About IRB Applications
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What is Interim?The Dilemma
When applying to the IRB, a researcher must have developed his or her study documents to allow thorough review by the IRB. Sometimes, researchers will seek sponsored funding from external organizations with the intent to: (1) develop the research plan using a portion of the funding, then (2) subsequently submit a developed protocol to the IRB for approval. Since an IRB approval letter is required to obtain funds, this presents a serious dilemma - the researcher cannot develop the human subjects research protocol without the funding; however, OSP has been told not to release funding without IRB approval.
The Solution
The IRB may grant interim approval for studies needing the release of funds for study procedures not involving human subjects (e.g., designing survey instruments, developing the study design, etc.).
Granting Interim approval is supported by 45 CFR 46.118 (after clicking on this link, scroll down the new page to 46.118).
Amendments to Protocols (Policy No. 6.01)Once the IRB has approved a non-exempt project, it must be carried out as planned/described in the original IRB submission package. Any changes to the IRB application must be approved by the IRB prior to implementation of changes, unless it is in the best interest of research participants. Examples of changes to the IRB application include changes in subject population, recruitment plans, research procedures, study instruments, consent form language, and wording within study instruments. Along with any additions to study procedures or study instruments, the IRB must approve the removal of study procedures or study instruments.
Proposed changes to the research protocol of Exempt protocols must be submitted to the IRB and approved prior to implementation.
Continuing Review Requests (Policy No. 6.00)All Expedited and Full Review protocols must either receive Continuing Review approval or be reported as closed prior to the protocol's expiration date (see "When is Continuing Review Required?" to help you decide whether to close or continue your protocol). A protocol's expiration date is located on the IRB approval letter.
If continuing review is not approved by the IRB prior to the expiration date, activities involving human subjects must cease immediately. Human subjects activities may continue on an expired protocol only if it is in the best interest of study participants; however, such a circumstance (including justification) must be reported to the IRB immediately.
Continuing review is not applicable for exempt research. Exempt research does not expire.
Continuing review is required unless data collection at all sites is complete AND data analysis at Virginia Tech is complete. If you are still analyzing or using data for any type of research write-up (e.g., dissertation paper, journal publication, etc.), the study must be re-approved by the IRB.
If data collection at all sites is complete and data analysis at Virginia Tech is complete, you may report the study as "closed" at any time by sending an email to irb@vt.edu. Remember to provide your IRB number or study title.
If, after the study is closed, there is a desire to reanalyze the data, the protocol must be re-opened (see below "How Do I Re-Open a Closed or Expired Protocol?" for further information).
Failure to report your project as closed or have your study re-approved on or before the study's expiration date will result in the issuance of an expiration letter that will be sent to you, and possibly your Department Head, Dean, OSP, sponsoring agency, and the Office for Human Research Protections (OHRP).
The expiration letter will serve as notification that subject enrollment, and use of and collection of data from existing subjects must be halted. Researchers are encouraged to contact the IRB office (irbadmin@vt.edu) immediately upon receipt of an expiration letter.
Federal regulations make no provision for any grace period extending the conduct of research beyond the expiration date of IRB approval. Data collected in the interim period prior to re-approval will typically not be approved for analysis or publication purposes.
Issuance of an expiration letter may result in a compliance audit of all research conducted under the principle investigator and/or further sanctions. For funded projects through OSP, issuance of an expiration letter may result in a halt of funds.
Incomplete re-approval submission packages will be sent back to the Principal Investigator. This may result in a late submission and expired protocol.
If no longer than one year has passed since the protocol expired or was properly closed, submit a request for continuing review. With your application for continuing review inform the IRB office as to whether any human subjects activities have occured under the protocol during the lapse of IRB approval.
If it has been longer than one year since the protocol expired or was properly closed, submit a new application. If the protocol is being "re-opened" for data analysis purposes only, the new protocol may cover only data analysis activities.
For expedited and full Board research, the IRB office will often send 2 reminder emails (typically one four weeks prior and the other two weeks prior to the study's Continuing Review Due Date). However, obtaining re-approval (i.e., continuing review approval) prior to the study's expiration date is that of the investigators, and not that of the IRB office.
If the IRB Chair gave �Expedited approval� for the original request, and if there have not been any adverse incidents, and if the level of risk to the subjects has not increased, then the Chair is authorized to provide re-approval of the project.
