Ethical principles

As should be clear from above, there are many potential tensions in the drug safety system - e.g. risk vs. benefit, individual vs. population good, potential therapeutic gain from innovation vs. uncertainty. These are set in a background of commercial and political imperatives, the latter largely being the economics of healthcare. The need for an ethical approach and ethical safeguards is therefore manifest. 

In terms of researching the safety of medicines in human subjects, there is an overarching code of ethical principles - The Declaration of Helsinki - which was originally developed under the auspices of the World Medical Association in 1964. The last significant revision was in 2000 and this is currently a fairly brief document with some 32 points. The most significant ones in the context of safety are  

These have an underlying theme, i.e. individual patient safety is paramount. 

When experimental research is being conducted (i.e. there is some intervention which would not occur in ordinary practice -e.g. randomisation), informed consent is considered essential. For non-experimental research (i.e. mere observation of ordinary practice), consent of individuals is generally not required and may not be feasible. The patient s right to privacy is a key issue and individual patient data need to be anonymised and held securely. Confidentiality legislation varies considerably between countries and potential future increases in stringency may threaten the viability of epidemiological research. 

There are various other specific ethical issues that face industry personnel and are relevant to safety. For example  

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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... 

Ethical Principles for Medical Research Involving Human Subjects. 

With an older population, higher demand, increasing cost and limited resources we have problems to satisfy all needs and priorities. These priorities and decisions are hard to do for the practitioner in relation to the patient and to the society. Priorities should be based on the three ethical principles (human dignity, needs and solidarity, cost-effectiveness) described in Box 3.7. Greater needs (severe diseases and low quality of life) and the weakest people (i.e. the elderly) should have priorities. Cost-effectiveness principles should only be used when comparing treatment methods for the same disease. 

Box 3.7 The three ethical principles (National centre for priority setting in health care 2008)... 

Based on these principles the priorities could be made at different levels. This should be started at the highest level among politicians and others, with mutual, transparent, long lasting decisions. Of course this is problematic. With the three ethical principles in mind we must all think of what we can do with limited resources and make our own priorities. EBM principles and methods as described above should be used. Some factors that increase the health-care costs are presented in Box 3.8, and should be considered. Several of the solutions presented in this and other chapters can be used. 

The statement s final points cut to the political issue of race, equality, and democracy social equality as an ethical principle does not depend upon equality of endowment among diverse human beings there is no evidence for the belief that groups differ in capacities for intellectual and emotional development differences within a given race may outstrip differences between races and there is no evidence that racial mixture is disadvantageous from a biological point of view.32... 

Since the Kefauver-Harris Amendmenf was adopted in 1962, pharmaceutical manufacturers have been held responsible by the FDA for providing new medications fhaf are bofh safe and effective. In addition to the Kefauver-Harris Amendment, the Belmont Report (written in 1979), established the ethical principles and guidelines for conducting research. The FDA requires that clinical trials be conducted in compliance with a protocol that has been... 

The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, The Belmont Report Ethical Principles and Guidelines for the Protection of Human Subjects of Research, Department of Health, Education, and Welfare, Washington, DC, April 18, 1979. 

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. 

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. 

Regulatory authorities stipulate the need for ethical principles to be observed when conducting clinical trials. Clinical trials should never be conducted to gain knowledge per se. They should be based on risk-benefit considerations, informed consent, and respect for human individuals. Furthermore, subjects should be protected without being taken advantage of. 

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 European Union (EU) and its Member States promote responsible research in order to help society draw the maximum benefit from scientific inquiry and in order to protect the rights of citizens, researchers, and other members of society (EU 2007). All EU-funded research activities must comply with an ethical code according to Article 3 of the Sixth Framework Programme (FP6, 2002-2006) that states All the research activities carried out under FP6 must be carried out in compliance with fundamental ethical principles. No further guidance specifically directed toward the use of human data in the risk assessment of chemical substances is provided. 

In the evaluation of human health risks, sound human data, whenever available, are preferred to animal data. Animal and in vitro studies provide support and are used mainly to supply evidence missing from human studies. It is mandatory that research on human subjects is conducted in full accord with ethical principles, including the provisions of the Helsinki Declaration (World Medical Association 2000). 

The design, conduct and analysis of the trial should comply with highest clinical, scientific and ethical principles. 

It is a clear ethical principle that the privacy of the individual should be respected and maintained. The law too, both in common law (i.e. judge-made law) and through certain statutory provisions (specifically Member States implementation of the 1995 Directive on the protection of personal data 95/46/EEC)... 

Munir, K., and Earls, F. (1992) Ethical principles governing research in child and adolescent psychiatry. / Am Acad Child Adolesc Psychiatry 31 408 14. 

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