Institutional Review Board

Conducting Research  |  Research Topics and Issues

A.Research Subject to IRB Review

1.Scope of IRB Review

The scope of the IRB's charge is broad. Generally, any research involving living humans, human tissues or specimens, or humans' records or data that is conducted by any personnel of the Johnson Space Center or otherwise conducted at or sponsored by NASA/JSC, requires IRB review, irrespective of the risks, scope, funding, or location of the research. Specifically, IRB review is required for any human subjects research that

is conducted by NASA personnel, visiting researchers, or students;

is sponsored by the NASA;

is performed with or involves the use of facilities or equipment belonging to the NASA;

involves NASA personnel as part of the research team.

2.Pilot and Feasibility Studies

Pilot studies may be designed to develop or refine research procedures and instruments prior to using it in a larger scale trial. Although data collected through pilot studies may not ultimately be used in research reports and publications, pilot studies represent part of the research process that leads to the development of, or contribution to, generalizable knowledge. For this reason, pilot studies required IRB review and approval before they are conducted.

Pilot and feasibility studies, regardless of the number of subjects, require the same scrutiny as full-scale research projects and must be submitted for IRB review and approval. Pilot and feasibility studies should be identified as such in the application. Subjects should be told that the study is a pilot.

It is not the number of subjects that determines if review is needed. The determining factor is whether or not human subjects are involved. A pilot study that includes only one subject requires the same consideration by the IRB as a project that requests the participation of 100 or more subjects.

B.Types of Research

1.Drugs, Medical Devices, and Biologics

Drugs, Devices, and Biologics include those both approved for marketing by the FDA and those in the FDA test phase for medical devices and drugs, and are subject to FDA restrictions. FDA forms are available online at:

U.S. Food and Drug Administration

Descriptions of drugs should include dose, rate, route, and schedule of administration, comparison of the test dose to commonly prescribed test doses, and discussion of expected side effects of the drug in this dose range and frequency. Doses and frequencies which are outside that used in standard clinical practice should described explicitly and additional risk of toxicity discussed.

Any investigational drugs(s), biologics, or device(s) to be used in the study should be noted and named, and described with the phrase "investigational" or "experimental" rather than "new";

Investigational products must include IND or IDE status, holder of the IND or IDE (sponsor or investigator), and be used in exactly as described in the protocol filed with the FDA.

Include provisions to pre-screen subjects when possible for drug hypersensitivity prior to beginning the study.

Subjects should be pre-screened, whenever possible, for hypersensitivity to any administered drugs or biologics before the study begins. If a study requires the intravenous administration of any substance, at least one Co-I and a licensed physician must be present.

No subject who has had an allergic diathesis (predisposition) or any anaphylactoid or frank anaphylactic reaction, including, but not limited to, a reaction to a medication, diagnostic agent, food, or insect venom, will be selected for research involving intravenous/intramuscular administration of any drug. Using the results of the physical exam and a review of the medical history, the examining physician will certify that each subject meets the medical standards for participation and that the procedures in the given study present no apparent additional risk of an allergic reaction for that subject.

Medications which may cause or exacerbate urinary retention, constipation stone formation, bone loss, or behavioral side effects should be avoided, if possible, during space flight in order to reduce medical risk to crews.

PIs and monitoring physician(s) must discuss regularly with the subjects all risks associated with provocative procedures or intravenous/intramuscular drug administration. These risks must also be described in the lay summary in simple and non-technical language. The PI must also ensure that appropriate experiment-specific and general support medications are available for any adverse event that might occur.

The mission scientist and monitoring physician must evaluate the potential interactions that may result from a test subject participating in multiple experiments, whether on the same flight or during a bedrest project. This evaluation must include the sequence and type of experiments, drug interactions, and the impact of experimental medical hardware. This evaluation should be included in the package presented to the IRB.

The crew surgeon will summarize the risks associated with provocative procedures or intravenous/intramuscular administration of drugs during presentation at the Flight Readiness Review (FRR).

Controlled substances used in research projects require specific oversight by the monitoring physician. The research protocol must include the plan for ordering and tracking controlled substances.

Storage and Handling of Dangerous Drugs and Controlled Substances Used for Research Purposes - May 5, 2010 (SA-WI-027)

2.FDA Significant and Non-Significant Risk Devices

FDA regulations (21 CFR 812.2) state that for studies involving use of an investigational device, the investigator (or sponsor) must obtain either a "significant risk" Investigational Device Exemption (IDE) from the FDA, or a determination of "non-significant risk" from the Institutional Review Board. FDA provides criteria for the investigator and institutional review board to use in making these decisions and provides examples of non-significant and significant risk devices.

