**2. Clinical trials on women of reproductive age, pregnant or breastfeeding**

Until the early 1990s of the twentieth century, the inclusion of women of reproductive age in clinical trials Phases I and II is very limited. One of the reasons behind this is FDA's 1977 guideline, which recommended excluding women with childbearing potential from participating in early phases of drug trials. The recommended exclusion was broadly applied to any 'premenopausal female capable of becoming pregnant', but explicitly did not apply to women with life-threatening diseases [2]. The results of such a major limitation were:


Thus, in 1993, under pressure from the public and the scientific community, FDA issued 'Guidelines for the Study and Evaluation of Gender Differences in the Clinical Evaluation of Drugs', according to which women should be allowed to determine for themselves the appropriateness of participating in early clinical trials [2].

In 1998, experts from the World Health Organisation (WHO) and United Nations (UN) issue a report 'Women and Health Mainstreaming the Gender Perspective into the Health Sector' [3]. The report concludes women need to be included in clinical trials, but their participation must be accompanied by informed consent.

**3.** Students and employees

126 Clinical Trials in Vulnerable Populations

**8.** People affected by mental health disorders

ethics committees and investigational staff.

additional steps in the course of obtaining informed consent.

**2. Clinical trials on women of reproductive age, pregnant or** 

with life-threatening diseases [2]. The results of such a major limitation were:

**5.** Ethnic minorities

**6.** Older people

**breastfeeding**

fective drugs;

prescribed both men and women.

priateness of participating in early clinical trials [2].

**7.** Military

**4.** People suffering from multiple chronic conditions or terminally ill

Each of the listed groups has its specific need, which has to be taken into consideration. While standard requirements towards clinical trials life cycle are outlined in European legislation, some ethical issues related to the vulnerable groups of patients need to be also part of ethical codes of conduct or local legislation. These include additional requirements related to the objectives of the study, risk-benefit assessment, strict adherence to the study protocol and

It is important to constantly improve access to treatments available for vulnerable groups. Therefore, medical products of significant clinical value should be appropriately studied for their effects in these specific populations. Vulnerable groups of patients require more detailed approach and in cases when the legislation does not provide needed level of detail or is outdated, ethical issues outlined in the chapter could be taken into consideration by members of

Until the early 1990s of the twentieth century, the inclusion of women of reproductive age in clinical trials Phases I and II is very limited. One of the reasons behind this is FDA's 1977 guideline, which recommended excluding women with childbearing potential from participating in early phases of drug trials. The recommended exclusion was broadly applied to any 'premenopausal female capable of becoming pregnant', but explicitly did not apply to women

• the rights of sick women were limited, as they cannot get timely treatment with more ef-

• the efficacy of many medical products on the women was unknown, although they were

Thus, in 1993, under pressure from the public and the scientific community, FDA issued 'Guidelines for the Study and Evaluation of Gender Differences in the Clinical Evaluation of Drugs', according to which women should be allowed to determine for themselves the approThus, the inclusion of women of **reproductive age** in clinical trials remains a pivotal issue. Ethical committees must ensure proportional participation of both sexes in order to obtain reliable trial data; however, the inclusion of women in the study should only take place when drug safety data is available and measures to protect women's and future offspring's health are undertaken. Women should receive information about the risks on their reproductive system and contraception methods during the study. They should immediately inform the medical team in the event of planned or already occurred pregnancy.

Studies on **pregnant women** should only be conducted in cases when the required data cannot be obtained from another patient's categories and when the purpose of the study corresponds to the mother's and foetus's health needs with minimal risk. It is mandatory that the informed consent is obtained, and information about possible consequences for the health of the women, foetus or future child is promptly communicated.

Studies related to monitoring **pregnancy, childbirth and the postpartum period** are usually conducted to evaluate the standards and pathologies during pregnancy, childbirth, postpartum and breastfeeding periods. Some of them are targeting diseases arising during pregnancy (hypertension, diabetes, etc.). In cases when a standard therapy does not work, it is necessary to conduct experimental treatment. In cases when the benefit is minimal and the risk for a woman or foetus is indefinite or high, the testing should be stopped. However, provided that the test drug is vital for a pregnant woman, her consent may be sufficient to implement the experimental therapy—even if the risk to the foetus is unknown or exceeds the minimum.

There are no specific guidelines for the inclusion of **breastfeeding women**. Nonetheless, the ethical committee should pay close attention to the safety of the health of breastfed children (mother's own child or the one who gets the breast milk). Medical team should regularly take samples from the breast milk and monitor the composition and protein component in colostrum or milk.

As defined by European legislation, along with standard requirements, additional conditions should be in place for a clinical trial on pregnant or breastfeeding women. Some of them are as follows:


In cases where there is no direct benefit for the trial subjects (pregnant or breastfeeding woman, or her embryo or child), a clinical trial can only be allowed:


The ethical expertise usually assesses and determines the risks and the benefits of clinical trials. The main principle is that the best interests of the child shall be a primary consideration. In practise, risk assessment on children depends on many factors. For example, taking a small quantity of blood from a child suffering from haemophilia creates risk, significantly exceeding the minimum. Children suffering from a chronic disease usually perceive easier various medical treatments. So they are at less risk compared to children who have no similar experi-

Ethical Aspects of Vulnerable Group of Patients in Clinical Trials

http://dx.doi.org/10.5772/intechopen.70318

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During clinical trials on children, it is important to reduce and mitigate painful manipulations, by applying effective methods of pain reduction—usage of corresponding equipment

• No incentives or financial benefits are allowed. The only exception that can be considered

• The clinical trial aims to validate data already collected on adult population to confirm it

When attracting healthy volunteers, it is imperative that they take the decision to participate in a clinical trial on their own and without pressure. They should receive all needed information related to the trial and declare their voluntary informed consent. Volunteers are usually compensated for their time, discomfort and possible risks. Thus, ethical commission is to make sure that these cash compensations are not unreasonably high and that attracted patients are not from category that is easily persuaded and influenced (*people with low incomes* 

Healthy volunteers are usually patients in Phase I clinical trials. The task of this phase is to evaluate drug's safety, determine a safe dosage range, pharmacokinetics and side effects.

The researcher should consider possible action in the event that a patient volunteer gets sick or hurt during the tests. These actions must be thoroughly listed in the informed consent

• Whether the patient will receive medical treatment and at whose expenses in case he gets

• Opportunity to withdraw from the clinical trial at any time without having to provide any

and personnel trained or experienced in working with children.

Clinical studies on minors would also include some additional requirements:

is a compensation for expenses directly related to the clinical trial. • The medical condition being treated occurs only in minors population.

• The clinical trial relates directly to a medical condition of a child.

**4. Clinical trials on students and employees**

sick or hurt during the course of the study

• Primary point of contact in case of injury

ence in illness.

can be applied in minors.

*or without education*).

justification

form:

• if it holds minimal risk to the subjects [4].
