Protocol Violations that Present Unreasonable Risks – In certain circumstances, failure to comply with the study’s protocol could be considered a failure to protect the rights, safety, and welfare of subjects because the non-compliance exposes subjects to unreasonable risks.

FDA recommends that investigators should do everything they can to minimize such risks, which can be done by adhering closely to the study protocol. Clinical trials can take a number of twists and turns and it is not uncommon for the unexpected to occur. For this reason, ensuring and maintaining compliance with all of FDA’s regulations can be difficult.

That is why where are here to help. We have a proven track record of helping our clients comply with all relevant requirements and we can do the same for you. To learn more about our clinical quality and GCP services, contact us today.

How does the IRB IEC help protect the rights and well-being of subjects after it provides approval to the principal investigator to conduct the clinical trial?

I. IRB Organization – 1. What is an Institutional Review Board (IRB)? Under FDA regulations, an IRB is an appropriately constituted group that has been formally designated to review and monitor biomedical research involving human subjects. In accordance with FDA regulations, an IRB has the authority to approve, require modifications in (to secure approval), or disapprove research.

1. This group review serves an important role in the protection of the rights and welfare of human research subjects.
2. The purpose of IRB review is to assure, both in advance and by periodic review, that appropriate steps are taken to protect the rights and welfare of humans participating as subjects in the research.

To accomplish this purpose, IRBs use a group process to review research protocols and related materials (e.g., informed consent documents and investigator brochures) to ensure protection of the rights and welfare of human subjects of research.2. Do IRBs have to be formally called by that name? No, “IRB” is a generic term used by FDA (and HHS) to refer to a group whose function is to review research to assure the protection of the rights and welfare of the human subjects.

Each institution may use whatever name it chooses. Regardless of the name chosen, the IRB is subject to the Agency’s IRB regulations when studies of FDA regulated products are reviewed and approved.3. Does an IRB need to register with FDA before approving studies? As published in the Federal Register on January 15, 2009, (74 FR 2358), 21 CFR Part 56, Institutional Review Boards, was amended with regard to IRB registration (21 CFR 56.106).

This amendment requires each IRB in the United States (U.S.) that reviews FDA-regulated studies to register. IRB registration information is entered into an Internet-based registration system maintained by the Department of Health and Human Services (HHS).

1. See Guidance for Institutional Review Boards (IRBs) Frequently Asked Questions – IRB Registration ).4.
2. What is an “assurance” or a “multiple project assurance?” An “assurance,” is a document negotiated between an institution and the Department of Health and Human Services (HHS) in accordance with HHS regulations.

For research involving human subjects conducted by HHS or supported in whole or in part by HHS, the HHS regulations require a written assurance from the performance-site institution that the institution will comply with the HHS protection of human subjects regulations,

1. The assurance mechanism is described in 45 CFR 46.103.
2. Once an institution’s assurance has been approved by HHS, a number is assigned to the assurance.
3. The assurance may be for a single grant or contract (a “single project assurance”); for multiple grants (“multiple project assurances” – formerly called “general assurances”); or for certain types of studies such as oncology group studies and AIDS research group studies (“cooperative project assurances”).

The Office for Human Research Protection (OHRP) is responsible for implementing the HHS regulations. The address and telephone number for OHRP are: 1101 Wootton Parkway, The Tower Building, Suite 200, Rockville, MD 20852; Toll-Free Telephone within the U.S.: (866) 447-4777, Telephone: (240) 453-6900, FAX: (240) 453-6909.5.

1. Is an “assurance” required by FDA? Currently, FDA regulations do not require an assurance.
2. FDA regulations apply to research involving products regulated by FDA – federal funds and/or support do not need to be involved for the FDA regulations to apply.
3. When research studies involving products regulated by FDA are funded/supported by HHS, the research institution must comply with both the HHS and FDA regulations.6.

Must an institution establish its own IRB? No. Although institutions engaged in research involving human subjects will usually have their own IRBs to oversee research conducted within the institution or by the staff of the institution, FDA regulations permit an institution without an IRB to arrange for an “outside” IRB to be responsible for initial and continuing review of studies conducted at the non-IRB institution.

Such arrangements should be documented in writing. Individuals conducting research in a non-institutional setting often use established IRBs (independent or institutional) rather than form their own IRBs. Also see the information sheets entitled “Non-local IRB Review” and “Cooperative Research.” 7. May a hospital IRB review a study that will be conducted outside of the hospital? Yes.

IRBs may agree to review research from affiliated or unaffiliated investigators, however, FDA does not require IRBs to assume this responsibility. If the IRB routinely conducts these reviews, the IRB policies should authorize such reviews and the process should be described in the IRB’s written procedures.

• A hospital IRB may review outside studies on an individual basis when the minutes clearly show the members are aware of where the study is to be conducted and when the IRB possesses appropriate knowledge about the study site(s).8.
• May IRB members be paid for their services? The FDA regulations do not preclude a member from being compensated for services rendered.

Payment to IRB members should not be related to or dependent upon a favorable decision. Expenses, such as travel costs, may also be reimbursed.9. What is the FDA role in IRB liability in malpractice suits? FDA regulations do not address the question of IRB or institutional liability in the case of malpractice suits.

FDA does not have authority to limit liability of IRBs or their members. Compliance with FDA regulations may help minimize an IRB’s exposure to liability.10. Is the purpose of the IRB review of informed consent to protect the institution or the subject? The fundamental purpose of IRB review of informed consent is to assure that the rights and welfare of subjects are protected.

A signed informed consent document is evidence that the document has been provided to a prospective subject (and presumably, explained) and that the subject has agreed to participate in the research. IRB review of informed consent documents also ensures that the institution has complied with applicable regulations.11.

Does an IRB or institution have to compensate subjects if injury occurs as a result of participation in a research study? Institutional policy, not FDA regulation, determines whether compensation and medical treatment(s) will be offered and the conditions that might be placed on subject eligibility for compensation or treatment(s).

The FDA informed consent regulation on compensation requires that, for research involving more than minimal risk, the subject must be told whether any compensation and any medical treatment(s) are available if injury occurs and, if so, what they are, or where further information may be obtained.

What are the responsibilities of an investigator?

