This article presents an ethical framework for conducting international traditional medicine research, including clinical trials. The authors emphasise the need for such research to both have a social value — which may justifiably differ across countries — and be scientifically valid. They highlight the role that international collaborations can play in achieving the ethical requirements for traditional medicine research.

Ensuring that traditional medicines are safe and effective is a major challenge. This study uses mathematical models to show that the treatments that become popular through communities and get passed down through generations are not necessarily the most efficacious. Often, ineffective treatments that are based on superstition can spread because, the authors say, their very ineffectiveness means that patients use the treatment for longer than medicine that actually works.

This review article outlines the basic principles of traditional Chinese and Indian medicine, and the differences in how these are being integrated into national health systems. The authors discuss progress in drug discovery including traditional medicinal plants and the role of supporting industries — from breeders to manufacturers — in commercialising traditional medicine.

This series of commentaries and research articles — published by The Lancet, the Peking University Health Sciences Centre and the China Medical Board — addresses China's major health challenges, strategies and future. It has been produced by a group of 63 scientists from 10 countries with Chinese scientists making up two-thirds of the authors.

The research papers give scientific evidence on key health issues including the emergence and control of both infectious and chronic non-infectious diseases in China as well as the performance of China's healthcare system.

Authors of the series' commentaries further discuss a range of topical issues affecting China's health system, including the state of biomedical science and technology (see 'Progress in Chinese biomedicine a massive challenge'), medical research ethics, the lessons learnt from China's schistosomiasis control programme and the challenges the country faces in controlling HIV/AIDS.

This report is the WHO's official record of data produced by its technical programmes and regional offices in close consultation with countries and in collaboration with researchers and development agencies. The WHO produces the statistics to provide an evidence base for strategies to improve global public health.

The report clearly shows that the global burden of disease is shifting from infectious diseases to non-communicable diseases, with chronic conditions such as heart disease and stroke now being the chief causes of death globally. The shifting trends indicate that leading infectious diseases — diarrhoea, HIV, tuberculosis, neonatal infections and malaria — will become less important causes of death globally over the next 20 years.

The report documents in detail "the levels of mortality in children and adults, patterns of morbidity and burden of disease, prevalence of risk factors such as smoking and alcohol consumption, use of health care, availability of health care workers, and health care financing."

The WHO has provided its own estimates of how non-communicable diseases are set to rise in developing countries. These authors pool data from national registries and international databases to compare data on the differing burden from individual diseases. They outline the risk factors associated with the diseases.

The main three killers are cardiovascular disease, diabetes, and cancer. The paper ranks different types of cancer by how many people in developing countries they kill (lung and breast cancer are the deadliest) and also ranks diabetes prevalence by country (India, followed by China, has the highest prevalence).

To tackle these diseases, say the authors, people need to look closely at the risk factors in their life – eating healthily and exercising can do much to reduce the chances of getting one of these diseases.

This Compilation lists the human subjects research legislation, regulations or guidelines for 79 countries, the European Union and the Commonwealth of Independent States, and several international organisations. It was developed for IRBs/Ethics Committees, researchers, funding agencies and others involved in international research with the aim of helping these groups familiarise themselves with the laws, regulations and guidelines of countries in which research will be conducted. A description of the methods used to collect and update the information is included.

This paper maps African countries' knowledge base through patent applications and publications. It shows South Africa as academically, and technically, the strongest country of the continent. The number of publications is growing in other African countries, but patenting remains limited all-round.

The paper ends on a positive note, arguing that African countries already possess the basis for knowledge-driven development.

This 'sounding board' article in the New England Journal of Medicine is the most substantive of the three articles that stimulated international debate about the ethics of placebo-controlled trials in developing countries (the other two were editorials in the New England Journal of Medicine (see above) and The Lancet).

Lurie and Wolfe take the view that placebo-controlled trials of a less expensive course of antiretrovirals to prevent mother-to-child transmission of HIV were unethical and would lead to hundreds of preventable HIV infections in infants. They identify 18 placebo-controlled trials involving more than 17,000 women, of which two trials were conducted in the United States and the remainder in developing countries. All the participants in the US studies received some form of antiretroviral treatment. In contrast, some or all of the participants in 15 of the trials in developing countries (nine of which were funded by the US) were not provided with such treatment.
 
