Institutional Review Board

Preparing for Research  |  User Guide to Application Process

A.Overview of the JSC and NASA Flight IRBs' Application Process

1.General Instructions

NASA IRB Review is required if all three questions below are affirmative:

1.   Is the study research, i.e. a systematic investigation designed to contribute to generalizable knowledge?

2.   Does the study involve human subjects (including studying identifiable human biological specimens, medical records and/or other private information)?

3.   Is the study being performed by NASA personnel or does it access NASA facilities or subjects?

If it is uncertain whether the project or activity requires IRB review or a “not human research” determination is required, please complete the following:

Project Description-NHR determination

Please note that human research protocols require a scientific peer review prior to submission to the JSC IRB that includes evidence of approval (e.g., e-mail correspondence, award letter). Proposals generated in response to a NASA Research Announcement (NRA) or an Announcement of Opportunity (AO), etc. must follow the schedule imposed by NASA Headquarters and the JSC IRB review schedule.

2.Exempt Reviews

Certain human subject research activities can be exempted from the Common Rule (45 CFR 46) regulatory requirements and the allowed categories are found at 45 CFR 46.104.

To be considered for an exemption, a new protocol submission must be entered into e-IRB. Any changes to an exempted protocol must be submitted in e-IRB for review.

Upon the revision of the Common Rule, changes to the exemption categories were made therefore, beginning on January 21, 2019, the IRB will apply the new exemption categories to new protocols seeking an exemption.

3.Expedited Reviews

The IRB is allowed by 45 CFR 46.110 to review human subject research by expedited procedures.

An IRB review done by expedited procedure means that the review was conducted by the IRB chairperson or by his/her designee.

Categories of research that may undergo an expedited review procedure:

https://www.hhs.gov/ohrp/regulations-and-policy/guidance/categories-of-research-expedited-review-procedure-1998/index.html#footnote1

4.Letter of Support/Endorsement

The IRB may request letters of support from a NASA division chief, program leader, or science management office that they have assessed the scientific merit, weighed the priority of the proposed research in light of the existing portfolio of approved studies, and affirmed the potential to meet accrual goals. The endorsement may address the following items:

Provide assurance that the proposed research fits within the mission and focus of the program;

Updated endorsement in conjunction with an amendment that proposes significant changes to the study design, e.g. adding a participant population or significantly changing the objectives of the study.

The JSC IRB may request letters of support from an authorized official of a non-NASA institution involved in a study (Off-Site Research), especially if they are involved with study procedures or subject recruitment, indicating knowledge and endorsement of the project. The endorsement may address the following items:

Agreement by the institution’s administration for the study to be conducted at that site;

Review of the project by someone at the other institution for appropriateness for its human subject population, and adequacy of the facility to perform the procedures as approved by the IRB;

Written confirmation that the facility personnel have the appropriate expertise to carry out the research procedures;

Assurance the personnel from the facility have appropriate training in human subjects protection.

The IRB may request letters of support from an investigator from a non-NASA institution on the facility’s letterhead stationery he/she has reviewed the proposed research and fully supports the study.

5.Financial Conflicts: Disclosure Statement of "Key Persons"

a.Disclosure

Each "Key Person" shall provide a signed, current conflict of interest statement that accurately states:

No actual, potential, or imputed financial conflict of interest exists in connection with this proposal and research, or,

Contains a detailed and complete disclosure of any actual, potential, or imputed conflict of financial interest that will arise in connection with this proposal and research.

"Key Person" for purposes of this conflict of interest process includes, but is not limited to: Principal investigators (PIs), Co-PIs, faculty advisors, study coordinators, recruitment staff, personnel performing study procedures or interventions related to this proposal and research, and individuals responsible for the protocol development, design, conduct, or the reporting of research.

Examples of individuals who would not be defined as a "Key Person" would include technical staff such as coders, statisticians, data entry personnel, IT support, administrative staff (which would include secretarial support, and logistics personnel).

This signed conflict of interest statement shall be submitted on the official letterhead of the Key Person's institution.

b.Background

On May 5, 2004, DHHS issued revised guidance of Financial Relationships and Interests in Research Involving Human Subjects: Guidance for Human Subjects Protection

Guidance for Human Subjects Protection

"Conflict of interest" refers to situations in which financial or other personal considerations may compromise, or have the appearance of compromising, an investigator's professional judgment in conducting or reporting research. A conflict of interest depends on the situation, and not on the actions or character of an individual investigator.

c.Conflict of Interest Statement in Human Subjects Consent Forms

The IRB application includes a section called "Statement of Financial Interest," and the question: "Do you or the other investigators have a financial interest in the outcome of the study?" Financial interests of the research team include the interests of their spouses and dependent children.

