I’ve submitted an IRB application, now what?
IRB submissions are reviewed on a first-come, first-served basis. Click here for instructions on how to check the status of your application.
Your will review your application and request clarifications on any unclear or missing items. When responding to these clarifications, refer to these instructions. In response to the IRB, researchers should provide a point by point response to each question, make edits within study documents in tracked changes, and revise the ESTR SmartForm application, as needed. This question/answer cycle will occur until the IRB has all the information needed to make a determination. This cycle can be completed by the Principal Investigator and/or the Primary Contact. The IRB will issue a determination letter in ESTR once the review is complete and the IRB has approved the study.
The IRB asked me to submit an updated, tracked changes version of my application documents into the ESTR SmartForm. How do I do this?
Instructions on how to change or update study documents can be found here. The IRB requires any revised document be returned in track changes mode so the edits made are visible. When submitting revised study documents, please make sure to click ‘Update’ rather than ‘Delete’ or ‘Add’:
How long does IRB review take?
IRB review turnaround varies depending on the quality and completeness of the submission, complexity of the project, required ancillary reviews, and responsiveness of the PI to clarifications requested from the IRB Review Specialist. Generally, “target” IRB review turnaround time can be found here.
The IRB asked me to submit a CITI certificate/human subjects training certificate. Where can I access the training and what should I complete?
Harvard offers online human research training through the Collaborative Institutional Training Initiative (CITI) Program, which can be accessed via the Harvard University CITI Single Sign-On page. Specific instructions on how to sign up and what modules to take can be found in the Investigator Manual here.
To check the status of each study team member’s CITI training, follow these instructions.
The IRB has asked me to link other projects to my ESTR record using something called Manage Related Projects. What does this mean? How do I do this?
The Research Administration Systems – or Research Compliance Suite – currently includes four online application systems which are managed by School-based administrative offices:
| Application | Support Website | Responsible Harvard Administrative Contacts |
| ESTR – for IRB applications | ESTR Support Site | For HSPH, HMS, HSDM: Office of Regulatory Affairs and Research Compliance |
| Data Safety – for research data management plans | Data Safety Support Site | HSPH School Security Officer: Andy Ross
HMS/HSDM School Security Officer: Joe Zurba |
| Agreements – for Data Use Agreements | Agreements Support Site | HSPH: Pat O’Neill, Sponsored Programs Administration (SPA)
HMS: Melissa Korf, Office of Research Administration (ORA) |
| OAIR – for financial conflict of interest and outside activities reporting | OAIR Support Site | HSPH: https://www.hsph.harvard.edu/faculty-affairs/outside-activities/
HMS: https://ari.hms.harvard.edu/outside-activities/outside-activity-reporting |
All four applications are housed on the same platform and can be linked. If the IRB asks you to link a record from Data Safety, Agreements, and/or OAIR to your ESTR record, they have done so because the status of the associated record impacts IRB review. To Manage Related Projects, or link the records together, follow these instructions.
My research integrates clinical standard of care and research activities. The IRB asked me to differentiate these components within my IRB application. What does this mean? How do I do this?
Often times research builds upon existing clinical practices or standard of care that patients will receive in a clinic/hospital/medical setting. The IRB will only review research activities, and not standard of care activities, so it is essential that the IRB application only describe the research component(s) of the project. The purpose of differentiating between standard of care and research is to avoid any therapeutic misconception of care. Individuals receiving care should fully understand that research procedures are voluntary. It should be clear that if patients decide not to participant in research, that they are still entitled to medical care.
IRB application documents should only describe what a participant will experience as a result of the research, and not what they will experience as part of a standard clinical or medical procedure. Any costs associated with routine clinical/medical care should not be reflected as costs of the study. Any care the participant receives as part of routine clinical/medical care should not be conveyed as a benefit of the research.
Below is a comparison of similarities and differences between Research and Standard of Care:
- Similarities
- The researcher and health care provider can be the same person.
- The setting may be a hospital, health care clinic, or other health service provider’s office.
- The treatments may seem the same.
- The consent process includes a discussion about exactly what will happen to the patient during the procedure. The consent process is in place to ensure the safety of the patient.
- Differences
- The participant will undergo additional procedures.
- The participant may need to complete additional paperwork (e.g. consent form, survey).
- There may be additional responsibilities and expectations of the participant (e.g. time spent at study visits, additional interviews, ongoing access to medical record, long-term follow up).
- The consent form for research will only explain research procedures, and not standard of care.
- IRB review of human research is required.