Clinical Investigator Responsibilities American Society of Clinical Oncology, Alexandria, VA; Clinical Trial Support Unit Hematology/Oncology, Hospital for Sick Children, Toronto, Ontario, Canada; Translational Research Management, Los, Angeles, CA; Coalition of Cancer Cooperative Groups and Eastern Cooperative Oncology Group, Philadelphia, PA Find articles by American Society of Clinical Oncology, Alexandria, VA; Clinical Trial Support Unit Hematology/Oncology, Hospital for Sick Children, Toronto, Ontario, Canada; Translational Research Management, Los, Angeles, CA; Coalition of Cancer Cooperative Groups and Eastern Cooperative Oncology Group, Philadelphia, PA Find articles by American Society of Clinical Oncology, Alexandria, VA; Clinical Trial Support Unit Hematology/Oncology, Hospital for Sick Children, Toronto, Ontario, Canada; Translational Research Management, Los, Angeles, CA; Coalition of Cancer Cooperative Groups and Eastern Cooperative Oncology Group, Philadelphia, PA Find articles by American Society of Clinical Oncology, Alexandria, VA; Clinical Trial Support Unit Hematology/Oncology, Hospital for Sick Children, Toronto, Ontario, Canada; Translational Research Management, Los, Angeles, CA; Coalition of Cancer Cooperative Groups and Eastern Cooperative Oncology Group, Philadelphia, PA Find articles by © 2011 by American Society of Clinical Oncology When conducting a clinical trial, it is important that clinical investigators successfully meet all research expectations, including regulatory requirements and the Guidelines for Good Clinical Practice.

Clinical investigators face challenges during the conduct of clinical trials that are distinctly different from those encountered during the routine practice of medicine. Many of these challenges stem from regulatory requirements, the Guidelines for Good Clinical Practice (GCP) and the rigorous nature of clinical trials.

When conducting a clinical trial, it is important that clinical investigators successfully meet all research expectations. A clinical investigator’s primary responsibility is to conduct research that contributes to generalizable knowledge while protecting the rights and welfare of human participants.

This article, part of the Journal of Oncology Practice series on attributes of exemplary clinical trial sites, discusses select investigator responsibilities and provides practical advice on how to promote compliance in practice. It is important to conduct research in an ethical manner. Investigators must be diligent throughout the conduct of a clinical trial: while designing the protocol, when deciding which trials to conduct, during the performance of the study, and after conclusion of the study ().

Although there are multiple regulatory safeguards designed to ensure the ethical conduct of research, it is ultimately the investigator’s responsibility to make certain that the research is fair and equitable to study participants. When the investigator is also the sponsor of the study, then responsibilities also include protocol design.

The 1979 Belmont Report established basic guidelines intended to prevent ethical problems related to research. The report outlines three basic principles: respect for persons, beneficence, and justice. Detailed discussion about each of these principles and the differences between clinical practice and research is provided in the report.

Additional information about the report and related topics is available, free of charge, through the Web site of the Office for Human Research Protection (OHRP). The majority of investigators respect the importance of conducting ethical research, but even the most cognizant investigators may encounter unexpected challenges.

1. For example, an ethical dilemma can arise when the control arm of a trial does not correlate with the standard treatment typically prescribed by the physician.
2. Issues like this need to be discussed during trial design and considered as part of the decision to implement new trials at the site.
3. Clinical investigators need to review the protocol in detail and understand the primary end point of every study they oversee.

This practice prevents inadvertent issues that can affect patient safety and/or the scientific integrity of the study. For example, if a study is designed to provide adjuvant treatment to patients, but the investigator is slow to identify the first signs of relapse, then the quality of the science suffers and potentially affects approval of the agent by the US Food and Drug Administration (FDA).

1. Understanding the research protocol and investigator’s brochure helps to prevent potential issues.
2. In addition to understanding study-specific requirements, investigators and their teams are encouraged to obtain training that more broadly addresses issues related to the conduct of clinical research.
3. All clinical investigators should have participated in educational opportunities covering International Conference on Harmonization GCP, Human Subject Protection, and requirements for the shipping of biologic specimens.

The Society of Clinical Research Associates also offers several training opportunities, including a workshop focused on investigator responsibilities and a course cosponsored by the FDA pertaining to regulatory issues. Public Responsibility in Medicine and Research and the Collaborative Institutional Training Initiative are also both reliable sources for education and training.

Training may also be offered by study sponsors or your institution. Informed consent is a process that extends beyond a patient simply signing a consent form. Clinical research requires that individuals be fully informed about the study they are being offered. Throughout the informed consent process, potential research participants should be given the opportunity to learn about the research study and have all their questions answered.

According to the Belmont Report, individuals must be given the opportunity to make informed choices with regard to how they will be treated and what interventions they will participate in. Potential participants should be informed about the risks; anticipated benefits; and any alternative treatment options they have, including hospice care.

An appropriate informed consent process needs to be conducted by a qualified individual who understands the clinical trial protocol and has knowledge about the potential benefits and adverse effects of the therapeutic agent under investigation. If the investigation is a randomized, controlled clinical trial, research staff should be certain to alert potential participants to the concept of randomization.

The potential participant must also be informed about the treatment that will be given to individuals who are randomly assigned to the control arm of the trial. They should be told that neither they nor their provider can control which arm of the trial they are randomized to.

• Patient-oriented educational materials about clinical trials are available, free of charge, on ASCO’s patient education Web site,,
• The informed consent document is a record of what was discussed during the informed consent process.
• This document needs to be approved by an institutional review board before the initiation of a study and should be written at a reading level that is appropriate for potential research participants.

Whenever possible, individuals interested in enrolling onto a clinical trial should be given a copy of the informed consent document to review at home and discuss with their friends and family. After having ample opportunity to review the informed consent form and consider all of their options, the potential participant should be given another opportunity to ask questions.

It is very important that research participants sign the most current approved version of the informed consent form for the trial they are participating on. Many sites institute “version control” to prevent errors by maintaining an electronic file of informed consent documents and permitting staff to have access only to the most current version of the consent form for each protocol.

Maintaining these files electronically ensures that an old version of the informed consent document is not inadvertently used. OHRP provides extensive information about the informed consent process via their Web site and recently produced helpful videos to instruct providers on how to appropriately conduct the informed consent process.

When conducting clinical research with an investigational agent, such as a drug or biologic, an investigator must comply with all applicable FDA rules and regulations. An investigator must also complete the Statement of Investigator (FDA Form 1572) before participating in an FDA-regulated investigation.

