What’s so Special about Special Routing?

May 2023 Issue

(Note: this article is an update of an article with the same name published in February 2020. There has been much turnover among the special routing signatories as well as slight modifications to the review processes since the original article was published.)

Author(s):

• Matt Ogrodnik, MS, CIP
  Director, Office of Human Research Affairs

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• Introduction
• Special Routing in the Initial Review Submission Form
• Special Routing in the INSPIR Application
• Summary

Introduction

The IRB is charged with assessing whether a research project adequately protects human subjects, but there are many other federal regulations, state laws, and institutional policies that must be followed. INSPIR, the IRB’s electronic system, has the ability to route a submission to individuals who represent non-IRB required reviews. Although their sign offs allow the submission to proceed to the IRB, it does not necessarily represent their final approval; but rather, that they have entered this research project into their own tracking and review system. In particular, separate approval is required from the Human Gene Therapy Committee, the Institutional Biosafety Committee, and the Perinatal Research Review Committee; and no research activities can begin without their approval even if IRB approval has been obtained.

This article will discuss each of the processes conducted by these ancillary signatories and/or committees, and explain what information they need in order to sign off in INSPIR and permit the study to reach the IRB for review. Each process is slightly different, so in order to better inform the research community, each individual signatory has provided information on their respective process for this article.

In all cases, the INSPIR Special Routing will proceed more smoothly if the individual signatory is already aware of the study. Therefore, it is highly recommended that the PI contacts any relevant individuals as early in the study planning process as possible.

The specific individuals assigned to each of the departmental or committee sign-offs is subject to change due to personnel turnover. Please see the following page for the most up-to-date contact person for each routing sign-off:  http://www.bumc.bu.edu/irb/inspir-ii/inspir-ii-instructions-for-investigators/dept_sign_off/.

Special Routing in the Initial Review Submission Form

1. Does this study involve human research subjects from Labor & Delivery, the post-partum inpatient floors, the neonatal intensive care unit (NICU), or the Well Baby Nursery of Boston Medical Center; or, is this research that solely involves the study of pregnant or inpatient postpartum patients at Boston Medical Center (including chart review research)?

Sign-off: Maternal Child Department: VRAGOVIC, OLIVERA (Olivera.Vragovic@bmc.org)

Process: When a study is routed for sign-off that involves information from patients from Labor & Delivery, the post-partum inpatient floors, the Neonatal Intensive Care Unit (NICU), or the Well Baby Nursery of Boston Medical Center, then a discussion is initiated with the PI to discuss the study and assess their needs.

For prospective studies: We will review what is required for recruitment in these clinical spaces (including a folder containing the protocol, consent form, and a list of research staff with their photos). After agreement that the study may progress to the next level of review, the sign-off is completed. This INSPIR sign-off does NOT mean that the review process is complete; ultimately, approval must be obtained from the Perinatal Research Review Committee process. The INSPIR sign-off is made prior to review by this Committee so that the review by the IRB is not delayed. The PI is responsible for obtaining approval from this Committee before starting their study, even if the IRB has approved it for the human subject part of the research. A link to our Perinatal Research Guidelines and forms is here: https://hub.bmc.org/departments/pediatrics/pediatric-research

For retrospective chart reviews:  The Perinatal Research Review Committee may determine that the study warrants involvement from a member of the OB/GYN or Pediatrics departments and will discuss this with the PI prior to sign-off.

2. Does your research fall under any of the following categories?

• Trials that are recruiting patients with cancer for treatment of disease or symptoms;
• studies pertaining to cancer prevention or detection
• studies of cancer survivors, i.e. people who have had a previous diagnosis of cancer.
• Studies collecting data on patients with cancer, whether prospectively or retrospectively

Sign-off: Cancer/oncology research from ANY department (not just Oncology): KULKE, MATTHEW 

Process: The PIs of cancer/oncology studies involving patient consent and/or treatment should contact the Cancer Center early in the study planning process, well before submission to the IRB. Such studies are referred to and reviewed initially within the relevant BU/BMC Cancer Center disease groups to ensure that studies are scientifically and clinically appropriate, and feasible within the Cancer Center. Following approval by disease group leaders, they are reviewed by the Senior Research Manager, with final review and sign-off by the Cancer Center co-Director. Thus, the Cancer Center will be able to quickly provide the INSPIR sign-off when the study is submitted. Minimal risk studies, typically those not requiring patient consent or not requiring treatment, are reviewed directly by the Senior Research Manager, with final sign-off by the Cancer Center co-Director. 

