IRB Frequently Asked Questions

1. What is an IRB?

   IRB is an abbreviation for the Institutional Review Board. The IRB is an administrative body established to protect the rights and welfare of human research subjects recruited to participate in research activities conducted under the auspices of the institution with which it is affiliated. The IRB has the authority to approve, require modifications in, or disapprove all research activities that fall within its jurisdiction as specified by both the federal regulations and local institutional policy. The official name of the IRB committees at CHOP is The Committees for the Protection of Human Subjects. For more information about the CHOP IRB, its membership and structure, go to CHOP Institutional Review Board.

2. How do I contact the IRB?

   For IRB contact information, please contact the IRB.

3. What is an FWA number and what is CHOP’s FWA number?

   FWA stands for Federal Wide Assurance, which must be submitted to the Office of Human Research Protections (OHRP) in order for an IRB to review research that receives federal funding. An FWA is a document that assures an institution's commitment to comply with the federal research regulations, with national and international ethical principles, and with federal, state and local laws related to the protection of human research subjects. CHOP's FWA number is FWA00000459. For more information about FWAs, go to Federal Wide Assurance (FWA).

4. What is an Institutional Official and who is that at CHOP?

   The Institutional Official (IO) is responsible for ensuring that the Human Research Protection Program (HRPP) functions effectively and that the institution provides the resources and support necessary to comply with all requirements applicable to research involving human subjects. The IO represents the institution named in the Federalwide Assurance (FWA). The IO is the individual who is legally authorized to act for the institution and, on behalf of the institution, obligates the institution to the Terms of the Assurance. At CHOP, the Institutional Official is Matthew Hodgson, MA, MS, CHRC, CCRP.

5. What is the difference between laws, regulations and IRB policies/procedures?

   There are a variety of federal regulations and state laws that apply to human subjects research. In addition, the Office of Human Research Protections (OHRP) and the US Food and Drug Administration (FDA) have issued guidance documents and other materials that reflect their agency's current thinking. The IRB's Standard Operating Procedures (SOPs) provide the institution's standard approach to the interpretation of the federal regulations, best practice standards and state and local law. The SOPs serve as a reference for the IRB membership, IRB Office staff, and the CHOP community of investigators. Regulations are necessarily grey and their interpretation can evolve over time. The IRB SOPs, therefore reflect our current understanding of the Office of Human Research Protections (OHRP) and the FDA's interpretation of the regulations. In addition, the IRB has identified a number of ways to implement additional flexibility in its SOPs for research that is neither federally funded nor federally regulated. For more information go to Regulations and IRB policies.

1. Who can make the determination that an activity is (or is not) human subjects research?

   At CHOP, the investigator is permitted to make the determination that what they are doing does not meet the definition of human subjects research. Only activities that meet the definition of human subjects research require submission to the IRB for a review and approval or for a determination of exemption. However, there are many situations where it may be unclear whether or not the proposed activities meet the definition of research and if it does, whether or not it involves human subjects. Requests for the IRB to make a determination as whether or not an activity meets the definition of human subjects research should be submitted via the eIRB system. Examples:

   A QI may produce as a byproduct information that is worth sharing. Depending on the design of the project, it might or might not be human subjects research.

   Receipt of a large Medicaid data set containing hundreds of thousands of records might contain birth dates and dates of service. If the investigator is uncertain, the IRB would need to determine if the individuals would be readily identifiable or not.

2. Is innovative care designed to enhance the well-being of an individual using an FDA approved drug or device research?

   No. The FDA and the IRB do not regulate the practice of medicine. Since the drugs, biologic or device is approved and the intent is to provide care for an individual patient and not to produce generalizable knowledge, this is not human subjects research.

3. Is a database (registry) designed for use in future research considered research?

   Yes. If the database/registry is being designed and used for the purposes of future research then even though no research activities are planned per se, this is considered research and also falls under the requirements of HIPAA. If the database will be used primarily for clinical care or hospital operations purposes, then prior IRB review is not required. However, any research that intends to use the information from the database would require IRB review.

4. Does a case report require prior IRB review?

   No. The CHOP IRB does not consider retrospective case reports to meet the definition of research. However, prospective research involving just a single subject do not qualify as case reports just because the research is limited to one individual.

5. What about a case series?

   It depends; a determination from the IRB may be necessary. A case series can be several notable cases reported at the same time. The IRB does not consider this to be research. In IRB SOP 407: Determining When a Proposal Meets the Definition of Human Subjects Research, the IRB excludes case series of 5 or fewer patients from review. Case series with 6 or more cases must be submitted to the IRB as research or for a determination that they do not meet the definition of research. The rationale for this requirement is that case series involving greater than 5 records frequently involve dozens of records and could be more appropriately classified as descriptive or observational research. See the IRB's webpage on Study Design.

6. We are conducting a Quality Improvement/Quality Assurance project and have no plans to publish; do we need IRB review?

   Maybe. Publication is a consideration but it does not distinguish research from non-research QI/QA projects. The intent of QI/QA is to improve the care of patients at CHOP, often using proven care strategies and methods and most are not research. The project may still produce generalizable knowledge that clinicians would wish to share with others. If the QI/QA project intends to test an as yet unproven care strategy using a standard research methodology, then it is likely that the project is research. For more information, see the OHRP Quality Improvement Activities Frequently Asked Questions website, Is this Quality Improvement?, or the CHOP Screening Checklist for Quality Improvement (QI) Projects.

7. What about receipt of deidentified datasets or biospecimens?

   No. Use of de-identified datasets or biospecimens is not human subjects research. In order for the data/biospecimens to be de-identified, there can be no identifiers and there can be no link to identifiers. A coded specimen that can be linked back to individuals is not considered de-identified. If the providers have access to the key but will not provide the recipient with any PHI, then from the recipients’ perspective the data or specimens are de-identified. The provider of the data/specimens must either provide a letter stating that they will not provide any identifiers, or have policies which clearly state that they will not provide identifiers. For details of the requirements for data sharing, see Guidance on Engagement of Institutions in Human Subjects Research

8. Can I share de-identified data or biospecimens with another investigator?

   Yes. Use of deidentified data or specimens does not constitute human subjects research. However, the investigators must adhere to both the limitations (if any) specified in the consent form used to obtain the specimens and the subject's expressed preferences with regard to future use. If re-use of study data or biospecimens for future research is a possibility, then the consent form must include information about future use. For most studies, subjects should be able to opt-in or opt-out without affecting their ability to enroll in the main study. The IRB's Consent Form Templates include example language for optional future use. The subjects' preferences should be noted as part of the study record to ensure that future use of data and specimens matches each subject's decision.

9. If CHOP is not enrolling subjects in the research but is functioning as the data coordinating center (DCC) does this require review by the IRB?

   It depends. If the research is funded by the DHHS or if the DCC will receive identifiable subject information, then the CHOP is engaged in the research and the IRB must review the activities of the DCC. If the DCC will only receive de-identified data and the funding is not from DHHS, then there is no obligation to obtain IRB approval. Having monitors (CRAs) from the DCC perform source-data verification during a site visit does not engage the DCC in Human Subjects Research unless it receives PHI from the site.

1. Who reviews my study/application?

   When an application is received by the IRB, it is triaged (based on information in the application) to be reviewed either by the convened board or, the IRB chair or a designee of the chair (vice chairs, the IRB director, assistant director or a senior Analyst). Before being forwarded to the reviewer, the application is pre-reviewed by an Analyst to ensure that it is ready to be reviewed (e.g. scientific review has been conducted, the protocol and consent form are attached, as applicable).

