Mr. Denis Desautels
Auditor General of Canada
240 Sparks Street
Ottawa, Ontario
K1A 0A6

Dear Auditor General:

On November 20, 1997 I recommended that your audit of the Department of Health's Health Protection Branch (HPB) include an audit of the handling of mefloquine.

Today I want to bring to your attention another example of HPB's disregard for both compliance with the Food and Drug Act and with its own mandate to protect the public. HPB hired the individual at the centre of the military's illegal use of mefloquine, Dr. Martin Tepper. How can HPB be respected as a regulator if it hires someone who apparently broke the very rules that underpin HPB's authority with the public?

The Department of Defence (DND) gained access to the drug by agreeing to the requirements of the Mefloquine Safety Monitoring Study (the Study) as set out in regulations under the Food and Drug Act. Dr. Tepper was designated under the Study as "co-investigator", the doctor responsible for the use of the drug at DND.

When on March 25, 1991 Dr. Tepper signed the HPB "Statement of Investigator of New Drugs" as required under the Food and Drug Act, he agreed to be bound by certain requirements of the Act. The "Statement of Investigator" listed specific obligations that as a co-investigator Dr. Tepper had agreed to accept:

"5. The undersigned realizes that the new drug is being sold or distributed by the manufacturer for the sole purpose of the clinical testing to obtain evidence with regard to safety, dosage and effectiveness of the new drug."

"7. The undersigned agrees:

(i) not to permit the new drug to be used except by myself or under my direction and for the investigation;

(ii) to report immediately to the manufacturer and if so required to the Assistant Deputy, Health Protection Branch...regarding all serious adverse reactions encountered;

(iii) to maintain adequate records of all investigations and to furnish reports at appropriate intervals to the manufacturer on all quantities of the new drug received."

The Study required that information on the adverse effects of the drug be "distributed to the patients." and that safety data "be collected and efficacy" be "monitored for each subject receiving" the drug. (term 7)

The Study stated unequivocally that it was "understood that the drug supplies are exclusively for use in patients under the auspices of this study." The continued supply of the drugs were "dependent upon the receipt by Hoffmann-La Roche Ltd., and by the Health Protection Branch on request, of dispensing records for Lariam, and of safety data on all travellers who received Lariam." (term 10)

The Study (in a section entitled "Ethical Considerations") indicated the "study and the provision of the drug, [were] subject to all applicable requirements of the Canadian Food and Drug Regulations." And further that "any clinical adverse event or abnormal laboratory test value that [was] serious, or unexpected and potentially relevant, must be reported immediately to the responsible personnel at Hoffmann-La Roche and to the Health Protection Branch (telephone contact)." (terms 11 and 12)

Dr. Tepper respected neither the terms of the clinical study nor his responsibilities as an "investigator of new drugs". As you are aware Dr. Tepper would have been in receipt of reports from military doctors describing "intolerable side effects", of attempted suicides, of halicunations and the like. Dr. Tepper failed to report these adverse events to either the manufacturer or HPB, as was required by the Food and Drug Act.

HPB would have known of Dr. Tepper's illegal use of mefloquine before hiring him. On October 20, 1994, HPB made demands on the manufacturer as to the administration of the drug and it was to Dr. Tepper that Hoffmann-La Roche turned, on October 20, 1994, to make an urgent information request in regard to the release of mefloquine:

"In September and October of 1992 shipments of [mefloquine] were made to [DND] under the auspices of the [Mefloquine] Safety Monitoring Study. You were a co-investigator in that study...

"In reviewing our records we are unable to find distribution accounts of the tablets shipped to [DND]. One of the requirements of the study was that investigators maintain logs of the distribution of lariam and forward these logs to Hoffmann-La Roche Ltd.

"We have received a written request from [HPB] for the following information regarding the use of Lariam that was provided under the Safety Monitoring Study...

"The HPB request was received today October 20, 1994 at 14:50. The HPB has asked that this information be provided to them within 24 hours."

On October 24, 1994, Dr. Tepper responded and I interpret that response as an admission that he had not met his obligations under the Food and Drug Act and had illegally administered an unlicensed drug to Canadian soldiers.

Once they were formally made aware (by Hoffmann-La Roche) that Dr. Tepper might have been directly involved in DND's illegally administering of mefloquine, I fail to understand why the department took no disciplinary action against him.

Not only did they fail to take disciplinary actions against Dr. Tepper, they actually hired him.

If the department does not take the requirements of its own clinical licensing studies seriously, then we can hardly expect the hundreds of other doctors who are involved in such studies to take their own obligations seriously.

Yours sincerely,