Monitoring antimalarial safety and tolerability in clinical trials: a case study from Uganda.
Malar J
; 7: 107, 2008 Jun 11.
Article
en En
| MEDLINE
| ID: mdl-18547416
ABSTRACT
BACKGROUND:
New antimalarial regimens, including artemisinin-based combination therapies (ACTs), have been adopted widely as first-line treatment for uncomplicated malaria. Although these drugs appear to be safe and well-tolerated, experience with their use in Africa is limited and continued assessment of safety is a priority. However, no standardized guidelines for evaluating drug safety and tolerability in malaria studies exist. A system for monitoring adverse events in antimalarial trials conducted in Uganda was developed. Here the reporting system is described, and difficulties faced in analysing and interpreting the safety results are illustrated, using data from the trials. CASE DESCRIPTION Between 2002 and 2007, eleven randomized, controlled clinical trials were conducted to compare the efficacy, safety, and tolerability of different antimalarial regimens for treatment of uncomplicated malaria in Uganda. The approach to adverse event monitoring was similar in all studies. A total of 5,614 treatments were evaluated in 4,876 patients. Differences in baseline characteristics and patterns of adverse event reporting were noted between the sites, which limited the ability to pool and analyse data. Clinical failure following antimalarial treatment confounded associations between treatment and adverse events that were also common symptoms of malaria, particularly in areas of lower transmission intensity. DISCUSSION AND EVALUATION Despite prospectively evaluating for adverse events, limitations in the monitoring system were identified. New standardized guidelines for monitoring safety and tolerability in antimalarial trials are needed, which should address how to detect events of greatest importance, including serious events, those with a causal relationship to the treatment, those which impact on adherence, and events not previously reported.CONCLUSION:
Although the World Health Organization has supported the development of pharmacovigilance systems in African countries deploying ACTs, additional guidance on adverse events monitoring in antimalarial clinical trials is needed, similar to the standardized recommendations available for assessment of drug efficacy.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Ensayos Clínicos Controlados Aleatorios como Asunto
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Sistemas de Registro de Reacción Adversa a Medicamentos
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Artemisininas
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Malaria
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Antimaláricos
Tipo de estudio:
Clinical_trials
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Guideline
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Prognostic_studies
/
Qualitative_research
Límite:
Child
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Child, preschool
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Humans
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Infant
País/Región como asunto:
Africa
Idioma:
En
Revista:
Malar J
Asunto de la revista:
MEDICINA TROPICAL
Año:
2008
Tipo del documento:
Article
País de afiliación:
Reino Unido