Obserapre

National Defence and Health CanadaNonĆcompliance with conditions and inadequate monitoring with respect to the preĆlicensing use of an antiĆmalarial drug National Defence participated in a clinical trial of an anti-malarial drug, but didnot follow the study protocol when the drug was administered to Canadian Forcespersonnel deployed to Somalia. Despite a requirement in the protocol to do so, theDepartment did not obtain consent from the personnel who received the drug, didnot systematically monitor for efficacy, and did not provide to the study sponsorrecords of the drug’s administration or reports of adverse reactions to the drug. Once Health Canada approved the conditions for the clinical trial of the drug, itmade no attempt to monitor the study to ensure that the trial was adhering to theprotocol with its reporting requirements and procedures to protect patients’well-being. Health Canada is responsible for the regulation and licensing of drugs in Canada.
An unlicensed drug may be made available only through special measures, such asa clinical trial when Health Canada has approved the study design and protocol fortesting the drug. Some studies test the drug in “real world” conditions and are thusa potentially valuable source of information about adverse drug reactions amongspecific populations, efficacy problems in certain environments, and so on. and effective. Only licensed drugs can be measures are not available in Canada.
or health hazards associated with hostile drug for a specific patient), or through a “clinical trial”, which tests the drug to obtain evidence on its safety, dosage andeffectiveness. A clinical trial is conducted be subject to discipline under the National Defence Act if they refuse to submit to a to do so. National Defence officials told us that it is policy not to seek written, ensuring that the investigators follow the since such consent is often not compatible inform Health Canada of any seriousadverse reactions (other than those already identified) or deaths associated with the Report of the Auditor General of Canada – April 1999 become resistant to other drugs. Althoughlicensed in a number of countries since the National Defence did not consistently
late 1980s, it was not licensed in Canada follow the protocol for the Mefloquine
Safety Monitoring Study
conditional on satisfying the requirements Safety Monitoring Study. The Departmentkept records of all but 362 of the 3,500 compassionate access” clinical trial called sponsorship of the drug’s manufacturer.
chloroquine-resistant malaria was present had access to mefloquine under controlled the drug’s distribution, nor did it obtainthe consent of those receiving the drug, members were given an oral briefing onmalaria, mefloquine, and the possible sideeffects, but did not get the written the direction of 21 principal investigators, travellers who received the drug. Further, who were medical doctors in travel clinics even though all supplies of the drug used investigational use only”, the Department did not systematically monitor efficacy or stipulated that informed consent was to be disease surveillance system and a periodic for each subject receiving [mefloquine]”.
All data and records were to be providedregularly to the sponsor (the a number of side effects of the drug forwhich patients were to be monitored,including gastrointestinal, central nervous the study beginning in March 1991, with a severe side effects were rare, mefloquine was not prescribed for pilots or others in occupations ‘‘requiring fine co-ordination Report of the Auditor General of Canada – April 1999 the responsibility of the manufacturer, as hazardous or life-threatening”.) Although 69,000 doses of mefloquine had beenprovided to the Canadian Forces medical October of 1992, information on their use and to terminate the study if it believes it is not being conducted properly. However, conduct of these studies or clinical trials.
obtained about safety and efficacy ofmefloquine.
was not the only participant in the studywho failed to provide the manufacturer manufacturer ’s final report on the study reported by all 21 principal investigators, stated that the inability to obtain the actual been provided with any evidence that such on the basis of pills dispensed. The report authority was sought, or even discussed in National Defence, with Health Canada orwith the manufacturer. National Defence investigators in the study but there were Food and Drugs Act and Regulations, inJuly 1998 National Defence established a the U.S. and Europe since the late 1980s, medical products. This position serves as a October 1994, when the use of the drug by Canadian soldiers in Somalia became anissue in the media, did Health Canada askthe manufacturer for copies of the records Health Canada took no steps to ensure
the mefloquine study protocol was
provided to National Defence in 1992.
followed by National Defence
The manufacturer did not have any suchrecords, although the study protocol called ensure that it was followed. They said that Report of the Auditor General of Canada – April 1999 represent a potentially valuable source ofinformation about the drug and its use.
National Defence’s response: Despite the
shortcomings identified in this audit obligations as a participant in a clinical observation, cases of potentially lethal malaria were prevented and the health and safety of Canadian Forces personnel were not compromised. At the time of the Somalia deployment, mefloquine was already licensed in 29 countries, including the United States, and the drug had an established record of safety and efficacy. noted that, as a result of this situation, This record is further supported by the recommendations of the World Health Organization and by Health Canada’s granting of a Canadian licence in January of 1993, which coincided with the arrivalof the main body of Canadian troops in dispensed through clinical trials, HealthCanada has the responsibility to review Health Canada’s response: It is Health
and approve the trial design and protocol.
Canada’s policy that the monitoring of It needs to assure itself that the conditions study protocols rests with the sponsor of of clinical trial protocols are met in order to preserve the integrity of the process and manufacturer), as well as associated institutional research ethics boards, and Food and Drug Regulations. “Open label” data safety monitoring committees. trials provide an opportunity to test the Physicians conducting clinical trials do so under provincial/territorial jurisdiction and processes are in place to monitor the potential hazards or problems that may not compliance of medical professionals with surface under laboratory conditions. They Assistant Auditor General: Maria BarradosPrincipal: Ronnie CampbellDirector: Carol Motuz For more information, please contact Ronnie Campbell.
Report of the Auditor General of Canada – April 1999

Source: http://www.oag-bvg.gc.ca/internet/docs/9900ce.pdf