21 CFR 812.2 "Guidance for Institutional Review Boards and Clinical Investigators, 1998 Update, Medical Devices"

Definition of a Significant Risk (SR) Device is defined by 21 CFR 812.3 as an investigational device that:

Is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject;

Is purported or represented to be for a use in supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject;

Is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject; or

Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject.

21 CFR 812.3

A non-significant risk (NSR) device is one that does not meet the definition of a significant risk device.

Non-Significant/Significant Risk Decision

The IRB may agree or disagree with the investigator's initial non-significant risk assessment. If the IRB agrees, and approves the study, the investigation may proceed without FDA approval. If the IRB disagrees, the study can only be conducted as a study involving a significant risk device, and the investigator or sponsor must notify the FDA that a significant risk determination has been made for the device. While the institutional review board is serving as FDA's surrogate with respect to review and approval of non-significant risk devices, the ultimate decision in determining if a device is SR or NSR is the FDA's. On some occasions, FDA may overrule an IRB's decision that a device presents non-significant or significant risk. When FDA overrules an IRB's nonsignificant risk determination, an IDE application must be submitted to FDA. On the other hand, when FDA considers the device to be non-significant risk, FDA may return an IDE application to the investigator, and the IRB must then determine if it wants the study to take place at its institution as a non-significant risk device investigation.

Criteria for Determining Significant vs. Non-Significant Risk. To determine if a device involves a significant risk, the IRB must consider the nature of the harm that may result from use of the device. If a device being investigated might cause significant harm to any of the subjects, the device should be considered "significant risk". Also, if the subject must undergo a procedure as part of the study, the IRB must consider the potential harm caused by the procedure as well as the potential harm caused by the device. Devices for which the potential harm to subjects could be life-threatening, could result in permanent impairment of a body function, or permanent damage to body structure, or could necessitate medical or surgical intervention to preclude permanent impairment of a body function are included among those devices that present significant risk. The determination of significant risk depends on the use of the device in the particular study as well as the inherent risks of the device itself.

3.Non-FDA Approved Hardware and Equipment

Research participants must receive a full and informed disclosure when the experiment will involve:

Hardware or a equipment that has been approved for use outside the US but is not FDA approved;

Hardware or a equipment that may have been approved for a use other than its intended use;

Hardware or equipment that is not in use anywhere and is completely experimental.

The PI must explain why the use of the hardware or equipment in this study poses nonsignificant risk, and attach any other supporting information (e.g., any reports of prior investigations). The PI must also explain whether the FDA or any other IRB has determined the device to be significant or non-significant risk.

Note: A Significant Risk device is one that presents potential for serious risk to the health, safety, or welfare of a subject and the device (1) is intended an implant; (2) is used in supporting or sustaining human life; (3) is of substantial importance in diagnosing, curing, mitigating or treating disease, or prevents impairment of human health; or (4) otherwise presents a potential for serious risk to the health, safety, or welfare of a subject. A non-significant risk (NSR) device is one that does not pose significant risk.

C.Statistics

1.Experimental Design and Statistical Analysis Rationale

a.Research Project Criteria

Provide rationale for the requested number of human subjects and repeated observations and why this will provide sufficient information to answer the main research questions.

Include a brief description of the proposed experimental design, containing identification of subject groups (e.g. treatment, controls, etc) how many subjects per group, number of repeated observations per subject, etc.

b.Hardware Validation Study

Explain why the requested number of subjects and repeated observations provides data with enough information to adequately characterize hardware performance.

Include a brief description of the proposed experimental design, containing identification of subject groups (e.g. treatment, controls, etc) how many subjects per group, number of repeated observations per subject, etc.

c.Considerations

Avoid justification in terms of statistical power for comparing means based on guessed or overly optimistic performance of a proposed new countermeasure, hardware device, etc.

Be aware that deciding simply whether population means are different (such as by P < 0.05) may not in itself be an effective way of addressing study goals. For example, it may be more important to quantify how effective a countermeasure is and how its effect varies among the population of potential users (i.e astronauts).

In this light, one should describe how the data would be analyzed, then justify sample size and number of repeated observations based on how accurately one would expect the analysis results to be, regardless of whether the new device, treatment, etc. actually proves "better" than the existing or control situation.

Example: "Mean change in VO2 max for subjects undergoing the proposed training will be estimated by comparing the post-bedrest measurement of VO2 max to the average of three pre-bedrest measurements for each subjects, with the observed changes then averaged over subjects in each group. Based on between and within-subject variation of change in VO2 max estimated from [provide reference], with 10 subjects and 3 trials per subject pre and post bedrest, we expect to be able to estimate the mean change in VO2 max with a standard error of about 0.2 L/min., which is about 10% of the range of VO2max change typically observed in control subjects. This level of accuracy will provide useful information about the degree of effectiveness of the new training procedure."

