Definitions

An employee or nonemployee with a formal or informal relationship with UMassD is considered affiliated. An unaffiliated member has no close association with UMassD beyond serving as an IRB member.

Ancillary reviews allow individuals, departments, offices, and other additional reviewers to give feedback, approval, and/or provide documentation on the submission in parallel with the IRB review. During the IRB review, the staff of the IRB office will manually select the reviewer or reviewing organization/department each time a review is needed or required. IRB staff can add ancillary reviewers to a study, modification, or continuing review.

Refers to the condition in which the identities of research participants are not known to the researchers and cannot be linked to individual responses or data. In an anonymous study, no personal identifiers (such as names, addresses, or any other data that can directly link responses to an individual) are collected. This ensures that it is impossible for anyone, including the researchers, to trace the data back to a specific participant. Anonymity provides a high level of privacy and is crucial in protecting the confidentiality of participants, particularly in studies involving sensitive topics.

A request for reconsideration of an IRB determination related to research involving human subjects. This includes decisions on approval status, conditions for approval, or issues of noncompliance. Appeals are reviewed by the convened IRB that made the original decision or, for expedited reviews, the corresponding convened IRB may review the appeal.

A legally binding written document that commits an institution to comply with the Federal Policy (Common Rule) and other applicable Federal and VA standards for the protection of human subjects.

Also called a Reliance Agreement, is the agreement that documents respective authorities, roles, responsibilities, and communication between an institution/organization providing the ethical review and a participating institution relying on the ethical review. For more information please see: IRB Guidance on Reliance Agreements.

The official notification by the institution to the supporting Federal department or agency component that a research project or activity involving human subjects has been reviewed and approved by an IRB in accordance with an approved assurance.

Persons who have not attained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted. In the United States, the general age of consent is 18 years. However, in Massachusetts, the age of consent for medical treatments and procedures may vary depending on specific circumstances such as the nature of the treatment or procedure and the minor's status (e.g., emancipated minors, married minors, or those seeking certain medical services like reproductive health care). Therefore, researchers must determine the applicable age of consent based on the specific context and legal requirements of the jurisdiction where the research is conducted.

Research involving any information or material, regardless of its physical form or characteristics, that is owned by the United States Government, and determined under Executive Order 12356, April 2, 1982, or prior orders to require protection against unauthorized disclosure and is so designated.

Educational inquiry activities conducted solely to fulfill a course requirement that lack the intent to develop or contribute to generalizable knowledge and do not involve the public dissemination of findings. Generally, projects are designed to provide students with training in and experience with research methods, for more information see: IRB Guidance on Class Projects.

A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of the interventions on biomedical or behavioral health-related outcomes.

A study in which two or more institutions coordinate, with each institution completing a portion of the research activities outlined in a specific protocol.

A collaborative research approach that combines methods of inquiry with community capacity-building strategies to bridge the gap between knowledge produced through research and what is practiced in communities to improve their health and well-being.

The IRB interprets condition as referring to a specific (or a set of specific) physical, psychological, neurodevelopmental, or social characteristics that an established body of scientific evidence or clinical knowledge has shown to negatively affect a person's health and well-being, or to increase their risk of developing a health problem in the future.

Any situation in which an individual (or the individual’s spouse, domestic partner, children, and/or dependents) is involved in research has a personal, professional, financial, or other interest that could potentially influence their objectivity, judgment, or decision-making regarding the review, approval, or oversight of research protocols. Conflicts related to research may involve the sponsor, product or service being tested, or competitor of the sponsor held by the individual or the individual’s immediate family, including:

• Involvement in the design, conduct, or reporting of the research.
• Financial interests related to equity holdings, exclusive of interests through mutual funds, compensation related to the research in the preceding 12 months, or proprietary interests (patent, trademark, copyright, or licensing agreement).
• Ownership interest, stock options, or other ownership interest of any value exclusive of interests in publicly traded, diversified mutual funds.
• Compensation of any amount in the past year or of any amount expected in the next year, excluding compensation for costs directly related to conducting research.
• Board or executive relationship, regardless of compensation.
• Reimbursed or sponsored travel by an entity other than a federal, state, or local government agency, higher education institution, affiliated research institute, academic teaching hospital, or medical center.
• Affiliation with organizations, companies, or ventures related to the research that could result in a direct financial benefit.
• Personal or professional relationships with the researchers sponsors or investigators of the research could create bias or the appearance of bias.
• Any other circumstance that could reasonably be perceived as affecting the impartiality or integrity of the review process.