2. I have submitted an application in eIRB. How do I know where it is in the review process?

   The current study state (i.e. where the submission is in the review process) is always indicated in the red bar in the top left hand corner in your eIRB workspace. Examples of common states your submission may be in are:

   • “In Department/Division Review” (the study awaits review by your Department Chair or Division Chief and has therefore not yet been submitted to the IRB);
   • “In Pre-Review” or “In Review” (it is being reviewed by the IRB);
   • “Changes Requested” (it is with you to respond to stipulations); or
   • “Ancillary Approval Pending” (all IRB issues have been addressed but approval from one or more ancillary committees, such as Conflict of Interest, Technology Transfer etc., may be outstanding).

   If the approval of ancillary committees is pending, you can find which ones are outstanding and which approvals have already been received by looking at the information at the top of your study workspace (the section where e.g. the study name, PI, study coordinator, and funder are listed) under "Ancillary Review Status".

3. Who should I contact with questions about the stipulations sent to me?

   The first contact for questions about stipulations sent to you is the Analyst assigned to the study (either by email, phone, office hours or one-on-one meeting as necessary). S/he will then either be able to provide you with the information needed or, if necessary, will contact the reviewer to set up a teleconference or meeting between the PI and the reviewer. In general, questions about the eIRB application and consent form should be directed at the Analyst for the study first. Questions regarding the protocol, reasons for deferral, risk/benefit or waiver determinations should be directed to the reviewer.

4. Are the same Analyst and reviewer looking at all amendments to my study?

   While it is the IRB’s goal to maintain consistency and keep the same Analyst/reviewer pair on a study throughout its duration, this has to be balanced by the necessity of a timely flow of submissions through the office. Depending on the nature of the amendment (staff change, change to recruitment materials versus substantial changes to the study design) and overall workload (full board meetings, high submission volume, vacation schedules), amendments will also be assigned to Analysts/reviewers who have not reviewed the study before.

5. My submission is time sensitive. How do I let the IRB know?

   If a submission is time sensitive, (e.g. due to a just-in-time grant funding), please indicate this at the time of submission (as a comment in the workspace). Upon receipt of a JIT notice, please promptly contact the IRB. This allows the IRB to triage accordingly. As the IRB will have to prioritizie such submissions over those of other investigators, please attach the correspondence (from e.g. the funding agency) indicating the deadline for approval with the IRB submission.

1. I'm an investigator for a multi-center study; do I need to write a CHOP-specific protocol?

   The IRB doesn't want and will not accept a CHOP-specific protocol for multi-center studies (unless you are the PI and this will be the protocol used at all sites). The IRB will accept one and only one protocol to serve as the official protocol for multi-center research. The IRB is obligated to ensure that the research uses sound scientific design. When there is more than one protocol the IRB cannot be certain if all centers will include all of the required procedures or carry them out the same way. If there is a need to describe study activities at CHOP than aren't well-described in either the protocol or the in the eIRB application, a protocol addendum may be created. Provided that the protocol is well-written, this should rarely be necessary.

2. What is the difference between the number of subjects enrolled and the number evaluable?

   The Enrolled total is the number of subjects who consent to participate in the study. For a retrospective study, it would be the number of charts reviewed or specimens received. The Evaluable number is the total of the subjects that reach the required endpoint for the study.

   Example: 100 subjects might enroll, 10 fail screening, and 20 drop out before the final study visit that is required for assessing the primary efficacy endpoint. The enrolled number is 100, the evaluable number is 80 and 90 subjects will be included in the safety analysis.

   Example: 24 subjects are enrolled in a PK study but only 18 provide enough blood samples for their data to used in estimating PK parameters. The evaluable number is 18 and the enrolled is 24. All 24 subjects will be part of the safety analysis.

3. I've enrolled 25 subjects but only 5 have completed the study; how many do I list on the continuing review form as evaluable?

   During a study with multiple visits, the investigator will not know how many of the enrolled subjects will ultimately be evaluable. The evaluable total at the time of continuing review should be based on those who have completed the study or reached the study visit where the primary endpoint assessment is made.

4. I know how many evaluable subjects are needed from the power analysis; how do I estimate the enrolled number?

   The investigator should estimate the number of subjects who will fail screening, drop-out or be unable to complete required study procedures. This number when added to the required evaluable number will give an estimate of the number who will need to be enrolled. If fewer subjects drop-out then anticipated, the study might wind up with more evaluable subjects then anticipated. However, under-estimation of the number of subjects who will need to enroll in order to achieve the required evaluable total is often the bigger problem. Under-estimation can result in protocol deviations and burdens the investigator and IRB with protocol amendments to increase the approved enrollment number.

5. How many subjects should I estimate for the CHOP target for multicenter studies?

   The total evaluable number for all sites is determined by the study protocol. The IRB prefers that the investigator use the highest total that could conceivably be enrolled at CHOP. This avoids the need for protocol amendments just to increase the permissible enrolled number.

1. Who makes the determination that the research is exempt?

   At CHOP, the IRB's SOPs place the responsibility on the IRB for making the determination. At other institutions, others may be responsible or share the responsibility with the IRB.

2. Is a protocol needed to submit for a determination of exemption?

   No. The CHOP IRB does not require a full protocol. A description of the study should be entered into eIRB Question 3.01 (1.0). The question reads "Provide a summary of the proposed study including: 1) the age range of subjects; 2) projected enrollment at CHOP and total enrollment study-wide; and 3) description of study procedures. If the study will enroll children, provide the justification for involving children in this research. The information provided should include enough details so that the IRB can determine that the research qualifies as exempt. For studies which require a limited IRB review, additional information regarding the privacy of subjects and confidentiality of the data must be included. The eIRB application will ask the investigator to provide information regarding how the data is stored, how confidentiality of the data will be ensured, etc.

3. Does Category 2 apply to research involving children?

   Surveys and observations of behavior require IRB approval, usually through expedited review. The lone exceptions are observations of public behavior or educational tests where the investigator does not participate in the activities being observed, for example, watching children play on a playground.

   When research is not federally funded, the CHOP IRB's SOPs permit an expansion of Category 2 (1) to include adolescents for whom the IRB would otherwise waive the requirement for parental permission, and (2) for research that involves interviews or questionnaires with adults even when the subject of the research is a child.

4. When would a record review study not qualify for exemption under category (4)(iii)?

   Exempt category 4(iii) includes the secondary use of data (not including specimens) if all of the abstracted data is regulated by HIPAA (meaning that subjects’ personal health information is being used or disclosed). The data can be recorded in an individually identifiable manner (e.g. a master list can be maintained, etc.), and both prospective and retrospective data can be used. For this exempt category to apply, HIPAA must apply to ALL individuals whose individually identifiable or coded data is recorded.

   If, for example, an investigator reviews medical records to obtain individually identifiable patient data on complications of tracheostomy for research purposes, HIPAA would apply to the use of patient data (personal health information about the patient is being collected). If the investigator also records which clinician performed the procedure to determine how years of experience impact complication rates, HIPAA would NOT apply to the use of clinician data (no personal health information is being collected about the clinician). The study would therefore NOT qualify under category 4(iii).

   In order for the study to qualify for exemption, the data about the clinicians would need to be recorded without identifiers and without a way to re-identify these individuals (i.e. no master list). The study would then qualify for exemption under category 4(ii) for the clinician data and 4(iii) for the patient data.

   Please note: Category 4(iii) only applies to the use of data (when HIPAA applies) and not biospecimens.

5. Do I need to obtain HIPAA authorization for exempt research?

   It depends. If the exempt research involves the use or disclosure of PHI, HIPAA applies. Investigators would either have to obtain HIPAA authorization or justify why the criteria for a waiver or alteration of HIPAA are met.

