Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Ther Clin Risk Manag. 2008 Aug;4(4):803-19. doi: 10.2147/tcrm.s1025.
Malaria is of continuing concern in nonimmune traveling populations. Traditionally, antimalarial drugs have been developed as agents for dual indications (treatment and prophylaxis). However, since 2000, when the 5th Amendment to the Declaration of Helsinki (DH2000) was adopted, development of new malaria prophylaxis drugs in this manner has ceased. As a consequence, there may not be any new drugs licensed for this indication in the foreseeable future. Major pharmaceutical companies have interpreted DH2000 to mean that the traditional development paradigm may be considered unethical because of doubt over the likelihood of benefit to endemic populations participating in clinical studies, the use of placebo, and the sustainability of post-trial access to study medications. In this article, we explore the basis of these concerns and suggest that the traditional development paradigm remains ethical under certain circumstances. We also consider alternative approaches that may be more attractive to sponsors as they either do not use placebo, or utilize populations in endemic countries who may unambiguously benefit. These approaches represent the way forward in the future, but are at present unproven in clinical practice, and face numerous regulatory, logistical and technical challenges. Consequently, in the short term, we argue that the traditional clinical development paradigm remains the most feasible approach and is ethical and consistent with the spirit of DH2000 under the appropriate circumstances.
疟疾仍然是非免疫旅行者群体持续关注的问题。传统上，抗疟药物是作为双重适应证（治疗和预防）的药物开发的。然而，自 2000 年《赫尔辛基宣言》（DH2000）第 5 次修订版通过以来，以这种方式开发新的疟疾预防药物已经停止。因此，在可预见的未来，可能没有任何新的药物获得该适应证的许可。大型制药公司将 DH2000 解释为，由于怀疑参与临床研究的流行地区人群可能受益、使用安慰剂以及试验后获得研究药物的可持续性，传统的开发模式可能被认为不道德。在本文中，我们探讨了这些担忧的依据，并认为在某些情况下，传统的开发模式仍然符合道德规范。我们还考虑了其他可能对赞助商更有吸引力的方法，因为它们要么不使用安慰剂，要么利用可能明确受益的流行地区人群。这些方法代表了未来的发展方向，但目前在临床实践中尚未得到证实，并且面临着许多监管、后勤和技术挑战。因此，在短期内，我们认为传统的临床开发模式仍然是最可行的方法，在适当的情况下是符合道德规范的，也符合 DH2000 的精神。