3. Is the study being conducted in the Ambulatory Pediatrics clinical area, Inpatient Pediatric Unit or Pediatric Intensive Care Unit, or Pediatric Emergency Room?

Sign-off: Pediatric Research Leadership: WACHMAN, ELISHA (Elisha.Wachman@bmc.org)

Process: Researchers should review our Pediatric Research Guidelines for all pediatric clinical areas available on the Hub: https://hub.bmc.org/departments/pediatrics/pediatric-research. Questions should be directed to our Pediatric Research Leadership team by emailing Elisha.Wachman@bmc.org. Considerations before submitting a study include feasibility, incorporation of studies within the context of clinical care, and connection with clinical leaders on the unit in advance which are outlined in the guidelines on the Hub. 

4. Does your study fall under any of the following categories:

• involves subjects who are being recruited from the psychiatry or behavioral health services at Boston Medical Center or mental health clinical programs affiliated with Boston Medical Center;
• will be utilizing data of patients who are or have been getting psychiatric treatment at Boston Medical Center or its affiliates; or
• will require the assistance of staff or faculty of the Division of Psychiatry at Boston Medical Center or its affiliates.

Process: Prior to a study being submitted in INSPIR, the PI should contact the Division of Psychiatry to complete an internal departmental form describing the research, subject population, recruitment strategies, resources, personnel and timeline. This is reviewed by a committee led by Dr. Hannah Brown, the Vice-Chair of research. The committee will work with the PI to assure that all policies and procedures are followed, and the signatory receives a summary of this process prior to the INSPIR submission. Thus, when a study is routed for sign-off, the signatory would have already been aware of the study, and the materials are reviewed in INSPIR. The IRB submission will receive sign-off, and the PI will work with the research committee for final departmental approval and an implementation strategy. For studies submitted to the IRB that have not undergone this process, sign-off will be delayed until the above process is complete.

5. Does the study take place in the GCRU or use its resources?

Sign-off: General Clinical Research Unit (GCRU): DENIS, RIDIANE (ridianed@bu.edu)

Process: The PI is expected to reach out to the GCRU prior to submitting the INSPIR application, in order to assess the feasibility of implementing the study in the GCRU, and to initiate GCRU budget discussions. If this has occurred, then the INSPIR sign-off is granted promptly. If this discussion has not occurred, and the GCRU has not been able to review the protocol, then the INSPIR sign-off may be delayed.

6. Does the study require inpatient or outpatient nursing care, other than by nurses who work for the investigator or the GCRU, to help conduct the research (e.g., assessing physical/mental status of subjects, administering medications, checking vital signs, performing nursing procedures, completing data forms for implementation of the study)?

Process: In order to prevent a lack of resources or delay in study approval, study teams should contact the Nursing Department for any study requiring nursing resources well before submission to the IRB. The Nursing Department reviews the study to evaluate what the role of the nurse is in the study and the burden of nursing in general; for example, responsibilities such as medication administration and/or patient education, and what the burden of the nurse will be on top of their regular duties. This review also includes evaluating what type of education is provided for the nurses involved, and who would be responsible for this.  If there are any questions or missing information, a discussion is initiated with the IRB analyst or the study team, and a comment is made at the time of sign-off.  

7. Is the PI of the study a nurse at Boston Medical Center?

Sign-Off: Nursing Department: COREY, PAMELA (Pamela.Corey@bmc.org)

Process: This sign-off is obtained in order to identify all nurse PIs in order to track the nursing research that is occurring on-site.  BMC is now Magnet designated, and that designation requires that research by nurses be tracked.   In the past, often some nurses were involved in research and this was not comprehensively tracked.  This sign-off allows the nursing department and leadership to be aware of what is occurring and who is involved, as well as provide support to the nurse PI. This also has renewed focus with the increasing numbers of nurses now pursuing their Doctorate in Nursing Practice degrees and conducting research. 
 