The authors list areas of agreement between the critics and supporters of such trials, and conclude that the sole point of disagreement is over what is the most appropriate standard of care to provide to the control group. They argue that given the current scientific evidence it would be possible to design shorter, more affordable antiretroviral treatment programmes without the need to conduct placebo-controlled trials.

This editorial is one of three articles that started the current debate about appropriate standards of care in clinical trials (the other two were an article by Peter Lurie and Sydney Wolfe in the same edition of the New England Journal of Medicine (see below), and an editorial in The Lancet). Marcia Angell criticises the placebo-controlled trials that were conducted to test an intervention to reduce mother-to-child transmission of HIV.

The article refers to the importance of researchers being in equipoise (i.e. not knowingly giving some groups of participants inferior treatment) and of not subsuming the interests of individual participants for the greater good. The author lists justifications that were given by research sponsors for this work: that participants were not being denied treatment that they would otherwise receive and that a placebo-controlled trial was the fastest and most efficient way to obtain information of relevance to the areas where the research was being conducted.

Angell concludes that these justifications were reminiscent of those of the infamous Tuskegee study where participants in the United States were not informed that they were enrolled in research, and were denied effective treatment for syphilis when this became available. Concern is expressed that the HIV study appears to mark a retreat from ethical principles about research conducted in developing countries as set out in international guidance - for example, participants received a local standard of care rather than the ‘best’ current treatment as required in the Declaration of Helsinki - and the reasons for this are critically examined.

This "education and debate section" focuses on the 2000 revision of the Declaration of Helsinki, and comprises four articles commissioned from researchers working in the developing world, the developed world, the pharmaceutical industry, and a patient representative.

South African researcher Stephen Tollman argues that "despite the increasingly inclusive aspirations of the revised declaration, some of the absolute and exclusionary language could unintentionally endanger research in developing countries". Consumer advocate Hilda Bastian lists nine gains for consumer rights arising from the revision, but goes on to discuss a number of perceived problems in more detail. UK researcher Richard Doll distinguishes five different types of medical research and claims that "strict application of the declaration’s principles would make a wide range of clinical, biological and epidemiological research impracticable or invalid".

To some extent this conclusion is mirrored in the article from two members of the pharmaceutical industry. Laurence Hirsch and Harry Guess of Merck Laboratories say that several provisions in the revision do not provide better protection of research participants in clinical trials, and inadvertently hamper the development of safe and effective vaccines and drugs.

Evelyne Shuster opens this article with the Nuremberg Code - the precursor to the Declaration of Helsinki and other international and national guidance on the ethics of medical research. 

Shuster discusses the role of physicians in the formulation of the Code during the famous Nuremberg trials of Nazi physicians. The lawyers' arguments about unethical research conducted in Germany, France, the Netherlands, Britain and the United States demonstrate how views about what constitutes acceptable and unacceptable research have changed over the last century. 

The article goes on to summarise how medical researchers have used the Code, and its effect on guidance and regulation over the five decades following its publication. 

In this article Asad Jamil Raja discusses some of the revised provisions in the 2000 revision of the Declaration of Helsinki and considers their implications for developing countries. Two points singled out for particular consideration are paragraph 19 (which requires a "reasonable likelihood" that research populations will benefit from the results of research) and the controversial paragraph 30 (which concerns what should happen after research).

The article goes on to consider the role of the pharmaceutical industry in medical research and proposes three measures to improve the ethics of healthcare: an examination of the ethics of the pharmaceutical and biotechnology industry, for the World Health Organisation to play a more proactive role in resource allocation for global healthcare and health research, and measures to strengthen the capacity for ethical review in developing countries.

Particularly useful for those in developing countries about to embark on an HIV vaccine trial, this article describes the social, behavioural and ethical issues that arose in 1996 when Uganda was preparing for Africa's first HIV vaccine trial (which ran from 1999-2000).

Most notable were misconceptions about vaccine safety and its effects, such as whether the vaccine itself could cause disease, or was a treatment for infection. The authors describe the strategies employed to overcome these barriers, for example, through public outreach education and media communication.

This study examined the effectiveness of two different methods of informing prospective participants about HIV research in Haiti. The first group of participants received information in a single interview with a physician. In a subsequent assessment of their understanding, only 20 per cent passed a questionnaire test.