Disclosure of conflicts deemed related to research is essential for maintaining transparency, integrity, and public trust in the review and oversight of research. Conflicts must be identified and managed appropriately to ensure that decisions are made in the best interests of safety, compliance, and ethical conduct. Conflict of interest must be disclosed at the beginning of the review of any documents and meeting attendance.

Refers to the ethical and legal duty of researchers to protect participants' personal information from unauthorized access, use, disclosure, or loss. It involves ensuring that any data collected from or about participants is kept secure and is only accessible to authorized individuals who need the information for legitimate research purposes. Maintaining confidentiality is crucial for fostering trust, protecting participants' privacy, and ensuring the integrity of the research process.

When an overt or implicit threat of harm is intentionally presented by one person to another to obtain compliance. See also undue influence.

Persons who have impaired ability to make decisions as a result of intellectual or mental health challenges as well as adults who have lost capacity to make decisions because of clinical status or situations such as unconsciousness.

The IRB Chair or an Experienced IRB Member designated by the IRB chair to conduct Non-convened Reviews. For non-convened reviews, IRB staff who meet the definition of an Experienced IRB Member conduct the review.

An IRB member is considered experienced if the IRB chair deems the IRB member to have sufficient experience in and knowledge of conducting IRB reviews.

The first date that the protocol is no longer approved. The date after the end date of the approval period.

Refers to a product or technology designed to support, enhance, or monitor general health and well-being, but not intended for medical or diagnostic purposes. These devices typically focus on promoting healthy behaviors, improving quality of life, or providing general wellness information rather than diagnosing, treating, or preventing diseases.

Characteristics of General Wellness Devices:

1. Non-Medical Purpose: These devices are not intended to diagnose, treat, cure, or prevent any specific medical condition. They focus on general health and wellness rather than medical interventions.
2. Wellness Monitoring: They may track various aspects of an individual's daily activities, such as physical activity, sleep patterns, heart rate, or stress levels, to help users manage their overall well-being.
3. Health Promotion:They aim to encourage healthy lifestyle choices and behaviors, such as regular exercise, balanced nutrition, and stress management.
4. Examples: Common examples include fitness trackers, smartwatches with wellness features, general health apps, and wellness scales. These devices provide feedback and data that can help individuals make informed decisions about their lifestyle but are not classified as medical devices.
5. Regulatory Classification: In many jurisdictions, general wellness devices are not subject to the same regulatory requirements as medical devices, provided they do not make specific medical claims or serve medical purposes.

Any activity that either:

• Is Research as Defined by DHHS and involves Human Subjects as Defined by DHHS; or
• Is Research as Defined by FDA and involves Human Subjects as Defined by FDA.

Human Subject as Defined by DHHS: A living individual about whom an investigator (whether professional or student) conducting research:

• Obtains data (information or biospecimens) through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or
• Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens.

For the purpose of this definition:

• Intervention: includes any procedure, treatment, or action taken as part of a research study that is intended to modify the health, well-being, or behavior of the participants. This can include physical procedures such as surgeries or medical treatments, as well as behavioral or educational strategies, and any other activities designed to alter the participants' experiences or outcomes. Interventions are undertaken to evaluate their effects on the participants and may involve direct interactions with participants or the use of devices, drugs, or other therapeutic modalities.
• Interaction: efers to communication or interpersonal contact between the investigator and the subject.
• Private Information: is information about behavior occurring in a context where an individual can reasonably expect no observation or recording, and information provided for specific purposes that an individual can reasonably expect will not be made public (e.g., medical records).
• Identifiable Information: is information where the identity of the subject is or may be readily ascertained by the investigator or associated with the information.
• De-identified data:  is any data collected from a study participant for which their identifiable private information has been permanently unlinked.

Human Subject as Defined by FDA: An individual who is or becomes a subject in research, either as a recipient of the test article or as a control. A subject may be either a healthy human or a patient. A human subject includes an individual on whose specimen a medical device is used. If the activity involves a new drug or medical device, a new use for an approved drug or device, or if data will be submitted to the FDA or held for their inspection, IRB approval is required to proceed.

Spouse, domestic partner, and dependent children.

The University Chief Research Officer.

