Continuing Review Of An Approved And Ongoing Study Posing

Continuing review is a critical component of ethical oversight in research, particularly for studies that pose more than minimal risk to participants. It's a process that ensures ongoing research remains ethically sound, scientifically valid, and compliant with regulations and guidelines. In this article, we will discuss the essentials of continuing review for approved and ongoing studies, focusing on studies that pose greater risks to participants.

Understanding the Purpose of Continuing Review

The primary purpose of continuing review is to protect the rights and welfare of human subjects participating in research. It acknowledges that circumstances and knowledge can change over time, potentially impacting the risk-benefit ratio of a study. Continuing review is not simply a formality; it's an active process of reassessment.

Here's a breakdown of the core goals:

• Risk Reassessment: To determine if the risks to participants remain reasonable in relation to the anticipated benefits. This involves reviewing any new information that may affect the risk profile.
• Adverse Event Monitoring: To evaluate reports of adverse events, unanticipated problems, and protocol deviations to identify trends and assess their impact on participant safety and the study's integrity.
• Compliance Verification: To ensure the study is being conducted in accordance with the approved protocol, informed consent documents, and relevant regulations and institutional policies.
• New Information Evaluation: To review any new scientific findings, regulatory changes, or ethical considerations that may impact the study's design, conduct, or the information provided to participants.
• Informed Consent Adequacy: To ensure the informed consent process remains adequate and informative, providing participants with the information they need to make an informed decision about their continued participation.

When is Continuing Review Required?

Institutional Review Boards (IRBs) are responsible for determining the frequency of continuing review for each approved study. The level of review required and the frequency depend on the risk associated with the research. While some studies, particularly those involving minimal risk, may be eligible for expedited review or be exempt from continuing review altogether, studies posing more than minimal risk invariably require ongoing review.

Factors influencing the need for continuing review:

• Level of Risk: Higher-risk studies necessitate more frequent and rigorous review.
• Study Duration: Long-term studies require continued monitoring to ensure ongoing ethical and safety considerations are addressed.
• Vulnerable Populations: Research involving vulnerable populations (e.g., children, prisoners, individuals with cognitive impairments) often requires more frequent review.
• Regulatory Requirements: Regulations such as those from the FDA and DHHS dictate the requirements for continuing review.

The Continuing Review Process: A Step-by-Step Guide

The continuing review process typically involves the following steps:

1. Submission of Continuing Review Documents:

Researchers are responsible for submitting the required documentation to the IRB in advance of the approval expiration date. Common documents include:

• Continuing Review Application: This form updates the IRB on the study's progress, any changes to the protocol, and any relevant new information.
• Summary of Progress: A concise summary of the study's progress, including the number of participants enrolled, data collected, and any significant findings.
• Adverse Event Reports: A comprehensive report of all adverse events, unanticipated problems, and protocol deviations that have occurred since the last review.
• Current Informed Consent Document(s): A copy of the current informed consent document(s) used in the study.
• Relevant New Information: Any new scientific findings, regulatory changes, or ethical considerations that may impact the study.
• Updated Investigator Brochure (if applicable): In studies involving investigational drugs or devices, an updated investigator brochure provides current safety and efficacy information.

2. IRB Review of Submitted Documents:

The IRB reviews the submitted documents to assess the study's ongoing ethical and scientific validity. This review may involve:

• Assessment of Risk-Benefit Ratio: The IRB evaluates whether the risks to participants remain reasonable in relation to the anticipated benefits, considering any new information or adverse events.
• Evaluation of Adverse Event Reports: The IRB thoroughly examines adverse event reports to identify trends and assess their impact on participant safety and the study's integrity.
• Verification of Compliance: The IRB ensures the study is being conducted in accordance with the approved protocol, informed consent documents, and relevant regulations and institutional policies.
• Review of New Information: The IRB considers any new scientific findings, regulatory changes, or ethical considerations that may impact the study's design, conduct, or the information provided to participants.
• Assessment of Informed Consent Adequacy: The IRB ensures the informed consent process remains adequate and informative, providing participants with the information they need to make an informed decision about their continued participation.

3. IRB Actions Following Review:

Based on its review, the IRB may take one of the following actions:

• Approval: The IRB approves the study for another specified period, typically one year, if it determines that the research continues to meet ethical and regulatory requirements.
• Approval with Modifications: The IRB may require modifications to the protocol, informed consent documents, or other aspects of the study to address concerns identified during the review. The study cannot continue until these modifications are implemented and approved.
• Suspension: The IRB may suspend the study if it determines that there are serious ethical or safety concerns that need to be addressed before the research can continue.
• Termination: In rare cases, the IRB may terminate the study if it determines that the risks to participants are unacceptable or that the research is not being conducted in accordance with ethical and regulatory requirements.

4. Communication of IRB Decision:

The IRB communicates its decision to the principal investigator (PI) in writing, including any required modifications or conditions of approval. The PI is responsible for ensuring that all study personnel are aware of the IRB's decision and any required changes to the study.

Key Considerations for Studies Posing Greater Risk

Studies that pose more than minimal risk to participants require particularly careful attention during continuing review. These studies often involve:

• Invasive Procedures: Studies involving invasive procedures, such as surgery or biopsies, carry inherent risks that must be carefully monitored.
• Experimental Therapies: Studies evaluating experimental therapies may involve uncertain risks and benefits.
• Vulnerable Populations: Research involving vulnerable populations requires extra safeguards to protect participants' rights and welfare.
• Complex Protocols: Studies with complex protocols may be more prone to errors or deviations, which can increase the risk to participants.