FDA Form 1572 is a legally binding document designed to inform clinical investigators of their research obligations and secure the investigators’ commitment to follow pertinent FDA regulations. By signing this form, the investigator confirms that they will abide by all FDA regulations.

• Falsifying information on the FDA Form 1572 can lead to the investigator being disqualified.
• Moreover, if the investigator’s action is determined to be fraudulent in nature, criminal action can be taken, potentially resulting in disbarment of the investigator.
• This underscores the importance of reading and understanding all elements of the form, including the investigator responsibilities explicitly listed in section 9.

Individuals who want to learn more about FDA Form 1572 are encouraged to read the FDA guidance document, “Information Sheet Guidance for Sponsors, Clinical Investigators, and IRBs,” which provides detailed information about FDA Form 1572 and answers frequently asked questions.

1. Investigators should be especially mindful to read and understand section 9 of FDA Form 1572.
2. This section lists the commitments the investigator is agreeing to on completion of the form.
3. A principal investigator needs to be certain that all commitments are upheld on every study they are responsible for.

Even if certain tasks have been delegated, it is the investigator’s responsibility to ensure that all study-related responsibilities are appropriately fulfilled. One area of frequent inquiry pertains to section 6 of FDA Form 1572, which asks for the names of all subinvestigators who will be assisting with the investigation.

According to FDA Regulation 21 CFR 312.3(b), “In the event an investigation is conducted by a team of individuals, the investigator is the responsible leader of the team. ‘Subinvestigator’ includes any other individual member of that team.” FDA guidance clarifies that individuals should be listed if they make direct and significant contributions to the data or perform study-related procedures.

According to the guidance document, “In general, if an individual is directly involved in the performance of procedures required by the protocol, and the collection of data, that person should be listed on the 1572.” The guidance also provides specific examples of the types of individuals who should be listed.

1. The FDA guidance document also clarifies that everyone listed as either an investigator or subinvestigator must disclose financial interests to the study sponsor.
2. The FDA has a separate guidance document related to financial disclosure, “FDA’s Guidance for Industry Financial Disclosure by Clinical Investigators.” If the investigation is funded by Public Health Service agencies such as the National Institutes of Health National Cancer Institute, then the investigator must also comply with Regulation 42 CFR Part 50, Subpart F: “Responsibility of Applicants for Promoting Objectivity in Research for Which PHS Funding Is Sought.” The FDA and Public Health Services have several different conflict of interest disclosure requirements, including different disclosure thresholds.

Investigators are responsible for supervising the proper handling, administration, storage, and destruction of investigational agents (ie, drug accountability). Although these tasks can be delegated to an appropriately qualified individual, the investigator maintains ultimate responsibility.

If an investigator delegates this task to a pharmacist or pharmacy technician who is not already dedicated to research, that individual needs to receive training specific to the responsibilities associated with the disposition and use of investigational agents. These responsibilities differ greatly from those associated with standard practice and are important for promoting patient safety and the collection of quality research data.

Oversight begins as soon as the investigational agent is ordered. The individual who receives the shipment needs to document the quantity of the agent that was received on the drug accountability record form (DARF). Beyond completing the standard documentation requirements on the DARF, staff should be aware of any protocol-specific recordkeeping requirements.

• For example, some agents are shipped with a temperature-monitoring device, requiring that staff record whether the agent was maintained within the proper temperature range throughout shipment.
• If the monitoring device indicates that the agent was exposed to a temperature outside the range specified by the trial sponsor, then further action may be needed.

After receipt of the agent being used in a clinical trial, the agent needs to be stored in a secure location, at the temperature specified by the sponsor. Stored investigational agents need to be separated according to study protocol. In addition, an individual drug accountability form must be maintained for each agent as well as for each dosage formulation for every protocol.

• Even if a certain agent is also used in standard practice or on more than one research protocol, the drug supply for each clinical trial must be kept separate and accounted for on an individual accountability form.
• Careful recording of the preparation and use of the investigational agent must also be maintained.

Documentation is needed regarding which individual calculated the dose to be administered, prepared the agent for use, and administered the agent; all verifications that occurred throughout the process should also be documented. The amount of agent that is dispensed from the supply needs to be recorded on the DARF, and any agent that remains after completion of the trial should be shipped back to the trial sponsor or destroyed.

An investigator should also be aware of any specific requirements mandated by the trial sponsor. The Investigator Handbook published by NCI is a helpful reference for investigators conducting NCI-funded trials. The Clinical Trials Support Unit is also a helpful resource for individuals conducting NCI-sponsored phase III clinical trials.

Drug accountability not only ensures safe and proper use of investigational agents but also is an important component of audits conducted by the FDA and/or sponsor. Staff education is important in helping staff understand the special requirements associated with agents used on clinical trials.

• Routine internal audits are a helpful way to verify that investigational agents are being appropriately maintained and that documentation is accurate.
• Facilitating good communication between the pharmacy staff and research team helps to ensure proper oversight of investigational agents.
• It is required to document all adverse events that occur during the course of the clinical investigation.

Keeping a log of adverse events is a helpful organizational tool, and such logs should be reviewed during regularly scheduled research team meetings. It is important that a principle investigator be aware of adverse events because the event may trigger the need for a dose adjustment.

1. Serious or unanticipated events should be addressed immediately and may require meeting outside regularly scheduled team meetings.
2. Serious, unanticipated adverse events need be reported to both the institutional review board and sponsor within a short timeframe.
3. It is advisable that a research site develop a standard operating procedure (SOP) to help maintain consistent adverse event reporting.

SOPs are not required in any federal regulations, but they are very helpful in maintaining consistent processes at the site and are a useful resource when training new research staff. An SOP is also a helpful reference when determining which events need to be reported.

The OHRP and FDA both have developed helpful guidance documents for adverse event reporting., These guidance documents explain the regulations associated with reporting adverse events and are an important reference when a research site is developing or updating their SOP for adverse event reporting.

The importance of maintaining accurate records when conducting clinical research cannot be overstated. It is important that all collected data match information found in source documents, such as a pathology report or the patient’s medical record. In addition, issues such as protocol deviations must be well documented.

A situation that occurs today may not be reviewed or questioned until months or years in the future. It is nearly impossible to recall particular study conduct events during an audit unless they have been well documented. When a protocol deviation occurs, the site should document the event on a deviation log and develop a corrective action plan that clearly describes how similar events will be prevented in the future.