A record of information an institution keeps about another collaborating institution/organization for one or more Collaborate Studies or Multi-Site Studies.

The IRB of Record is the IRB responsible for the ethical review and oversight of a research study, particularly in multi-site studies where multiple institutions are involved. This IRB has the authority to approve, require modifications in, or disapprove research activities. The IRB of Record assumes primary responsibility for ensuring that the study complies with all applicable ethical guidelines, regulatory requirements, and institutional policies. This designation is usually formalized through agreements such as reliance agreements or IRB authorization agreements (IAA), which outline the specific responsibilities and expectations for the IRB of Record and any relying institutions.

An individual or judicial or other body authorized under applicable law to consent on behalf of a prospective subject to the subject’s participation in the procedures(s) involved in the research. If there is no applicable law addressing this issue, then this individual is recognized by institutional policy as acceptable for providing consent in the nonresearch context on behalf of the prospective subject to the subject’s participation in the procedure(s) involved in the research.

The probability and magnitude of harm or discomfort anticipated in the research that are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.

• For research involving prisoners: Minimal Risk is the probability and magnitude of physical or psychological harm that is normally encountered in the daily lives, or in the routine medical, dental, or psychological examination of healthy persons.
• When following Department of Defense regulations: the definition of minimal risk based on the phrase “ordinarily encountered in daily life or during the performance of routine physical or physiological examination or tests” shall not be interpreted to include the inherent risks certain categories of human participants face in their everyday life. For example, the risks imposed in research involving human participants focused on a special population should not be evaluated against the inherent risks encountered in their work environment (e.g., emergency responder, pilot, soldier in a combat zone) or having a medical condition (e.g., frequent medical tests or constant pain).

Per the FDA, a medical device is an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, software, material, or other similar or related article, including any component, part, or accessory, which is:

• Recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them,
• Intended for use in the diagnosis, monitoring, or alleviation of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in humans or other animals, or
• Intended to affect the structure or any function of the body of humans or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of humans or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes. The term "device" does not include software functions excluded pursuant to section 520(o).

Note: This definition covers a broad range of products, from simple tools like tongue depressors and bandages to complex technologies like pacemakers and MRI machines. See also software as a medical device.

A study in which two or more institutions coordinate, with each institution completing all research activities outlined in a specific protocol.

A newborn child under 28 days of age.

A neonate that, although alive following delivery, is not viable.

A neonate following delivery, survives (given the benefit of available medical therapy) to the point of independently maintaining heartbeat and respiration. If a neonate is viable, it may be included in research only to the extent permitted by, and by, the requirements of Subparts A and D of 45 CFR 46.

Any of the following:

• Determination of whether an activity is Human Research (Including Determinations: 118 and nonengaged).
• Determination of whether Human Research is exempt from regulation.
• Reviews of non-exempt research using the expedited procedure.
• Determinations of which subjects can continue in expired research.

Failure to follow the regulations or the requirements or determinations of the IRB.

• Allegation of Noncompliance: An unproven assertion of Noncompliance.
• Finding of Noncompliance: Noncompliance in fact.
• Corrective Action Plan (CAP): an outline of specific steps to be taken to remedy the cause of
• General Noncompliance: Deviation from the approved research protocol or practices commonly accepted by the scientific community.
• Continuing Noncompliance: A pattern of noncompliance that is likely to continue without intervention or failure to work with the IRB to resolve noncompliance.
• Serious Noncompliance: Noncompliance violations that deviate from the approved research protocol and practices commonly accepted by the scientific community; adversely affect the integrity of the study, the rights, safety, and welfare of researchers, the general public, subjects, and the environment; place a human subject at increased risk of harm; cause harm to a human subject; affect a human subject’s willingness to participate in research; or damage or compromise the scientific integrity of research data; or require revision to the approved protocol;. The actions of the investigator pose a substantive harm to the health and/or safety of personnel, students, the institution, and/or the public environment.
• Need to Know Individuals: For Research Noncompliance: PI, IRB Chair, Chair of the Respondent’s department, applicable IO, DIEC, Office of the General Counsel, and Provost (if externally funded). For IRB Noncompliance: DIEC and applicable IO.

