Herbal medicine research and global health: an ethical analysis Jon C Tilburt a & Ted J Kaptchuk b Abstract Governments, international agencies and corporations are increasingly investing in traditional herbal medicine research. Yet little literature addresses ethical challenges in this research. In this paper, we apply concepts in a comprehensive ethical framework for clinical research to international traditional herbal medicine research. We examine in detail three key, underappreciated dimensions of the ethical framework in which particularly difficult questions arise for international herbal medicine research: social value, scientific validity and favourable risk–benefit ratio. Significant challenges exist in determining shared concepts of social value, scientific validity and favourable risk–benefit ratio across international research collaborations. However, we argue that collaborative partnership, including democratic deliberation, offers the context and process by which many of the ethical challenges in international herbal medicine research can, and should be, resolved. By “cross-training” investigators, and investing in safety-monitoring infrastructure, the issues identified by this comprehensive framework can promote ethically sound international herbal medicine research that contributes to global health. Bulletin of the World Health Organization 2008;86:594–599. الرتجمة العربية لهذه الخالصة يف نهاية النص الكامل لهذه املقالة. .Une traduction en français de ce résumé figure à la fin de l’article. Al final del artículo se facilita una traducción al español Introduction not faced in more conventional drug It is already widely used for immune Traditional herbal medicines are development. boosting in AIDS. In vitro pharma- naturally occurring, plant-derived As attention and public funding cokinetic studies suggest potential substances with minimal or no industrial for international traditional herbal interference with vaccines, and animal processing that have been used to treat medicine research collaborations models show liver toxicity at very high illness within local or regional healing grows, more detailed analysis of ethical doses. There are no systemic side-effects practices. Traditional herbal medicines issues in this research is warranted. reported for humans in the literature. are getting significant attention in global Scant literature has addressed selected A few case series have shown mixed health debates. In China, traditional issues such as informed consent and results. Local leaders are requesting the independent review related to tradi- government agency conduct a large, herbal medicine played a prominent 6,7 role in the strategy to contain tional herbal medicine research. Here randomized controlled trial (RCT) of and treat severe acute respiratory we apply a practical, comprehensive Africa Flower to test its efficacy as a syndrome (SARS).1 Eighty per cent of and widely accepted ethical framework novel adjunctive therapy to slow pro- African populations use some form to international traditional herbal gression to AIDS. medicine research.8 We examine in de- of traditional herbal medicine,2,3 and tail difficult questions related to social the worldwide annual market for these Ethical framework value, scientific validity and favourable products approaches US$ 60 billion.2 Cases like these present challenging risk–benefit ratio. We conclude with Many hope traditional herbal medicine questions related to the role of traditional implications for future research in this research will play a critical role in herbal medicines in public health. area, focusing on the importance of global health. China, India, Nigeria, In general, international research on collaborative partnership. the United States of America (USA) traditional herbal medicines should be and WHO have all made substantial subject to the same ethical requirements Case 9 research investments in traditional as all research related to human subjects. herbal medicines.2 Industry has also A government agency from a devel- An ethical framework previously invested millions of US dollars looking oped country is conducting an HIV- outlined by Emanuel et al. and revised for promising medicinal herbs and treatment trial in Africa. A traditional for international research8 offers a useful novel chemical compounds.4,5 This is herbal medicine, Africa Flower, has starting point for thinking about the still a relatively modest investment been used for decades to treat wasting ethics of international traditional herbal compared to the overall pharmaceutical symptoms associated with HIV. Local medicine research. This framework industry; however, it raises interesting traditional medicine healers believe includes eight ethical requirements ethical questions, some of which are Africa Flower is an effective antiviral. for clinical research (Table 1).8 a Department of Clinical Bioethics, National Institutes of Health, Bethesda, MD, United States of America. b Osher Institute, Harvard Medical School, Boston, MA, USA. Correspondence to Jon C Tilburt (e-mail: [email protected]). doi:10.2471/BLT.07.042820 (Submitted: 2 April 2007 – Revised version received: 2 October 2007– Accepted: 25 October 2007 ) 594 Bulletin of the World Health Organization | August 2008, 86 (8) Special theme – Ethics public health Jon C Tilburt & Ted J Kaptchuk Ethics and herbal medicine research These ethical requirements are universal Table 1. A comprehensive framework for research ethics and comprehensive but must be adapted to the particular social context in which Ethical requirement Definition the research is implemented.8 Of these, fair subject selection, independent Collaborative Research leadership must include bilateral representation based review, informed consent, and respect partnership on mutual respect between equal partners with community advice. It includes a responsibility to invest in the scientific training and for enrolled subjects have been discussed capacity-building for ongoing research in a host country where such previously in the literature on the resources are not well developed. ethics of global health research and Social value Knowledge gained from the research should have the potential to raise few issues unique to international 8 lead to new generalizable knowledge or improvements in health. traditional herbal medicine research. Partners should specify in advance to whom benefits will accrue and However, social value, scientific validity, in what way. and favourable risk–benefit ratio raise Scientific validity Research should be designed to produce beneficial and generalizable specific challenges in international herbal knowledge. This includes designing research so that it can be medicine research that have not been feasibly implemented in the settings where it will be conducted. adequately discussed. Fair subject selection Subjects should be selected on the basis of scientific importance, not based on convenience, vulnerability or bias. Social value Favourable risk– The potential benefits of individual participation should outweigh the All research should hold the potential benefit ratio risks of participation. Benefits to the community or population being to achieve social value. Different entities studied should also be optimized. Compelling societal benefit can may view the social value of traditional justify risks to individuals in certain circumstances. medicine research differently. Public- Independent review To maintain the integrity of the research, bodies not tied to the health officials are often eager to define investigators must agree that the risks and potential benefits of the the safety and effectiveness of herbal research are justified. medicines for conditions such as Informed consent Investigators must obtain valid permission for study participation from malaria.3 Conversely, harm can arise subjects in a manner that is sensitive to the cultural context in which with the unscrupulous use of herbs the study is conducted. such as Africa potato (various Hypoxis Respect for subjects Researchers should have a plan for how the research results will be species).7 While some claim that such disseminated; ensuring participants know their right to withdraw, and medicines have “stood the test of time”, monitoring the research for relevant adverse events. they nonetheless pose serious challenges to investigators and regulators from developed countries, in which standards While public-health entities may may want to use traditional herbal of proof are closely linked to proven be concerned with defining the risks medicine research to expand the in- efficacy in RCTs. Accordingly, there and benefits of herbal medicines al- fluence of their culture’s indigenous has been a serious investment in herbal ready in use, entrepreneurs and cor- herbal practices in the global health- medicine research by public-health porations hope herbal medicines may care market. For instance, Nigeria’s bodies in many countries. China yield immediate returns from herbal president recently established a national recently launched a safety research medicine sales, or yield clues to prom- committee on traditional medicine programme focusing on herbal medicine ising chemical compounds for future with the expressed desire to boost injections from traditional Chinese pharmaceutical development. They Nigeria’s market share of traditional medicine.10 South Africa recently test individual herbs, or their compo- medicine.14 In developed countries, included the need for investigating nents,