This corrective action plan then becomes a source document. Research staff might also use this corrective action plan to guide the development of a new SOP that will help prevent similar deviations in the future. As with many investigator responsibilities, an investigator is permitted to delegate tasks associated with data collection and documentation to a qualified individual.

• However, it is important that the investigator know that this individual will appropriately conduct the tasks being delegated.
• One way to ensure clear communication between an investigator and staff is to use a delegation log, which is a signed record of which study tasks have been assigned to which individual.

It is important that the investigator be available to staff to answer questions and make decisions. Holding routine meetings between the investigator and staff is an important way to ensure effective communication among study team members. Staff can use these meetings as an opportunity to raise concerns and document any action that was taken in response to those concerns.

• The frequency of the meetings may vary on the basis of trial complexity and the number of individuals enrolling onto the trial.
• To ensure the most efficient use of in-person meetings, the research team should develop a meeting agenda.
• Such agendas can vary depending on the needs of the site.
• For example, some sites prepare the agenda on the basis of items that have been delegated to the staff ().

Other sites prefer to use their patient list to structure the agenda. These sites may keep a table listing every patient enrolled or considering participation, then update the chart with related action items. Regardless of the structure, routine meetings are a good opportunity for the investigator to review and sign off on any documentation such as adverse events that are not serious or unanticipated (serious, unanticipated adverse events must be addressed immediately at the time of the event).

1. All updates or action items should be recorded on meeting minutes and then signed by the investigator.
2. To help with organization, research sites often use electronic systems to maintain research documents.
3. Some sites find it helpful to develop a shared drive that is organized identically across all studies.

Because study documents (ie, budget documents, notes to file, and consent forms) are all saved in a consistent format across studies, this type of organization makes it easy to cross-train staff and promotes a seamless transition when staff turnover occurs.

• When it comes to the conduct of clinical research, an investigator has numerous responsibilities.
• Because of the magnitude of this topic, we were unable to address all investigator responsibilities within the context of this article, but we hope the reader will access the external resources that were referenced for additional information.

We also encourage the reader to pursue clinical investigator training to better understand the full totality of their responsibilities as an investigator. The ASCO statement addresses the minimum requirements for sites conducting quality clinical trials as well as the attributes of exemplary sites.

• Both minimum requirements and exemplary attributes were based on a review of the literature, current regulatory requirements, and consensus among community and academic clinical researchers.
• In order to conduct quality clinical research, sites should meet the minimum requirements.
• It should be noted, however, that the exemplary attributes are voluntary and suggested as goals, not requirements.

Not all attributes will apply to all clinical trial sites, and many sites may be able to conduct high-quality clinical trials without accomplishing all attributes. The information contained in this article is general in nature. It is not intended to be, and should not be construed as, legal advice relating to any particular situation.

• Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article.
• Certain relationships marked with a “U” are those for which no compensation was received; those relationships marked with a “C” were compensated.

For a detailed description of the disclosure categories, or for more information about ASCO’s conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Conception and design: Allison R. Baer, Susan Devine, Chris David Beardmore, Robert Catalano Administrative support: Allison R. Baer Collection and assembly of data: Allison R. Baer, Susan Devine, Chris David Beardmore, Robert Catalano Data analysis and interpretation: Allison R. Baer, Susan Devine, Chris David Beardmore, Robert Catalano Manuscript writing: Allison R. Baer, Susan Devine, Chris David Beardmore, Robert Catalano Final approval of manuscript: Allison R. Baer, Susan Devine, Chris David Beardmore, Robert Catalano

1. International Conference on Harmonisation, Good Clinical Practice (ICH GCP).1.34 Investigator.,2. Zon R, Meropol N, Catalano R, et al. American Society of Clinical Oncology statement on minimum standards and exemplary attributes of clinical trial sites.

J Clin Oncol.2008:2562–2567.3. US Department of Health and Human Services, Office for Human Subjects Research. Belmont Report. Ethical Principles and Guidelines for the Protection of Human Subjects of Research.,4. International Conference on Harmonization, Good Clinical Practice (ICH GCP).1.36 investigator’s brochure.

,5. Society of Clinical Research Associates. Education.,6. Public Responsibility in Medicine and Research. Education.,7. Collaborative Institutional Training Initiative.,8. Cancer.Net.Clinical Trials.,9. US Department of Health and Human Services. USGOVHHS.,10.

1. US Food and Drug Administration.
2. Statement of investigator (Title 21, Code of Federal Regulations Part 312),11.
3. US Food and Drug Administration.
4. FAQs on debarments/disqualifications: Questions and answers on debarments and disqualifications.,12.
5. US Food and Drug Administration.
6. Information Sheet Guidance For Sponsors, Clinical Investigators, and IRBs.

Frequently Asked Questions—Statement of Investigator (Form FDA 1572),13. US Food and Drug Administration. Investigational New Drug Application, Code of Federal Regulations, 21CFR312.3.,14. US Food and Drug Administration. Financial Disclosure by Clinical Investigators.

Guidance for Industry – Financial Disclosure by Clinical Investigators.,15. National Archives and Records Administration. Electronic Code of Federal Regulations. Title 42: Public Health. Part 50—Policies of General Applicability, Subpart F—Responsibility of Applicants for Promoting Objectivity in Research for Which PHS Funding Is Sought.

,16. National Cancer Institute, Cancer Therapy Evaluation Program. Investigator’s Handbook. A Manual for Participants in Clinical Trials of Investigational Agents Sponsored by DCTD, NCI.,17. Cancer Trials Support Unit. About the CTSU.,18. US Department of Health and Human Services, Office for Human Research Protections.

Whose responsibilities would typically include activities at both the sponsor and the study site?

In the conduct of a clinical trial, a sponsor is an individual, institution, company or organization (for example, a contract research organization) that takes the responsibility to initiate, manage or finance the clinical trial, 1 but does not actually conduct the investigation.

Who is responsible for ongoing safety evaluation of the investigational product?

