Institutional Review Board

Conducting Research  |  Reportable Events

A.Preface

Note: If your study is Active in eIRB, submit using the designated eIRB Reportable Events form.

https://eirb.jsc.nasa.gov/EIRB/

B.Reportable Events

1.Brief Overview

Under federal regulations for the protection of human subjects, investigators have an obligation to promptly report adverse or unexpected events occurring in human participants. NASA Procedural Requirements (NPR 7100.1) devotes Chapter 11 to: "Reports on Injuries, Illness, or Disease and Medical Care." The Department of Health and Human Services has similar regulations (45 CFR 46.103(b)(5)) for the protection of human subjects, including following written procedures for ensuring the prompt reporting to the Institutional Review Board, appropriate institutional officials, and federal departments or agencies:

any unanticipated problems involving risks to human subjects or others;

any serious or continuing noncompliance with HHS regulations or determinations of the IRB;

any suspension or termination of IRB approval.

In accordance with NPR 7100.1 and 45 CFR 46.111, the NASA IRB reviews accounts of reportable events submitted by the Principal Investigators to determine:

If the risks to subjects are reasonable in relation to anticipated benefits

If the risks to subjects are minimized

If the protocol and informed consent document accurately and completely present risk information to the human volunteers

Whether subjects already enrolled should be advised of newly identified risks.

2.Determining Cause

One of the most important components of event reporting is determining the cause of the event. It is imperative that the investigator assess causality in terms of overall study participation and make an independent determination as to whether the event was thought to be related to any study-related activity (i.e. study intervention, test article use, study-related tests or procedures).

3.Reportable Event Categories

a.Medical Events

Any injury, illness, disease, or death, whether expected or not **, incurred by the subject as a possible result of a research protocol or engineering evaluation;

** Note: "whether expected or not," reflects NASA policy and differs from the 45 CFR guidance.

Any change in the experimental environment or in the subject that could forecast medical problems;

Medical adverse events may include (but are not limited to) the following:

Adverse drug reactions, trauma, animal bites or scratches, thrombophlebitis, etc.;

Any subject illness or injury that may be related to the experiment (i.e. muscle soreness, strains, or other discomforts);

Abnormal physical exam or laboratory finding, symptom, or disease temporally associated with the subject's participation in the research, whether or not considered related to the subject’s participation in the research;

Any subject complaint occurring after the protocol activity if there is reason to believe the complain is pertinent to the protocol activity.

b.Adverse Events, Non-Medical (aka UPIRTSO)

(Also known as Unanticipated Problems Involving Risk to Subjects or Others - UPIRTSO)

Events or outcomes that are (1) unexpected; (2) related or possibly related to participation in the study, and (3) exposes subjects or others to a greater risk of harm or discomfort related to the research than was previously known or recognized;

Result in, or indicate a potential for a change to the study, risk to enrolled or potential participants, study personnel, and

Necessitate corrective action or modification of the conduct of study activities, study protocol, or consent form(s);

May represent psychological, emotional, economic, or social harm, or overall subject well-being;

Must be reported whether they occur during the course of the study, after study completion, or after subject withdrawal or completion if it affects the safety and welfare of either currently or previously enrolled subjects;

Unanticipated problems include other problems generally not considered to be adverse events.

Important Notes:

An adverse event may be unrelated to the experimental intervention, but nevertheless related to study participation.

Harm to a subject need not occur in order for an event to be an unanticipated problem involving risks to subjects or others.

The problem or event may involve risks to someone else (e.g. subject’s family members, research personnel, others);

Serious unanticipated events that happened at another site, or using the investigational agent under a different protocol, may have relevance.

c.Protocol Violation/Deviation

There are several types of deviations from protocol procedures and each type has a different IRB reporting requirement. Protocol violations are divided into two categories: major or minor. (Protocol deviations that constitute unanticipated problems involving risks require use of the Adverse Event, non-medical, pathway.)

Major Protocol Violations

Major protocol violations are any unapproved changes in the research study design and/or procedures that are within the investigator's control and not in accordance with the IRB-approved protocol that may affect the participant's rights, safety or well-being, or the completeness, accuracy and reliability of the study data. All major violations must be reported to the JSC IRB Chair, JSC Human Research Program (and/or funding personnel), and the JSC Safety Office (if applicable). Criteria for defining major violations include any of the following:

Absence of consent or alteration of the consent process without prior written IRB approval;

Lapse in IRB approval for a study (must always be reported to the IRB as a protocol violation);

Use of an expired or incorrect informed consent document;

Unapproved change that has harmed, or posed a significant or substantive risk of harm, to the study participant;

Violation that results in a change to the participant’s clinical or emotional condition or status;

Unapproved change that is evidence of willful or knowing misconduct on the part of the investigator(s);

Suspension or disqualification of an investigator;

Noncompliance with NASA policies, federal regulations, state laws, and/or requirements or determinations of the IRB or provisions of the approved study;

Any computer data security breach (i.e. lost or stolen computer/laptop and/or removable media used as storage devices, such as a flash drive or CD) on which personally identifiable information may have been or be acquired by an unauthorized person.

Minor Protocol Violations/Protocol Deviations

Minor or administrative protocol deviations are defined as those which do not "affect the scientific soundness of the research plan or the rights, safety, or welfare of human subjects." Criteria for minor protocol violations include all of the following:

Did not harm or pose a significant risk of substantive harm to the research subject, and

Did not result in a change to the participant's clinical or emotional condition or status, and

Did not damage the completeness, accuracy and reliability of the data collected for the study, and

Did not result from willful or knowing misconduct on the part of the investigator(s).

d.Data Safety Monitoring Board

Investigator's responsibility to submit all DSMB reports to the IRB upon receipt;

Indicate if there is any increased risk to the subject population;

Include any recommended changes.

e.Updated Study Safety Information

Audit or monitoring report

Interim study results

FDA Safety Alerts

Publication in the literature, or other findings

Revised Investigator's Brochure

Any information that requires prompt reporting according to the protocol or the study sponsor.

4.Principal Investigator Roles and Responsibilities

Promptly report adverse events to the IRB as soon as possible after learning of the event and initiate appropriate investigations;

If applicable, must also report the event to Institutional Officials and to the applicable regulatory agencies;

Must accurately document, assess causality, and follow-up all definite, probable and possible study related reportable events and safety-related information (such as DSMB updates and holds on study activities due to safety concerns);

Must suspend research activity immediately if an injury, unexpected illness, or significant anomaly occurs, unless such suspension would endanger the subject;

Evaluate the event's impact on the risk/benefit ratio of the study;

When appropriate, make changes to the informed consent document and/or study protocol resulting from the reportable event and submit a modification for review and approval;

When appropriate, ask subjects to sign an updated informed consent document describing new information;

Provide an adverse event form copy to TSS for subject's chart, if an event occurs;

Enter documentation into the subject's chart if a notation is pertinent to subject's compliance during study testing.