The consent procedure was then modified to include three meetings with a Haitian social worker over 7-10 days before a final meeting with a physician-researcher. Of those participants agreeing to take part in the research, 80 per cent passed the comprehension test.

Noting the lack of practical guidelines on how best to inform and test the understanding of research participants in developing countries, Fitzgerald and colleagues conclude that a formal assessment of comprehension should be a routine part of the consent process.

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This article from the Gambia Government / Medical Research Council Joint Ethical Committee is an early response to the criticisms in the New England Journal of Medicine and The Lancet that placebo-controlled trials to prevent mother-to-child transmission of HIV were unethical.

The authors express concern that important research in developing countries would be threatened if research practice were changed in response to such criticisms. In particular, research that only compared new interventions with the best available therapy in developed countries would fail to provide information about interventions that are relevant and affordable for the local situation.

The authors note that there is sometimes a need to re-examine interventions that have proved effective in developed countries before it is possible to make an informed public health decision about introducing them in the developing world. They conclude that "stopping trials in Africa that are trying to help improve the health of poor people so that those in affluent countries can have peace of mind seems a tortured form of ethical logic".

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In this article Lindegger and Richter focus on two contentious aspects of informed consent. The first is the problem of 'social desirability' whereby participants may consent to take part in research because they wish to impress researchers or to please others in the community. The second is ways to determine whether participants' comprehension of the research is adequate to enable them to make an informed choice.

Other topics that are covered are conflicts that can occur between ethical principles and cultural practices when consent to research is sought, and how decisions about whether or not to take part in research should be made by communities and individuals. While consideration of these issues takes place within the context of South African HIV vaccine trials, the issues raised and the useful discussion that follows have a much wider relevance.

This, the first edition of South African guidelines for good practice in the conduct of clinical research, is closely related to the regulatory requirements of the country's Medicines Control Council and the National Department of Health. Noting that the South African context is an unusual combination of significant disease burden and extensive high-tech medical expertise and infrastructure, the guidelines set out "clearly articulated standards of good clinical practice in research that are also relevant to local realities and contexts". Guidance is also provided on the minimum standards that are acceptable for conducting clinical trials in South Africa. Very usefully, throughout this document there is reference to national and international guidance documents that have informed the drafting, and/or provide further context to the recommendations.

The guidance opens by setting out the principles of respect for persons, beneficence, non-maleficence and justice. These are considered to require that distinct components be built into research studies, including "relevant and appropriate study rationale, optimal study design, investigator competence, a balance of risks and benefits for participants, transparency, patient privacy, ethical review and impartial oversight of consent procedures". Specific sections of the guidance consider the review and approval process for research, the protection of study participants, the responsibilities of researchers and sponsors, quality assurance and data management. The final section focuses exclusively on ethical considerations for clinical and epidemiological research on HIV/AIDS.

In this article Brian Vastag looks at the initial mixed response to the October 2000 revision of the Declaration of Helsinki, in particular those provisions relating to the use of placebos and the availability of therapies to participants after research is over.

The views range from enthusiastic support — Delon Human, Secretary General of the World Medical Association suggests that the revision is an ideal that sets an ethical standard "which I don’t think can be set high enough" — through to disapproval — Robert Temple MD, director of the FDA’s Office of Drug Evaluation comments, "I think it’s scientifically and ethically incorrect".

The article goes on to outline ongoing controversies about what standards of care are ethical in research in developing countries. It concludes that while the question of who should meet the costs of satisfying the Declaration's requirements is unclear, the revised Declaration provides developing countries with "the leverage to demand more consideration from medical researchers".

A debate is now underway within the relief community about the proper ethical guidelines to apply when doing research in refugee populations and among internally displaced peoples. Refugees are vulnerable subjects for research for several reasons. For example, they are often part of complex emergencies where human rights abuses are rampant, and because they have limited political rights.

International guidance on research ethics, such as the Declaration of Helsinki and CIOMS guidelines, do not address the special circumstances raised when enrolling refugees in research. Jennifer Leaning explains that the debate pivots on the tension between the need to develop evidence-based emergency health measures and the need to protect vulnerable populations from possible exploitation or harm. The article contains a summary of proposed guidelines to reduce the risk of unethical research being conducted amongst refugee populations.

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