8. Will the study be dealing with Lasers, Light Emitting Diodes, Photon Induced Photo Acoustic Streaming (PIPS), or Low level Light Therapy (LLLT)?

Sign-off: For all IRB protocols dealing with Lasers, Light Emitting Diodes, Photon Induced Photo Acoustic Streaming (PIPS), and Low level Light Therapy (LLLT) must be submitted for review and sign-off to: MOREAU, MADISON (Madison.Moreau@bmc.org, Biomedical Engineering), TRAINOR, SHAWN (Shawn.Trainor@bmc.org, Deputy Laser Safety Officer, Clinical Lasers), and KURKOMELIS, JOHN (kurk@bu.edu, Laser Safety Officer)

Process: To avoid delays, the PI should initiate these contacts well before the INSPIR application is submitted.

Biomedical Engineering: This sign-off is typically approved immediately with a comment noting that the device must be inspected by Clinical Engineering for electrical safety when it arrives and before use.

Clinical Lasers and Light Units:
For clinical lasers and light units, the following information is verified prior to sign-off:

• Whether Clinical Engineering is aware of the unit in question (and they have their own sign-off, as noted above)
• Whether the proposed use is routine or new at BMC
• Whether all operators are properly trained and credentialed

For units not designed for clinical use, contact is made with the PI to obtain more detailed information about the light source in order to confirm that exposure to the subject is below the limits in the ANSI standards. If Class 3B or 4 lasers are involved, the signatory also checks operator training, whether the PI has been authorized by this office to use lasers for research purposes, and what kinds of administrative and engineering control measures are in place to ensure subject and employee safety. Specifically, verification is obtained that for clinical procedures, the physicians involved are credentialed, the staff is trained in laser safety, and the correct eye protection will be made available at the time of use.

The language in the consent form is also reviewed to confirm that risk is communicated effectively.

The above-described review must be completed before INSPIR sign-off is granted.

9. Does your study involve research-only radiological imaging studies (i.e. imaging studies that are not being taken as part of standard care)?

Sign-off: Radiology: SOTO, JORGE (Jorge.Soto@bmc.org)

Process: The Radiology review allows the department to assess both resource and safety issues. For imaging involving non-ionizing radiation [i.e., Magnetic Resonance (MR)], sign-off indicates that the department is aware of the study, and safety issues are addressed as part of the IRB review (note that a checklist filled out by the PI is used to identify potential MR safety issues). For imaging involving ionizing radiation (such as radiographs, CT scans, or nuclear medicine examinations), Radiology will not sign off until after the study has been approved by the Radiation Safety Committee. Note that all such studies should also answer Yes to the question in the INSPIR application referenced below concerning the exposure of subjects to ionizing radiation for research purposes only. The PI of any study involving imaging using ionizing radiation not required for standard of care should contact the Radiation Safety Committee early in the planning stages of the study. After the study has been approved by the Radiation Safety Committee, then when the INSPIR application is submitted and routed for sign-off, no additional specific information is requested from the investigators. The packet is reviewed (protocol and application) and in the majority of cases, the information is complete and sign-off is granted.

10. Will any School of Dental Medicine students or residents be involved in the design or conduct of the research study?

Sign-off: Office of Research – Dental School: PYKE, BARBARA (bpyke@bu.edu)

Process: The protocol is reviewed to ensure compliance with the GSDM Clinical Research Policy. This mainly involves confirming that the PI is not a student or resident; only GSDM faculty members can serve as PIs. The study staff are also reviewed to confirm that the students and/or residents listed on the protocol have completed the training that is required under the GSDM Clinical Research Policy. If questions arise, the PI will be contacted, but generally the required information is available and the review is done quickly and without contacting the applicant. Once it is clear that the applicant is compliant with the policy, sign-off on the INSPIR submission is provided.