Ethics of Safety Reporting of a Clinical Trial

• 1 From the Department of Pharmacology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India
• 2 Member of Institutional Ethics Committee, Institute of Neurosciences, Kolkata, West Bengal, India
• 3 Member of Dermatology Clinical Trials Special Interest Group, IADVL Academy of Dermatology, India

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1. 4 Department of Dermatology, Bankura Sammilani Medical College, Bankura, West Bengal, India
2. 5 Member of Institutional Ethics Committee of Human Research, Medical College, Kolkata, West Bengal, India
3. 6 Coordinator of Dermatology Clinical Trials Special Interest Group, IADVL Academy of Dermatology, India

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• 1 From the Department of Pharmacology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India
• 2 Member of Institutional Ethics Committee, Institute of Neurosciences, Kolkata, West Bengal, India
• 3 Member of Dermatology Clinical Trials Special Interest Group, IADVL Academy of Dermatology, India
• 4 Department of Dermatology, Bankura Sammilani Medical College, Bankura, West Bengal, India
• 5 Member of Institutional Ethics Committee of Human Research, Medical College, Kolkata, West Bengal, India
• 6 Coordinator of Dermatology Clinical Trials Special Interest Group, IADVL Academy of Dermatology, India

Address for correspondence: Dr. Amrita Sil, Department of Pharmacology, UCM Building, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India. E-mail: Received 2017 May; Accepted 2017 May. : © 2017 Indian Journal of Dermatology This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

• Clinical trial related injury and serious adverse events (SAE) are a major area of concern.
• In all such scenarios the investigator is responsible for medical care of the trial participant and also ethically bound to report the event to all the stakeholders of the clinical trial.
• The trial sponsor is responsible for ongoing safety evaluation of the investigational product, reporting and compensating the participant in case of any SAE.

The Ethics Committee and regulatory body of the country are to uphold the ethical principles of beneficence, justice, non-maleficence in such cases. Any unwanted and noxious effect of a drug when used in recommended doses is an adverse drug reaction (ADR) whereas if causal association is not yet established it is termed adverse event (AE).

An AE or ADR that is associated with death, in-patient hospitalization, prolongation of hospitalization, persistent or significant disability or incapacity, a congenital anomaly, or is otherwise life threatening is termed as an SAE. The principal investigator reports the event to the licensing authority (DCGI), sponsor and Chairperson of the Ethics Committee (EC) within 24 hours of occurrence of the SAE.

This report is furthered by a detailed report by both the investigator and the EC and given to the DCGI who then gives a final decision on the amount of compensation to be given by the sponsor or the sponsor’s representative to the grieving party. K EY W ORDS : Adverse event, Compensation, Safety report, Serious adverse event What was known? In routine clinical practice, in case of any adverse events the role of doctor is to ensure that the condition is managed and he/she informs the patients relative and decides the further course of action based on his own judgement or referring the patient to his colleague.

• The compensation if any is decided by the court of law on the appeal made by the patient/relatives based on misconduct/malpractice.
• A trial of drugs on human participants must have a record not only of the effectiveness of the drug but also of its safety profile as toxicity outweighs the benefit-risk ratio, making drugs unsuitable for human use.

Adverse reactions may be spontaneously reported by a participant to an attending physician, elicited by the investigator during the trial or laboratory related. Such reactions may also be attributed to the drug after the completion of the trial. In all such scenarios, the investigator is responsible for medical care of the trial participant and also ethically bound to report the event to all the stakeholders of the clinical trial.

The trial sponsor is responsible for ongoing safety evaluation of an investigational product (IP) and reporting and compensating the participant in case of any serious adverse event (SAE). The Ethics Committee (EC) and regulatory body of the country are to uphold the ethical principles of beneficence, justice, and nonmaleficence in such cases.

Thus, to be ethical while conducting trials as investigators or evaluating the safety report as an EC member, it is pertinent to understand the various terminologies used in safety reporting, reporting requirements of adverse reactions, responsibility of the various stakeholders in the trial, causality assessment of an adverse reaction, and guidelines of compensation in case of a SAE.

Is there IRB in Europe?

Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ⋆ Vial Institutional review boards (IRB), also known as independent ethics committees (IEC) in the European Union, are formally designated independent bodies that safeguard the rights, safety, and well-being of all human subjects involved in a trial.

These bodies review and monitor clinical trial documents (protocol, informed consent documents, investigator brochures, and advertising material) in advance and by periodic review in accordance with written operating procedures. The IRB has the authority to approve, require modifications prior to giving a favorable opinion, disapprove, or terminate/suspend any prior approval of the research.

Records must be kept for three years after the completion of the trial. IRBs are composed of medical and nonmedical members that have no conflicting interest with the clinical trial. Regulations require IRBs to have a diverse membership, which can be in terms of race, gender, cultural background, and community members.

Who is responsible for providing an up to date IB to the IRB or IEC in general?

The Investigator’s Brochure (IB) is a comprehensive compilation of clinical and nonclinical data on the investigational product (drug, supplement, device or other product) maintained by a drug developer or investigator that contains the body of information about the investigational product obtained before and during a drug trial.

1. The IB is a document of critical importance throughout the drug development process and is updated with new information as it becomes available.
2. The purpose of the IB is to compile data relevant to studies of the investigational product in human subjects gathered during preclinical and other clinical trials to provide the investigator with information necessary for the management of study conduct and study subjects throughout a clinical trial.

An IB facilitates understanding of the rationale for, and their compliance with, many key features of the protocol, such as: Information in the IB should be presented in a concise, simple, objective, balanced, and non-promotional form that enables a clinician, or potential investigator, to understand it and make his/her own unbiased risk-benefit assessment of the appropriateness of the proposed trial.

When the investigational product is marketed and its pharmacology is widely understood by medical practitioners, an extensive IB may not be necessary. In these cases, a basic product information brochure, package leaflet or an expanded background information section in the trial protocol may be permitted by regulatory authorities as an alternative, provided that it includes current, comprehensive, and detailed information on all aspects of the investigational product that might be of importance to the investigator.

The IB should be reviewed at least annually and revised as necessary in compliance with a sponsor’s written procedures. When new information relevant to the clinical trial becomes available, it should be communicated to the investigators, and possibly to the Institutional Review Boards (IRBs) prior to a scheduled revision of the IB.

1. Generally, the sponsor is responsible for ensuring that an up-to-date IB is made available to the investigator(s) and the investigators are responsible for providing the up-to-date IB to the responsible IRBs/IECs.
2. An IB contains a “Summary of Data and Guidance for the Investigator” section, of which the overall aim is to “provide the investigator with a clear understanding of the possible risks and adverse reactions, and of the specific tests, observations, and precautions that may be needed for a clinical trial.

