Declaration of Helsinki

To ensure that that the rights, safety and well-being of trial subjects are protected, in accordance with ethical principles that were developed by the World Medical Organisation and set out in the Declaration of Helsinki. 

Clinical trials shall be conducted in accordance with the Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects... 

Assuming that standard codes of conduct, for example, the Nuremburg Code (1947) and the World Medical Association s Declaration of Helsinki, are followed by researchers, the element of consent will already have been satisfied. In fact, as far as the element of consent to the intrusion into privacy goes, the medical community s doctrine of informed consent is a very strict application of the element of consent. We may note that the specific informed consent of an individual human subject of research may not be adequate to the decisions surrounding data mining. 

First, the most recent (October, 2000) revision of the Declaration of Helsinki (World Medical Association, 2000) calls for discontinuing the use of placebo controlled trials in patients. While this is not currently binding on U.S. trials (FDA has specifically said that they will not mirror this as a requirement), and is intended to protect the health of participating patient subjects by precluding having some denied existing efficacious treatments (which would be the effect in most—but not all—cases), it will also likely cause the numbers of subjects required in a trial to increase. This will further stretch the economic aspects of limitations on the power of trials to assess potential drug safety in what will be the intended patient population. Trials are already very expensive each additional subject enrolled costs 15,000 or more in a Phase 11 or 111 trial. 

Declaration of Helsinki, other documents and collection of related sites... 

World Medical Organization, Declaration of Helsinki Ethical Principals for Medical Research Involving Human Subjects, Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964. 

Outcomes from the trial must be communicated to the subjects promptly and in an unbiased way. In addition to the ethical guidelines by the NIH, the World Medical Association has formalized a document called the Declaration of Helsinki—Ethical Principles for Medical Research Involving Human Subjects to describe the constraints on research involving human beings. Those countries that have signed this declaration are bound by the ethical principles. An extract of this document is given in Exhibit 6.3. 

Exhibit 6.3 World Medical Association Declaration of Helsinki... 

Ethical Principles for Medical Research Involving Human Subjects The World Medical Association has developed the Declaration of Helsinki as a statement of ethical principles to provide guidance to physicians and other participants in medical research involving human subjects. Medical research involving human subjects includes research on identifiable human material or identifiable data. 

Over the years, scientific research with human subjects has provided valuable information to help characterize and control risks to public health, but its use has also raised particular ethical concerns for the welfare of the human participants in such research as well as scientific issues related to the role of such research in assessing risks. Society has responded to these concerns by defining general standards for conducting human research. As an example, studies carried out for the authorization of a medical product, have to be conducted in line with the World Medical Association s Declaration of Helsinki, which describes the general ethical principles for medical research involving human subjects (World Medical Association 2004). The Helsinki Declaration was first issued by the World Medical Association in 1964 and has been revised several times since then. 

The procedures for assuring quality of clinical trials have evolved over the past 30 years, culminating in several published guidelines. There are three key documents - the GCP guidelines of the ICH, the Code of Federal Regulations (21 CFR) of the United States and the Declaration of Helsinki. " ... 

The principles of medical research are based on the Declaration of Helsinki. The general assemblies of the World Medical Association (WMA) have, since 1964, made recommendations for guiding physicians in clinical research involving human subjects. Although not legally binding, the Declaration forms the foundation of all other significant international documents on the ethical conduct of biomedical research. 

In October 2000, the latest revision of the Declaration of Helsinki was approved by the WMA (see Appendix 1). The new version is very different from previous versions, with more detail on how clinical trials should be conducted. It requires that study subjects should have access to the best treatment identified by the study once the study has been completed. It also recommends that local participants in a study should be able to benefit from the study results, whether they are positive or negative. These principles were approved to avoid the exploitation of economically poor countries. In addition, the Declaration requires greater transparency regarding economic incentives involved in clinical research. 

The new version of the Declaration of Helsinki (Edinburgh, 2000) (see Appendix 1) has highlighted concerns in the use of placebos... 

The recent publication of the revised version of the Declaration of Helsinki has in Section 29 the following statement ... 

World Medical Association (WMA). Declaration of Helsinki, 52nd WMA General Assembly, Edinburgh, Scotland. Available at http //www. 

Lewis JA, Jonsson B, Kreutz G, et al. Placebo-controUed trials and the Declaration of Helsinki Committee on Proprietary and Medicinal Products. Br J Clin Pharmacol 2001 52 223-9. 

In October 2000, the latest revision of the Declaration of Helsinki" was approved by the... 

Globally, there is concern that biased results could be produced from studies conducted by investigators who own shares or other financial benefits in the pharmaceutical company sponsoring their trials. The Declaration of Helsinki (2000) requires that sources of fimding, institutional affiliations and possible conflicts of interest should be declared in any publication. All studies conducted on products that are likely to be part of a submission to the US FDA require the sponsor to make a disclosure of financial holdings of the investigators that participate in all studies. Any significant pa)unents (US 25000)... 

Ethical issues and randomisation There are ethical issues with randomisation. There are two t)rpes of ethics which are associated with human, medical research - individual and collective ethics. Individual ethics recognises the primacy of the individual and is aimed at doing what is best for the subjects in the current trial. In contrast, collective ethics is aimed at doing what is best for all future patients who will benefit from the results of the current trial. Clearly, there is a tension between these two principles that is recognised in the declaration of Helsinki, which comes down on the side of the individual ... 

Generally speaking, the FDA will require placebo-controUed studies wherever possible to demonstrate efficacy at the dose to be marketed and these are termed pivotal studies. Pivotal studies do not have to be placebo controlled, however, and in some areas, such as depression, the ICH guidelines suggest a three-arm study, with both an active comparator and a placebo control. The Declaration of Helsinki, revised in 2000, suggested that in some disease areas, placebo-controlled studies are to be examined very carefuUy for their ethical content. This includes areas where conventional best therapy is generally acceptable. In this case, great care needs to be taken with the choice of active comparator. 

Compliance with the ICH Good Clinical Practice Guidelines (incorporates the Declaration of Helsinki) or equivalent should be required. 

Declaration of Helsinki (amended 1975,1983,1989, 1996 and 2000). World Medicinal Association Inc. Eerney-Voltaire, Erance. 

The clinical trial guidelines published by the TGA specify that all clinical trials must be conducted in accordance with the Declaration of Helsinki, October 1996. The World Medical Association updated the Declaration of Helsinki in October 2000 but these changes were not adopted in Australia due to concerns in relation to the interpretation of two new clauses. 

A very useful review of the history and development of the Declaration of Helsinki in the last four decades from its evolution from the principles enunciated in the Nuremberg Code of 1947 to the current version has been published in the British Journal of Clinical Pharmacology and is recommended reading, it includes the texts of the various versions of the Declaration. 

---