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Mefloquine to prevent malaria

BMJ 1998; 316 doi: (Published 27 June 1998) Cite this as: BMJ 1998;316:1980

Interpretation of study was not based on evidence

  1. Ron H Behrens, Consultant in tropical and travel medicine* (
  1. Hospital for Tropical Diseases, London NW1 0PE
  2. Global Drug Safety, F Hoffmann-La Roche, Basle, Switzerland*
  3. University of Alberta, Edmonton, Canada T6G 2B7
  4. University of Toronto, Toronto, Canada
  5. Headquarters Defence Secondary Care Agency, Ministry of Defence, London WC2H 8LD
  6. International Health Division, Liverpool School of Tropical Medicine, Liverpool University, Liverpool L3 5QA

    EDITOR—Croft and Garner's interpretation of their systemic review of controlled studies involving mefloquine cannot qualify as evidence based.1 They have selected two outcome measures, non-compliance and withdrawal, as proxy markers for drug tolerance without any evidence of correlation of this behaviour to tolerability. In Orht's study,2 which makes up 43% of the mefloquine group withdrawals, four of the seven withdrawals were because soldiers were redeployed and the remaining three were because of protocol failures3 and concurrent fever, none of which was obviously related to tolerability. In clinical studies where subjects were at no risk of malaria the threshold and reason for withdrawal from prophylaxis may be different from those of travellers, whom the authors claim will behave similarly despite a different risk of malaria.

    The author's argument that a symptom based outcome is less objective than a withdrawal based outcome when measuring tolerability is subjective. The claim that poor compliance or withdrawal from mefloquine is more likely to leave travellers incompletely protected compared with other regimens is unsupported and selectively used to discredit mefloquine. Their study and others3 confirm that mefloquine is an effective antimalarial prophylactic drug. To restrict its use to the fittest and healthiest travellers on the basis of differences in undefined withdrawal rates in non-travellers because no current studies define its true tolerability is naive.

    An important issue, which the authors have failed to acknowledge, is that the tolerability of any prophylactic regimen needs to be counterbalanced by the risks of morbidity and mortality associated with the disease it is used against. Under the banner of an evidence based analysis the authors have used a limited dataset, which is arguably inadequate for meta-analysis, to reflect their …

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