Evidence of Lack of Informed Consent During the 2001-2002

ADF Mefloquine Trials

Dr. Remington Nevin rnevin@jhu.edu

•  Open-label trial to describe the tolerability of mefloquine prophylaxis in comparison to doxycycline

•  Motivated by the rationale that “there are limited data on the tolerability of mefloquine for long-term prophylaxis in military personnel”.

•  Conducted from April 2001 to May 2002 •  Involved the administration of 250 mg mefloquine

weekly to 1,157 subjects. •  An initial off-label loading dose of mefloquine was

used, in which 250 mg mefloquine was administered on every other day for the first three days of the trial

“AVM Smart said all those who took the drug signed a consent form, which warned them of the potential side effects…”

Reference: Reilly R. Top medic says ADF has ‘nothing to hide’ over controversial drug trials. Townville Bulletin. March 11, 2016.

Reference: http://www.defence.gov.au/Health/HealthPortal/Malaria/Documents/ Mefloquine%20-%20doxycycline.pdf

Reference: Boudreau E, Schuster B, Sanchez J, et al. Tolerability of prophylactic Lariam regimens. Trop Med Parasitol 1993;44(3):257-65.

Reference: Overbosch D, Schilthuis H, Bienzle U, et al. Atovaquone-proguanil versus mefloquine for malaria prophylaxis in nonimmune travelers: results from a randomized, double-blind study. Clin Infect Dis 2001;33(7):1015-21.

Reference: Kitchener SJ, Nasveld PE, Gregory RM, Edstein MD. Mefloquine and doxycycline malaria prophylaxis in Australian soldiers in East Timor. Med J Aust 2005;182(4):168-71.

Conclusions •  Information in the ADF consent forms

undermined critical manufacturer’s safety information and understated known risks in the medical literature

•  ADF subjects were not given information necessary to provide fully informed consent for their use of the higher-risk mefloquine loading dose

•  These failures increased the risk to ADF subjects of experiencing lasting harm from the drug