Statistical methodology for the evaluation of vaccine efficacy in a phase III multi-centre trial of the RTS,S/AS01 malaria vaccine in African children
GlaxoSmithKline Biologicals, Wavre, Belgium; Centre de Recerca en Salut Internacional de Barcelona (CRESIB), Hospital Clínic, Universitat de Barcelona, Spain; KEMRI/CDC Research and Public Health Collaboration, Kisumu, Kenya; National Institute for Medical Research, Dar es salaam, Tanzania; Ifakara Health Institute, Ifakara, Tanzania; KEMRI-Wellcome Trust Research Program, Kilifi, Kenya
Background: There has been much debate about the appropriate statistical methodology for the evaluation of malaria field studies and the challenges in interpreting data arising from these trials. Methods. The present paper describes, for a pivotal phase III efficacy of the RTS, S/AS01 malaria vaccine, the methods of the statistical analysis and the rationale for their selection. The methods used to estimate efficacy of the primary course of vaccination, and of a booster dose, in preventing clinical episodes of uncomplicated and severe malaria, and to determine the duration of protection, are described. The interpretation of various measures of efficacy in terms of the potential public health impact of the vaccine is discussed. Conclusions: The methodology selected to analyse the clinical trial must be scientifically sound, acceptable to regulatory authorities and meaningful to those responsible for malaria control and public health policy. Trial registration. © 2011 Lievens et al; licensee BioMed Central Ltd.
malaria vaccine; rts s as 01; unclassified drug; malaria vaccine; Africa; article; child; clinical assessment; clinical evaluation; controlled study; disease severity; double blind procedure; drug efficacy; fever; follow up; groups by age; human; immunization; infant; major clinical study; malaria; malaria control; newborn; outcome assessment; parasitemia; phase 3 clinical trial; preschool child; randomized controlled trial; risk assessment; statistical analysis; Africa; biostatistics; clinical trial; controlled clinical trial; immunization; immunology; malaria; methodology; treatment outcome; vaccination; Africa; Biostatistics; Child; Child, Preschool; Double-Blind Method; Humans; Immunization, Secondary; Infant; Malaria; Malaria Vaccines; Treatment Outcome; Vaccination