Agency-Specific Definitions of Noncompliance:

• Department of Defense (DOD): Noncompliance includes failure of a person, group, or institution to act in accordance with Department of Defense (DOD) instruction 3216.02, its references, or applicable requirements such that the failure could adversely affect the rights, safety, or welfare of a human subject; place a human subject at increased risk of harm; cause harm to a human subject; affect a human subject’s willingness to participate in research; or damage or compromise the scientific integrity of research data.
• National Institutes of Health (NIH): The NIH defines noncompliance as failure to adhere to HHS regulations, NIH policies, and guidelines, including those related to the Responsible Conduct of Research (RCR), which covers a broad range of research misconduct and noncompliance issues.
• Office for Human Research Protections (OHRP): Noncompliance is defined as failure to follow the regulations or the requirements of the institutional review board (IRB). This can include both intentional and unintentional actions that violate the regulatory requirements or IRB determinations.
• Food and Drug Administration (FDA): Noncompliance is defined as the failure to adhere to federal regulations governing the conduct of clinical trials, including FDA's regulations on good clinical practice (GCP) and human subject protection. This includes violations of protocols, informed consent requirements, and other GCP standards.
• Department of Education (ED): The ED defines noncompliance as failing to follow the Common Rule or ED-specific regulations for human subjects research. This includes failure to adhere to informed consent requirements, IRB approval, and other protections for human research participants.
• Environmental Protection Agency (EPA): The EPA defines noncompliance in human subjects research as failure to comply with the EPA's regulations and guidelines on human subjects protection. This includes deviations from the Common Rule as well as additional EPA-specific requirements aimed at protecting human subjects in environmental research.

Members whose training and professional experience incline them to view scientific matters from a layperson's perspective.

An institution that participates in a Single IRB (sIRB) Study.

Any individual involuntarily confined or detained in a penal institution. The term is intended to encompass individuals sentenced or sanctioned to such an institution under a criminal or civil statute, individuals detained in other facilities by statutes or commitment procedures which provide alternatives to criminal prosecution or incarceration in a penal institution, and individuals detained pending arraignment, trial, or sentencing.

• For Department of Defense (DOD) research the term includes military personnel in either civilian or military custody.

An IRB member with a deep understanding of conditions from the perspective of prisoners, who is not an employee of a correctional facility.

Refers to the protection of an individual's personal information and their right to control the access and use of that information. It encompasses ensuring that participants can make informed decisions about what personal information they share, how it is collected, who has access to it, and how it is used. 

Information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public.

PHI refers to any information about health status, provision of health care, or payment for health care that is created or collected by a Covered Entity (or its Business Associate) and can be linked to a specific individual. This information is protected under the Health Insurance Portability and Accountability Act (HIPAA).

PII refers to any information that can be used to distinguish or trace an individual's identity, either alone or when combined with other personal or identifying information that is linked or linkable to a specific individual. This information is protected under various privacy laws and regulations, depending on the context (e.g., the Privacy Act, GDPR, etc.).

Refers to a systematic method for collecting, analyzing, and using information to answer specific questions about the effectiveness and efficiency of projects, policies, programs, or services. The primary purpose is to assess whether the program/service is achieving its intended goals and to measure the current situation regarding a specific phenomenon or set of factors. These evaluations are typically used for internal decision-making or informational purposes and data may be shared only with the sponsor/client/requesting party and, where appropriate, the faculty advisor. These activities typically do not require IRB approval provided specific conditions are met. 

Refers to a systematic pattern of actions aimed at constantly optimizing productivity, communication, and value within an organization to measure the attributes, properties, and characteristics of a product or service in the context of the expectations and needs of customers and users. QI projects are designed to improve the quality of a service, program, or process within a specific institution. These activities typically do not require IRB approval provided specific conditions are met. 

Review of administrative and regulatory issues unrelated to the regulatory criteria for approval that under the regulations must be determined by a convened IRB or reviewer using the expedited procedure.

A financial interest is Related to the Research when the interest is in:

• A sponsor of the research;
• A competitor of the sponsor of the research;
• A product or service being tested; or
• A competitor of the product or service being tested.

A systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.

