The way ethics approval procedures for research involving human participants are organised is highly dependent on the applicable legislation in the country where the research will be performed in combination with potential additional obligations sets by the host institution. Without going into detail, research with human participants can be broadly divided into research projects on medical-scientific and healthcare-related topics on the one hand, and non-medical research on the other hand.  

Some important definitions: 

Experiment (as defined by the Human Experiments Act): any test, study or research carried out on a human person, for the development of the knowledge specific to the exercise of the health care professions. 

Clinical study (as defined by the article 2 of the CTR): any investigation in relation to humans intended to: 

• discover or verify the clinical, pharmacological or other pharmacodynamic effects of one or more medicinal products. 
• identify any adverse reactions to one or more medicinal products; or 
• study the absorption, distribution, metabolism and excretion of one or more medicinal products. 
• with the objective of ascertaining the safety and/or efficacy of those medicinal products. 

Clinical trial (as defined by the article 2 of the CTR): a clinical study which fulfils any of the following conditions: 

• the assignment of the subject to a particular therapeutic strategy is decided in advance and does not fall within normal clinical practice of the Member State concerned. 
• the decision to prescribe the investigational medicinal products is taken together with the decision to include the subject in the clinical study; or 
• diagnostic or monitoring procedures in addition to normal clinical practice are applied to the subjects. 

Medical device (as defined by the article 2 of the MDR): any instrument, apparatus, appliance, software, implant, reagent, material or other article intended by the manufacturer to be used, alone or in combination, for human beings for one or more of the following specific medical purposes:  

• diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease,  
• diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or disability,  

• investigation, replacement or modification of the anatomy or of a physiological or pathological process or state,  
• providing information by means of in vitro examination of specimens derived from the human body, including organ, blood and tissue donations, and which does not achieve its principal intended action by pharmacological, immunological or metabolic means, in or on the human body, but which may be assisted in its function by such means. 

In order to perform medical-scientific and healthcare-related research, it is also imperative that researchers become familiar with the universal principles of the Declaration of Helsinki and the Oviedo Bioethics Convention. Moreover, researchers are required to follow the principles of Good Clinical Practice (GCP). 

Research often involves working with human participants and in particular methodological tools, e.g., surveys, questionnaires, interviews, standardised tests, direct observations, ethnography, recording experiments with volunteers, physical interventions of all sorts. Because of the possible impact of research practices, researchers must carefully reflect the ethical implications of the chosen subjects, methodologies and consider ways to mitigate the harm (psychological, social, legal, economic, environmental, etc.) that might occur. Research entailing more than minimal risk typically involves: 

• potentially vulnerable categories of individuals such as children/minors, patients, people subject to discrimination, people/groups unable to give consent, people of dissenting opinion, immigrant, minority communities, sex workers, etc. 
• personal or sensitive topics which might induce psychological stress, anxiety or humiliation, dissenting voices, critique towards others, etc. 
• deception 
• seeking respondents through the internet/social media (e.g., using identifiable visual images or discussing sensitive issues) 
• …

When performing studies with human participants, there are a number of biases you should take into account when setting up your study. The list below is not exhaustive but gives you an idea of potential pitfalls. 

Informed consent

Research participation must at all times be entirely voluntary. To be able to make this decision as a participant, researchers must inform them as consciously and deliberately as possible. Researchers must obtain and clearly document participant’s informed consent prior to their participation in the research. 

Important to note is the distinction between providing consent to participate in a research study (‘ethical consent’) and consent as a legal basis for processing personal data. For ethical reasons, you may need participants’ consent to participate in a specific study (this may be legally required or ethically recommended). Such ethical consent for the participation in a research study does not necessarily equal consent as the legal basis for processing personal data. 

Key principles of informed consent

Participants must be given an informed consent form and a detailed information sheet that:  

• is written in a language and in terms they can understand (the language used must be understandable for a 14-year-old) 
• describes the aims, methods and implications of the research, the nature of the participation and any benefits, risks or discomfort that might ensue. 
• clearly communicates the burden of the research participant and ensures it’s reasonable and proportional. 
• explicitly states that participation is voluntary, and the participants have the right to refuse participation and to withdraw their participation, at any time and for no reason. 
• states how biological samples and data will be collected and protected during the project, and, either destroyed or reused subsequently. 
• states what procedures will be implemented in the event of unexpected or incidental findings (in particular, whether the participants have the right to know, or not to know, about any such findings). 

