Opening Statement to the Standing Committee on Public Accounts

Audit Observation on Pre-Licensing Use of Mefloquine
(April 1999 Report of the Auditor General)

Mr. Chairman, thank you for this opportunity to present the results of the audit note in our April 1999 report. This note deals with procedures concerning the pre-licensing use of an anti-malarial drug – mefloquine - by Health Canada and National Defence. This issue had been raised in media reports and in the House as well as in letters to the Auditor General. As is our usual practice in response to public and parliamentary concerns, we review them carefully and make some preliminary inquiries. If necessary we conduct an audit if we feel that it is a matter that is significant enough to be brought to Parliament’s attention. That was the course we took in this case, resulting in the preparation of the audit observation.

Mefloquine is recommended by the World Health Organization and others for use against some types of malaria that have become resistant to other drugs. Although licensed in a number of countries since the late 1980s, it was not licensed in Canada until January 1993. Prior to that time, it was available only through special programs.

In 1992, National Defence obtained the unlicensed anti-malarial drug through a clinical trial for use with Canadian Forces personnel being deployed to Somalia.

Health Canada licenses manufacturers to produce and sell drugs that have been demonstrated to be safe and effective. Only licensed drugs can be sold in Canada, except under specific, controlled conditions. It was under such a set of conditions – a "clinical trial" – that National Defence obtained mefloquine. The study design and protocol governing this trial must be approved by Health Canada.

The study protocol specified the investigators’ responsibilities, including keeping accurate records of dispensing information and reporting all adverse drug reactions. It stipulated that informed consent was to be obtained from all participants – soldiers in this case – and specified that "safety data will be collected and efficiency will be monitored for each subject receiving mefloquine." All data were to be provided regularly to the manufacturer.

Mr. Chairman, let me say that we don’t question whether the drug should have been given to the soldiers – they had to be protected from malaria. The problem is that National Defence did not follow the prescribed safety monitoring study protocol for mefloquine in the fall and winter of 1992-93 when the drug was distributed to about 900 soldiers deployed on a peacekeeping mission. This happened even though the Department had followed all the rules in earlier distribution to DND travellers.

In concrete terms, not following the protocol means that:

• Canadian Forces members were given an oral briefing on malaria, mefloquine, and the possible side effects, but did not get the written documentation given to other DND travellers who received the drug;
• the Department did not systematically monitor efficacy or adverse reactions for each person receiving the drug; and
• although 69,000 doses of the drug had been provided to the Canadian Forces unit in Petawawa, records of their use and adverse reactions or side effects were not reported.

DND officials told us that the reason they did not follow the protocol was that they believed that they had received authorization from Health Canada to follow a different set of procedures that would not require informed consent. However, this was not the case. No such approval had been sought or obtained by National Defence.

National Defence has since implemented some organizational changes that it believes will minimize the likelihood of this happening again. Mr. Chairman, your Committee may want to obtain further information about these organizational changes.

In situations where unlicensed drugs are being dispensed through clinical trials, Health Canada has the responsibility to review and approve the study design and protocol. It needs to assure itself that conditions of clinical trial protocols are being met, in order to preserve the integrity of the process and to satisfy conditions set out under the Food and Drug Regulations.

We were concerned about the fact that, although Health Canada had approved the protocol for the Mefloquine Safety Monitoring Study, it took no steps to ensure that it was followed. In fact, the Department has no procedures for monitoring these studies. We were told that monitoring was the responsibility of the manufacturer. Mr. Chairman, your Committee may wish to ask Health Canada officials how they assure themselves that the protocols for safety monitoring studies are followed.

When the use of the drug by Canadian soldiers in Somalia became a media issue in the fall of 1994, Health Canada asked the manufacturer for copies of the records of the 69,000 doses of mefloquine provided to National Defence in 1992. Neither the manufacturer nor DND could provide the information. Nevertheless, Health Canada took no further action.

The failure of Health Canada to monitor the study and the failure of National Defence to provide the manufacturer with the data mean that potentially valuable information about the safety or effectiveness of the drug under "field" conditions was not collected.

Mr. Chairman, there is a need to strengthen measures for ensuring compliance with the approved protocols for clinical trials.

Mr. Chairman, that concludes my opening statement and we would be pleased to answer your Committee’s questions.