Role of the Institutional Review Boards (IRBs) at a Phase 1 CRO

Introduction to Institutional Review Boards (IRBs)

An Institutional Review Board (IRB) is an independent committee that reviews, approves, and monitors biomedical research that involves human participants. The primary purpose of an Institutional Review Board is to provide ethical oversight to clinical trials and ensure the protection of study participants’ rights and welfare. As such, Institutional Review Boards are responsible for reviewing protocols, informed consent forms, and protocol amendments and monitoring the risks associated with ongoing studies.

Institutional Review Boards first came to be after a long history of unethical research practices, which included those during the Nuremberg Trials. These ethics breaches led to the establishment of several codes of ethics, such as the Nuremberg Code and the Declaration of Helsinki. Documents such as these outline fundamental clinical research ethics that minimize risk and harm to the participant and prioritize subject welfare. Over time, these principles found their way into regulations such as Good Clinical Practice (GCP, ICH E6) guidelines, establishing IRBs as an essential component of global research.

Institutional Review Boards operate within strict regulatory frameworks, with the aim of being consistent and upholding high ethical standards. Examples globally include:

• FDA: FDA regulations grant IRBs the authority to approve, disapprove, or request modifications for research involving human subjects. To do so, IRBs are expected to review research protocols and associated materials (e.g., investigator brochures, informed consent forms) throughout the conduct of a study.
•  Health Canada: Research Ethics Boards (REBs) are the equivalent of IRBs in Canada. Clinical studies not associated with Health Canada or the Public Health Agency of Canada (PHAC) must be reviewed by the REB of the institution conducting the research. 
•  European Medicines Agency (EMA): EMA has a similar process as outlined in the Clinical Trials Regulation (EU No 536/2014), which requires clinical trials to get approval from an ethics committee.

A key component of any Institutional Review Board is the diversity of its members. IRBs are typically composed of several members, including legal experts, clinical professionals, and community representatives. The multidisciplinary team ensures that evaluations are comprehensive and consider all aspects of subject safety and scientific validity.

Functions of Institutional Review Boards

The Institutional Review Boards role is multifaceted, touching on several areas of clinical trial conduct related to ethics.

Review and approval of clinical trial protocols

Before initiating a clinical study, the institutional review board thoroughly evaluates the study protocol to confirm that it upholds ethical and regulatory compliance. This evaluation includes a review of the study’s objectives, methods, and risks. The IRB does this in collaboration with both the principal investigator (PI) and sub-investigators (sub-PI). The IRB ensures minimal risk to participants, and the PI is responsible for study execution.

Protection of human participants

The most critical Institutional Review Board role is ensuring participant safety, which involves:

• A thorough risk assessment. The institutional review board should determine possible risks and risk mitigation measures through pre-emptive identification of study hazards and ethical dilemmas.
• Informed consent evaluation. In addition to the protocol itself, an IRB will review the informed consent documents, ensuring that they adequately detail the study and its potential risks.

Ongoing oversight of trials

The Institutional Review Board role extends beyond the review of the initial protocol and informed consent documents. The Institutional Review Board will continue to monitor the study throughout its duration, including:

• Safety: The institutional review board monitors adverse event reporting throughout the trial.
• Protocol amendments: With each protocol change, the IRB will ensure that participant safety and ethical compliance are upheld.
• Specialized oversight for complex trials: Some studies have unique IRB considerations. For example, Phase 1 clinical trials such as Human Abuse Liability (HAL) assessments or first-in-human trials have specific complexities.

Specific Role in Phase 1 Clinical Trials: Differentiating Factors

As mentioned, Phase 1 clinical trials have some unique risks that must be considered from the IRB and industry perspectives. For example, Phase 1, first-in-human studies, have inherent uncertainties regarding dose and adverse events. IRBs should ensure that the study protocol and informed consent appropriately manage the risks surrounding these uncertainties.

Impact of Institutional Review Boards on CRO Operations: Business Relevance

To effectively manage the risks associated with Phase 1 clinical trials, CROs work collaboratively with IRBs before and during study conduct. For example, the IRB, CRO team, investigators, and compliance officers work together to:

• Ensure equitable participant selection and informed consent.
• Consider the ethics of the trial in specific contexts, such as when involving special populations (e.g., rare disease groups or ethnically diverse cohorts).
• Design consent forms that are transparent and accessible, reducing dropout rates and enhancing participant trust.
• Approve urgent protocol changes (e.g., by virtue of unforeseen adverse events) during active Phase 1 clinical trials.