6. When do I need to submit an amendment for exempt research?

   In general, amendments are only required for exempt studies if the changes made to the research could affect the determination of exemption. Please note that staff changes are never required for exempt studies. Examples of the need for such amendments include:

   • For studies determined to be exempt under category 7, additional changes to the research must be reported to the IRB through an amendment. An amendment should be submitted whenever changes include moving information or specimens from the original location where they are maintained, storing information or specimens for longer than they otherwise would have been, granting other investigators (e.g. external to CHOP) access to the information or specimens, and any other change that introduces or alters risks to the privacy or security of the information or the specimens. As noted above, staff changes are not required for exempt studies.
   • An investigator conducting a chart review now wants to include mental health records (as defined by CHOP policy (IM-2-04)). Written consent will now have to be obtained. As the study now requires consent, it no longer meets the exemption criteria under category 4 (iii).
   • A study includes surveys with adults and was determined to be exempt under category 2(i). If the investigator now wishes to survey children, the study may no longer meet the criteria for exemption.
   • An investigator obtains new NIH funding. If the study was previously determined to be exempt under the expanded exempt criteria (which only apply to non-federally funded, non-FDA regulated studies; see IRB SOP 302;), in light of the newly obtained federal funding, the expanded exempt categories may no longer apply.

    

1. What happens to research that is minimal risk but isn't on the list?

   It depends. If the research is federally funded or subject to FDA oversight, then the IRB must review the research at a convened meeting. At the convened meeting, if the IRB can determine that the research is minimal risk, then it can assign it to Category 9. Category 9 means that the IRB can review all subsequent amendments and continuing IRB reviews using expedited procedures. The most common procedures that fit under this category are blood draws that are greater than 2 times per week, exposure to low levels of ionizing radiation and skin biopsy.

1. When does a submission need to be received in order to placed on the agenda?

   To be ensured that a study will be reviewed at a convened meeting, it must be received by the IRB by Tuesday in the week prior to the scheduled meeting. It is often not possible add items to the agenda that are received after this deadline.

2. Do all studies that require full board review have to go back to the full board for subsequent reviews?

   No. Some studies are determined by the full board to be minimal risk. These are reviewed using expedited procedures for all future reviews. Many amendments to full board studies involve minor changes that do not affect risk to subjects and these may also be reviewed using expedited procedures. Finally, studies whose only remaining procedures involve follow-up or data analysis usually do not require full board review.

3. What about new studies or amendments that are urgent and can't wait for the next full board meeting?

   The CHOP IRB also includes a rapid action IRB, officially titled the CHOP Executive IRB, that can be convened with one or two days notice to review items that are emergencies or urgent matters. In the event that there is insufficient time for this IRB to meet and if the emergency involves an FDA-regulated investigational test article, the investigator may exercise the emergency exemption from prior IRB review. They should call the IRB to confirm whether or not the IRB is able to review the submission prior to the proposed use.

1. What is the difference between a waiver of documentation of consent and a waiver of consent?

   When the IRB grants a waiver of consent, consent is not necessary for enrollment.

   When the IRB grants a waiver of documentation of consent, the investigator needs to obtain the subject’s consent but not the subject’s signature to document it. In this case, the investigator can document having obtained consent (e.g. on the verbal consent form or in the study chart).

2. Can I record any individually identifiable private information and obtain a waiver of documentation of consent under 46.117(c)(1)(i)?

   In order to waive documentation under (c)(1)(i), all of the data collected must be anonymous which means recorded without any identifying information.

3. If the study is FDA-regulated, can I obtain a waiver of documentation under 46.117(c)(1)(i)?

   The FDA regulations mandate that all subjects be identifiable in order to permit an audit of the source documents so there is no FDA equivalent to 46.117(c)(1)(i).

4. Which research procedures can take place and still waive documentation of consent?

   To waive the requirement for documentation under 46.117(c)(1)(ii) or 56.109(c)(1), the procedures in the research must be limited to those that don't require written consent as part of clinical care. Examples include: Blood draw, Questionnaires, Chest X-ray, and DXA scan.

5. Why does the IRB require that I have a consent form approved if I have obtained a waiver of documentation of consent?

   The IRB must ensure that the subject is provided with the necessary information to make an informed decision about study participation. The waiver of documentation is merely related to the requirement for a subject to sign, and thus document, their consent.

6. When do I need to give the subject an information sheet?

   When the IRB waives documentation of consent under (c)(1) or under 50.109(c) of the FDA regulations, it can require the investigator to provide the subject an Information Sheet when the IRB decides that subjects should have some information to refer back to after completion of the study. The contents of the Information Sheet do not need to match those of a consent form but should contain at a minimum:

   • The title of the research
   • Contact information for the investigator
   • An explanation of the purpose of the research
   • A description of the procedures

7. What if HIPAA applies to the research, can I still obtain a waiver of documentation of consent?

   HIPAA at 45 CFR 164.512 permits oral authorization instead of written authorization provided that the study meets the criteria for alteration or waiver of HIPAA. If the research involves individually identifiable health information, then the investigator must also do one of the following:

   • Request an alteration (sometimes referred to as a partial waiver) of Written Authorization, or
   • Obtain Written Authorization for use of PHI using a stand-alone HIPAA Authorization

1. Do the Regulations require the same elements for assent as they do for consent?

   No, assent is not consent. At a minimum, the child should understand the purpose of the research (in age-appropriate terms), an explanation of the procedures, that their participation is voluntary and that they have the right to withdraw (change their mind) at any time. Assent must be affirmative. Failure to disagree is not evidence of assent. Children should not be asked to make risk-benefit assessments, nor should they have to deal with financial aspects (additional costs).

2. Should children be told how much money they will be paid?

   It is respectful to be honest with all participants, especially children. If they are going to be compensated, they should be told how much and the basis for payment. Children younger than 9 can not understand payment based on effort and should receive a flat payment (if any). Children 9 and up can understand the concept of being paid more for more work/effort etc.

3. How must assent be documented (does the child need to sign the assent form)?

   It is up to the IRB to decide whether or not assent must be documented and if it must be documented, the way in which it will be documented.

   There is quite a bit of variability between IRBs ranging from no documentation - to documentation in the medical record - to documentation on the consent form - to documentation on an assent form. The CHOP IRB prefers that investigators document assent on the consent form using a separate assent documentation page that follows the consent signature/parent permission page. The CHOP IRB usually (but not always) makes the child's signature on the form optional. The Assent documentation page (available on the Consent Template page) includes a section for the investigator to indicate that the child was incapable of providing assent.

4. When does the IRB require children to sign the assent form or assent section of the consent form?

   It is up to the IRB to determine whether or not the child must sign the form. The CHOP IRB takes into account the nature of the research, ages of the participants and other factors that might make signature more or less compelling.

5. When can the IRB waive the requirement for assent?

   The IRB may waive assent for children in cases where the IRB determines that the child or children are incapable of providing assent. For example, an oncology study may be too complex for children younger than 12 or 14 to understand but a study limited to collecting a blood sample might be understandable to a 6 or 7 year old.

   The IRB can also waive the requirement for assent under the following circumstances:

   1. the intervention offers a prospect for direct benefit ((e.g., a Phase III clinical trial) approved under 45 CFR 46.405/21 CFR 50.52));
   2. the benefit related to the intervention is important for the child's health (e.g., a novel chemotherapy drug or drug to treat a serious illness); and
   3. the intervention is only available in the context of the research (new drug or treatment regimen). See the Waiver of Assent accordion on the Assent of Children page for more information.

6. What if my study enrolls children ages 2 - 17 years; do I need assent of everyone?

   Only children capable of providing assent should be both involved in the discussion and asked to provide assent. The IRB expects that the investigator will submit a proposal describing which age groups will be able to provide assent and which will not. This should be based on the type and complexity of the research and the population being enrolled. Children too young to assent should still have the research explained to them in terms appropriate to their level of understanding and maturity.

1. Do I need to submit the Short Form Consent documents?

   No. The IRB no longer requires the investigator to upload the short form consent documents that are already available on the IRB's website. These documents are locked and are already certified translations. The investigator only needs to submit a Study Summary Document.

2. When may the short form consent process be used instead of a translated consent form?

   The short form written consent is intended when few subjects with limited English proficiency (if any) are expected to enroll.