The continuing review request must be reviewed by the Full IRB at its monthly meeting unless one of the following applies: 1) the research is permanently closed to the enrollment of new subjects; all subjects have completed all research related interventions; and the research remains active only for long-term follow-up of subjects; or 2) where no subjects have been enrolled and no additional risks have been identified; or 3) where the remaining research activities are limited to data analysis; or 4) continuing review of research, not conducted under an investigational new drug application or investigational device exemption where categories for expedited approval do not apply, but the IRB has determined and documented at a convened meeting that the research involves no greater than minimal risk and no additional risks have been identified.
Deadline = Two weeks before monthly Board meeting at which the research must be reviewed and approved to not expire (the Board typically meets the second Monday of each month). See approval letter for expiration date and continuing review due date.
The IRB has the authority to Approve for continuation, Contingently Approve if explicit clarifications are required, Table if general clarifications are required, or Disapprove continuation.
The goals of IRB re-approval are to ensure that the risk/benefit ratio is still acceptable, that the measures taken to safeguard subjects are adequate, that the approved IRB Application/protocol is followed, and that the project reflects any changes that have been made in the regulations for human subjects research since the last approval.
IRB review of proposed research is an ongoing process, not a one-time step. Regular reevaluation ensures that research is conducted responsibly. Even in responsibly conducted studies, a one-time review is inadequate, since the risks can really be understood only after research has begun, and since the regulations for human subjects research are constantly being refined as the risks and benefits are better understood. Unexpected developments in a project can raise questions about the conduct of the research, and new findings can raise questions about the project. Periodic review by researchers and the IRB helps in assessing risks and maintaining a favorable risk/benefit ratio.
The Department of Health and Human Services (DHHS) Regulations, Title 45 Code of Federal Regulations Part 46 (45 CFR 46), require at Section 46.109(e) that "an IRB shall conduct continuing review covered by this policy at intervals appropriate to the degree of risk, but not less than once per year... ." OHRP interprets "not less than once per year" review to mean review on or before the 1-year anniversary date of the previous IRB review required by 45 CFR 46, even though the research activity may not begin until some time after the IRB has given approval. OHRP guidance on Continuing Review.
The IRB may require certain protocols be reviewed more than annually. Any study requiring more than annual review will have a limited set approval time period. The frequency of continuing review is to be determined by the IRB appropriate to the protocol under review. The IRB may require more than annual review because of any of the following:
- Noncompliance history
- Marginal risk / benefit ratio
- As necessitated by protocol
Identification and Reporting of Unanticipated Problems / Adverse Events (Policy No. 6.02)If a sponsor funds or supports the study, then the Principal Investigator is responsible for notifying the sponsor of any adverse events. If the study is a multi-site project, the PI is responsible for notifying the other sites, as appropriate. Similarly, if the study is a multi-site project, and the unanticipated problem occurs at a site other than the University, then the PI must notify the VT IRB.
Serious unanticipated problems will be reviewed and handled by the full IRB, whereas minor unanticipated problems will be reviewed and handled by the IRB Chair.
When a participant or researcher in a research study experiences an unanticipated problem, the Principal Investigator (PI) must report this incident to the IRB within 5 days. A summary of the unanticipated problem must be submitted to the IRB using the Adverse Event Report form (above).
The University defines an unanticipated problem as new findings or unexpected events whose nature, severity, and frequency are not described in the information provided to the IRB or to study participants.
The University defines an unanticipated problem as any of the following:
- An actual unforeseen harmful or unfavorable occurrence to participants or others that relates or possibly relates to the research protocol (injuries, psychological harm)
- An unforeseen development that potentially increases the likelihood of harm to participants or others in the future
- Breach of confidentiality or privacy
- A participant complaint about research procedures
- Unexpected risk that is not listed in the consent form
Notify the VT IRB of any serious unanticipated or anticipated problems via email within 24 hours of becoming aware of the occurrence, and follow-up with a detailed summary of the problem using the Adverse Event Report form within 5 days.
Serious = Results in death, is life threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, cancer, overdose or is congenital anomaly/birth defect; reportable event even if identified in current investigator brochure/protocol.
See below section for examples of serious problems.
