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Review

Clinical development of new prophylactic antimalarial drugs after the 5th Amendment to the Declaration of Helsinki

, &
Pages 803-819 | Published online: 08 Aug 2008

Figures & data

Table 1 Characteristics of currently available drugs for malaria prevention

Table 2 Characteristics of future prophylaxis drugs

Figure 1 Clinical development of new drugs for malaria prevention.

Note: Antimalarial drugs have traditionally been developed for both malaria treatment and prophylaxis as outlined in the panel on the left. Malarone, the last drug approved in the United States, and developed prior to the adoption of the 5th Amendment of the Declaration of Helsinki (DH2000), is used as an example. Major pharmaceutical companies now consider this approach to be unethical because placebos must be used and the Phase III prophylaxis studies utilize semi-immune individuals in malaria-endemic countries who would not normally benefit from malaria prophylaxis. The development of Malarone (atovaquone-proguanil) has also been criticized because the high cost of treatment made sustainable post-trial access to the drug difficult. Our perspective is that the traditional approach remains ethical and consistent with DH2000 for the reasons stated at the bottom of the left panel and discussed in the accompanying text. The three panels to the right outline potential alternative clinical development pathways based on studies conducted in the traditional target population for prophylaxis (Western travelers), mixed populations of endemic country and nonendemic country immunes or focused on novel forms of prophylaxis. These resolve some of the DH2000 ethical concerns but have varying degrees of feasibility as indicated in the figure and discussed in the accompanying text.
Figure 1 Clinical development of new drugs for malaria prevention.

Table 3 Possible phase III-equivalent study designs