   The short form consent process is ideal for situations where a subject whose preferred language is not English presents unexpectedly and a translated consent form is not available. If many subjects with limited English proficiency are expected to enroll, then a translated consent form should be used rather than the using a short form consent document.

3. Who needs to sign the short form consent document and the summary document?

   These forms are signed by the individuals who understand the information on the individual form. The short form (in the subject’s preferred language) will be signed by the subject and the interpreter/witness. The study summary document (in English) will be signed by the study team member and the interpreter/witness. The Summary Document signatures attest that the information in the document was presented to the subject and that their questions were answered. The signatures on the short form document that the subject understood the information presented.

4. Is the witness certifying the medical accuracy of the information provided by the investigator or the Study Summary Document?

   No, the witness is not certifying the accuracy of the medical information. The witness is attesting that the information has been presented in a language understandable to the subject, and that the subject understood the information.

1. How does written authorization differ from informed consent?

   Informed consent is specified by required elements that ensure that the subject understands the nature of the research and its risks and potential benefits and agrees to participate in research. A subject's written Authorization is for the use and disclosure of protected health information in the course of research that are not otherwise permitted under the Privacy Rule. An authorization specifies a set of core elements, including a description of the protected health information to be used and disclosed, the person authorized to make the use or disclosure, the person to whom the covered entity may make the disclosure, an expiration date, and, in some cases, the purpose for which the information may be used or disclosed.

   There are circumstances where HIPAA authorization, but not consent, may be required. This may be the case for screening procedures. For additional information concerning screening procedures, see Recruitment vs Screening.

2. If consent is not required for screening procedures but HIPAA authorization is, do I need to submit a HIPAA authorization form?

   The investigators should submit a stand-alone HIPAA authorization form to the IRB. While the IRB does not approve stand-alone HIPAA authorization forms, it does check them for accuracy and to ensure that they contain the required elements. The IRB's responsibilities related to HIPAA are described in more detail in the IRB's Role in HIPAA.

3. Can I review my own office records to plan for a new study without IRB approval?

   You cannot use, access, or record PHI on human subjects without doing one of the following three things:

   1. a Written Authorization; or
   2. IRB Waiver of Written Authorization; or
   3. submitting a certification to the IRB for Work preparatory to Research.

   The IRB will acknowledge the certification after it is submitted but does not approve the submission.

   If the review of records does not involve use of PHI then it can proceed without IRB approval or submission of a Work Preparatory to Research certification. For example, if a database administrator runs a report to count up the number of potential subjects with a specific medical condition between the ages of 1 and 5 years, that search would not involve use of PHI by the investigator. The report would simply provide a summary of the number of potential subjects. If PHI is viewed, recorded or used in any way, the investigator must submit a Work Preparatory to Research certification before doing the work.

4. Do I need to obtain consent and HIPAA authorization to do study recruitment?

   It depends.

   If recruitment is limited to review of existing medical records as part of an IRB-approved protocol, then HIPAA authorization and consent are not required (a waiver of HIPAA authorization and a waiver of consent [when applicable] can be granted by the IRB). The subjects will have an opportunity, at the time they are approached to participate, to provide informed consent and HIPAA authorization. The investigator is obligated to protect the PHI of prospective subjects just as they are obligated to protect the PHI of every patient cared for at CHOP.

   If the investigator intends to screen potential subjects for eligibility by asking them questions, these questions are considered part of the research. Consent and HIPAA authorization may have to be obtained for screening procedures. For additional information, see Recruitment vs Screening or IRB's Role in HIPAA.

5. I am submitting a Work Preparatory to Research attestation so that I can review my records to identify how many potential subjects are in my clinic. What information, if anything can I retain when I'm done?

   The data collected must be limited to the minimum necessary to meet the objectives of the Work Preparatory to Research (e.g., establish feasibility, plan the study, identify potentially eligible subjects, etc.). Study data may not be collected, but the investigator may retain names and contact information to be used, after the study is approved by the IRB, for recruitment purposes.

6. There are decedents whose records will be included amongst those in the study; do we need to file the Decedents HIPAA Attestation?

   The HIPAA attestation for the use of decadents PHI is only for research that will be exclusively limited to decedents. The attestation provides a means for the investigator to attest to their intent to adhere to the requirements of HIPAA related to the use of decedents PHI. The IRB receives the investigators attestation and checks it for appropriateness; it does not issue an approval. The investigator will receive the IRB's acknowledgment of receipt. If decedents PHI is used as part of a study that also enrolls human subjects, the investigator can request a waiver of HIPAA authorization for the use of decedents PHI.

7. I am doing research in Botswana, does HIPAA apply to research performed at international sites?

   Since the research is taking place in an international setting, HIPAA authorization is not required from study participants. However, HIPAA protections apply to the use and collection of protected health information (PHI) by agents of the University of Pennsylvania and the Children's Hospital of Philadelphia as part of this research. This means that as an investigator, you are obligated to treat the data to the same protections as if it were collected from subjects at CHOP.

1. Can a pregnant woman take part in a survey study involving questionnaires if the IRB hasn’t specifically approved participation of pregnant women?

   No. If the research is federally funded, pregnant women may take part in research only when the IRB has approved the research under Subpart B.

   However, if the research is not federally funded and if the risks are not greater than minimal, then under IRB SOP 502, approval under Subpart B is not required. The most frequent procedures where this applies include questionnaires, surveys and reviews of medical records of women who are pregnant.

2. What if it isn't obvious that the woman is pregnant, do we still need to ask?

   Most studies that involve interventions or procedures will be required to include questions about possible pregnancy and/or pregnancy tests.

   However, if the study involves a simple questionnaire and it is not obvious that the prospective participant is pregnant, the IRB may, under these circumstances not require the investigator to add this question when it is not appropriate to the research in question.

3. What do I need to do if a subject becomes pregnant during a study?

   There are issues that may require review. The IRB should be contacted as soon as possible to discuss these potential issues.

   1. Unless pregnancy is included as an anticipated event in the study protocol (e.g., a study about fertility); the pregnancy must be reported as an unanticipated problem to the IRB;
   2. If the IRB has not approved the participation of pregnant women, the study intervention should be stopped immediately unless continuing the study intervention would be in the woman's or the fetus's best interest;
   3. If there are no study interventions (an observational study), the investigator may amend the study and request that the study be approved under Subpart B;
   4. If there are any interventions or procedures which could negatively impact fetal development, the subject should be followed until delivery and possibly beyond to ensure that there are no serious adverse events that have been sustained, such as birth defects. For some interventional studies, this may also apply to the partner of a male subject. This plan must be included in the protocol and application.

1. Do I have to report all internal (occurred at CHOP) SAE's to the IRB?

   Only SAEs that are unexpected and related. For example, hospitalization of children with Sickle Cell Disease for painful crisis is expected as would be death after cardiac surgery. These events do not have to be reported promptly because they do not represent unanticipated problems involving risks to subjects. Well-written protocols anticipate and delineate the likely serious events and list the ones that will not be reported as SAEs.

2. Do I have to report every external SAE report that the sponsor sends me?

   The IRB does not want to see most of these reports; only events that are serious, unexpected and related to the research activity need to be reported. A single event, by itself, is usually insufficient to make a judgment about change in possible risks to subjects. If in the investigator's judgment, the event was expected as a result of the subject's age, existing condition, other treatment administered or another factor, there is no need to report the event. The report must be maintained in the study file.

3. What about the external SAE follow-up reports?

   The IRB does not want to receive follow-up reports that add no additional information about possible risks to subjects.

4. Why do sponsors send all of these reports if they aren't of any benefit?

   Sponsors believe that they are complying with the regulatory requirements. They are unwilling to classify SAEs as unrelated to the study drug or other intervention even when there are other plausible and much more likely explanations. From the IRB's perspective, a report is only useful if the sponsor believes that the event is of sufficient significance to modify the protocol, the consent form or the Investigators Brochure. Less than 1% of the SAE reports received by the IRB result in a change to the research. As a result, the IRB has issued a Memo clarifying its requirements for external SAE reports.

