DOMAIN 2: Ethical and Participant Safety Considerations

Encompasses care of patients, aspects of human subject protection, and safety in the conduct of a clinical trial


Differentiate Between standard of care and clinical study activities

FUndamental Level:

A1.       Explain that a clinical study is unconfirmed research and not accepted standard of care

Example: Explains to a study participant that procedures that are part of the protocol are not necessarily standard of care.


B1.       Demonstrate the importance of conducting clinical trial activities as per the protocol

Example: Explains to clinical staff the timing of a research blood draw versus standard blood draw timing for the shift.


C1.       Develop a protocol that appropriately includes distinct research activities and standard of care

Example: Appropriately distinguishes between activities that should be billed to insurance versus incorporated into sponsored cost.


Define the concepts of “clinical equipoise” and “therapeutic misconception” as they relate to the conduct of a clinical study

Fundamental Level:

A1.       Recognize that clinical equipoise and therapeutic misconception are fundamental ethical principles and concerns that underlie clinical research

Example: Identifies and discusses the two comparators in a controlled clinical trial and why each has been selected.

Skilled Level:

B1.       Explain the rationale of clinical equipoise and therapeutic misconception, and can demonstrate comprehensive knowledge and understanding of how they may impact patient understanding

B2.       Consistently apply knowledge of clinical equipoise and therapeutic misconception during the course of the study

B3.       Recognize, interpret, and seek assistance where required to address participant concerns regarding therapeutic misconception or clinical equipoise

Example: Identifies during ICF process whether the potential participant truly understands the study is research and does not have a predictable outcome.

Advanced Level:

C1.       Act as an expert resource to potential study participants and staff in their understanding of clinical equipoise and therapeutic misconception

Example: Leads the development of an in-service training by interpreting study protocols in relation to clinical equipoise and therapeutic misconception.


Apply relevant national and international principles of human subject protections and privacy throughout all stages of a clinical study

Fundamental Level:

A1.       Explain the importance of complying with global guidelines and recommendations, as well as local regulations regarding the safety, wellbeing, and rights of all subjects participating in a clinical trial anywhere

Example: Identifies examples of autonomy, justice and beneficence in the recruitment and consent process for a clinical protocol

Skilled Level:

B1.       Critically appraise and implement within a clinical study protocol, the principles of human subject protection and privacy

Example: Designs recruitment strategies that ensures inclusion of all appropriate populations.

Advanced Level:

C1.       Supervise the implementation of activities required to protect a clinical study participant´s privacy, safety, well-being, and rights in a clinical trial being conducted in any region

C2.       Respond to questions posed by a regulatory body (e.g. IRB.IEC) regarding the methods by which a clinical study protects the privacy and safety of participants

Example: Explains to an IRB/IEC the plans for ensuring participant confidentiality for a clinical study being submitted for review.

Fundamental Level:

A1.       Identify the historical events which have led to the development of the current informed consent regulations

A2.       Identify the key documents that ensure the protection of human participants in clinical research (Declaration of Helsinki, Belmont Report, CIOMS, Nuremberg report, ICH guidelines, Investigators Brochure, product label, etc.)

Example: Identifies and explains the three principles of the Belmont Report and the difference between FDA regulations and ICH GCP guidelines.

Skilled Level:

B1.       Recognize the critical nature of communicating the potential risks or hazards, as well as the benefits of a clinical study, using terminology and a manner that is understandable by the potential study participants during the informed consent process

B2.       Apply knowledge of the key doctrines and tenants for the regulations and guidelines coupled with available safety information when drafting an informed consent document for a clinical study

Example: Composes the informed consent document for a clinical study and includes the potential risks and benefits in an understandable manner for the study participants.

Advanced Level:

A1.       Implement processes and control measures to ensure human subject protection regulations requirements are met across studies

A2.       Evaluate the informed consent document in relationship to the study protocol to assure that it not only meets current regulations and guidelines but also provides the information needed for a potential study participant to make an informed decision regarding their participation in the study

Example: Serves as an effective member of an IRB to ensure human subject protection.


Explain the evolution of the requirement for informed consent from research participants and the principles and content of the key documents that ensure the protection of human participants in clinical research


Describe the ethical issues involved when dealing with vulnerable populations and what additional safeguards should be in place for those populations

Fundamental Level:

A1.       Identify which populations are considered vulnerable

A2.       Understand that regulations are in place to protect vulnerable populations

Example: Understands these groups as being vulnerable: children, prisoners, pregnant women, mentally disabled persons, and economically or educationally disadvantaged persons and accurately describe additional safeguards in place for each group.