If the answer is yes:

Disclose the nature of the financial interests

Briefly describe this interest in the Purpose and Background sections of the consent form or in the section headed with the question "Who pays for this study?"

The consent form must disclose which agency or institution (e.g., NASA, NSBRI, NIH, DOD, CDC, foundations, or industry sponsors) is funding the research or providing study drugs or equipment for the study.

If the study is not being funded by an external agency, then the internal funding source (Division funds, personal grants) should be identified.

d.Conflict of Interest Disclosure with Protocol Submissions

A Conflict of Interest Statement must be submitted with all human subjects initial and renewal protocols. The disclosure must be written on letterhead from the PI's institution.

If there is no conflict of interest, use the following Conflict of Interest Statement:

"I do not receive any research support from non-public sponsors of research. I do not perform any validation research of a drug or device. I do not receive any gifts or income from individuals associated with my research studies. I do not use my position with ____________ (fill in the blank with name of employer, i.e. NASA, KBRWyle, Leidos) or proprietary or confidential information obtained in performing my duties, in any marketing, investing, or commercial ventures."

If a potential conflict of interest exists, answer affirmatively and disclose the relationship with the company or entity.

Financial interests often range from intellectual property interests to consulting fees to other special arrangements.

A financial interest related to research does NOT automatically mean that the investigator cannot participate in the research. The IRB will determine if the conflict of interest can be reduced, eliminated or managed in order to allow participation in the research project.

B.JSC and NASA Flight IRBs' Review Process

1.Decisions

The JSC or Flight IRB will inform the PI in writing of one of four decisions following review:

Approved: the research protocol is accepted and the study can begin.

Modifications Required/Contingent Approval: The IRB approves the study in principle. However, the investigator must provide a written response regarding items of concern, usually minor items such as clarifications or revisions in the protocol or consent form. The study cannot begin until the concerns of the IRB have been satisfactorily addressed and the response is approved.

Deferred: The IRB is not prepared to approve the study without additional information and review. This decision may occur when serious concerns are raised about issues of human subject protection or when other major changes are required to reconsider the protocol. The PI must respond to the request in writing and this response is reviewed by the IRB at a subsequent IRB meeting. Usually, the revised protocol is granted approval or additional minor modifications are requested at the time of the second review. However, the study may be returned again if the IRB requests it.

Disapproval: The IRB finds that the protocol is not acceptable in principle. A denial of approval cannot be overturned without substantial modifications to the risk-benefit aspect of the protocol. The revised protocol must be resubmitted for all required approvals.

Suspension or Termination:

The IRB has the authority to suspend or terminate previously approved research that is not being conducted in accordance with IRB requirements, that has been associated with unexpected serious harm to subjects, or that has been disapproved by another IRB.

2.General Conditions of Approval

IRB approval is granted according to 45 CFR 46.111. Please note the following about IRB approval:

The PI may not recruit subjects or initiate research until final approval has been received in writing from the IRB.

A subject must be informed about the study and their consent documented by signing a consent document.

The IRB and other departments if appropriate (such as the legal office) must approve all advertisements (e.g. signs, pamphlets, letters) that solicit research participants prior to its use. The advertisements should be included with the protocol for review.

The PI must verify that arrangements have been made to comply with the level of medical monitoring required by the IRB prior to initiation of a test protocol.

3.Responding to a Modifications Requested Determination

To receive final approval in the shortest possible time, please follow the guidelines below in preparing your response to your contingent approval.

Protocol Comments: Answer the IRB's concerns about the study protocol point-by-point. For example, if there are several recommendations in the IRB letter, you should address each of these points individually in a separate numbered or labeled paragraph in your response, then make changes to the protocol as appropriate. In your letter, answer each point fully; do not simply refer to changes in the protocol. If you disagree with the IRB's recommendations and do not wish to make certain changes, you should explain why in the response. Without an explanation, the response will not be complete and approval may be delayed.