This understanding should be based on the available physical, chemical, pharmaceutical, pharmacological, toxicological, and clinical information on the investigational product(s). Guidance should also be provided to the clinical investigator on the recognition and treatment of possible overdose and adverse drug reactions that is based on previous human experience and on the pharmacology of the investigational product”.

The sponsor is responsible for keeping the information in the IB up-to-date. The IB should be reviewed annually and must be updated when any new and important information becomes available, such as when a drug has received marketing approval and can be prescribed for use commercially. Owing to the importance of the IB in maintaining the safety of human subjects in clinical trials, and as part of their guidance on Good Clinical Practice (GCP), the U.S.

Food and Drug Administration (FDA) has written regulatory codes and guidances for authoring the IB, and the International Conference on Harmonisation (ICH) has prepared a detailed guidance for the authoring of the IB in the European Union (EU), Japan, and the United States (US).

What are the principal investigator roles and responsibilities in research?

Principal Investigator – The Principal Investigator (PI) is ultimately responsible for assuring compliance with applicable University IRB policies and procedures, DHHS Federal Policy Regulations, and FDA regulations and for the oversight of the research study and the informed consent process.

What are the responsibilities of an IRB IEC?

The International Council on Harmonisation (ICH) defines an institutional review board (IRB) as a group formally designated to protect the rights, safety and well-being of humans involved in a clinical trial by reviewing all aspects of the trial and approving its startup.

Is a principal investigator required to comply with the IRB for?

Principal investigators (PI) are responsible for obtaining Institutional Review Board (IRB) approval before beginning any human subjects research. When you submit a protocol to the IRB for review as the PI, you agree to comply with federal regulations and University policies and procedures for the study duration.

What is sponsor role and responsibilities?

Sponsors. Sponsors are business leaders who play a key role in promoting, advocating and shaping projectwork. They oversee the project and programme management functions and remains accountable for ensuring the realisation of the specified benefits over time.

Is the sponsor responsible for subject safety?

During protocol development, the sponsor should identify those processes and data that are critical to ensure human subject protection and the reliability of trial results. The sponsor should identify risks to critical trial processes and data.

What are sponsor responsibilities in research?

All research requires a sponsor. The sponsor is the individual, company, institution or organisation that takes on legal responsibility for the initiation, management and/or financing of the research. Specifically, the sponsor takes responsibility for ensuring that the design of the study meets appropriate standards and that arrangements are in place to ensure appropriate conduct and reporting.

Who is responsible for assuring the safety of study participants?

Principal Investigator (PI) – The Principal Investigator has the primary responsibility for ensuring the ethical conduct of the research study. This includes protecting human subjects’ rights, safety and welfare, protocol compliance, and adherence to institutional, state and federal regulations and guidance.

1572 Statement of the Investigator 21 CFR 312.50: General Responsibilities of Investigators 21 CFR 812.100: Responsibilities of Investigators: Biologics 21 CFR 812.110: Responsibilities of Investigators: Devices DHHS: Office of Human Research Protections (OHRP): Frequently Asked Questions ICH E6: Good Clinical Practice OSU HRPP: PI Responsibilities at OSU

The PI oversees all aspects of a clinical trial from protocol design, recruitment, data collection, analysis and interpretation of results, but some tasks can be delegated to other research team members (Co-Investigators and Key Personnel). The PI is responsible for ensuring that all research team members have appropriate education, training and qualifications to assume delegated study tests.

Who is responsible for safety reporting?

How are safety events reported to the approving HREC? – The Sponsor-Investigator is responsible for reporting individual safety events and an annual safety report to the approving HREC using forms developed by the relevant state department of health.

Who is responsible for participant safety in clinical trials?

The clinical investigator – The clinical investigator is in charge of all parts of a clinical trial. In some settings this person is called the principal investigator, or PI. The main responsibility for patient safety in a clinical trial belongs to the clinical investigator. This includes letting the study sponsor know right away when severe side effects occur.

What is difference between IRB and IEC?

What is the difference between an IRB and IEC? – Clinical trials conducted in the European Union are held accountable by Independent Ethics Committees (IECs). In the United States, Institutional Review Boards (IRBs) have oversight and must abide by the United States Food and Drug Administration (FDA) regulations.

Countries other than those in the European Union and the United States have individual committees and regulations. There are two types of IRBs and I ECs, local and central. Local comm ittees support individual research institutions and are responsible for reviewing only their clinical trials. Cen tral boards oversee the review of clin ical studies for many different organizations.

More specific guidelines on IRB and IEC responsibilities, composition, functions, and operations are listed in this addendum,

Who is exempt from IRB?

Exempt Review: Institutional Review Board (IRB) Office – Northwestern University Exempt human subjects research is a specific sub-set of “research involving human subjects” that does not require ongoing IRB oversight. Research can qualify for an exemption if it is no more than minimal risk and all of the research procedures fit within one or more of the exemption categories in the federal IRB regulations.

• Studies that qualify for exemption must be submitted to the IRB for review before starting the research.
• Pursuant to NU policy, investigators do not make their own determination as to whether a research study qualifies for an exemption — the IRB issues exemption determinations.
• There is not a separate IRB application form for studies that could qualify for exemption – the appropriate protocol template for human subjects research should be filled out and submitted to the IRB in the eIRB+ system.

Although the HHS IRB regulations list eight exemption categories, NU has opted to implement six of those categories at this time (see the list below). Of the six exemption categories listed below, only exemption category 6 (for taste and food quality evaluation and consumer acceptance studies) applies to studies that are FDA-regulated.

1. The Belmont principle of Respect for Persons generally requires that subjects be given the opportunity to choose whether or not to participate in research.
2. For this reason, voluntary informed consent should be obtained from participants for any exempt research where the investigator will be collecting data through interaction with participants.

For exempt research studies that will collect data through interaction with participants, the NU IRB expects that researchers provide participants with consent information that includes, at a minimum:

1. An explanation that they are being asked to participate in a research study.
2. The identity and affiliation of the researcher.
3. A clear description of the study procedures and how data will be used in the future.
4. A statement that participation in the research is voluntary.
5. Contact information for questions and concerns about the research.

