Ethical problems of evaluating a new treatment for melioidosis
BMJ 2003; 327 doi: https://doi.org/10.1136/bmj.327.7426.1280 (Published 27 November 2003) Cite this as: BMJ 2003;327:1280
- Allen C Cheng, infectious diseases physician (allenc@menzies.edu.au)1,
- Michael Lowe, general physician2,
- Dianne P Stephens, director3,
- Bart J Currie, professor in medicine1
- 1Menzies School of Health Research and Northern Territory Clinical School, Flinders University, PO Box 41096, Casuarina NT 0811, Darwin, Australia,
- 2Division of Medicine, Royal Darwin Hospital, Tiwi NT 0811, Darwin, Australia
- 3Intensive Care Unit, Royal Darwin Hospital
- Correspondence to A C Cheng
- Accepted 11 September 2003
When mortality from melioidosis fell sharply after multiple changes in management at an Australianhospital, doctors wanted to identify whether a new drug was responsible. But designing a trial that was ethically acceptable proved impossible
Effective treatment of patients requires that is based on the best available evidence, ideally a randomised controlled trial. However, when observational evidence suggests that a treatment has a large benefit, the potential risks to participants make a randomised trial hard to justify. We had to abandon a trial to evaluate the use of granulocyte-colony stimulating factor (G-CSF) in patients with melioidosis in septic shock because we were unable to balance the risks to patients against the scientific uncertainty. This article describes the problems experienced and considers other methods of obtaining good evidence.
Our problem
Melioidosis, the infection caused by Burkholderia pseudomallei, is endemic in South East Asia1 and is the commonest cause of death from bacteraemic pneumonia in the Northern Territory of Australia.2Patients with severe infection present with septic shock, a condition associated with a high mortality. The Royal Darwin Hospital has treated 341 patients with culture confirmed melioidosis over 13 years, with an overall 18% mortality. Forty two of these patients presented with severe sepsis.
In 1998, the hospital decided to start treating patients with melioidosis and septic shock withgranulocyte-colony stimulating factor (G-CSF). The decision was based on the evidence available atthat time (box). G-CSF was introduced at the same time as the hospital appointed a specialist in intensive care medicine. Previously, anaesthetists had supervised the unit, and the appointment resulted in appreciable changes to management protocols, including the more aggressive use of haemodynamic monitoring, empiric antibiotic protocols, the adoption of a closed intensive care model, andearly enteric feeding.
Mortality from severe melioidosis fell from 95% (20 of 21 patients) to 10% (2 …
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