Notify the VT IRB of any deviations from IRB approved study procedures or documents within 5 days of becoming aware of the deviation by emailing the Post Approval Monitoring Officer, Louisa Gay, at lgay@vt.edu.
Minor anticipated adverse events (adverse events described in the risks section of the consent form) are to be reported during the continuing review process.
The IRB Chair will send a response to the principal investigator regarding possible actions, which could include:
- Acknowledge report, no further action required;
- Request additional information;
- Request a meeting with principal investigator and/or other parties;
- Monitor the study for additional adverse events;
- Recommend a change in the IRB Application/protocol and/or consent form(s);
- Determine if current subjects need to be informed of adverse event;
- Determine if actions taken by the investigator adequately addressed the adverse event or request further actions to be administered by the investigator;
- Temporarily suspend enrollment and/or study treatments pending the collection of additional information;
- Permanently suspend enrollment and/or study treatments.
Exercise Studies:
* Fainting;
* Joint injuries;
* Spinal injuries;
* Stress fractures;
* Heart attack;
* Stroke;
* Miscarriage of pregnancy;
* Any problems requiring intervention by a physicianErgonomic Studies:
* Joint injuries;
* Stress fractures;
* Prolonged muscle pain (> 3-4 days);
* Injury to head, neck, spine, limbs, hands, or feet;
* Miscarriage of pregnancy;
* Any problems requiring intervention by a physicianDXA Scans:
* Female participants discover after the fact that they were pregnant at the time of the scan;
* Miscarriage of pregnancy;
* Birth of a child with congenital defects subsequent to participation in a studyTransportation / Driving Studies:
* Vehicle accidents resulting in injury to subjects and/or vehicle occupants and/or other individuals;
* Any vehicle accident regardless of initial determination of "no injuries"Blood Collection:
* Fainting;
* Uncontrolled bleeding after venipuncture;
* Evidence of acute nerve injury/damageInterpersonal Actions:
* Spousal/partner/child abuse following involvement in a study where these actions might be triggered;
* Peer bullying of children involved in or who decline participation in studies
Significant emotional responses/reactions including, but not limited to:
* Inconsolable crying;
* Extreme sadness; depression;
* Rage (directed toward researcher, self, or others);
* Indication of suicidal thoughts;
* Self-mutilation or self-abuse;
* Alteration in family relationships as a result of participating (or deciding to not participate) in studies;
* Inadvertent disclosure of non-paternity;
* Lowered self esteem or other psychological problems related to failure to be selected for a study (after screening);
* Aggravation of psychological condition when placed on a wait list where standard or experimental treatment is not readily provided
Prior to participation: loss of income while being placed on a wait-list
Subsequent to participation:
* Loss of job;
* Loss of business/clientele;
* Loss of state or federal benefits;
* Loss of health benefits or significant increase in health insurance costs post-participation
Subsequent to participation
* Arrest or incarceration because personal information revealed or "deduced";
* Civil suits directed toward subject because personal information, revealed or "deduced", is claimed to have harmed someone outside of the study (i.e., slander/defamation of character, "discovery" of repressed memories of physical or sexual abuse leading to civil or criminal actions, falsification of job applications alleged if past "history" revealed)
Reporting a Project ClosedYou may report an Expedited or Full Review project as closed if data collection at all sites is complete AND data analysis at Virginia Tech is complete. If you are still analyzing or using data for any type of research write-up (e.g., dissertation paper, journal publication, etc.), the study should not be closed. Exempt projects do not need to be closed.
A project can be closed at any time using the IRB Protocol Management system (see link at end of this page). You will be prompted by the IRB office a month prior to the project's IRB approval expiration date to renew your IRB approval or report your project closed.
Once you report your project closed using the IRB Protocol Management system, you will not hear back from the IRB office (in other words, the closure does not need to be approved by the IRB).
To begin any of the above applications, go to IRB Protocol Management.
Subsequent to participation:
* Ostracism/expulsion from civic, social or religious groups;
* Stigmatization/persecution because personal information revealed or "deduced" (i.e., HIV positive, infection with sexually transmitted diseases [STDs], sexual preference, past crimes/offenses, mental illness);
* Student complaints about pressure to participate or of being penalized for deciding to not participate;
* Damage to the doctor/patient relationship;
* Minor "thrown out" of parent's house;
* Permanent expulsion of minor or adult students from school/educational institution