title: Design of a Phase III cluster randomized trial to assess the efficacy and safety of a malaria transmission blocking vaccine.
abstract: Vaccines interrupting Plasmodium falciparum malaria transmission targeting sexual, sporogonic, or mosquito-stage antigens (SSM-VIMT) are currently under development to reduce malaria transmission. An international group of malaria experts was established to evaluate the feasibility and optimal design of a Phase III cluster randomized trial (CRT) that could support regulatory review and approval of an SSM-VIMT. The consensus design is a CRT with a sentinel population randomly selected from defined inner and buffer zones in each cluster, a cluster size sufficient to assess true vaccine efficacy in the inner zone, and inclusion of ongoing assessment of vaccine impact stratified by distance of residence from the cluster edge. Trials should be conducted first in areas of moderate transmission, where SSM-VIMT impact should be greatest. Sample size estimates suggest that such a trial is feasible, and within the range of previously supported trials of malaria interventions, although substantial issues to implementation exist.
authors: Agence de Médecine Préventive, 13 Chemin du Levant, 01210 Ferney-Voltaire, France. Electronic address: idelrieu@aamp.org.
authors: Isabelle
authors: I
authors: Delrieu
authors: PATH, Bâtiment Avant Centre, 13 Chemin du Levant, 01210 Ferney-Voltaire, France. Electronic address: dleboulleux@path.org.
authors: Didier
authors: D
authors: Leboulleux
authors: PATH, 207 Route de Ferney, 1218 Grand Saconnex, Geneva, Switzerland. Electronic address: kivinson@path.org.
authors: Karen
authors: K
authors: Ivinson
authors: Agence de Médecine Préventive, 13 Chemin du Levant, 01210 Ferney-Voltaire, France. Electronic address: bgessner@aamp.org.
authors: Bradford D
authors: BD
authors: Gessner
mesh_terms: D000818:Animals; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D017780:Malaria Vaccines / Q000009:adverse effects / Q000276:immunology / Q000592:standards; D016778:Malaria, Falciparum / Q000517:prevention & control* / Q000635:transmission*; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology; D018571:Sentinel Surveillance
chemical_list: D017780:Malaria Vaccines
keywords: Cluster randomized trial; Malaria; Transmission blocking vaccine; Trial design