title: [Internal validity of clinical trials for Plasmodium vivax malaria treatment: analysis of evaluation study of in vivo Plasmodium vivax emergence of resistance to standard doses of primaquine].
abstract: Parasite resistance can be defined as the ability of a parasite strain to survive and/or to multiply despite the administration and absorption of a drug given in doses equal or higher than those usually recommended, but within the limits of tolerance of the patients. Therefore, the ideal study design to be used to monitor emergence of parasite resistance would use historical controls or any valid baseline data. Moreover, it is desirable to have some control of remaining determinants of therapeutic failure, not related to biological parasite resistance, which could vary over time and would have potential to distort the analysis for detecting emergence of parasite resistance. Here we comment on the internal validity of studies, which aim to assess the in vivo Plasmodium vivax emergence of resistance to standard doses of primaquine used routinely by health services. Few studies have paid attention to the need to control for other determinant factors of therapeutic failures or made any attempt to compare current findings with cure failure rates of historical controls from a given geographical area. Therefore, attention to the internal validity (and limitations) of study conclusions in these types of study is strongly advised.
authors.affiliation: Fundação Nacional de Saúde de Cuiabá, Cuiabá, MT, Brasil. eduarte@terra.com.br
authors.forename: Elisabeth Carmen
authors.initials: EC
authors.lastname: Duarte
authors.forename: Lorrin
authors.initials: L
authors.lastname: Pang
authors.forename: Cor Jesus Fernandes
authors.initials: CJ
authors.lastname: Fontes
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage*; D001938:Brazil; D002986:Clinical Trials as Topic / Q000592:standards*; D004351:Drug Resistance; D006801:Humans; D016780:Malaria, Vivax / Q000188:drug therapy* / Q000276:immunology; D010966:Plasmodium vivax / Q000187:drug effects*; D011319:Primaquine / Q000008:administration & dosage*; D015203:Reproducibility of Results
chemical_list: D000962:Antimalarials; D011319:Primaquine