**Ethical Aspects of Vulnerable Group of Patients in Clinical Trials Clinical Trials**

**Ethical Aspects of Vulnerable Group of Patients in** 

DOI: 10.5772/intechopen.70318

Ekaterina Ivanova, Ilko Getov and Hristina Lebanova

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

Ekaterina Ivanova, Ilko Getov and Hristina

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

Lebanova

#### **Abstract**

The current publication aims to review and analyse the ethical aspects and regulations to protect the category of vulnerable patients, as defined in the European legislation. These patients need special protection and require more detailed approach throughout the clinical trials' life cycle.

**Keywords:** clinical trials, vulnerable patients, ethical aspects, informed consent

### **1. Introduction**

According to the National Institutes of Health USA, the number of clinical trials shows a stable trend for growth. Nearly 28% of all clinical trials worldwide are conducted in Europe [1]. It is therefore important that clinical trials are regulated legally and monitored with needed level of detail. They must also comply with the ethical standards that promote respect for human beings and protect their health and well-being.

Often, researchers included patients who are vulnerable and need special protection. The chapter aims to provide an overview of the ethical issues in clinical trials with vulnerable patients.

Based on European legislation, specifically Regulation (EU) No. 536/2014 of the European Parliament and Council and ICH GCP E6 (R1), several categories of so-called vulnerable groups of patients might be defined:


Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons


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 additional steps in the course of obtaining informed consent.

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

Ethical Aspects of Vulnerable Group of Patients in Clinical Trials

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

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Thus, 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

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

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

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

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

• The clinical trial is required to indicate a direct benefit for trial subject (pregnant or breastfeeding woman, or her embryo or child). The benefit should outweigh the risks involved.

• If the research involves a breastfeeding woman, additional actions need to be taken to en-

In cases where there is no direct benefit for the trial subjects (pregnant or breastfeeding

medical team in the event of planned or already occurred pregnancy.

the women, foetus or future child is promptly communicated.

must be accompanied by informed consent.

the minimum.

or milk.

as follows:

sure no negative impact on child's health.

woman, or her embryo or child), a clinical trial can only be allowed:

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 ethics committees and investigational staff.