Below is a table published by the FDA that highlights the differences between Clinical Research and Medical Treatment by various domains:
| Clinical Research | Medical Treatment | |
| Intent | Answers specific questions through research involving numerous research volunteers. | Address the needs of individual patients. |
| Intended Benefit | Generally designed and intended to benefit future patients. | Intended to benefit the individual patient. |
| Funding | Paid for by drug developers and government agencies. | Funded by individual patients and their health plans. |
| Timeframe | Depends on the research protocol. | Requires real-time decisions. |
| Consent | Requires written informed consent. | May or may not require informed consent. |
| Assessment | Involves periodic and systematic assessment of patient data. | Based on as-needed patient assessment. |
| Protections | Protected by government agencies, institutional review boards, professional standards, informed consent, and legal standards. | Guided by state boards of medical practice, professional standards, peer review, informed consent, and legal standards. |
| Certainty | Tests products and procedures of unproven benefit to the patient. | Uses products and procedures accepted by the medical community as safe and effective. |
| Access to Information | Considered confidential intellectual property. | Available to the general public through product labeling. |
| Release of Findings | Published in medical journals, after clinical research ends. | Individual medical records are not released to the general public. |
Here is an example of how a researcher should use lay language to convey clinical or medical concepts in both the IRB application and materials given to study participants:
Clinical/Medical Phrasing:
“Pre-Operative Measurements”
-
- Prior to surgery, the labial keratinized tissue will be measured at the mid aspect of the tooth to be extracted as follows:
- Gingival width; Distance from the Free Gingival Margin (FGM) to the Mucogingival Margin (MGJ) measured at the midbuccal aspect of the tooth Vestibular depth (using a bilateral retractor and a UNC 15mm probe) Alveolar ridge: width measured on the CT scan at 5mm apical to the bone crest in the mid- mesial-distal aspect of the tooth to be extracted.
- The vertical distance of the line connecting neighboring Cemento-Enamel Junctions (CEJ) to the buccal FGM (measured just prior to surgery).
Simplified Phrasing for IRB & Research Participants (for the same procedures above):
Prior to the surgery measurements will be taken:
-
- Pre-Operative measurements will be taken of teeth, gums and bone before tooth extraction after the patient has been numbed.
- Gums will be measured by placing a periodontal probe (a small ruler) on top of the tissue.
- Gum thickness will be measured with a thin needle and rubber stopper.
- Intra-operative dimensional measurements will be taken during tooth extraction. The patient will still be numb.
- Bone width will be measured with a caliper (an instrument that gently goes around the bone).
- Teeth and bone will be measured by placing a periodontal probe (small ruler) on top of the structures.
- Pre-Operative measurements will be taken of teeth, gums and bone before tooth extraction after the patient has been numbed.
The IRB is holding up my approval for a pending Ancillary Review. What is an Ancillary Review and how do I resolve this?
Ancillary Reviews were established to support compliance with Harvard-specific policies that can intersect with human subjects research, but for which the IRB is not responsible for reviewing. Ancillary Review is triggered and obtained by the IRB, and is typically performed in parallel with the IRB review. IRB staff will inform the PI during their review if/when Ancillary Review is required. Some Ancillary Reviews may be required before the IRB can grant final approval or enter into a reliance agreement (“cede review”). The table in the Investigator Manual list all Ancillary Reviews, their associated policies/websites, if the Ancillary Review holds up IRB approval, and who the Ancillary Review Contact is.
Once I get IRB approval, do I need to do anything else?
Yes! A few things are required after the IRB completes their review and a determination is granted:
- Locate the IRB determination letter and read it in full. Instructions on where IRB determination letters can be found are here.
- The study team should address any pending items or IRB requests documented in the letter within the timeframe requested in the letter.
- Locate and use the IRB-approved study documents on the Documents tab of the ESTR record. Instructions on where to find IRB-approved documents can be found are here.
- For international research – If local IRB/ethics review is required, it must be obtained before any human subjects research activities are conducted in-country. Note that no human subjects research activities can occur in-country until local review has been secured.
Additionally, the IRB recommends keeping the following in mind once IRB approval has been granted:
- Any change or update to the research must be submitted via a Modification.
- Any study requiring annual review must submit a Continuing Review application 21 days prior to expiry.
- All reports of new information must be submitted via the Report New Information activity.
- Human subjects training must be renewed every 3 years.
- Reach out to the Quality Improvement Program (QIP) for research support services at any time (e.g. regulatory binder set up, study monitoring, etc.)
- Once the study is eligible for closure, a closure request must be submitted via the Close Study activity.