Studies that qualify for an exemption do not undergo continuing review. Modifications do not need to be submitted for exempt studies so long as the research remains minimal risk and stays within the boundaries of the exemption categories that the IRB found were applicable to the research, If your study has received an exemption from the IRB, please contact the IRB if you are planning to:

• add procedures that could affect risks to participants; or
• add procedures that do not fit within the exemption categories; or
• add new types of participants to your study that include vulnerable populations (e.g., adding children, individuals with cognitive impairments, prisoners, etc.)
• change of Principal Investigator

Examples of changes that would likely require IRB review:

• Removal of the consent process, or use of deception or incomplete disclosure.
• Significant changes to the recruitment procedures.
• Adding sensitive questions to a survey or interview process (e.g. questions regarding illegal activities; traumatic events such as childhood, sexual, or domestic abuse; suicide; or other probing questions that could reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects’ financial standing, employability, educational advancement, or reputation).
• Collection of new or additional identifiable information.
• Changes to the data storage plan which may affect confidentiality.

Exempt studies may also be subject to the HIPAA Privacy Rule. For instance, a study involving medical record review to gather a dataset that would be eligible for Exemption Category 4 involves access to Protected Health Information (PHI) and should request a waiver of HIPAA authorization.

• Exemption 2(iii) and Exemption 3 do not apply to research with children.
• Exemptions other than Exemption Category 6 do not apply to FDA-regulated research.
• OHRP Exempt Categories 45 CFR 46.104 – (HRP-312)
• Category 1

Research conducted in established or commonly accepted educational settings that specifically involves normal educational practices that are not likely to adversely impact students’ opportunity to learn required educational content or the assessment of educators who provide instruction.

• Evaluating the use of accepted or revised standardized tests
• Testing or comparing a curriculum or lesson
• A program evaluation of pharmacy continuing education

Category 2 Research that only includes interactions involving educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior (including visual or auditory recording) if at least one of the following criteria is met:

1. The information obtained is recorded by the investigator in such a manner that the identity of the Human Subjects cannot be readily ascertained, directly or indirectly through identifiers linked to the subjects; OR
2. Any disclosure of Human Subjects’ responses outside the research would not reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects’ financial standing, employability, educational advancement, or reputation; OR
3. The information obtained is recorded by the investigator in such a manner that the identity of the Human Subjects can be readily ascertained, directly or indirectly through identifiers linked to the subjects, AND an IRB conducts limited IRB review. (See “WORKSHEET: Limited IRB Review (HRP-319).”)

Examples:

• Surveying teachers, nurses, or doctors about a technique or an outcome
• Interviewing managers about a management style or best practice
• Conducting a focus group about an experience or an opinion of a community program

Category 3 Research involving benign behavioral interventions in conjunction with the collection of information from an adult subject through verbal or written responses (including data entry) or audiovisual recording if the subject prospectively agrees to the intervention and information collection and at least one of the following criteria is met:

1. The information obtained is recorded by the investigator in such a manner that the identity of the Human Subjects cannot readily be ascertained, directly or indirectly, through identifiers linked to the subjects; OR
2. Any disclosure of the Human Subjects’ responses outside the research would not reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects’ financial standing, employability, educational advancement, or reputation; OR
3. The information obtained is recorded by the investigator in such a manner that the identity of the Human Subjects can be readily ascertained, directly or indirectly through identifiers linked to the subjects, AND an IRB conducts limited IRB review. (See “WORKSHEET: Limited IRB Review (HRP-319).”)

(i) For the purpose of this provision, benign behavioral interventions are brief in duration, harmless, painless, not physically invasive, not likely to have a significant adverse lasting impact on the subjects, and the investigator has no reason to think the subjects will find the interventions offensive or embarrassing.

Provided all such criteria are met, examples of such benign behavioral interventions would include having the subjects play an online game, having them solve puzzles under various noise conditions, or having them decide how to allocate a nominal amount of received cash between themselves and someone else.

(ii) If the research involves deceiving the subjects regarding the nature or purposes of the research, this exemption is not applicable unless the subject authorizes the deception through a prospective agreement to participate in research in circumstances in which the subject is informed that he or she will be unaware of or misled regarding the nature or purposes of the research.

Healthy adult subjects are asked to take part in two two-hour-long assessments of memory, attention and information processing speed before and after 1 hour of cognitive enhancement exercise using specially designed computer software. The procedures are conducted during a single visit, and subjects are encouraged to take breaks when desired.

Category 4 Secondary research for which consent is not required: Secondary research uses of identifiable private information or identifiable biospecimens, if at least one of the following criteria is met:

1. The identifiable private information or identifiable biospecimens are publicly available; OR
2. Information, which may include information about biospecimens, is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained directly or through identifiers linked to the subjects, the investigator does not contact the subjects, and the investigator will not re-identify subjects; OR
3. The research involves only information collection and analysis involving the investigator’s use of identifiable health information when that use is regulated under 45 CFR parts 160 and 164 (HIPAA), subparts A and E, for the purposes of “health care operations” or “research” as those terms are defined at 45 CFR 164.501 or for “public health activities and purposes” as described under 45 CFR 164.512(b); OR
4. The research is conducted by, or on behalf of, a Federal department or agency using government-generated or government-collected information obtained for non-research activities, if the research generates identifiable private information that is or will be maintained on information technology that is subject to and in compliance with section 208(b) of the E-Government Act of 2002, 44 U.S.C.3501 note, if all of the identifiable private information collected, used, or generated as part of the activity will be maintained in systems of records subject to the Privacy Act of 1974, 5 U.S.C.552a, and, if applicable, the information used in the research was collected subject to the Paperwork Reduction Act of 1995, 44 U.S.C.3501 et seq.

Note: Exemption Category 4 only applies to the re-use of data and specimens that were or will be collected for non-research purposes or from research studies other than the proposed research study. The research materials typically will be publicly available materials, medical records, or existing repositories of clinical specimens.

A researcher is given two datasets that contain private, identifiable information. The researcher uses the identifiers to merge the two datasets but strips the resulting (merged) data of identifiers immediately after the merge and before conducting data analysis. The resulting data used for the analysis is completely de-identified with no link to identifiers.

Category 5 Research and demonstration projects which are conducted or supported by a Federal department or agency, or otherwise subject to the approval of department or agency heads (or the approval of heads of bureaus or other subordinate agencies that have been delegated authority to conduct the research and demonstration projects), and that are designed to study, evaluate, improve, or otherwise examine: public benefit or service programs, including procedures for obtaining benefits or services under those programs, possible changes in or alternatives to those programs or procedures, or possible changes in methods or levels of payment for benefits or services under those programs.