Here are some specific considerations for these types of studies:

• Adverse Event Monitoring: Implement a robust system for monitoring and reporting adverse events, including clear definitions, reporting timelines, and procedures for investigating and managing events.
• Data Safety Monitoring Board (DSMB): For high-risk studies, consider establishing a DSMB to provide independent oversight of participant safety and data integrity.
• Interim Data Analysis: Conduct interim data analyses to identify potential safety signals or efficacy trends that may warrant modifications to the study.
• Informed Consent Re-Evaluation: Regularly re-evaluate the informed consent process to ensure it remains adequate and informative, particularly if new information emerges that may affect participants' decisions.
• Protocol Adherence Monitoring: Implement procedures to monitor protocol adherence and address any deviations promptly.
• Risk Mitigation Strategies: Develop and implement specific risk mitigation strategies to minimize the potential for harm to participants.

Common Challenges and How to Address Them

The continuing review process can present several challenges for researchers and IRBs. Here are some common issues and strategies for addressing them:

• Incomplete or Late Submissions: Ensure researchers understand the requirements for continuing review and provide them with ample time to prepare their submissions. Provide templates and guidance documents to facilitate the process.
• Lack of Clarity in Adverse Event Reporting: Establish clear definitions for adverse events and provide researchers with training on how to report them accurately and completely.
• Difficulty Assessing Risk-Benefit Ratio: Use a structured approach to assess the risk-benefit ratio, considering both the potential risks to participants and the potential benefits of the research. Involve experts with relevant expertise in the review process.
• Keeping Up with New Information: Stay informed about new scientific findings, regulatory changes, and ethical considerations that may impact ongoing studies. Subscribe to relevant newsletters, attend conferences, and consult with experts in the field.
• Managing Protocol Deviations: Implement procedures for identifying, reporting, and managing protocol deviations. Investigate deviations to determine the cause and implement corrective actions to prevent future occurrences.

The Role of Technology in Streamlining Continuing Review

Technology can play a significant role in streamlining the continuing review process and improving its efficiency and effectiveness. Electronic IRB (eIRB) systems can automate many aspects of the process, such as:

• Submission and Tracking of Documents: eIRB systems allow researchers to submit continuing review documents electronically and track their status in real-time.
• Automated Reminders: The system can send automated reminders to researchers and IRB members about upcoming deadlines and required actions.
• Centralized Data Storage: eIRB systems provide a centralized repository for all study-related documents, making it easier to access and review information.
• Workflow Automation: The system can automate many of the steps in the review process, such as routing documents to reviewers and generating approval letters.
• Reporting and Analytics: eIRB systems can generate reports and analytics on IRB activities, providing insights into workload, turnaround times, and other key metrics.

By leveraging technology, IRBs can reduce administrative burden, improve communication, and enhance the quality and efficiency of the continuing review process.

Training and Education: Ensuring Competency in Continuing Review

Effective continuing review requires that researchers and IRB members have the necessary knowledge, skills, and training. Institutions should provide comprehensive training programs on:

• Ethical Principles of Research: Review the ethical principles that guide research involving human subjects, such as respect for persons, beneficence, and justice.
• Regulatory Requirements: Provide detailed information on the regulatory requirements for continuing review, including those from the FDA and DHHS.
• IRB Policies and Procedures: Familiarize researchers and IRB members with the institution's specific policies and procedures for continuing review.
• Adverse Event Reporting: Train researchers on how to identify, report, and manage adverse events.
• Informed Consent: Provide training on the principles of informed consent and how to develop and implement effective consent processes.
• Risk Assessment: Teach researchers and IRB members how to assess the risks and benefits of research studies.
• Data Safety Monitoring: Provide training on the principles of data safety monitoring and the role of DSMBs.

Ongoing education and professional development are essential to keep researchers and IRB members up-to-date on the latest developments in research ethics and regulations.

The Future of Continuing Review

The field of research ethics is constantly evolving, and the continuing review process must adapt to meet new challenges and opportunities. Some potential future directions include:

• Increased Use of Technology: As technology continues to advance, we can expect to see even greater use of eIRB systems and other tools to streamline the continuing review process.
• Focus on Quality Improvement: There is a growing emphasis on quality improvement in research ethics, with a focus on identifying and addressing systemic issues that can impact the effectiveness of continuing review.
• Integration with Data Analytics: Integrating data analytics into the continuing review process can help IRBs identify trends and patterns that may indicate potential safety or ethical concerns.
• Patient Engagement: Engaging patients in the continuing review process can provide valuable insights into the participant experience and help ensure that research is conducted in a way that is respectful and responsive to their needs.
• Adaptive Review Processes: Developing adaptive review processes that can be tailored to the specific risks and complexities of individual studies.

Conclusion

Continuing review is an indispensable safeguard for protecting research participants, particularly in studies that pose more than minimal risk. By diligently monitoring ongoing research, assessing new information, and verifying compliance, IRBs play a critical role in ensuring that research remains ethically sound and scientifically valid. As research continues to evolve, so too must the continuing review process, embracing new technologies, strategies, and perspectives to promote the highest standards of ethical research conduct.