Informed consent principles

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. 

The underlying principle is that subjects should only participate in a clinical trial if they agree to do so after they have fully understood the trial and its implications. In all studies, informed consent must be obtained from the subject or, where special situations occur, from his or her representative. How this is achieved depends on the study design, procedure and the country where the study is being conducted. Typically, it requires a... 

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. 

The principle of autonomy entails that persons should be treated as inherently valuable individuals with the moral right to make decisions about their own lives. To the extent that one s actions and choices do not negatively affect others, individuals with the capacity to make their own decisions should be free to do as they wish, even if their choices are risky or harmful to themselves. The principle also entails that persons with diminished autonomy, such as those who are illiterate or retarded, deserve to have their interests protected. Many moral obligations for professionals engaged in scientific research or health care are derived from the principle of autonomy, such as the physician-researcher s obligation to fully inform potential research subjects and respect the individual s informed consent or informed refusal. This obligation is founded on the principle that individuals are the appropriate decision makers for choices that do not harm others. 

The principle of justice states that individuals should be given what they deserve, be that benefit or burden. Cases that are alike should be treated similarly, and relevant distinctions should be drawn consistently. The principle of justice does not specifically state what distinctions are fair or which criteria are reasonable it simply requires that, once criteria are determined, they be applied fairly. Justice is important in many areas, such as recruitment of research subjects for pharmaceutical studies. For example, researchers must guard against distributing the burdens of participation disproportionately among populations that are poorly equipped to give informed consent, such as children or the mentally incompetent. 

Once the animal studies are completed human studies can commence, moving through phase I (up to 50 naive patients to establish a sufficient immune response) phase (several hundred patients in several locations) to phase III in which expanded studies on as many as thousands of patients. The trials require to be randomized and closely controlled by being blinded to avoid bias in interpretation. The patients all have to provide informed consent and strict adherence to good clinical practices in accordance with ethical principles is required to ensure risk-benefit considerations justify the risks associated with all trials of this type. The safety of the patients is an overall requirement and trials must be supervised by the appropriate independent ethics committee or the local Institutional Review Board. 

Failure Modes in Management. If the patient has not accepted the principle of drug treatment, then there is a need for renewed explanation and education to lay the groundwork for informed consent regarding a treatment plan. Those who fail to accept the principle of drug treatment usually take little or no medicine, and when they do take an occasional dose, it is often immediately prior to a scheduled visit to the doctor. Pre-visit dosing masks the clinical eye to otherwise poor compliance, but is readily identifiable with proper measurements (Feinstein, 1990). 

The design and conduct of the clinical studies presented in the examples below was in conformance with these principles. Subjects were included only after informed consent was given. All studies were part of a sound clinical development plan of the sponsor. 

All consent documents and the entire informed consent process should be designed and implemented to be in compliance with the above-stated regulations, as well as consistent with the principles of the Declaration of Helsinki, World Medical Assembly, Revised 1996, 48th General Assembly, the accepted... 

The Nuremberg Code is based on the principle of informed consent and this is exactly what doctors, nurses, health care agencies like the CDC, FDA, ABA, WHO and the pharmaceutical companies violate with common vaccination policies. 

Cardozo s opinion concerned a case in which surgery was performed without the patient s consent, but the principle he expressed can be applied to any procedure that contains some risk of patient harm. Treatment may not be instituted without the patient s consent, and this consent cannot be legally secured without the patients being informed of the hazards, the possible complications, and both the expected and the unexpected results of treatment. In addition, practitioners must not make any misrepresentations, either by misstating known focts or by withholding pertinent information. This obligation to communicate forms the basis for the doctrine of informed consent. 

Legislation that ensures the protection of human research subjects in the United States includes the 1979 publication of the Belmont Report on the Ethical Principles and Guidelines for the Protection of Human Subjects of Research.f This report concerns the fine line between biomedical research and the routine practice of medicine and explores the criteria that determine the risk-benefit ratio in the consideration of conducting clinical research. It also addresses basic guidelines for the proper selection of human research subjects and further defines the elements of informed consent. 

