DDReg Pharma

DDReg Pharma

Guidance on Informed Consent in Clinical Investigations

Within the realm of clinical research, the process of obtaining informed consent stands as a crucial cornerstone of ethical practice, serving to protect the rights and well-being of human participants. The U.S. Food and Drug Administration (FDA) recognizes the changing landscape of clinical investigations and the necessity to align with the 2018 Common Rule and thus has issued extensive guidance in this regard. This comprehensive guidance encompasses a wide array of considerations, offering valuable insights to various stakeholders such as institutional review boards (IRBs), clinical investigators, sponsors, and more.

The process of obtaining informed consent comprises three essential elements: firstly, the disclosure of essential information to potential research subjects, enabling them to make an informed decision; secondly, facilitating the understanding of the disclosed information; and thirdly, ensuring the voluntary nature of the decision to participate or not in the research. It is imperative that informed consent is legally effective and obtained before the research begins, as outlined in the HHS regulations at 45 CFR 46.116 and 45 CFR 46.117.

Purpose and Scope

The Guidance document offers both general guidance concerning the FDA’s requirements for obtaining informed consent in clinical investigations of drugs, biologics, and medical devices that fall under the agency’s purview. It serves a pivotal role in providing clear directives and strategies for compliance to stakeholders that are involved in clinical investigations. It goes beyond mere regulatory compliance, emphasizing ethical interaction and transparent communication with potential participants or their representatives. By comprehending and adhering to these guidelines, stakeholders ensure a comprehensive approach that empowers participants to make informed choices prior to enrolling in clinical studies.

The guidance underscores that informed consent is not a one-time interaction; rather, it is a dynamic process involving ongoing engagement with participants. This entails providing them with necessary information and addressing any questions or concerns that may arise throughout the course of the study.

Following are the responsibilities mentioned in the guidance for different stakeholders –

Institutional Review Board (IRB) Responsibilities

IRB Review and Approval 

The IRB is a crucial oversight body that ensures ethical and regulatory compliance in clinical research. It’s primary responsibility is to review and approve the informed consent form and process before the research begins. This review ensures that the information provided to participants aligns with regulatory requirements, including those outlined in 21 CFR part 50. The IRB confirms that the consent process adequately protects participant’s rights, safety, and well-being.

Comprehensive Review

The IRB doesn’t only assess the consent form itself but also examines all related materials, such as recruitment materials and additional information given to participants. This comprehensive review aims to prevent coercion or undue influence by ensuring that all information provided to potential participants is clear, accurate, and appropriate.

Protection of Vulnerable Subjects 

If the research involves vulnerable populations (such as minors, pregnant women, or prisoners), the IRB takes additional steps to protect their rights and welfare. The IRB might include experts experienced in working with such populations to provide specialized guidance during the review process.

Additional Information 

While the regulatory requirements specify the minimum information that must be included in the consent form, the IRB has the authority to require the inclusion of extra information if it enhances the protection of participants’ rights and well-being. This could involve disclosing financial relationships or other relevant details that might impact participants’ decision to participate.

Managing Financial Interests 

In cases where financial relationships and interests are relevant to the research, the IRB assesses whether participants should be informed about these matters. Financial interests could potentially influence participant’s decisions or perceptions of the research, so the IRB considers appropriate measures to address these concerns.

Source of Funding and Financial Arrangements 

The IRB determines whether participants need to be informed about the source of funding, financial arrangements, and interests of parties involved in the research. This decision is made in consideration of participant’s understanding and the potential impact on their willingness to participate.


Clinical Investigator Responsibilities

Safeguarding Rights

The clinical investigator is responsible for ensuring the rights, safety, and welfare of research participants throughout the study. This involves protecting participants from harm, ensuring their privacy and confidentiality, and addressing any concerns they may have.

Informed Consent 

Obtaining informed consent is a critical responsibility of the clinical investigator. This involves explaining the study purpose, procedures, potential risks and benefits, and other relevant information to participants or their authorized representatives. The investigator ensures that participants have a clear understanding before they agree to participate.

Delegation of Consent 

In some cases, the investigator may delegate the task of obtaining informed consent to other qualified individuals. However, the investigator retains ultimate responsibility for ensuring that proper informed consent is obtained and that the delegate is competent to carry out this task.

Financial Relationships

The investigator assesses whether any financial relationships or interests could potentially influence the study or interactions with participants. If such relationships exist, the investigator takes appropriate measures to address conflicts of interest and mitigate their impact on the research.

Sponsor Responsibilities

Model Consent Form

Sponsors often provide clinical investigators with a model consent form that serves as a template. This model form can be customized to fit the specific needs of the local study site while ensuring that it adheres to regulatory requirements.

FDA Communication 

The sponsor acts as an intermediary between the FDA and the clinical investigator. After receiving FDA comments on the consent form, the sponsor promptly communicates any required modifications to the investigator and the IRB. This collaboration ensures that the consent form is refined and approved before the study begins.

Local Requirements 

For multicenter studies, the sponsor ensures that the consent form addresses local and institutional requirements. This might involve making adjustments to the form to meet the needs of different study sites while maintaining consistency with the overarching study design.

Medical Devices

If the investigation involves medical devices requiring an Investigational Device Exemption (IDE) application, the sponsor includes the consent forms as part of the application. The FDA reviews these forms for conformity to regulations, and any deficiencies must be addressed before the clinical investigation can proceed.

FDA Responsibilities

Review and Feedback

The FDA reviews the informed consent forms submitted by sponsors and provides comments primarily to the sponsors. These comments address modifications that may be needed to ensure that the consent forms align with regulatory requirements and provide participants with clear and accurate information.

Review Triggers

The FDA may request submission and review of consent forms based on certain triggers, such as the presence of unusual toxicity, vulnerability of the study population, unique study designs, significant potential risks, or situations where subjects are asked to forego effective treatment.


If the FDA identifies concerns about the adequacy or compliance of consent materials, it communicates these concerns to the sponsor. This communication allows the sponsor to address any issues before the study begins.


The U.S. FDA’s comprehensive guidance on informed consent in clinical investigations emphasizes ethical practices and transparent communication. It provides valuable direction to stakeholders, ensuring that informed consent becomes an empowering process for participants. IRBs play a pivotal role in safeguarding rights, while clinical investigators ensure participant well-being. Sponsors facilitate alignment with regulations, and the FDA’s review enhances integrity. Together, these efforts uphold ethical standards, protect participants, and advance responsible clinical research.

References and Further Reading