11. Has the CTO Intake Form been submitted to the Clinical Trials Office for this study?

If No:

Does your study involve the provision of any of the following Boston Medical Center (BMC) clinical services or use of BMC infrastructure listed below (if this is a chart review, select “No”):

• Investigational Pharmacy Service (For study drug maintenance and dispensation. Follow IPS policy. No offsite study drug storage allowed.)
• Investigational Device (IDE) implants
• Infusion services
• Radiology (e.g. MRI, CT/PET/MUGA Scans)
• Pathology (e.g. Histology Slides)
• Lab Medicine (Processing or Providing Analysis of blood/tissue samples)
• Cardiology (e.g. EKGs)
• Ophthalmology (e.g. Retinal Exams)
• Performing Physical Exam in BMC clinical space
• Drawing Blood in BMC clinical space

Sign-off: BMC Clinical Trial Office (CTO): PORRECA, MICHAEL (Michael.Porreca@bmc.org) OR CHUNG, AMY (Amy.Chung@bmc.org) OR SHIELDS, BRYANT (Bryant.Shields@bmc.org)

Process: This review is done to ensure that the CTO is aware of all studies that need CTO services. Such studies can largely be broken down into two groups:

• Studies managed by CTO (Industry-sponsored clinical trial with a BMC PI)
• Studies supported by CTO (Any clinical research at BMC or BU involving: Participant service/item/intervention ranging from minor blood draw to device implantation, including but not limited to: observational imaging, drug/vaccine/vitamin studies, Evaluation and Management (E&M), Investigational pharmacy service (IPS), and pathology blood/tissue processing.)

Any study that falls into one of the above two categories must be entered into Velos to begin the CTO workflow. If CTO is unsure of a study’s need to be entered into Velos, further inquiries are initiated with the study team.

Currently, CTO does not require Velos entry before sign-off so as to not delay IRB review of the study.

12 and 13.
12. Does your study involve procuring and/or processing samples, i.e., tissue or slides, through Pathology at BMC?

Sign-off: BMC Pathology: DUFFY, ELIZABETH (Elizabeth.Duffy2@bmc.org) OR NORBERG, ERIN (Erin.Norberg@bmc.org)

13. Does your study include activities that requires the involvement of Laboratory Medicine services at BMC including but not limited to specimen procurement, lab testing, phlebotomy, point of care testing such as urine pregnancy, use of lab CLIA, etc.?

Process: This routing was created because BMC Pathology and Laboratory Medicine identified that they were receiving numerous ad hoc requests for pathology/laboratory services after the study had been IRB-approved, which presented issues for both the lab and the studies because there are services the lab does not offer, and services that are charged for which the studies may not have budgeted for. PIs of studies that may require pathology or laboratory services should reach out to the DG-Path Lab Research Study Group (DG-PathLabResearchStudyGroup@bmc.org) early in the study planning process to begin discussions. The ideal scenario is for study teams to contact path/lab before they complete their IRB application, but this sign-off was put in place as a “catch”. When sign-off is prompted, the comment to contact the pathology/laboratory group is added, and the INSPIR sign-off is immediately granted.

Special Routing in the INSPIR Application

8.0 Navigation Menu

8.6 Does this study involve collecting biological samples for research purposes?

Sign-off: Institutional Biosafety Committee (IBC): GHOSH, SAJAL (sajal@bu.edu)

Process: IBC review is needed for all studies that use recombinant or synthetic nucleic acid materials, biohazardous materials such as human clinical samples (including human blood, human tissues or cells, human body fluids),  and infectious agents including, but not limited to HIV-1 and HTLV (a complete list of agents requiring IBC approval is available on the IBC website). The PI of such studies should begin the IBC approval process as early in the study planning process as possible. IBC’s role is to oversee that all regulatory requirements are being followed while investigators are working with any biohazardous material, and to ensure everything is being done safely for the researchers, public, and the environment. The mandates evaluated are from various entities such as NIH (NIH guidelines on recombinant and synthetic nucleic acids), CDC, OSHA, Mass Department of Public Health, and Boston Public Health Commission.

When IBC receives an IRB application for sign-off, the following are evaluated:

1. What is the study about?
2. Are they storing any clinical samples in any BMC or BU research laboratories?
3. Are they processing or using any clinical samples in any BMC or BU research laboratories?
4. Who are the PI and Co-investigators?
5. Does the PI or the Collaborator have IBC approval for storage or processing of clinical samples?

If the answer is “Yes” for question 5, INSPIR sign-off is granted immediately. Also, if the study involves collection of clinical samples that never come to BMC or BU, or if BMC or BU is only involved in coordinating the study or is involved in analyzing the data only, then INSPIR sign-off is granted immediately.

