Ginkgo biloba and acetazolamide for acute mountain sickness: Authors' reply

Ginkgo biloba and acetazolamide for acute mountain sickness

Authors’ reply

Jeffrey H Gertsch

resident physician

Buddha Basnyat

medical director

E William Johnson

resident physician

Peter S Holck

associate professor

The recruitment of Western trekkers in the prevention of high altitude illness trial (PHAIT) study was based on logistics and practicality. Sherpas and other Nepalis residing in or adjacent to the Everest region and above 2000 m are highly resistant to the effects of altitude and would thus be poor research participants. Whereas many Nepalis working in the Everest region reside at altitudes below 1500 m (potentially eligible research candidates), a fair number of porters live in higher regions that would make some degree of acclimatisation likely.

Furthermore, many lowland dwelling Nepalis working in the trekking industry as porters will relocate temporarily for the season to wait for work at the airstrip in Lukla (2500 m), where tourists begin their trek. Many eligible lowland Nepalis will therefore acclimatise en masse in the first several weeks of the trekking season, providing a narrow window for enrolment.

Moreover, one of us (BB) tried in 2001 to study lowland porters as subjects but failed to yield adequate data primarily because of poor enrolment and a high rate of loss to follow up. We agree that more evidence is needed about the epidemiology and treatment of altitude sickness in lowland Nepalis.

Excluding bias in clinical trials conducted in the Everest region is inherently problematic because of logistical issues unique to the area. Healthy vacationing trekkers who decline participation in a clinical trial are often not interested in taking the time to provide further information. The argument against bias in our model stems from the large homogeneous cohort evaluated under strict double blinding and in agreement with CONSORT guidelines, as well as the lack of any differences within groups or in comparing those enrolled with those lost to follow up. The failure to collect data on those who chose not to enrol in the trial is a weakness of the PHAIT study and was dealt with in a subsequent clinical trial (B Basnyat and J Gertsch, unpublished data).

All people passing through the village of Namche Bazarre (a common destination for all trekkers visiting the Everest region) were approached for enrolment in a clinical trial testing pharmacological prevention of acute mountain sickness. Data on reason for non-enrolment were collected from 1931 people (around 80-90% of all people ascending that season). Most (86%) declined for reasons generally unrelated to the substance of the trial: taking a predetermined route away from the study end point (44.8%), not wanting to take drugs of any kind (18.6%), wanting to ascend the mountain without any "help" (11.2%), and other reasons (11.3%). In contrast, only 14% did not meet inclusion criteria, with those already taking acetazolamide being 8.3% of the 1931 approached, and those with altitude or other illness being only 1.4% of the 1931. Furthermore, no differences were found in preliminary baseline statistical comparisons between those who were enrolled (n=247) and those who were not enrolled and willing to provide baseline data (n=21) (B Basnyat and J Gertsch, unpublished data).

It is often a difficult task to exclude enrolment bias completely in clinical research trials, these data oppose an argument of significant bias in our research model. We are therefore confident that the data from the PHAIT study is a fair and convincing test of ginkgo’s efficacy under the conditions tested.

Competing interests: JHG has been funded by Pharmaton to attend a research symposium and received reimbursement for on-site living costs incurred during the implementation period of the study.

1. Begg C, Cho M, Eastwood S, Horton R, Moher D, Olkin I, et al. Improving the quality of reporting of randomized controlled trials: the CONSORT statement. JAMA 1996;276:637-9.