Clinical trials ethical considerations

The initial strategy for Phase I is to conduct a single-dose safety study in normal volunteers. The first trial demands close 24-hour supervision in a clinical setting. Ethical considerations may, however, demand that only patients be used, for example, when evaluating an anticancer agent with predictable toxicity. A repeat dose tolerance and pharmacokinetic study in normal or patient volunteers is then conducted for chronically administered drugs. These studies will provide the necessary safety information to support efficacy testing. 

The number of partidpants must be chosen so that the trial wUl have suflEdent statistical power , particularly in the case of confirmatory trials. As a general prindple, the greater the number of data, the greater the confidence there is in demonstrating that a statistical difierence between two groups exists, or not. However, numbers of participants will be constrained by cost considerations, the availability of suitable subjects and, above all, by the ethical prindple that subjects should not be enrolled in clinical trial unless they add scientific value. 

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. 

Explain the reasons for ethical considerations before a clinical trial is conducted. 

Due to problems in some early clinical trials, where subjects were taken advantage of, regulatory authorities require that clinical subjects be treated fairly. Ethical considerations should be undertaken to safeguard subjects safety and well-being. 

The Helsinki Declaration covers all the important ethical considerations, such as the involvement of a qualified physician in any clinical trial, putting the well-being of the study subject before science and society, the use of scientific principles in the design of the study, the need for informed consent and a review by an ethics review committee in fact, all areas covered by the ICH GCP. 

Each study component has an ethical aspect. The ethical aspects of a clinical trial cannot be separated from the scientific objectives. Segregation of ethical issues from the full range of study design components demonstrates a flaw in understanding the fundamental nature of research involving human subjects. Compartmentalization of ethical issues is inconsistent with a well-run trial. Ethical and scientific considerations are intertwined (p. 4). 

An important issue on multiauthored papers is deciding who should be an author (single-authored empirical reports are extremely rare since contemporary clinical research typically requires considerable collaboration). Since many people are involved in the execution of a clinical trial, appropriate criteria are needed to decide on those who will be listed as authors. As in so many instances in this book, both scientific and ethical issues need to be addressed. It is unethical for someone who should not be an author to expect to be so. 

In general, according to EU law, applicants are expected to carry out controlled clinical trials, randomized and as appropriate against a placebo and an established medicinal product (an active comparator) of proved therapeutic value. However, applicants may justify use of other trial design. The treatment of the control groups will vary from case to case and also will depend on ethical consideration and therapeutic area. In some cases it may be more justified to compare the efficacy of a new medicinal product with that of an established medicinal product of proved therapeutic value rather than with a placebo. 

New compounds, while in principle more promising, pose a considerable problem in all aspects of the clinical trial. The example of VCDP shows the problems of acute toxicity (which is considerable), of late phototoxicity of the skin (which has not been analyzed), the administration of the compound (which needs to be optimized) and the availability of the compound (which is difficult to prepare in large quantities). Whereas these problems are not insurmountable for any new compound, ethical and practical questions must be answered satisfactorily before a clinical trial protocol can be prepared. 

Tack of an animal model and ethical considerations in the conduct of clinical trials have compounded the problem and slowed progress in vaccine development. 

The Helsinki Declaration covers all the important ethical considerations, such as the involvement of a qualified physician in any clinical trial, putting... 

The topic of ethics in clinical trials is addressed again in Section 3.16.1, where we talk about ethical considerations in choosing the nature of the control treatment used in trials involving investigational antihypertensive drugs. 

It is appropriate here to highlight the additional ethical responsibilities that are shouldered by those involved in statistical aspects of clinical trials, as outlined in the operational definition of Statistics presented in Chapter 1. Derenzo and Moss (2006) addressed the importance of ethical considerations in scientific and statistical aspects of clinical studies ... 

Ethical awareness and ethical responsibility are key aspects of statistical methodology in clinical trials. Areas where ethical and scientific considerations are inextricably linked include ... 

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