D.Data and Safety Monitoring Plan

All interventional studies involving more than minimal risk must include a DSMP. A DSMP is a plan established to assure that each research study has a system for appropriate oversight and monitoring of the conduct of the study to ensure the safety of participants and the validity and integrity of the data. The DSMP should indicate specifically whether or not there will be a formal Data Safety Monitoring Board (DSMB).

Key areas that should be included in the plan include:

Summary of safety concerns and description of the methods to monitor research subjects and their data to ensure their safety;

Type of data and events (i.e., efficacy data, adverse events, unanticipated problems involving risk to participants or others) that are to be captured under the monitoring plan;

A description of who will perform the monitoring reviews and at what frequency;

If a data monitoring committee will be used, description of its operation, including as appropriate:

A plan for conducting and reporting interim analysis;

Clearly defined stopping rules;

Clearly defined rules for withdrawing participant from study intervention(s);

Frequency of review, and if it is independent of the sponsor;

Procedures for communicating the outcome of reviews by the monitoring entity to the IRB, the study sponsor and/or other appropriate entities.

E.Data Privacy, Confidentiality, and Storage

Subject privacy and data confidentiality must be maintained in accordance with 1) NASA Policy Directive (NPD) 7100.8, "Protection of Human Research Subjects"; 2) NASA Procedural Requirements (NPR) 7100.1, "Protection of Human research Subjects"; and 3) to the extent allowed by Federal law.

Privacy concerns people, whereas confidentiality concerns data;

Briefly describe the plan for ensuring the privacy in accessing information from or about participants and in maintaining privacy in the research setting(s);

To address confidentiality issues, indicate all identifiers that may be included in the research records for the study and how these subject identities will be protected.

Data storage: describe how research data will be stored and secured to ensure confidentiality;

NASA may use information or data gained from the research project for conducting or validating future research projects, but will ensure that all information is de-identified.

Consequences to Participants of a Loss of Privacy

Information about a study participant, if disclosed inappropriately, as a result of participation in this investigation could be harmful to the participant. Release of individually identifiable medical/research data could adversely affect the participant's employability, insurance, and increase the risk of bias and discrimination. To avoid or minimize these risks, the study design includes safeguards to protect the confidentiality of the information collected.

F.Data Security

Indicate where the information is to be stored, the type of format to be used to store the information, whether the data are coded, and who will have access to the information and under what circumstances.

G.Data Sharing

Identify other investigators with whom data/samples will be shared. If data will be shared with other investigators, explain why this is necessary, and if relevant, justify releasing data with identifiers that would permit the recipient investigator to know or to infer the identity of the subject.

H.Blood Volumes, Human Tissues and Cells

1.Crew Venipuncture and Blood Volume Guidelines

a.Overview

Blood sample collection should minimize the number of needle sticks and catheter insertions, grouping data collections as much as possible for all studies. The number of proposed venipunctures and finger sticks must be part of the IRB review package for the individual proposal as well as for the final plan in which all the studies for a mission or ground-based study are combined.

The allowable experiment blood volume may be reduced by crew surgeon. Crew members who weigh less than 110 pounds may be limited in the maximum blood volumes permitted.

Medical Operations requires blood analyses as part of the crewmember standard health care. With crewmember consent, data from medical analyses may be made available to investigators when outlined in a Data-Sharing Plan.

NIH Data Sharing Policy and Implementation Guidance

The IRB has established standards for the total amount of blood (including the blood volumes required for medical care).

b.Space Flight Shorter Than 30 Days

Total pre-, in- and post-flight blood volume:

Maximum 450 ml per mission (6 weeks before launch to 6 weeks after landing).

In-flight blood draws:

Maximum 50 ml per week.

Blood volumes outside of this timeline:

Federal guidelines of 450 ml per 56 days.

c.Space Flight 30 Days and Longer

Up to 6 months before launch (L-6 months):

Maximum 450 ml per 56 days.

L-6 months to L-20 days:

250 ml per month, not to exceed a maximum volume of 500 ml.

L-20 days to launch:

Maximum 100 ml.

In-flight blood draws:

150 ml per month, except for the last 30 days of a mission, which will remain at 100 ml, with a maximum total in-flight volume of 450 ml. (Updated April 2015)

No later than the end of crew day R-1:

No blood may be drawn

Landing day:

Maximum 120 ml.