Consent Form Comments: You should respond to all substantive comments regarding the consent form point-by-point. You can respond to typographical and other purely editorial comments by making the corrections in the consent form and saying in your response that you have done so. As with protocol comments, if you disagree with the IRB on a particular comment and do not wish to make a requested change, you should explain why in the response.

Treatment and Compensation for Injury: NASA has a very strict policy regarding Treatment and Compensation for Injury that must exactly match the standard NASA language described on the IRB website.

Additional Modifications: If you intend to make new modifications to the study as well as respond to the IRB's comments, please be sure the modifications are described clearly and separately in your response.

4.Conditions of Approval

Approval Date

The day the IRB determines the protocol is approved or conditionally approved at a convened meeting or at the time of approval by expedited review.

Effective Date

This may be the same day as the approval day or may be the day when the PI has satisfactorily addressed the stipulations.

Expiration Date

An expiration date is clearly listed on the approval letter.

It is the investigator's responsibility to keep track of the expiration date and initiate the renewal process prior to the expiration date.

C.Modifications

1.Post-Approval Modifications Overview

Federal regulations require that all changes to a study, even minor ones, must receive IRB approval before they are implemented.

PIs must seek IRB approval before making any changes in approved protocols, even though the changes are planned for the period for which approval has already been given.

Minor changes (i.e., changes that do not involve increased risk or discomfort) may be approved by expedited procedures. If the change is not minor, the review of the request must be conducted during a fully convened meeting.

Modifications to ongoing research do not extend the original approval expiration date.

2.Modification Categories

a.Major Modifications

Any increase in risk to participants is more than minimal;

Any additional activity or procedure would not be eligible for expedited review if submitted as part of new research;

The research itself involves more than minimal risks and the changes significantly alter the study design.

Examples:

Increasing physical and/or psychological risk/discomfort to the participant;

Major change in the design or goal of the study;

Making multiple changes in the protocol, procedures, hardware, and/or consent;

Adding a new consent form;

Expanding the eligibility criteria;

Increasing the number of participants at risk;

Adding an element that may breach the privacy of the participant (e.g. adding focus groups);

Numerous modifications throughout the year where there may be confusion or a question as to the full scope of the study;

Re-starting study after a hold for safety concerns;

Changing, adding, or deleting drugs, devices, or other treatments being studied;

Change in the PI if it significantly changes the expertise or resources available in the study or requires other major changes in the conduct of the study.

b.Minor Modifications

Any increase in risk to participants is no more than minimal risk;

All additional activities or procedures would be eligible for review using the expedited procedures if submitted as part of new research;

Either the research itself involves minimal risks or the changes do not significantly alter the study design.

Examples:

Reduction of risk/discomfort to the participant;

Adding or removing an institution;

Changing minor procedures (e.g. adding small-volume blood draws, ultrasounds);

Adding minor risks (e.g. risks of small blood draws);

Changing, adding or deleting approved drugs, devices, or other standard treatments that are being sued in standard ways;

Changes or additions to recruitment and advertising;

Change in the PI if the new PI has a background and resources that are equivalent to the original PIs;

Changing the Co-I (Co-Investigator) or other key personnel;

Adding or revising a questionnaire or similar to the one already approved, e.g. uses many of the same questions;

Changing wording in the protocol, questionnaire, and/or consent that does not alter the meaning or procedure;

Consent form modifications that add or remove information from the consent form so that it is consistent with an already approved IRB requirement;

Updating a consent form to use IRB approved boiler plate language.

3.Written Notification of IRB Actions

The IRB approval letter will be sent when the modifications are approved. Please note:

Modifications do not change the expiration date;

Revisions in consent forms are valid only until the original approval date for the research expires.

D.Continuing Review/Renewals

1.Renewal/Continuing Review after Protocol Approval

Ongoing research studies require annual review, or more often if the IRB finds that the degree of risk to subjects warrants more frequent review. This renewal must take place prior to the expiration date noted on the approved protocol. There is no provision for a grace period extending the conduct of the research beyond the approval expiration date.

A renewal/continuing review -submissions includes the following information from the past year (cumulative data must also be included after the first renewal):

Number of subjects enrolled:

Completion of research milestones;

Number of subjects who withdrew prematurely, and reason(s) for their withdrawal;

Number of subjects experiencing an adverse event and details of the events and the outcomes;

Preliminary study results if available;

Current risk/benefit assessment based on available preliminary results.