5. My sponsor requires that I send all of the SAE reports to the IRB; what do I do?

   If the sponsor requires that they be sent, the IRB has issued a Memo outlining Procedures for Reporting External SAE Reports that provides a more detailed explanation. If these reports are sent to the IRB, an acknowledgement will be issued without review by the SAE subcommittee. This is not a productive use of the investigator's or the IRB's time. Hopefully, the FDA Guidance on Adverse Event Reporting to IRBs will diminish the frequency of these reports.

1. When should a protocol deviation be reported to the IRB?

   Major protocol deviations should be reported promptly since the IRB considers these to be Unanticipated Problems. Minor protocol deviations should be summarized in narrative form and included as part of the study report at the time of continuing review, if a continuing review is required.

2. What should be included in the Protocol Deviation Report?

   The report should be made in eIRB in the Reportable Events workspace and should include summaries of what happened, an analysis of why it happened and of an action plan describing the steps that have been/will be taken to prevent a recurrence.

3. Can an investigator ever deviate from the protocol-defined research plan?

   An investigator may deviate from the protocol whenever necessary to protect the subject's health, rights or welfare. For example, a study medication should be stopped if a subject develops an medically significant adverse reaction during administration. The physician should provide whatever medical treatment is needed necessary to the subject, without regard to whether the medications are permitted in the protocol. There is an obligation to deviate from the protocol in emergent or urgent situations.

4. Can the investigator deviate from the protocol for non-emergent, non-urgent situations?

   In non-urgent/emergent situations, the investigator should obtain IRB-approval for the planned deviation. Approval from the study sponsor or medical monitor may also be necessary but by itself is not sufficient. The investigator should submit a request for a "planned deviation" which is really a request for a "single subject" or "one-time" protocol amendment. If the investigator anticipates that there will be future requests for the same deviation, then the protocol should be amended.

1. For how long must I retain study documents, and when can I de-identify the records?

   All studies must comply with CHOP Data Retention Policy A-3-9 (available for download).

   For FDA-related studies, it is important to retain the key/link until the sponsor notifies you that it is no longer necessary (which will generally occur 2 years after the last marketing approval or, if no application is filed or approved, 2 years after the FDA is notified of discontinued application). This is vital since the FDA could choose to audit the study.

   For minimal risk studies, all study data (including identifiers) should be maintained for 6 years following study completion (or longer if required by the study sponsor).

2. How long do I need to keep copies of signed consent forms?

   The documents must be retained for must be retained for at least 6 years following study completion, or longer if required per CHOP Data Retention Policy A-3-9.

3. How long do I need to keep documentation of HIPAA Authorization?

   If a stand-alone HIPAA Authorization or a verbal HIPAA authorization is used, the documentation must be retained for at least 6 years following study completion, or longer if required per CHOP Data Retention Policy A-3-9.

1. Can CHOP certify a data sharing plan that includes data/specimens obtained from an outside investigator or a repository?

   It depends. The CHOP IRB must be able to verify that the submission of data to a NIH-designated repository and subsequent sharing for research purposes is consistent with the original informed consent document. When the data/specimens were obtained from studies not originally performed at CHOP, the IRB would need evidence that the consent forms included appropriate language permitting sharing for future research. In addition, the originating site would need to provide evidence that it had tracked each subject's choices regarding sharing for future use.

1. Does review of medical records to identify eligible individuals require consent?

   Review of CHOP medical records or clinic logs to try to identify potential participants is generally permitted as part of an IRB protocol without prospective consent or HIPAA authorization. The IRB will require that the investigator have a either a reasonable justification for access to the medical records (e.g., the child is their patient) or have the permission of the physician of record.

2. Does the screening consent form need to discuss the entire study or just the screening visit?

   The screening consent form (if one is required - see Recruitment vs Screening) should focus entirely on the procedures for the screening visit and not on the main study. The purpose of screening is to determine if the prospective subject, who has an interest in participating in the main study, is eligible or not. The information about the main study will be in the consent form for the main study.

3. Can I retain lists of potential subjects identified as part of Work Preparatory to Research?

   HIPAA permits investigators to retain lists of prospective subjects obtained during Work Preparatory to Research provided that the data does not leave the covered entity, the data sought is the minimum necessary for the proposed purpose and the data is needed for the proposed purpose. No contacts with study subjects identified as part of Work Preparatory to Research may take place prior to IRB approval of the research.

4. Do I need to get consent before telling someone about the study?

   Consent is not needed to present information about a study. Providing information (e.g. listing the inclusion and exclusion criteria so individuals can determine if they might be eligible) and answering questions about the main study is considered recruitment.

5. I'm contacting prospective subjects by telephone, do I need to get consent before asking any questions?

   The IRB may approve certain screening procedures without requiring prior informed consent of the prospective subject. If the requested information is obtained through only oral or written communication with the prospective subject and is limited to the minimum necessary for screening/determining eligibility for the main study, consent does not need to be obtained (for additional information, see Recruitment vs Screening).

   Note: Even if consent does not need to be obtained for screening procedures, HIPAA Authorization may still need to be obtained if HIPAA applies (the IRB's responsibilities related to HIPAA are described in more detail in the IRB's Role in HIPAA).

6. When do I need to get HIPAA Authorization?

   If you are using or accessing PHI as part of the screening procedures, either HIPAA Authorization must be obtained from the participant or the IRB must issue a waiver of HIPAA authorization.

7. Does the consent and HIPAA Authorization have to be in writing?

   If the research qualifies for a waiver of documentation of consent and partial waiver of HIPAA (verbal authorization), then these do not need to be in writing.

1. I want to use a marketed drug off label in clinic. Do I need to submit to the IRB or the FDA?

   Good medical practice and the best interests of the patient require that physicians use legally available drugs, biologics and devices according to their best knowledge and judgement. If physicians use a product for an indication not in the approved labeling, they have the responsibility to be well informed about the product, to base its use on firm scientific rationale and on sound medical evidence, and to maintain records of the product's use and effects. Use of a marketed product in this manner when the intent is the "practice of medicine" does not require the submission of an Investigational New Drug Application (IND), Investigational Device Exemption (IDE) or review by an Institutional Review Board (IRB). However, other institutional oversight requirements (e.g. Therapeutic Standards Committee approval) may apply. See FDA Guidance on "Off-Label" and Investigational Use Of Marketed Drugs, Biologics, and Medical Devices.

2. I want to conduct a clinical investigation using a marketed drug off label. Do I need to submit an IND application to the FDA?

   Maybe.
   Whether an IND is needed to conduct a clinical investigation of a marketed drug primarily depends on the intent of the investigation and the degree of risk associated with the use of the drug in the investigation. A clinical investigation of a marketed drug is exempt from the IND requirements if all of the criteria for an exemption in § 312.2(b) are met:

   • The drug product is lawfully marketed in the United States.
   • The investigation is not intended to be reported to FDA as a well-controlled study in support of a new indication and there is no intent to use it to support any other significant change in the labeling of the drug.
   • In the case of a prescription drug, the investigation is not intended to support a significant change in the advertising for the drug.
   • The investigation does not involve a route of administration, dose, patient population, or other factor that significantly increases the risk (or decreases the acceptability of the risk) associated with the use of the drug product (21 CFR 312.2(b)(1)(iii)).
   • The investigation is conducted in compliance with the requirements for review by an IRB (21 CFR part 56) and with the requirements for informed consent (21 CFR part 50).
   • The investigation is conducted in compliance with the requirements of § 312.7 (i.e., the investigation is not intended to promote or commercialize the drug product).

   See FDA Guidance on Determining Whether Human Research Studies Can Be Conducted Without an IND. and IND Exemptions for Studies of Lawfully Marketed Drug or Biological Products for the Treatment of Cancer

3. What are the IRB’s responsibilities in the selection of clinical investigators and research sites, and determining if an investigational new drug application (IND) or investigational device exemption (IDE) is required?