Post-landing (R+1) to R+45:

Maximum 300 ml.

After R+45 days:

Maximum 450 ml per 56 days.

d.Space Flight 1-Year Mission

For 1 year mission and the increased number of research investigations with a greater number of in-flight sessions requiring blood samples. There are no changes to the current monthly blood volume standard. The proposed change affects only the total allowable blood to be collected from each crew member. There will not be any changes to the current pre-fight and post-flight blood volume guidelines.

The In-Flight Blood Volume Standard is:

For missions of 6 months or less:

100 ml per month, maximum total in-flight blood volume of 450 ml.

For missions greater than 6 months:

100 ml per month, maximum total in-flight blood volume of 900 ml per year

e.Ground-Based Studies

These include closed-chamber and bed-rest studies as well as any other studies that require blood:

Maximum 450 ml per 56 days.

Total blood volumes are recorded in a data base in the Test Subject Screening Facility to ensure that participants in multiple studies do not exceed IRB recommendations for total blood volume.

Note: Blood volumes are derived from general recommendations for blood donations:

Donations from individuals who weigh more than 110 pounds (50 kg)

Donations from those who have a hematocrit greater than 35%.

Donations of one (1) unit (400-450 ml) from a given person every 8 weeks, assuming a blood replacement rate of 10 ml per day. [Autologous blood donors may give up to 2 units per week for 2 to 3 weeks before elective surgery, based on a more realistic blood replacement rate of 50 to 200 ml per day with adequate iron stores.]

2.Small Modifications to In-flight Blood Draw Limit Onboard ISS

a.Summary

The IRB/HRMRB maintains an in-flight blood draw limit of 100 ml per 30 days. In rare cases, rapid contingency on-orbit rescheduling may result in rolling 30-day blood draw totals slightly exceeding that limit. The IRB grants the crew surgeon the authority to approve a waiver to the 100 ml limit to allow the scheduled activity to proceed, provided that the crewmember concurs and the additional blood drawn will not raise the total to greater than 130 ml. In any such cases, ISSMP will notify the IRB within 3 days of the occurrence.

b.Background

All ISS Human Research Missions are planned with strict adherence to the IRB/HRMRB in-flight blood draw limits, specifically no more than 100 ml of blood drawn per 30 days in-flight. ISS planners develop a comprehensive Increment schedule prior to the start of the mission, but detailed weekly schedules are finalized in 15-minute blocks three weeks prior as the mission proceeds. Weekly schedules are further adjusted as in-flight events or other logistical issues necessitate. These real or near real time adjustments can sometimes shift planned blood draws into time frames that may result in somewhat more than 100 ml being drawn during a 30-day period. Often this occurs following a period of intensive schedule re-planning that requires schedule changes on short notice. For example, this may mean a 20 ml blood draw planned on Flight Day 32 must now occur on day 28, and what would have been a 30-day period involving only 90 ml of blood now involves 110 ml.

There are two types of scenarios that are the most likely to require a rapid waiver to the 100 ml/30 day blood draw limit:

Vehicle Traffic:

Unexpected launch, docking, or undocking delays can lead to rapid and significant changes to crew schedules, sometimes resulting in shifting of previously planned blood draws and breaking what had been satisfactory 30-day windows. A recent undocking delay nearly resulted in the need for a repeat blood draw within 24 hours, which would have violated the 100 ml constraint while not providing enough time for formal IRB approval.

Technical issues during blood draws:

In some cases, a blood tube with a faulty vacuum or an operator technical issue results in the incomplete filling of blood tubes, which must be supplemented with one or more additional tubes.

c.Justification

In some cases rapid schedule changes proposed by the flight controllers require ISSMP concurrence within 12-24 hours. Currently, if such a schedule change results in a 30-day blood draw total in excess of 100 ml, ISSMP must secure an approval from the IRB Chair. The process of securing even this expedited formal approval can exceed the response time required by the Flight Director and could result in a significant loss of science. This in turn can jeopardize the time a willing crewmember has already invested in the experiment. The risk is particularly great if such decisions are required after normal business hours or on weekends. Since the crew surgeon assigned to the mission has the greatest insight regarding the crewmember’s health and his or her ability to provide blood beyond the IRB limit, the crew surgeon may serve as a IRB proxy for real time waivers to blood draw limits.

3.Indwelling Venous Catheters

Provide rationale for such frequent sample collection

Considerations

Proposed duration of the sample collections

Site of venous access

Type of catheter proposed

Qualifications of those placing the catheters

Procedures for monitoring the catheter site

Use of heparin to maintain catheter patency