However, if the answer is “No” for question 5, and it is not clear what the response is for questions 3 and 4, then IBC sends an email to the PI asking them to further clarify the questions 1-5 via a questionnaire form. The PI must send back the completed questionnaire form before IBC will proceed to the next step. If the responses to the questionnaire indicate that samples are not being stored or processed in any BMC or BU research laboratory, then sign-off is granted.

If. however, the PI’s response indicates that they do store or process samples in a BMC or BU research laboratory and that work is not done in collaboration with a PI who has an approved IBC protocol for such processes, then IBC informs the PI that they have to submit an IBC application for the storage and processing work, and they may only start the actual work when the IBC application is approved.  IBC will personally coordinate with the PI and help them to start an IBC application, and with the submission process. Once the appropriate IBC application is submitted to the IBC office, INSPIR sign-off on the IRB application is granted. The INSPIR sign-off may come before the IBC application is approved, but the storage and processing work cannot begin until IBC approval, even if IRB approval has already been obtained.

8.5 Does this research involve genetic testing, gene therapy, or collection of genetic information?

If yes:

21.0 Genetics

21.1 How would you classify the genetic research component of this research?

  Gene transfer or gene therapy (these studies require review by the
  BU/BMC Human Gene Therapy Committee)

Sign-off: Human Gene Therapy Committee: GHOSH, SAJAL (sajal@bu.edu)

Process: IBC review is needed for all studies involving introducing anything foreign of biological origin, i.e., microbial, human cells, recombinant DNA, directly into humans OR if the research will involve the deliberate transfer of recombinant DNA, or DNA or RNA derived from recombinant DNA, into human research participants (human gene transfer). Early contact with the IBC is essential for such studies. Any study involving gene-transfer must have its own IBC approval, as administration of recombinant DNA product into humans (that will be expressed in humans) require a different line of IBC review. Here also, IBC will sign-off once the IBC application is submitted so that IRB review process can start simultaneously. But the actual administration of the rDNA drug must start only after IBC approval is secured.

8.7 Does this study involve administering drugs or biological agents?

Sign-off: Investigational Pharmacy Services (IPS): BLISS, SAMUEL (Samuel.Bliss@bmc.org) OR DENNAOUI, HUSAM (HusamAl-deen.Dennaoui@bmc.org) OR CAMUSO, MICHAEL (Michael.Camuso@bmc.or)

Process: Before signing off in INSPIR for studies that use drugs or biologics where the agent is received, stored, and/or administered at BMC or BU Medical Campus, the IPS reviews the submission components, such as the attached protocol, INSPIR application, and Investigator’s Brochure. The signatory reviewer makes an internal note that this project will be scheduled for a more comprehensive future IPS review as part of the IRB review process, and at the time of sign-off, inputs comments to highlight any elements that are missing or require correction. The Department of Pharmacy is responsible for the control and storage of all medications, diagnostic, nutritional supplements, and biologics used at BMC and the BU Medical Campus, including investigational products. Investigational products are defined as Investigational New Drugs (IND), FDA-approved comparator drugs, and protocol-required ancillary drugs.

8.9 As part of this study, will subjects be exposed to any procedures involving ionizing radiation for research purposes only?

Sign-off: Radiation Safety: 

LI, BAOJUN (baojunli@bu.edu), Chief Medical Physicist

MARTEL, CHRIS (cbmartel@bu.edu), Radiation Safety Officer

Process: Any study where this answer is “Yes” should also check “Yes” in the Special Routing question #10 described above covering research-only radiological imaging. As stated above, Radiation Safety review is required for studies involving scan(s) or procedure(s) that fall outside of standard of care, from x-rays or isotopes. The PI should contact Radiation Safety early in the study planning process to avoid delay. Radiation Safety will need to know the type of radiation, the number of exams, and estimated radiation dose (usually in units of mSv) that the subjects will receive beyond standard of care. This figure is used to categorize the risk to the subject and weigh it against the study’s benefits. For x-ray exposures, the Chief Diagnostic Medical Physicist evaluates and verifies that the exposure estimate is reasonable given the procedure(s) listed in the protocol. For radioisotope exposures, the Radiation Safety Officer performs the evaluation. They also review the language in the consent form to confirm that radiation risk is communicated effectively. Radiation Safety must complete their review before signing off in INSPIR.

