[External validity of clinical trials for treatment of dementia with ginkgo biloba extracts].

OBJECTIVES: Ginkgo bilobaextracts have been applied in the treatment of dementia of vascular origin and Alzheimer disease for a long time. However, in the most elaborated systematic review to date, Birks and colleagues drew quite a moderate conclusion in spite of the overall positive results. The reason for such a moderate interpretation often lies in the preference of internal validity such as randomisation and blinding, sometimes at the expense of external validity (conditions of everyday practice). Because of this, we analysed the clinical trials evaluated by Birks et al. in the light of the following questions: 1) To what extent are criteria of external validity considered? 2) Does the additional evaluation of external validity lead to differences in the estimation of efficacy? 3) What are the results of our analysis in regard to the efficacy of ginkgo biloba extract?
MATERIAL AND METHODS: The selection of the clinical trials was based upon those included in the review carried out by Birks et al. (2002). The criteria for evaluating external validity were developed by consulting physicians specialised in geriatrics, experts in herbal pharmaceutics and affected/ related individuals (patients and relatives).
RESULTS: We analysed 34 placebo-controlled clinical trials with a total of 37 comparisons. 21 trials showed significant results in favour of the ginkgo application in more than 50% of investigated outcome parameters, eight were significant for less than 50% of the parameters, four showed a trend in favour of ginkgo, and only two studies (with 4 comparisons) found no advantage for ginkgo. One of these negative studies used daily doses far below the usual dose range [corrected] We found no evidence for publication bias. None of the studies considered all criteria of external validity. Out of the seven studies with relatively high external validity and good overall quality, five showed a significant result in more than 50% of parameters, two in < or = 50%. Severe adverse effects were not mentioned in the studies. DISCUSSION AND
CONCLUSIONS: 1) In the clinical studies analysed external validity was taken into account only moderately, especially with respect to additional non-pharmaceutical interventions and selection of participants. 2) The evaluation according to external validity led to a different selection of studies that were used for estimation of the ginkgo efficacy without effects on the overall result. 3) Sufficient evidence of the efficacy of ginkgo bilobaextracts in the treatment of dementia of vascular origin and Alzheimer disease is provided in spite of methodological limitations. Further studies should focus on effectiveness, ginkgo-sensitive subgroups, more individualised therapeutic goals and corresponding outcome measurements.