• Systematic Investigation: An activity involving a prospective study plan that incorporates data collection and analysis, either quantitative or qualitative, to answer a study question. Investigations designed to develop or contribute to generalizable knowledge are those designed to draw general conclusions (i.e., knowledge gained from a study may be applied to populations outside of the specific study population or situation).
• Generalizable Knowledge: Knowledge gained from the study intended to draw general conclusions or to be applicable beyond the specific study population or situation. This includes developing or testing scientific theories or hypotheses and drawing conclusions intended to be shared beyond the studied populations or situations (e.g., presenting data at meetings, conferences, or seminars; publishing results in academic or scientific journals; writing books or book chapters; submitting grant proposals which include research findings; creating educational materials based on research findings; sharing data via repositories or databases; etc.)

Any experiment that involves a test article and one or more Human Subjects, and that meets any one of the following:

• Requires prior submission to the FDA under section 505(i) of the Federal Food, Drug, and Cosmetic Act, which involves any use of a drug other than the use of an approved drug in medical practice.
• Requires prior submission to the FDA under section 520(g) of the Federal Food, Drug, and Cosmetic Act, which evaluates the safety or effectiveness of a device; or
• Intends to submit results to, or hold results for inspection by, the FDA as part of an application for a research or marketing permit.

• Intent: The primary goal is to develop or contribute to generalizable knowledge, such as testing hypotheses.
• Professional Benefit: The project occurs in large part because of individual professional goals and requirements, such as seeking tenure or obtaining grants.
• Design: Research projects may involve randomization of individuals to different treatments, regimens, or processes.
• Institutional Mandate: Research activities are not typically mandated by an institution or program.
• Impact: Findings are not expected to directly affect institutional or programmatic practice.
• Inclusivity: Research usually involves a subset of individuals, with statistical justification for sample size used to ensure endpoints can be met. Universal participation of an entire clinic, program, or department is not expected.
• Direct Benefit: Participants may or may not benefit directly from the research. Any benefit to individuals is typically incidental or delayed.
• Dissemination: The intent to publish or present findings is generally presumed at the outset of the project as part of professional expectations and obligations. Dissemination of information usually occurs in research/scientific publications or other research/scientific forums, with results expected to develop or contribute to generalizable knowledge by filling a gap in scientific knowledge or supporting, refining, or refuting results from other research studies.

Human subjects data, documentation of subject eligibility and related information, original signed and dated consent forms (or record of such for verbal and waivers of signed consent), master keys/coding dictionary, review logs, as well as ancillary materials including administrative and financial records.

Engaged in Research refers to the involvement of an institution in non-exempt human subjects research. An institution is considered engaged in a research project when its employees or agents perform specific actions related to the research. This engagement necessitates holding or obtaining OHRP-approved Federalwide Assurances (FWAs) and certifying IRB review and approval to HHS. The determination of engagement depends on the specific facts of the research study and can be complex. 

Non-Engaged in Research refers to scenarios where an institution's involvement in a non-exempt human subjects research project does not meet the criteria for being considered engaged in research. Consequently, these institutions would not need to hold an OHRP-approved Federalwide Assurance (FWA) or certify IRB review and approval to HHS. 

Under federal regulations (§46.118), certain grant applications are submitted without specific plans for human subjects' involvement detailed in the proposal. These situations typically fall into three categories:

• Institutional grants where specific projects are determined by the institution.
• Research training grants where activities involving human subjects are yet to be selected.
• Projects where human subjects' participation depends on the development of instruments, completion of prior animal studies, or purification of compounds.

Applications falling under §46.118 may request a determination to satisfy federal sponsor requirements, such as Just-In-Time submissions, allowing access to funding for aspects of the project not involving human subjects. However, initiation of human subject research activities is contingent upon the completion and approval of a full application, including all required materials (e.g., consents, surveys, tools), and obtaining IRB approval (§46.111).

The adherence to ethical principles, professional standards, and regulatory requirements in the planning, conduct, and reporting of human subject research. Responsible conduct encompasses integrity, honesty, transparency, and accountability in all aspects of research activities, including experimental design, data collection and analysis, interpretation of results, authorship and publication practices, and adherence to relevant laws, regulations, and institutional policies. Researchers and institutional officials are expected to demonstrate responsible conduct to ensure the integrity and credibility of scientific research, protect the welfare of human subjects and animals, safeguard the environment, and maintain public trust in the research enterprise.

Actions that pose substantive harm to the health or safety of personnel, students, the public, or the environment, or a serious deviation from either the established research protocol or those practices that are commonly accepted by the scientific community in human subjects research. A violation may also occur when a researcher demonstrates other serious or continued noncompliance with federal, state, or local laws, regulations, or policies.

