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 decision-making and compliance with the requirements of the Food and Drug Act with regard to mefloquine's pre-market evaluation, mechanisms for monitoring adverse drug reactions and post-approval surveillance.

As you are aware the Department of National Defence illegally administered mefloquine to its soldiers bound for Somalia. The Health Protection Branch failed to respond to the breakdown in the Mefloquine Safety Monitoring or in any wayway enforce the requirements of the Food and Drug Act.

By 1993 Canadian military doctors had produced a number of reports detailing adverse effects observed when the drug was administered to soldiers under their care. I want to bring to your attention the information available to HPB through these reports.

As the use of mefloquine by Canadian soldiers provided the only opportunity to observe first hand the effects of the drug, the military use of mefloquine ought to have been of keen interest to HPB, since it was at this time that decisions were being made about the licensing of the drug.

From the beginning military doctors had concerns about mefloquine. Citizens could fairly assume that, as the licensing authority and the body ultimately responsible for the Safety Monitoring Study, HPB was aware of these concerns. The military protocol for the use of mefloquine dated March 18, 1991 states:

"Regarding the potential central nervous system (CNS) side-effects (eg. dizziness) and the precaution related to `pilots, divers and others with occupations requiring fine coordination and spatial discrimination where the onset of dizziness/vertigo can be hazardous or life threatening'...The US Army, which developed mefloquine, has some lingering concerns about CNS side-effects and infrequently uses mefloquine, favouring daily doxycycline use instead...For now in light of inadequate data, no Canadian Forces experience with the drug, and the lingering US army concerns, the Director of Preventative Medicine is uncomfortable with the use of mefloquine in critical safety situations, for example, piloting, diving, parachuting, rappelling, rock face climbing and live fire exercises."

Canada participated in the fall of 1992 in a relief mission to Somalia. The "Medical Post-Op Report" for the mission dated January 21, 1993 describes

"intolerable side-effects from mefloquine, including severe abdominal cramps up to four days after ingestion of the drug, insomnia, headaches, depressed mood, dizziness, diarrhoea and nausea."

Due to the adverse reactions mefloquine was "discontinued and replaced with doxycycline."

Following the relief mission to Somalia, Canada participated in a military. The "Post Deployment Report" from HMCS Preserver for the period of November 16, 1992 to April, 1993 of the military mission to Somalia observed:

"Numerous reactions to mefloquine were reported...A large percentage of the reactions were gastro-intestinal related: with nausea, burning epigastric pain and diarrhoea...Ten patients experienced nightmares, with one patient having feelings of unease and paranoia. One patient heard voices and talked to himself. All were switched to doxycycline with no subsequent problems."

In conclusion I would refer you to a paper presented at a military medicine conference in October 1993 entitled, "Medical Operations in Somalia, Surgical Section":

I believe that the UN's failures in Somalia are rather exceptional, considering previous peace-keeping successes. I believe a simple reason may exist. Canadian and American troops may have been impaired by the use of mefloquine.

Mefloquine is well known to have neurologic side effects...

We had one psychiatric hospitalization in Belet Uen, which did not respond to the usual treatment of battle stress. The diagnosis made by the psychiatrists at NDMC, after he was evacuated, was an organic brain syndrome, probably due to mefloquine. The suicide attempt in theatre may also be mefloquine related.

There are three of us presenting on Somalia today: Two of us had minor neuropsychiatric problems which occurred regularly in the 24 to 48 hours after our weekly mefloquine doses...

I believe that mefloquine causes sub-clinical adverse effects on cognition. The usual soldier taking the drug is not aware of any problems. Nevertheless, his thinking could be impaired...he would not recognize that his judgement was diminished. He would not recognize this because the adverse effect is on cognition, including impaired insight...

I would suggest a further restriction on mefloquine use...

The real difficulty in Somalia might be drug side-effects. It would be wise to conduct such a study of mefloquine..."

I would ask that your audit consider this failure by HPB to show even minimal oversight or interest in the only opportunity to observe the effects of mefloquine first hand either as part of pre-market evaluation or post approval surveillance.

Where was the oversight mandated by the Food and Drug Act?

Yours truly,

John Cummins, M.P.

Delta-South Richmond

Enclosures.

November 20, 1997

Ottawa--"The Department of Health ignored the illegal use of mefloquine and the shortcomings of the Safety Monitoring Study when it licensed the drug," said John Cummins, M.P. (Delta-South Richmond)

Cummins today called on the Auditor General to audit the licensing of the anti-malarial drug mefloquine by the Department of Health's Health Protection Branch (HPB).

The drug was illegally administered to Canadian troops bound for Somalia.

DND's use of the drug provided the only opportunity for Canadian doctors to directly observe the drug's possible adverse effects. HPB ought to have shown a keen interest in the findings of DND's participation in the Safety Monitoring Study. Sadly that was not the case.

Even after the problems associated with DND's use of mefloquine became highly publicized, HPB showed little or no interest in the illegal use of the drug or the failure to comply with the Safety Monitoring Study protocol. In fact, HPB has since hired the officer at DND who was responsible for the illegal use of the drug and who refused to comply with the requirements of the Food and Drug Act.

What use was made by HPB of the results of the Study in its decision to license the drug? Did the department monitor the Study and critically assess its findings prior to the licensing of the drug? Were there similar problems amongst other participants in the Study?

Did other participants treat the legal requirements of the Safety Monitoring Study as lightly as did the Department of National Defence?