Despite the principle of informed consent, ethical difficulties in human research remain. After all, when a new drug is developed, someone has to be the first person to take it. Even though federal law says that a drug must be tested extensively in animals before it is tried with people, some side effect not detected in the animal studies could still occur. 

Appendix A - Principles of Institutional Review and Informed Consent... 

There is a tendency to assume that the principles of informed consent are self-evident. In fact, evidence that this is not the case comes from many sources, such as ethics committees that are frequently dissatisfied with proposed informed consent documents, and sophisticated Western governments that, from time to time have conducted clinical trials without it (e.g. the Tuskeegee travesty). A recent gene therapy accident in the eastern United States, which led to the death of the participant, led to litigation which was centered not around whether the clinical trial was unduly hazardous but rather on whether the consent that the patient gave was truly and fully informed. 

Informed consent was first formulated under international law through the Declaration of Helsinki, and in response to the atrocities of the Second World War. The principles of informed consent are under continuous review and discussion (e.g. Marsh, 1990). This is to be expected when reasonable standards of informed consent are dependent not only on the design of a particular... 

Although discussed in detail elsewhere in this book, the two ethical principles guiding informed consent are those of autonomy and equipoise. Autonomy is the concept that the patient is an individual that is under no duress, whether subtle or obvious, actual or inferred, and is competent to make a choice according to his or her free will. Clinical trials conducted on persons in custody, or on subordinate soldiers, may both be violations of the patient s autonomy. Equipoise is the concept that the investigator, and those sponsoring the trial, are truly uncertain as to the outcome of the study in practical terms, this is a guarantee to the patient that an unreasonable hazard cannot result from unfavorable randomization because the treatment options are not known to be unequally hazardous. 

The following principles for conducting informed consent should be implemented for all clinical studies ... 

Above all, the rights of the individual must be seen to trump any need or possibility of scientific advance. The duty toward the individual must always have a far higher priority than some intangible benefit that might attach to the population as a whole in the future. In protecting the research subject, the first principle is informed consent . 

The Belmont report describes the basic ethical principles that underlie research involving human subjects respect for persons, beneficence, and justice. The report discusses application of informed consent, assessment of ri.sks and benefits, and selection of subjects. Its regulations require that IRBs have not fewer than five members who have the capability to judge research proposals in terms of community attitudes. Therefore, IRBs must include people whose primary concerns lie in the areas of legal, professional, and community acceptance rather than in the overall scientific design. 

The role of the clinical pharmacist in the surveillance of ethics principles and the maintenance of the rights of human can also be notorious, especially when referring to written information and the patient s informed consent. The most relevant study undertaken in Spain that evaluated the quality of the written information provided to patients was carried out by pharmacists involved in quality assurance and/or ethics commitees. The main outcome of this study was to confirm that most of the written information to patients (65.3% of clinical trials) required high-level studies to be completely understood by the patients. As far as we know, a more ambitious, multicentric study is currently under development on the true comprehension and awareness that patients have of the clinical trials in which they are involved. 

The principles of the Directive should remove the complexity of clinical trial application, authorization and regulation in existing, new, and future Member States. Thus, substantial amendments to protocol that impact on safety of the subjects or where there is a change in the interpretation of data on the IMP must be notified under the legislation underpinning the Directive. This common process will obviate current disparate national procedures that range from a simple notification scheme to a complex authorization proce-dure. Implementation of the Directive cannot be expected to alter national requirements for provision to examiners of Information to Subjects and Informed Consent forms in local languages. 

A placebo in a randomized clinical trial is no bar to operating informed consent. The physician can say to the patient If you agree to enter this trial you will have half a chance of receiving the new treatment under study and half a chance of receiving an inactive treatment. You will not be told which you have received and I will not know either until the trial is over. Furthermore, the patient could, in principle, read the whole... 

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