Despite this collaboration, the IRB’s role is to be the ultimate decision-maker when determining the safety and ethics of a trial. As a result, the Institutional Review Board heavily influences the study design and modifications to the protocol, which can ultimately affect the study timelines. In the context of early-phase clinical trial execution, the IRB may request changes to the protocol involving:

• Dosing: IRBs might recommend more conservative doses or gradual dose escalation plans to minimize the risk of adverse events.
• Patient population: IRBs will make sure that the inclusion and exclusion criteria avoid unnecessary risks while also maintaining the scientific rigor of the study.
• Informed consent: Some IRBs will request further clarification on consent forms to ensure study subjects know the trial risks.

CROs Harmonize Compliance Amongst Institutional Review Boards

Of its many responsibilities, Institutional Review Boards ensure compliance with international guidelines such as ICH-GCP. Additionally, IRBs enforce data security standards, ensuring that trial data is safeguarded under frameworks like HIPAA (US), GDPR (Europe), and PIPEDA (Canada). Thus, sponsors must consider the intricacies of IRB review at both a local and global level.

CROs bring local and global expertise, ensuring harmonization of requirements amongst regions. Though BioPharma Services has regional expertise in Canada, we also have a global reach with the ability to centralize IRB review to cover submissions for other study sites.

Innovative Practices in CRO-Institutional Review Boards Collaboration

CROs have several innovative practices that can streamline interaction with IRBs aside from their expertise in preparing for IRB review. For example, digital platforms, such as IRB portals, enhance submission accuracy, streamline processes, and improve transparency in CRO-IRB interactions.

CROs can also be particularly helpful for adaptive trial designs, where protocols might evolve quickly depending on interim results. In these incidences, CROs can support collaboration with IRBs for quick and efficient approval for protocols and informed consent forms.

Challenges and Solutions in Institutional Review Boards Reviews

There exist several challenges associated with IRB reviews that CRO expertise can support. These include:

• Long protocol reviews: IRBs review times can sometimes be lengthy when evaluating protocols with complex study designs or high-risk features.
• Revisions to consent documents: IRBs will often request several revisions of consent forms to ensure they are both comprehensive and accessible to the participant.
• Amendment approvals: IRBs will also require reviewing and approving protocol modifications that can cause delays in starting the clinical trials.

With the help of CROs, the industry can easily navigate many of these challenges associated with Institutional Review Boards reviews by:

• Supporting and streamlining submissions: CROs can work closely with sponsors to quickly finalize protocol and informed consent and implement protocol and informed consent modifications, as needed, for quicker review. Additionally, CROs can help anticipate potential IRB questions. In addition, CROs can work with IRB to expedite the approval time for initial submission and/or amendment submission.
• Bringing in expertise: CROs often work together with local and central IRBs to ensure ethical and regulatory compliance.

For example, in one study, a serious adverse event (SAE) occurred that was determined not to be related to the study drug. Despite this, the study was temporarily put on hold to allow for a thorough investigation. The IRB played a critical role in assessing the situation, ensuring patient safety, and upholding ethical standards. By promptly sharing the IRB’s feedback with Health Canada, BioPharma Services was able to expedite their review process, enabling the study to resume without unnecessary delays while maintaining trust and compliance with all stakeholders.

Institutional Review Boards as a Strategic Partner for Sponsors

Sponsors should consider Institutional Review Boards as a tool rather than a barrier to study conduct. Robust institutional review board oversight contributes to high-quality data, smoother regulatory approvals, and faster commercialization.

At BioPharma Services, we are committed to maintaining the sponsor’s ethical reputation in the industry. As such, BioPharma Services prioritizes close collaboration with the IRB to reduce long-term costs by preventing non-compliance penalties or protocol redesigns. To do so, BioPharma Services provides:

• Extensive expertise in preparing study documents (protocols, informed consent forms, etc.) that pass IRB scrutiny efficiently
• Efficient integration of IRB feedback to enhance trial design without compromising timelines
• Education to sponsors and their teams about IRB expectations to improve collaboration and reduce friction

In summary, Institutional Review Boards approval is critical to the safe, ethical, and timely execution of Phase 1 clinical trials. Interested in getting support for your Phase 1 clinical trial? Contact us to see how our collaboration with Institutional Review Boards ensures successful trial execution.

BioPharma Services, Inc., a HEALWELL AI and clinical trial services company, is a full-service Contract Clinical Research Organization (CRO) based in Toronto, Canada, specializing in Phase 1 clinical trials 1/2a, Human Abuse Liability(HAL) and Bioequivalence clinical trials for international pharmaceutical companies worldwide. BioPharma Services conducts clinical research operations from its Canadian facility, with access to healthy volunteers and special populations.