Guidance on Human Subjects Protections Considerations Related to COVID-19
The research regulations as well as ethical principles of research require an acceptable risk to benefit ratio. Given the risk of exposure to COVID-19, the risk to benefit ratio for each study must be re-assessed.
In line with CHOP's and the Research Institute's bioresponse plan to the COVID-19 outbreak, and given the rapidly evolving situation, the Institutional Review Board (IRB) and Office of Research Compliance (ORC) are providing the following guidance on human subjects research conducted at CHOP:
Research visits for studies that provide no direct benefit to the subject must be paused, with the exception of research procedures that can be effectively completed remotely, i.e. do not require in-person contact with study subjects. In-person contact also includes travel outside the home by study subjects or team members to conduct study activities, and travel required by study team members to process biospecimens. This includes all studies approved under 45 CFR 46.404 and 406;
All non-essential clinical trials must be paused, with the exception of research procedures that can be effectively completed remotely and safety-visits (as outlined below);
Essential clinical trials may proceed. Essential trials are those that enroll or follow patients with life-threatening or serious conditions for which clinical research holds out the prospect of direct benefit to individual subjects. Patients with life-threatening or serious conditions who are undergoing critical safety testing follow-up are included in this definition. Study activities should be completed remotely whenever possible;
In-person contact with either study subjects or biospecimens may continue only in the three following scenarios: (1) Essential clinical trials, (2) Safety visits that cannot be performed remotely on non-essential clinical trials, and (3) IRB approved COVID-19 clinical research (see FAQ below); and
Clinical trial monitor visits may occur if the monitor visit can take place remotely. All other study monitor visits should be postponed.
Frequently Asked Questions:
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.
I am the PI of a study and want to continue in-person contact with study subjects or biospecimens. I think my study falls into one the three scenarios which permit this (essential clinical trials, safety visits that cannot be performed remotely on non-essential clinical trials, or IRB approved COVID-19 clinical research). Do I need special approval to do that?
An additional process is being implemented for the IRB and Research Institute to review these three clinical research scenarios. This additional review is required to ensure that the risks to study subjects and research personnel are minimized during the COVID-19 pandemic and that appropriate resources are available to support this clinical research.
The Research Institute has issued guidance on how to obtain such an approval:
- A reportable event (a prospective protocol deviation) will need to be submitted in eIRB. Please see the IRB’s guidanceon what needs to be included in this submission;
- Investigators will need to complete and submit an Essential Clinical Research Survey in REDCap (a link to this survey will be sent to the Principal Investigator). This survey is designed to provide the IRB and the Research Institute with the information necessary to confirm the designation of essential clinical trial status and determine whether in-person contact with either study subjects or biospecimens is approvable;
- 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;
- The Essential Clinical Research Survey is also required for COVID-19 related research requesting in-person contact (which may include research that may not have the potential for direct benefit to the individual subjects, such as the collection of biospecimens from infected individuals). Such COVID-19-related projects will need to be submitted in eIRB as a new study or included as an amendment to an existing study, as applicable. The Essential Clinical Research Survey REDCap report will also need to be included in these submissions and should be attached in section 12.02 (4.0) of the eIRB application;
- The IRB has established a system to quickly review such submissions requesting to continue in-person contact with study subjects or biospecimens, regardless of whether they require expedited or full board review;
- Final determination of permission to continue in-person contact on a research study will be made jointly by the IRB, the Chief Clinical Research Officer, and the Vice President, Research Compliance & Regulatory Affairs. Please note that determinations may be revisited as the COVID-19 pandemic develops;
- To appeal a determination, please contact the IRB Office at IRBOffice [at] email.chop.edu.
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 Drugprocedure, or contact ORC (orc [at] email.chop.edu) 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.
Can I continue to collect data and conduct follow-up procedures with subjects by telephone or video-conference while in-person data collection is paused?
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, and Vidyo are all HIPAA-compliant applications offered at CHOP. Vidyo should only be used for clinical encounters.
Rather than having subjects come to CHOP, can I conduct home visits to collect data for my study with no direct benefits to subjects?
No. Traveling to a subject’s home still carries the COVID-19 related risks.
Do I need to submit a prospective protocol deviation or amendment for changes in visit schedules or conducting study visits remotely?
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.
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.
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.
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.
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.
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.
I am the PI of an essential clinical trial and 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.
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.
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.
I am conducting a study without the prospect of direct benefit. 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.
My study is monitored by the study sponsor or contract research organization (CRO). What should I tell these monitors about visiting CHOP for site initiation visits, ongoing monitoring visits, or close out visits?