Applies to investigators who are delinquent in meeting IRB requirements.

The re-analysis of existing data that were originally collected for a purpose other than the current research project. This may include data from publicly available datasets, de-identified datasets, or previously gathered data. Secondary data analysis can involve human subjects research if the data contains identifiable private information, requiring IRB review. However, if the data is fully de-identified or publicly available, it may be exempt from IRB oversight. Researchers must confirm the nature of the data and the original consent terms to determine the appropriate level of review.

Members whose training and professional experience primarily involve scientific activities and research, leading them to view scientific matters from a researcher's perspective.

A study in which two or more institutions (participating sites, or pSites) coordinate to complete the research activities, but all institutions rely on a single institution’s/organization’s IRB for ethical review. The reviewing IRB may or may not be affiliated with any of the pSites.

An online reliance system to request, track, and document reliance agreements between institutions.

SaMD refers to software intended to be used for one or more medical purposes that perform these purposes without being part of a hardware medical device. This definition includes any standalone software that is used to diagnose, monitor, or treat medical conditions.

Key aspects of SaMD:

• Medical Purpose: SaMD is intended to be used for medical purposes such as diagnosing, preventing, monitoring, treating, or alleviating disease.
• Standalone Software: SaMD operates independently of a hardware medical device, though it can interface with other devices and software.
• Regulatory Framework: SaMD must comply with the same regulatory requirements as other medical devices, including performance, safety, and efficacy standards set by the FDA.

Examples of SaMD include:

• Mobile applications that monitor patient health conditions.
• Software that uses algorithms to diagnose conditions from medical images.
• Programs that provide recommendations for patient treatment based on data analysis.

An action of the IRB, IRB designee, Institutional Official, or designee of the Institutional Official to temporarily or permanently withdraw IRB approval of some or all research procedures short of a Termination of IRB Approval. Suspended studies remain open and are subject to continuing review.

An action of the IRB, IRB designee, institutional official, or designee of the Institutional Official to permanently withdraw IRB approval of all research procedures. Terminated studies are permanently closed and no longer require continuing review.

An unanticipated problem involving risks to subjects or others is defined as any information that is:

1. Unanticipated: Unexpected in terms of nature, severity, or frequency given the procedures described in the research protocol documents (e.g., the IRB-approved research protocol and informed consent document) and the characteristics of the human subject population being studied.
2. Related or Possibly Related: Related or possibly related to participation in the research, where "possibly related" means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research.
3. Indicates Increased Risk: Suggests that the research places human subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized, even if no harm has actually occurred.

Federal Agencies Definitions:

• Office for Human Research Protections (OHRP): Unanticipated problems are incidents, experiences, or outcomes that are unexpected, related or possibly related to the research, and suggest that the research places participants or others at greater risk of harm. Institutions are required to have procedures for reporting these problems to the IRB and, where appropriate, to the institution’s officials and regulatory authorities.
• Food and Drug Administration (FDA): The FDA defines unanticipated problems as “unanticipated adverse device effects” (for medical devices) or “unexpected adverse drug reactions” (for drugs). These include serious adverse events not identified in the study protocol or investigator brochure and not expected based on prior information. Such events must be reported to the IRB, the sponsor, and regulatory authorities within specified time frames.
• National Institutes of Health (NIH): NIH follows the general OHRP and FDA definitions for unanticipated problems. These problems are typically unexpected, related to the research, and increase the risk to participants. NIH requires that these problems be reported to the IRB and NIH grant or contract officials in accordance with institutional policies and federal regulations.
• Department of Veterans Affairs (VA): The VA defines unanticipated problems as incidents, experiences, or outcomes not previously described in the research protocol or informed consent documents that indicate an increased risk of harm to participants. These problems must be reported to the VA’s IRB and the local VA research office in accordance with VA-specific regulations.
• Department of Defense (DOD): For DOD research, the term "Unanticipated Problem Involving Risks to Subjects or Others" includes any incident, experience, or outcome that is unexpected in terms of nature, severity, or frequency, given the procedures described in the research protocol documents and the characteristics of the human subject population being studied. It must be related or possibly related to participation in the research, where "possibly related" means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research. Additionally, it must suggest that the research places human subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized, even if no harm has actually occurred.

Occurs through an offer of an excessive or inappropriate reward or other overture to obtain compliance.