• states the procedures for sound research data management that will be put into place (see below).

It must be ensured that potential participants have fully understood the information and do not feel pressured or coerced into giving consent. Participants must normally give their consent in writing (e.g., by signing the informed consent and information sheets).

When getting consent requires extra attention

Research involving persons who are physically or mentally incapable of giving their consent (for example unconscious patients, elderly suffering from severe cognitive impairment, persons judged as lacking mental capacity), may only be conducted if the physical or mental state that prevents them from giving consent is a necessary characteristic of the group covered by the investigation. In such circumstances, the researcher should request the informed consent of the legal representative and maintain an active relationship with them throughout the research period. Whenever possible the assent, being the affirmative agreement, of the actual participant should be obtained in addition to the consent of the legal representative. In the absence of a legal representative and if the investigation cannot be postponed, the intervention may be started without the informed consent, following conditions and procedures approved by the relevant ethics committee and if it meets the conditions described in the relevant law. Permission to keep the person involved within the investigation must be obtained as quickly as possible from the person himself or from his legal representative. 

If consent cannot be given in writing, for example because of illiteracy, non-written consent must be formally documented and independently witnessed, i.e., by a person who isn’t involved in the study or associated with the research actors nor does have personal interest/benefit in the outcome of the study. There will be situations where standard procedures for obtaining written informed consent could be harmful or offensive to the participants, e.g., minority groups, with particular distrust towards official authorities or possible critical or personal (e.g., on sexual orientation) statements could be dangerous, etc. In such cases, alternative consent needs to be gained (e.g., orally).

Deception 

Some research activities or experiments make use of deception. Deception requires strong justification and appropriate assessment of the impact and the risk incurred by both researchers and participants. Retrospective informed consent should be obtained as soon as possible, and participants must also be debriefed. 

Data management in informed consent 

Besides the ethical aspects dealing with participants itself, there can also be ethical requirements related to the data that need additional clarification and approval of the participant via the informed consent. 

• Communication on the data should avoid professional jargon and focus on the added value for participants e.g., the security of data storage, policy on sharing and reuse of the data, anonymization, etc.  
• To ensure that data are kept securely, and that publication of any kind does not lead (either directly or indirectly) to a breach of agreed confidentiality and anonymity, extra care and special attention needs to be given to the (technical) aspects of collecting and storing your research data. Even so when electronic encoding tools are used.  
• In relation to working with human participants and personal data, extra measures need to be taken.  

Because research is a dynamic process and can contain different legal and ethical issues in the same project, it is advised to contact your local ethics committee to align all requirements especially in complex and sensitive topics. Due to the dynamic nature of research, it is important to recognise that ethics is not a mere checkbox exercise and that after obtaining ethics approval, new ethics issues may arise that require a new check by the ethics committee. 

Working in line with research integrity standards also means that the researchers carry out their activities within a legally and ethically correct scientific framework. Researchers are expected to know, respect and adhere to the legal rules and ethical practices of their own research domain, the laws and regulations, the general ethical principles and standards established in institutional, sectoral, national and international codes and standards of research integrity.

Ethical considerations & responsibilities 

Although their implementation and the accompanying procedures may differ from institution to institution, the main ethical considerations often come down to: 

• The well-being of human participants and laboratory animals. 
• The well-being of those carrying out the research activity 
• The interests of the wider society 
• The respect for cultural heritage, human rights and the environment 
• The safety of individuals or groups with special attention for minority or vulnerable groups. 
• Safeguarding the reputation of the research group, the faculty, the university and the scientific practice as a whole. 

Because research is a dynamic process and can contain different legal and ethical issues in the same project, it is advised to contact your local ethics committee to align all requirements especially in complex and sensitive topics. Due to the dynamic nature of research, it is important to recognise that ethics is not a mere checkbox exercise and that after obtaining ethics approval, new ethics issues may arise that require a new check by the ethics committee.