   The regulations at 21 CFR 56.107(a) require that an IRB "...be able to ascertain the acceptability of the proposed research in terms of institutional commitments and regulations, applicable law, and standards of professional conduct and practice..." In addition, the regulations at 21 CFR 56.111 require that an IRB determine that the proposed research satisfies the criteria for approval, including that "...risks to subjects are minimized...[and] reasonable in relation to anticipated benefits, if any, to subjects...".

   Qualification of investigators

   The IRB needs information about the qualifications of the investigator(s) to conduct and supervise the proposed research. The IRB may also need to assess the investigator’s training and experience specifically related to the proposed study, particularly if the proposed research involves higher risks, vulnerable subjects, or novel technologies. In its assessment, the IRB may also rely on the clinical investigator’s medical department/division for information about the clinical investigator’s qualifications, or require a statement regarding the investigator’s qualifications from the chair of the investigator’s department/division.

   Adequacy of the research site

   The IRB needs to assess the site where the proposed research will take place to ensure it can adequately execute the protocol requirements. Depending upon the nature and risks of the proposed research and the IRB's prior knowledge of, or relationship to, the institution or other site at which the research will take place, this may be relatively simple and straightforward or it may entail a more involved assessment.

   Verifying the determination of whether an IND or IDE is required for an FDA-regulated investigation

   It is the sponsor’s responsibility to make an initial determination on whether a clinical investigation meets the criteria for an IND exemption. At CHOP, the IND-IDE Support Program can help a CHOP sponsor determine whether a specific study meets these criteria. The sponsor needs to include their determination (and the basis for that determination, including any supporting documentation) to the IRB with their protocol submission in eIRB. The IRB will, based on the scientific literature and generally known clinical experience (as presented by the investigator), either agree or disagree that there is no significant increase in the risk (or decrease in the acceptability of the risk) associated with the use of the drug product.
   If the IRB agrees with the sponsor’s determination, no IND submission to the FDA is necessary.
   If the IRB disagrees or has concerns that cannot be addressed by the sponsor, the sponsor will need to submit to the FDA. The FDA will then either issue an exempt determination or decide that an IND is required. The FDA’s decision is final.
   See FDA Guidance on IRB Responsibilities for Reviewing the Qualifications of Investigators, Adequacy of Research Sites, and the Determination of Whether an IND/IDE is Needed.

4. I want to study a dietary supplement in a clinical investigation. Do I need to submit an IND application to the FDA?

   It depends.
   Under the Dietary Supplement Health and Education Act of 1994 (DSHEA), a dietary supplement is defined, in part, as a product taken by mouth that is intended to supplement the diet and that contains one or more dietary ingredients.
   Under DSHEA, a dietary supplement is not considered a drug if the intended use for which it is marketed is only to affect the structure or any function of the body (i.e., not intended to be used for a therapeutic purpose).
   Similarly, whether an IND is needed for a clinical investigation evaluating a dietary supplement is determined by the intent of the clinical investigation. If the clinical investigation is intended only to evaluate the dietary supplement’s effect on the structure or function of the body, an IND is not required.
   However, if the clinical investigation is intended to evaluate the dietary supplement’s ability to diagnose, cure, mitigate, treat, or prevent a disease, an IND is required under 21 CFR 312.
   See FDA Guidance on Determining Whether Human Research Studies Can Be Conducted Without an IND.

5. I am the sponsor. Can I charge for an investigational drug?

   Maybe.
   A sponsor can only recover the direct costs of making a drug available to subjects in a clinical trial — that is, those costs that are specifically and exclusively attributable to providing the drug to clinical trial subjects (21 CFR 312.8(d)(1)). These include costs to manufacture the drug in the quantity needed to conduct the clinical trial for which charging has been authorized or costs to acquire the drug from another source, including costs to ship and handle (e.g., store) the drug.
   Under 21 CFR 312.8(d)(3), to support its calculation of recoverable costs, a sponsor must provide documentation to the FDA describing recovery of direct costs and, if applicable, describing certain additional costs that may be recovered for intermediate-size patient population expanded access uses or treatment INDs or protocols. This documentation must be accompanied by a statement that an independent, certified public accountant has reviewed and approved the calculations (21 CFR 312.8(d)(3)).
   Once an authorization to charge has been obtained from the FDA, it needs to be attached to the eIRB application for the respective study. The consent form should reflect that the sponsor(-investigator) intends to charge for the drug.
   See FDA Guidance on Charging for Investigational Drugs Under an IND — Questions and Answers.

6. What is expanded access and how is it different from clinical trials?

   Expanded access refers to the use of an investigational drug when the primary purpose is to diagnose, monitor, or treat a patient’s disease or condition.
   The terms expanded access, access, and treatment use are used interchangeably. The terms compassionate use and preapproval access are also occasionally used in the context of the use of an investigational drug to treat a patient. Although these terms have been used informally in the United States and are used outside the United States, they are not defined or described in FDA regulations.
   The main distinction between expanded access and the use of an investigational drug in the usual studies covered under an IND is that expanded access uses are not primarily intended to obtain information about the safety or effectiveness of a drug. Expanded access to an investigational drug can only be provided under a treatment IND or protocol if the sponsor is actively pursuing, with due diligence, marketing approval of the drug for the expanded access use.
   Under FDA’s current regulations, there are three categories of expanded access:

   • Expanded access for individual patients, including for emergency use (21 CFR 312.310).
   • Expanded access for intermediate-size patient populations (generally smaller than those typical of a treatment IND or treatment protocol — a treatment protocol is submitted as a protocol to an existing IND by the sponsor of the existing IND) (21 CFR 312.315).
   • Expanded access for widespread treatment use through a treatment IND or treatment protocol (designed for use in larger patient populations) (21 CFR 312.320).

   See FDA Guidance on Expanded Access to Investigational Drugs for Treatment Use — Questions and Answers.

7. I want to treat one of my patients with an investigational drug. I need to do this as soon as possible. Do I need to submit to the IRB or FDA?

   Except for emergency expanded access use when there is not sufficient time to secure prospective IRB review, an investigator treating a patient with an investigational drug under expanded access is responsible for obtaining IRB review and approval consistent with 21 CFR part 56 before treatment with the investigational drug may begin.
   Generally, the investigator needs to contact the IRB to find out whether the IRB has sufficient time to review. If there is insufficient time for the IRB to review, FDA authorization is still required (21 CFR 312.310(d)), but it is not necessary to wait for IRB approval to begin treatment. However, the IRB must be notified of the emergency expanded access use within 5 working days of emergency use (21 CFR 56.104(c)).
   For further guidance, go to Single Patient Expanded Access or Emergency Use and contact CHOP’s IND/IDE Support Program.
   Also see the FDA Guidance on Expanded Access to Investigational Drugs for Treatment Use — Questions and Answers.

8. Do I need to obtain consent from a subject who receives an investigational drug through expanded access?

   Yes.
   Expanded access to an investigational drug for treatment use, including emergency use, requires informed consent as described in 21 CFR part 50. Investigators treating a patient(s) with an investigational drug under expanded access are responsible for ensuring that the informed consent requirements of part 50 are met (21 CFR 312.305(c)(4)). One of the purposes of informed consent is to ensure that the patient is informed that he/she will be treated with an investigational product and that there may be uncertainty about the safety and effectiveness of the product.
   See FDA Guidance on Expanded Access to Investigational Drugs for Treatment Use — Questions and Answers.

9. I am using a placebo in a clinical investigation. Does the placebo need an IND?

   Usually not.
   If the placebo consists of inactive ingredients (e.g. excipients considered to be generally recognized as safe (GRAS)), an IND is not required. A clinical investigation involving use of a placebo is exempt from the requirements of this part if the investigation does not otherwise require submission of an IND (21 CFR 312.2(b)(5)).
   See FDA Guidance on Exploratory IND Studies.