(i) Each Federal department or agency conducting or supporting the research and demonstration projects must establish, on a publicly accessible Federal Web site or in such other manner as the department or agency head may determine, a list of the research and demonstration projects that the Federal department or agency conducts or supports under this provision.

The research or demonstration project must be published on this list prior to commencing the research involving human subjects. Category 6 Taste and food quality evaluation and consumer acceptance studies, (i) if wholesome foods without additives are consumed or (ii) if a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural chemical or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the Dept.

Who controls IRB?

Where Does an IRB Get Its Authority? – In 1974, the Department of Health Education and Welfare promulgated the regulations on the Protection of Human Subjects that established the IRB. IRBs are administered on a federal level by the Office for Human Research Protections (OHRP), an office within the Department of Health and Human Services.

Who is responsible for IP accountability at site?

General Responsibilities: It is the responsibility of the Principal Investigator (PI) at the site of a clinical trial to ensure accurate and complete accountability and proper storage of investigational drugs/products used in a clinical trial.

What is the authority of the IRB?

What is the Institutional Review Board (IRB)? – The Institutional Review Board (IRB) is an administrative body established to protect the rights and welfare of human research subjects recruited to participate in research activities conducted under the auspices of the institution with which it is affiliated.

• The IRB is charged with the responsibility of reviewing, prior to its initiation, all research (whether funded or not) involving human participants.
• The IRB is concerned with protecting the welfare, rights, and privacy of human subjects.
• The IRB has the authority to approve, exempt, disapprove, monitor, and require modifications in all research activities that fall within its jurisdiction as specified by both the federal regulations and institutional policy.

The IRB shall have at least five members of varying backgrounds in order to provide complete and adequate review of human research and its institutional, legal, scientific, and social implications. The Board will also include at least one member who is not affiliated with the institution and one member who is not a scientist.

What is a clinical investigator responsible for in the informed consent process?

The Consent Process – Informed consent is more than just a signature on a form, it is a process of information exchange that may include, in addition to reading and signing the informed consent document, subject recruitment materials, verbal instructions, question/answer sessions and measures of subject understanding.

Institutional Review Boards (IRBs), clinical investigators, and research sponsors all share responsibility for ensuring that the informed consent process is adequate. Thus, rather than an endpoint, the consent document should be the basis for a meaningful exchange between the investigator and the subject.

The clinical investigator is responsible for ensuring that informed consent is obtained from each research subject before that subject participates in the research study. FDA does not require the investigator to personally conduct the consent interview.

The investigator remains ultimately responsible, even when delegating the task of obtaining informed consent to another individual knowledgeable about the research. In addition to signing the consent, the subject/representative should enter the date of signature on the consent document, to permit verification that consent was actually obtained before the subject began participation in the study.

If consent is obtained the same day that the subject’s involvement in the study begins, the subject’s medical records/case report form should document that consent was obtained prior to participation in the research. A copy of the consent document must be provided to the subject and the original signed consent document should be retained in the study records.

• Note that the FDA regulations do not require the subject’s copy to be a signed copy, although a photocopy with signature(s) is preferred.
• The IRB should be aware of who will conduct the consent interview.
• The IRB should also be informed of such matters as the timing of obtaining informed consent and of any waiting period (between informing the subject and obtaining the consent) that will be observed.

The consent process begins when a potential research subject is initially contacted. Although an investigator may not recruit subjects to participate in a research study before the IRB reviews and approves the study, an investigator may query potential subjects to determine if an adequate number of potentially eligible subjects is available.

What is the role of IRB and IEC in clinical trials?

The International Council on Harmonisation (ICH) defines an institutional review board (IRB) as a group formally designated to protect the rights, safety and well-being of humans involved in a clinical trial by reviewing all aspects of the trial and approving its startup.

How does an IRB protect the rights of human subjects participating in research?

Under FDA regulations, an Institutional Review Board is group that has been formally designated to review and monitor biomedical research involving human subjects. In accordance with FDA regulations, an IRB has the authority to approve, require modifications in (to secure approval), or disapprove research.

This group review serves an important role in the protection of the rights and welfare of human research subjects. The purpose of IRB review is to assure, both in advance and by periodic review, that appropriate steps are taken to protect the rights and welfare of humans participating as subjects in the research.

To accomplish this purpose, IRBs use a group process to review research protocols and related materials (e.g., informed consent documents and investigator brochures) to ensure protection of the rights and welfare of human subjects of research.

Regulations: Good Clinical Practice and Clinical Trials, Comprehensive list of regulations governing human subject protection and the conduct of clinical trials. Guidance for Institutional Review Boards and Clinical Investigators, A series of Information Sheets providing the Agency’s current guidance on the protection of people who are subjects of research. Topics include Institutional Review Boards and Sponsor-Investigator-IRB interrelationships, FDA clinical investigator inspections and sanctions, clinical trials protocols, informed consent, and documents necessary for the conduct of clinical trials. Information for Health Professionals, Additional links to information on subject protection from FDA and other government agencies. Clinical Safety Data Management (PDF – 49KB), Provides the definitions and terminology associated with clinical safety experience and the standards for expedited reporting of adverse drug reactions that occur during clinical trials. FDA Compliance Program 7348.809 – BIMO for Institutional Review Boards (PDF – 1050MB). FDA Compliance Program 7348.811 – Bioresearch Monitoring: Clinical Investigators.

Institutional Review Board Questions: Contact the Office of Good Clinical Practice, 301-796-8340, or [email protected]

What is the role of the IRB IEC in clinical trials?

The IRB/IEC first and foremost is responsible for safeguarding the rights, safety, and well-being of the human subjects participating in the trial.

How does the IRB protect human subjects?

What is the Institutional Review Board (IRB)? – The Institutional Review Board (IRB) is an administrative body established to protect the rights and welfare of human research subjects recruited to participate in research activities conducted under the auspices of the institution with which it is affiliated.

The IRB is charged with the responsibility of reviewing, prior to its initiation, all research (whether funded or not) involving human participants. The IRB is concerned with protecting the welfare, rights, and privacy of human subjects. The IRB has the authority to approve, exempt, disapprove, monitor, and require modifications in all research activities that fall within its jurisdiction as specified by both the federal regulations and institutional policy.

The IRB shall have at least five members of varying backgrounds in order to provide complete and adequate review of human research and its institutional, legal, scientific, and social implications. The Board will also include at least one member who is not affiliated with the institution and one member who is not a scientist.

Jack Gloop