At this time, no onsite monitoring is permitted through May 1, 2020. All onsite monitoring must be scheduled no earlier than May 4, 2020. The research community will be informed if this date needs to be extended. However, monitors may conduct remote monitoring activities where study-related data and materials can be securely reviewed electronically.
Exceptions to this policy, e.g., for COVID-19 related trials, must receive the approval of the Chief Clinical Research Officer.
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?
Please contact IRBoffice [at] email.chop.edu with any questions.
Final Rule Implementation
The updates to the Common Rule known the 2018 Final Rule are now, as of January 21, 2019, in effect. The Final Rule webpage details the many changes embedded in the updated Common Rule. The IRB has updated other sections on its website to reflect the revised regulations.
The Children's Hospital of Philadelphia's (CHOP) IRB is organized and operates in compliance with the Department of Health and Human Services regulations, as described in 45 CFR 46, for federally funded research and FDA regulations, as described in 21 CFR Parts 50 and 56, for FDA regulated research. In addition, the IRB operates in compliance with portions of the HIPAA Privacy Rule that apply to research, as described in 45 CFR Parts 160 and 164.
CHOP holds a Federalwide Assurance (FWA00000459). The CHOP IRB complies with the registration requirements for both OHRP and the FDA.
CHOP’s Human Research Protections Program has received full Accreditation from the Association for the Accreditation of Human Research Protections Programs (AAHRPP).
Committees for the Protection of Human Subjects (IRBs)
The Committees for the Protection of Human Subjects is the official name of the IRB committees that are appointed by and serve under the auspices of the CHOP Executive Committee of the Medical Staff.
The CHOP IRB reports jointly to the president of the medical staff and to Bryan Wolf MD, PhD, who is the institutional official responsible for human research protections. At present, there are two CHOP IRBs. IRB A has 11 members and 11 alternates and meets twice a month; the Executive IRB has 5 members (also members or alternates for IRB A) and meets on an as needed basis. Committee membership is consistent with the requirements of 45 CFR 46.107 and FDA 21 CFR 56.107 and CHOP medical staff bylaws.
The CHOP Research Institute Administrative manual includes Appendix J - Human Subjects Protection Committees - Institutional Review Board Charter, which fully describes the IRBs organization and structure (available only on the CHOP intranet).
Each IRB at CHOP includes voting members, including a chair and vice chairs, in addition to a variable number of alternate members. Members are selected for their willingness to serve, expertise and familiarity with research design and procedures. Members include faculty from a wide variety of clinical disciplines and specialties to ensure adequate expertise. The committees also include legal advisors, nurses, pharmacists and others to provide needed expertise, and community members and non-scientists to represent the viewpoint of the general community and lay audience. Representatives unaffiliated with CHOP also serve on each IRB.
The committee also includes members who can represent the interests of special and vulnerable populations. If necessary, the IRB will seek outside consultation to supplement existing expertise on the committee. By maintaining a diverse membership, CHOP's IRB are able to review the wide variety of research studies conducted at CHOP.
The membership of CHOP's IRBs complies with all federal regulatory requirements.
The IRB works closely with related committees, such as Radiation Safety, Institutional Animal Care and Use Committee (IACUC), the Institutional Biosafety Committee and the Clinical and Translational Research Center (CTSC), to ensure that the requirements of those groups are addressed before final approval of a project is provided.
Structure of CHOP's IRB Committee
The CHOP IRB is composed of 11 individuals each of whom is paired with an alternate member. (Figure) One member of the pair is expected to attend each meeting, which take place on the first and third Wednesdays of the month.
- The meetings are chaired by either the Chair or a Vice-chair of the Committees for the Protection of Human Subjects;
- Scientific members are represented by the yellow rectangles and include physicians, a nurse and pharmacist;
- Non-affiliated (preferably non-scientific) members are represented by the green rectangles;
- A statistician serves as a alternate and may substitute for any scientific member.
- The Director and the Assistant Director, IRB Analyst IIs, and IRB Analyst IIIs are also alternate members. This enables them to be designated by the chair to review and approve minor changes to research and continuing reviews of minimal risk research.
Working with the IRB: Resources for Investigators
The IRB Office provides administrative and technical support as well as regulatory expertise for the committees and serves as the primary contact for investigators. See Contact Us to get in touch with the IRB Office staff.
Streamlining Ethical Review This last reference should be of assistance to investigators whose IRBs do not take advantage of the flexibility permitted within the regulations.