phase of INESS, the current first-line artemisinin-based combination therapy (ACT) in Ghana and Tanzania will be evaluated. This will provide information on their safety and effectiveness, which is still unavailable despite their large scale utilisation.

Once a new anti-malarial drug is registered in a participating country, it will be introduced through the routine public health services in the districts hosting the selected INDEPTH Health and Demographic Surveillance System (HDSS) sites. New drugs will be evaluated using standardised systems to generate effectiveness and safety assessments which are comparable to those for currently recommended drugs.

INESS will be undertaken at eight sites in four sub-Saharan countries – including some of the world’s most severely malaria-affected communities. The four-year INESS project takes place in eight INDEPTH HDSS sites in Burkina Faso, Ghana, Mozambique and Tanzania.

The extensive geographic reach of the project provides an opportunity to evaluate antimalarial drugs over a wide range of epidemiological and health system settings. The INDEPTH HDSS sites have functioned for many years as health and demographic observatories. INESS studies target a population of more than 2 million participants.

INESS will consist of three key project components:

• Strengthening existing HDSS sites to undertake effectiveness and safety studies.
• Strengthening health facilities and their links to the HDSS sites.
• Implementing effectiveness and safety studies.

The research will focus on ACTs that are currently recommended by the WHO, and which pair up artemisinin derivatives with one or more antimalarials of a different class, e.g, Artemether-lumefrantine , Artesunate + amodiaquine, Artesunate + mefloquine, Artesunate + sulfadoxine-pyrimethamine, among others.

INESS is a necessary and well timed project for Africa

INESS is an African project with the potential to change the face of malaria treatment in Africa. It will contribute to the achievement of MDGs that focus on the development of new tools to tackle major epidemics, and on evaluation of the effectiveness of various treatments in specific health system settings.

Drug development is a slow, uncertain and complex process which consists of four key phases. Phases I, II and III clinical trials take place under controlled conditions on a few patients. Such trials for malaria drugs have already been done in Africa, and have established the initial safety and efficacy of newer antimalarials.

However, large scale Phase IV studies – thus far not undertaken in African settings – are now needed to determine the drugs’ exact effectiveness and rare side effects and contra-indications.

This data will assist national malaria control programmes to make policies on appropriate use of antimalarial drugs, especially, the newly registered drugs. The absence of such experience and evidence profoundly delays the uptake and access to advances in treatment.

Why Drug Effectiveness and Safety are Critical

The use of effective antimalarials remains the cornerstone of malaria control in the world. There are many malaria drugs on the market being used in various countries, including the more expensive drug combinations such as ACTs that have been developed to reduce the development of resistance to earlier drugs such as chloroquine and sulfadoxine-pyrimethamine (SP).

All ACTs are proven to be very efficacious, some up to 99 percent; but are estimated to be less than 30 percent effective due to bottlenecks of most African health systems such as: access/cost, patient adherence, provider behavior, acceptability, availability, quality, and safety. This is why the INESS project is very crucial, in assessing and documenting these processes.

Benefits and outputs of INESS

INESS is expected to strengthen health systems in the participating countries by rapidly introducing significant benefits in four different but related areas of health service delivery: data management, policy and health service management, access to optimal treatments, and better treatment outcomes. Specifically, INESS will lead to:

• reduced time between the moment the new anti-malarial drugs are registered and introduced for use. Introduction will be substantiated by readily available information about their efficacy and safety;
• the ability to generate large scale district-level effectiveness data for different antimalarial drugs, and to compare such data between countries and between districts within countries;
• better informed policy making in the participating countries and beyond. Information generated with INESS will enable policy makers to decide how to prioritise, how to integrate new antimalarial products into existing health delivery systems and how to deploy these new interventions;
• strengthened surveillance sites and government health systems as a result of the INESS capacity building component;
• strengthened safety monitoring systems because of linkages of Health Information System (HIS) and surveillance sites, which will enable the consolidation and amplification of research data. For example, it will be possible to trace patients on specific treatment regimes and link treatments to side effects, pregnancy outcomes or deaths in the community;
• enhanced capacity in Africa to monitor local health systems in order to track costs, effective coverage, and effects of new or alternative post-registration antimalarial treatments; and
• availability of other socio-economic data routinely captured by the surveillance sites, which is relevant for policy making but not directly related to malaria, such as population size, poverty levels, nutrition levels and the fertility index.

Information sharing

Information will be shared freely and promptly among health research sites, including those not directly participating in INESS. Information will also be shared with the national malaria control programmes and regulatory bodies in the various countries, as well as with policy makers, partners and other interested parties. Annual briefings and major stakeholder meetings will be convened to disseminate updates and outcomes of INESS studies at sub-regional and national levels.

The various Ministries of Health, WHO, NGOs and other major stakeholders will be involved at the sub-regional level. WHO will have access to the data and findings to facilitate the development of new antimalarial policy frameworks. The community at large will be informed through local media channels on regular basis.

Partners

• School of Public Health, University of Ghana, Ghana
• University of Cape Town(UCT), South Africa
• The Swiss Tropical Institute(STI), Switzerland
• Centre for Disease Control(CDC), United States of America(U.S.A)
• The London School of Hygiene and Tropical Medicine(LSHTM), United Kingdom(U.K)

For further information contact