1. What types of devices need to be included in the eIRB application?

   (1) Unapproved devices, (2) all investigational devices, meaning all those being studied for their safety or effectiveness regardless of whether they are FDA-approved/cleared or not, and (3) FDA-approved/cleared devices that are not approved for use for clinical use at CHOP.

2. How do I include a device in the eIRB application?

   Check the "Device" box in Section 5.04 (2.0). This will then require completion of Section 8.02. The information about the device - e.g. brochures, manuals, 510(K) clearance approval letters - should all be attached in Section 12.02 (3.0). Risk information should be included in the protocol, consent form and in eIRB Section 11.01 (1.0).

3. The device is not a physical instrument, it's medical software, a diagnostic test/assay, an MRI sequence, or a medical app. What type of storage plan is required?

   There needs to be a plan that explains how the use of the device is only used for this research study and that will limit access to members of the investigative team. For example, there needs to be a plan to limit the use of unapproved MRI sequences so that they are not used for clinical care.

4. Who decides whether a device is non-significant risk or significant risk?

   The sponsor is responsible for making the initial NSR-SR determination. The IRB is responsible for reviewing and concurring with or disagreeing with, the sponsor's assessment. If the sponsor has a letter from the FDA indicating that the device is NSR, the IRB must accept that decision (the FDA's determination is final). Otherwise, if the IRB disagrees with the sponsor's determination that the device is NSR, the sponsor must request that the FDA issue its opinion.

5. If the IRB has determined that the device meets the definition of an NSR device, do I need to get an IDE from the FDA?

   No. If the IRB concurs with the sponsor's NSR determination, then it is effectively issuing an abbreviated IDE to conduct the study. NSR device studies must follow the abbreviated requirements under 21 CFR 812.2(b) and the FDA's regulations for Human Subjects Protections and the IRB operations (21 CFR 50 and 56).

6. My sponsor initially determined my device is NSR but the IRB determined it was SR. What do I need to do?

   The sponsor must obtain one of the following from the FDA: (1) a determination that the device is an NSR device or (2) an IDE (in the event the FDA agrees that the device is an SR device).

7. My sponsor initially determined the device is an SR device. Can I submit the study to the IRB for review if the FDA hasn't issued the IDE yet?

   Yes. However, the IRB will not release its final approval until an IDE has been issued and documentation, including the IDE number, has been provided to the IRB.

1. An external IRB is the IRB of record for my study. Do I need to submit anything in eIRB, and if so, why?

   Yes. Even though the CHOP IRB may not have oversight over the study, CHOP's Human Subjects Protection Program (HRPP) still needs to know and track what human subjects research activities go on at the institution. In addition, the CHOP IRB must confirm that the consent form aligns with CHOP's requirements (e.g. HIPAA and injury compensation language), and CHOP Ancillary Committees may need to review and approve the study (e.g. the Investigational Pharmacy, Contracting, IBC, Conflict of Interest Committee, Medical Device Committee, etc.).

2. Once I have submitted in eIRB and indicated that an external IRB is the reviewing IRB, do I have to wait for an acknowledgement before I can start my research, and if so, why?

   Yes. The CHOP IRB must confirm that the consent form aligns with CHOP's requirements (e.g. HIPAA and injury compensation language), and CHOP Ancillary Committees may need to review and approve the study (e.g. the Investigational Pharmacy, Contracting, IBC, Conflict of Interest Committee, Medical Device Committee, etc.). Once all the institutional requirements are met, the CHOP IRB will send a letter to accept the reliance on the outside IRB. Human subjects research at CHOP for that particular study cannot start until that letter has been issued and reliance documentation has been executed.

3. If CHOP is relying on another IRB for my study, do I have to submit updates in eIRB, and if so, why?

   Yes. CHOP's Human Subjects Protection Program (HRPP) still needs to track what human subjects research activities go on at the institution. In addition, CHOP Ancillary Committees, such as the Investigational Pharmacy, need access to currently approved documents (such as the Investigator's Brochure).

4. How do I submit Cooperative Updates?

   In the main study workspace for the study in eIRB, under the 'Create' header on the left side of the workspace, find the "New Cooperative Update" button. Clicking on it will open a new smartform. After the smartform has been completed by the investigator, using the "Submit Cooperative Update" activity will send the submission to the IRB. The IRB has created a Job Aid (under 'eIRB Help') to facilitate the submission process.

   Note: Multiple, separate Cooperative Updates can be active at once.

5. Once I submit a cooperative update, do I have to wait for an acknowledgement before I can implement e.g. amendment changes?

   No. Once CHOP has accepted the reliance on an outside IRB, amendment changes can be implemented as soon as the reviewing IRB has approved the amendment.

6. I'm writing a grant for a multi-center study and would like CHOP to be the Reviewing IRB. What is the process?

   Contact the IRB Director to discuss the grant requirements and sIRB logistical issues.

7. What is CHIRP?

   CHIRP is the CHOP IRB's tool that allows investigators from external institutions who are relying on the CHOP IRB for IRB review to communicate directly with the CHOP IRB. See Single IRBs and IRB Reliance Agreements for more information.

8. The relying PI for my study has received an email from CHIRP, but the link states 'The invite token is expired'! What do I do?

   This error can be resolved by having the external PI navigate to the CHIRP homepage, and request a password reset. Note: Each time a password reset is requested, a new automated email is issued. The new email will invalidate any prior emails, so the relying investigator should be sure to always use the most recent email.

9. Do relying sites need to update their CHIRP application with investigators or their training(s)?

   Other than the relying PI and Study Coordinator, no. The CHIRP application asks relying sites to "Confirm that all study team members are in compliance with local institutional training requirements for human subjects research. (e.g. CITI training and/or other institution specific training)". Otherwise, any relying personnel-specific changes are the responsibility of the relying institution to manage.

Frequently Asked Questions:

1. Does the IRB continue to review research during the COVID-19 pandemic?

   Yes. The IRB continues to review research, including by the convened board, as usual. All IRB staff and chairs are working remotely for the foreseeable future, per the CHOP bioresponse plan. Convened IRB meetings will be held remotely until further notice. The IRB will prioritize COVID-19 research as well as requests for continued in-person contact for essential clinical research. A system has been put in place to ensure that urgent prospective protocol deviations to ensure subject safety during the COVID-19 pandemic are prioritized and can be reviewed quickly. For non-essential clinical research, the IRB will continue to prioritize studies with funding deadlines (e.g. JIT submissions). Please inform the IRB of such deadlines when submitting the proposal.

2. Can I have investigational medication shipped to a research participant’s home?

   Yes, it may be permissible to ship investigational medication to participants’ homes. See the Shipping Study Drug procedure, or contact ORC for guidance. If your plan to ship investigational drug to subjects is not described in your IRB-approved study, and your plan to ship is only temporary to reduce risks to subjects during the pandemic, you should inform the IRB of this activity at the time of the next continuing review. However, if you plan to make this a permanent solution, you must submit an amendment to the IRB. Please note: drugs may not be shipped to subjects if there are immediate side effects for which subjects need to be monitored.

3. Can I collect data and conduct follow-up procedures with subjects by telephone or video-conference instead of in-person data collection?

   Yes. This minimizes the COVID-19 related risks to subjects. If conducting the visit using a video conferencing application, try to use a HIPAA-compliant application licensed by CHOP. Skype, Bluejeans, WebEx, Microsoft Teams, and Vidyo are all HIPAA-compliant applications offered at CHOP. Vidyo should only be used for clinical encounters. As the hospital now allows in person visits, an amendment should be submitted to include this option in the protocol (unless the approved materials already allow for this). If you plan to bill for a research visit conducted remotely, please review CTFM’s guidance for registering remote study visits.