Skilled Level:

B1.       Accurately apply the appropriate safeguards with research participants

B2.       Anticipate situations when research participants may be considered vulnerable

Example: Applies knowledge of vulnerable populations to the subject consent process and identifies vulnerabilities and applies safeguards for participant protection.

Advanced Level:

C1.       Evaluate a study protocol to identify whether population is properly protected or additional safeguards are needed

C2.       Create strategies to engage vulnerable populations in research studies to allow them to make the best decision

C3.       Evaluate unique situations that affect participation of vulnerable patients

C4.       Evaluate whether vulnerable populations require special considerations from IRBs or regulatory authorities

Example: In a community research study of vulnerable populations, develops strategies that would protect participants during recruitment and retention.

Fundamental Level:

A1.       Recognize the cultural variations which exist when conducting multi-regional clinical trials for new investigational product development

A2.       Explain the concept of cultural competency and how it relates to the conduct of clinical research in diverse population groups

Example: Serves as a contributing member of a global medicines development team.

Skilled Level:

B1.       Compare and contrast the ethical principles guiding clinical research across different global regions (e.g., ICH guidelines vs. FDA regulations, other country regulations) 

B2.       Examine the pros and cons of conducting clinical trials in low and middle-income countries and differentiate the potential types of exploitation and benefits that populations in these countries may face in the conduct of a global clinical trial

Example: Recommends that clinical studies will only be conducted where the relevant infrastructure exists (e.g. cold chain storage) and in regions where the products will be marketed.

Advanced Level:

C1.       Assure that clinical trials incorporate concepts which recognize varying cultural perspectives and ethical issues across regions

C2.       Develop strategies to select clinical trial sites that appropriately balance the need to provide equal access to potential treatments

Example: Researcher designs a global medicine development program that considers the health needs of potential participants and ensures post trial access to investigational product.


Evaluate and apply an understanding of the relevant ethical issues and cultural variation as it applies to the commercial aspects of the clinical research and  investigational product development process

Fundamental Level:

A1.       Recognize the eligibility criteria for study participants (e.g., that include and exclude subjects) based on factors such as age, gender, the type and stage of a disease, treatment history, and other medical conditions that allows the research team to determine whether the subjects can take part in the study safely

A2.       Determine potential eligibility of study participants for a non-complex study (e.g., registries, survey studies)

Example: Identifies the inclusion and exclusion and eligibility criteria from a set of sample cases for an upcoming clinical study.

Skilled Level:

B1.       Articulate the necessity for a homogeneous patient population (based on criteria defined in the protocol) and the need for consistency in protocol recruitment

B2.       Describe the implications of deviations from inclusion/exclusion criteria on data quality and study validity and how results can be generalized to the public

B3.       Develop study materials (e.g., guidance documents, recruitment plans) to ensure appropriate application of inclusion/exclusion criteria

B4.       Determine potential eligibility of study participants for complex studies (e.g., biomedical or interventional)

Example: During a study audit, identifies deviations from eligibility guidelines, describes potential consequences, and discusses the required next steps.

Advanced Level:

C1.       Develop and edit eligibility criteria for new protocol development

C2.       Explain the rationale for choosing inclusion and exclusion criteria based on evidence or previous experience

Example: Performs an eligibility risk-assessment and risk mitigation plan for new clinical trials and corrective and preventive action strategies for deviations found during routine site audits.


Explain why inclusion, exclusion, and other criteria are included in a clinical protocol to assure human subject protection

Fundamental Level:

A1.       Recognize the processes (e.g., inclusion/exclusion, study procedures, adverse event identification and documentation, continuation of the study) that appropriately balance risk and benefit

Example: Identifies known and potential clinical risks associated with a clinical protocol and applies ongoing risk assessment activities during study visits with participants.

Skilled Level:

B1.       Implement the processes (e.g., inclusion/exclusion, study procedures, adverse event identification and documentation, continuation of the study) that appropriately balance risk and benefit

Example: Identifies key risk and benefit components that belong in a Strategic Recruitment and Retention plan or in an Informed consent.

Advanced Level:

C1.       Develop the processes (e.g., inclusion/exclusion, study procedures, adverse event identification and documentation, continuation of the study) that appropriately balance risk and benefit

C2.       Illustrate the risk and benefits principles and methods while designing and/or providing oversight through the selection and management of clinical study subjects

Example: Independently constructs a protocol, informed consent, and/or recruitment and retention plan that incorporates the principles and methods of distributing and balancing risks and benefits.


Summarize the principles and methods of distributing and balancing risk and benefit; through selection and management of clinical study subjects