UNICEF/UNDP/World Bank/WHO Special Programme for Research & Training in Tropical Diseases, World Health Organization, Geneva 27, Geneva, Switzerland.
J Med Ethics. 2010 Feb;36(2):116-20. doi: 10.1136/jme.2009.030874.
Placebo-controlled trials are controversial when individuals might be denied existing beneficial medical interventions. In the case of malaria, most patients die in rural villages without healthcare facilities. An artesunate suppository that can be given by minimally skilled persons might be of value when patients suddenly become too ill for oral treatment but are several hours from a facility that can give injectable treatment for severe disease. In such situations, by default, no treatment is (or can be) given until the patient reaches a facility, making the placebo control design clinically relevant; alternative bioequivalence designs at the facility would misrepresent reality and risk incorrect conclusions. We describe the ethical issues underpinning a placebo-controlled trial in severe malaria. To protect patients and minimise risk, all patients were referred immediately to hospital so that each had a higher chance of prompt treatment through participation. There was no difference between artesunate and placebo in patients who reached clinic rapidly; among those who could not, a single artesunate suppository significantly reduced death or permanent disability, a finding of direct and indirect benefit to patients in participating villages and elsewhere.
当个体可能被剥夺现有有益的医疗干预措施时，安慰剂对照试验会引发争议。在疟疾的情况下，大多数患者在没有医疗设施的农村村庄死亡。当患者突然因病情严重而无法口服治疗，但距离能够提供重症治疗的医疗机构还有数小时路程时，一种可以由非专业人员使用的青蒿琥酯栓剂可能具有价值。在这种情况下，默认情况下，在患者到达医疗机构之前，不会（或不能）给予任何治疗，这使得安慰剂对照设计具有临床相关性；在医疗机构进行替代的生物等效性设计将无法反映现实情况，并可能导致错误的结论。我们描述了严重疟疾中安慰剂对照试验的伦理问题。为了保护患者并将风险降至最低，所有患者都立即被转诊到医院，以便每个患者都有更高的机会通过参与获得及时治疗。在迅速到达诊所的患者中，青蒿琥酯和安慰剂之间没有差异；在那些无法迅速到达诊所的患者中，单次青蒿琥酯栓剂显著降低了死亡或永久性残疾的风险，这对参与村庄和其他地方的患者具有直接和间接的益处。