4. Can research-only home visits be completed at this time?

   Yes. Research-only home visits in an affected population can be completed provided the following criteria are met:

   • The visit can be conducted with adherence to the current non-remote staffing percentages;
   • Masking and hand sanitizing procedures will be followed as indicated on the CHOP Bioresponse page;
   • The Essential Clinical Research Survey will automatically generate a REDCap report in PDF format that will need to be included in the reportable event submission in eIRB;
   • Physical distancing can be maintained during the visit;
   • The family is agreeable to the visit.

5. Do I need IRB approval to perform hospital-required coronavirus screening on research subjects?

   No. The requirement for screening research participants prior to coming to campus is the same as for patients coming in for clinical care. The screening is not a research procedure. Therefore, IRB approval is not needed to perform these screenings. Please follow any CHOP bioresponse plan guidelines pertaining to COVID-19 screening. If investigators want to use the screening data as part of their research, this would require submission to the IRB.

6. Do I need to submit a prospective protocol deviation or amendment for changes in visit schedules or conducting study visits remotely?

   Maybe. CHOP IRB policies require that changes to IRB-approved research may not be initiated without IRB review and approval, except when necessary to eliminate apparent immediate hazards to the subject (45 CFR §46.108(a)(3)(iii)), and 21 CFR §56.108(a)(4)). CHOP also has a responsibility to ensure the safety of its employees. Therefore, while CHOP’s bioresponse plan to COVID-19 is in effect, these interim measures to reduce immediate hazards to research participants and staff are warranted and may involve deviating from IRB-approved study procedures prior to obtaining IRB approval.

   • For studies that provide no direct benefit to the subject (studies approved under 45 CFR 46.404 and 406): Protocols and parts of protocols may be paused without formal notification to the IRB to eliminate apparent immediate hazards to the subject. Conducting follow-up procedures with subjects by telephone or video-conference while in-person data collection is paused also does not require prompt submission to the IRB. However, any deviations will need to be tracked by the investigator (see the FAQ regarding tracking protocol deviations below);
   • For safety-related visits on studies with a prospect for direct benefit or if a research participant requires medical attention, the investigator needs to ensure that the appropriate referrals are made to protect subjects. The visit delay should be reported to the IRB as a prospective protocol deviation (if possible) or promptly after they occur;
   • When submitting a prospective protocol deviation, include the rationale (due to the potential risks of COVID-19) and the plan to ensure subject safety; or
   • If investigators anticipate making the changes to their research plan permanent (e.g. substitute telephone surveys or video-conference for in-person visits), IRB approval of a protocol amendment must be sought.

7. Do I need to track the protocol deviations?

   Yes. If investigators deviate from their approved protocol to eliminate apparent immediate hazards, please keep track of these deviations and report them to the IRB with the next continuing review, if one is required. If a continuing review is not required for your study, please keep track of these deviations in your study records.

8. How do I document the justification for these deviations in my study charts?

   Investigators can use the language from the Research Institute guidance: Due to the potential risks of COVID-19, CHOP has decided that all research visits for studies that provide no direct benefit to the subject should be paused, unless they can be effectively completed remotely.

9. I have a continuing review due soon. Do I still need to submit it and should I include information regarding the pause in research activity in the submission?

   Yes. You still need to submit your continuing review on time. Please keep track of the deviations and pause in study activity and report this to the IRB with the next continuing review. If research activities are paused due to institutional policies during the COVID-19 pandemic, describe this in the narrative. Once the current institutional restrictions on non-essential research are lifted, enrollment and other study activities can then resume. Please do not change the enrollment status to "Enrollment Temporarily Suspended", as an amendment would be required to re-open enrollment (creating unnecessary work for the investigator).

10. I am conducting a study that is currently only approved to obtain written consent? Can I continue enrolling by just getting verbal consent over the phone?

    No. That is not permissible.

11. Other than getting written consent in person, are there alternative methods to obtain written consent?

    The FDA has provided guidance on Alternative Methods of Obtaining Informed Consent(see section E.2). “Methods other than a face-to-face consent interview may be acceptable if those methods allow for an adequate exchange of information and documentation, and a method to ensure that the signer of the consent form is the person who plans to enroll as a subject in the clinical investigation or is the legally authorized representative of the subject. For example, the consent form may be sent to the subject or the subject's legally authorized representative by facsimile or e-mail, and the consent interview may then be conducted by telephone when the subject or subject's legally authorized representative can read the consent form during the discussion. After the consent discussion, the subject or the subject's legally authorized representative can sign and date the consent form and return the document to the clinical investigator by facsimile, scanning the consent form and returning it through a secure e-mail account, or by posting it to a secure internet address." The IRB also applies this to non FDA-regulated research. Investigators may also use the e-consent function in REDCap to obtain a signature on an informed consent form. NOTE: While REDCap can now be used to obtain electronic consent for FDA-regulated studies (it underwent Part 11 validation in early 2021), additional training with the REDCap administrators must be completed first. For guidance see the Part 11 E-Consent @CHOP page.Please note that if the approved research plan does not currently include obtaining consent via REDCap, an amendment (or prospective protocol deviation, if this is a temporary change that will be used during the COVID pandemic only) will need to be submitted for IRB review and approval to use this way of obtaining consent.

12. I need to re-consent a subject who is turning 18 years of age. The subject has limited English proficiency. If interpreters from CHOP’s language services are working from home and I can’t get their signature, how would I use the short form consent process?

    The short form consent process requires that a witness (who is bilingual) sign both forms. In usual circumstances, the interpreters are willing to also serve as the witness and sign as such. If that is not possible, investigators can have another witness, who has to be a person that (a) understands both English and the subject's preferred language and (b) is not part of the study team or otherwise involved with the study, witnesses the consent process.

13. I am conducting a study which relies on an outside IRB as the IRB of record. Do I have to contact the outside IRB if I’m pausing study procedures?

    Yes. You should contact the IRB of record and inquire whether they require a submission.

14. Do I need to let the NIH or other sponsors (e.g. industry) know that some protocol activities or in-person visits for a funded study will be paused?

    Probably. Investigators will need to work with their funders and regulatory sponsors to develop appropriate plans in light of the current circumstances. For industry-sponsored research, notify your sponsor or CRO contact. Contact your Sponsored Project Officer (SPO) for questions regarding NIH and all other non-industry sponsored research.

15. My study visits involve surveys and a research MRI. My IRB-approved protocol includes participant compensation for these visits. I have paused all in-person visits, but am still administering the surveys over the phone. Should I pay subjects for part of the visit or do I have to pay them the whole amount for the visit?

    Investigators should first contact the sponsor of the study, if applicable. If there is no study sponsor, investigators should use their discretion to administer payments. It is acceptable to split a payment. Investigators should ensure that they a) communicate the difference between what was disclosed in the consent form and what is being paid for the ‘partial’ visit to the participant, and b) pay equitably for equal effort (i.e. if partial payment is provided for phone surveys, all subjects in the study should be payed equally for completing the surveys). Please contact Matthew Hodgson, VP Research Compliance & Regulatory Affairs with questions regarding partial payments.

16. Where can I find more information regarding the COVID-19 situation for FDA-regulated and NIH-funded research? Is there additional guidance on telehealth or remote monitoring of participants?

    • OHRP Guidance on COVID-19

    • Considerations for the Conduct of Clinical Trials of Medical Products During Major Disruptions Due to Disasters and Public Health Emergencies

    • FDA Allows Expanded Use of Devices to Monitor Patients’ Vital Signs Remotely

    • OCR Notification of Enforcement Discretion for Telehealth Remote Communications During the COVID-19 Nationwide Public Health Emergency

    • Flexibilities Available to Applicants and Recipients of Federal Financial Assistance Affected by COVID-19

    • NIH FAQs - COVID-19 Flexibilities for Applicants and Recipients

    • CTEP Coronavirus Guidance

Please contact irboffice@chop.edu with any questions.