11.0 Subjects

11.5 Special Populations

Please indicate if any of the following populations will be targeted by your research:

  BMC Residents or Fellows

  BU Dental Students

  BU Medical Students

  Graduate Medical Sciences Students

Sign-off: Chief Medical Officer: MCANENY, DAVID (David.McAneny@bmc.org, approves studies to proceed to IRB review when medical residents or fellows are specifically recruited. He is also the signatory if any Boston Medical Center faculty, staff, laboratory personnel, or trainees are targeted for recruitment).

Process:  A review is conducted to determine if the targeted inclusion of BMC residents, fellows, faculty, staff, laboratory personnel, or trainees is appropriate; if the study is designed in a way that is likely to produce meaningful data; and if the protections against undue influence are sufficient.  If there are any concerns, the Chief Medical Officer or delegate will meet directly with the PI to discuss prior to sign-off.

Sign-off: Associate Dean, Student Affairs: JACKSON, ANGELA (hjackson@bu.edu, signs off on research targeting recruitment of medical students that involves the study of student affairs, such as aspects of student life, future career plans, the medical student experience, student wellness, and/or student attitudes)

Process: To protect our BUSM students while at the same time allowing for participation in research and other valuable initiatives, all research targeting medical students must be approved by the Associate Dean of Student Affairs or Associate Dean of Medical Education (depending on the focus of the research, as outlined in the sign-off description above) prior to proceeding to the IRB review process. Submissions are reviewed to ensure compliance with the Procedure for Surveys Targeting Medical Students. Sign-off is granted if the study meets the criteria outlined in this policy, and the study is designed in a way that is likely to produce meaningful data, the protections against undue influence are sufficient, and the time commitment for the medical students is not unduly burdensome.

Sign-off: Office of Research – Dental School: PYKE, BARBARA (bpyke@bu.edu). Protocols that specifically recruit dental students require this sign-off on behalf of the Dean of the School of Dental Medicine. This is also the signatory if any students or residents from the School of Dental Medicine will be involved in the design or conduct of the study)

Process: A brief review is conducted to make sure the School of Dental Medicine is aware of the proposed study and there is nothing out of the ordinary. Generally sign-off is provided, relying on the IRB to complete a thorough review.

24.0 Devices

24.2 Does this study involve the use of an investigational electrical (AC or battery) device?

Sign-off: Biomedical Engineering: MOREAU, MADISON (Madison.Moreau@bmc.org, signs off on studies using electrically powered devices (AC or battery) that are not FDA approved for the indication in this study)

Process: This sign-off is typically approved immediately with a comment noting that the device must be inspected by Clinical Engineering for electrical safety when it arrives and before use. To facilitate inspection, you will need to bring the device to Yawkey BN13 for a final approval and documentation. If the device cannot be brought in-person, we can make special arrangements. One important thing to note is that Clinical Engineering does not maintain research devices. It is the responsibility of the study PI to ensure the device receives proper maintenance and repairs, as needed.

Summary

In summary, numerous reviews may be required for research studies, depending on the details of the study design. There is great benefit to initiating these reviews WELL BEFORE submitting the INSPIR application, to get feedback on the study design and to initiate these separate review processes.

INSPIR is used to route research studies to a number of different institutional reviewers as an additional check that required reviews have been initiated. The assigned reviewers must sign-off in INSPIR before the study reaches the IRB. As demonstrated, each sign-off involves slightly different processes; and, therefore, it is important to understand the information that is needed from each in order to obtain INSPIR sign-off and start the IRB review process. It is also important to accurately fill out the initial review submission form to avoid delays in obtaining sign-off.

Please also remember that three of the reviews occur in parallel by separate committees: the Human Gene Therapy Committee, the Institutional Biosafety Committee, and the Perinatal Research Review Committee. Their sign-off allowing the submission to proceed to the IRB DOES NOT constitute approval from these committees. The PI is responsible for obtaining approval from these committees before starting their study, even if the IRB had approved it for the human subject part of the research. 

Along with the IRB, all of these groups are working hard to ensure that research studies adequately protect human subjects and are compliant with the other federal regulations, state laws, and institutional policies that must be followed.