As we make decisions on how to respond to the COVID-19 infections we want to begin by re-stating that our primary concern is the safety of our research participants and the research team members who work for YSM and the Health System. Our secondary goal is to preserve the scientific integrity of the research protocols.
This addendum to the guidelines does not change any underlying polices but updates procedures for the implementation of those policies. It recognizes the existence of several categories of research protocols which require different responses to accomplish the goals alluded to above. For example, non-interventional (non-therapeutic) studies are generally most appropriately placed on “pause”, whereas active phase I therapeutic protocols are generally most appropriately continued but with careful attention to limiting visits to those that correspond to required standard clinical care visits or to conversion of visits to telehealth / video-conferencing equivalents.
Major components of the following guidelines include: (1) further guidance on the role of the PI and of Departments; (2) development of Blanket Yale HRPP procedures for COVID-19 related study changes; (3) information on the YNHHS Investigational Drug Service approach to the investigational products plan; (4) further guidance on sponsor monitor visits; and (5) further clarifications from the Yale Clinical Trials.Gov team.
Blanket Yale HRPP communication for COVID-19 changes to studies
We are working with Yale HRPP and the IRB on any necessary blanket approvals that under normal circumstances would have been handled as a study-specific modification requiring individual study IRB approval. To facilitate this process, we are asking all PIs considering study modification due to COVID-19 to complete this survey.
The survey serves two purposes: (1) it allows the HRPP to keep track of all modifications covered by a blanket IRB approval due to COVID-19 impacts and 2) it allows the institution to keep track of modifications to research due to COVID-19 for operational purposes and to ensure compliance regardless of whether IRB approval is regulatorily required or not. This will also allow the HRPP staff document information in the IRB record on behalf of the PI as voluntary holds made by the PI, sponsor, or institution are typically required to be reported to the IRB as a Report of New Information (RNI) and certain types of modifications require IRB approval. The survey is very short and the intent was to make the notification less onerous.
Essential teams within the Yale HRPP Office and the Yale Center for Clinical Investigation (YCCI) will be monitoring the results of the surveys to ensure a timely response from HRPP and YCCI, typically within 1 business day. Questions can be directed to email@example.com or Clinicalresearchresources@yale.edu.
Examples of typical changes that may be made to studies because of COVID-19 may include:
- Replacing in-person study visits with "remote" options utilizing telemedicine
- Adding home visits from visiting nurses to conduct study procedures for subjects who cannot travel to the clinic
- Adding options for completing questionnaires or surveys electronically
- Allowing certain laboratory tests to be performed at a remote laboratory
- Shipping investigational products directly to research participants
- Replacing existing subject reimbursement method with the Yale/YCCI Bank of America reloadable debit card method (for more details contact Clinicalresearchresources@yale.edu)
- Conducting consent process on the phone or via digital tools (written informed consent will be documented but may involve e-consent or fax)
YNHHS Investigational Drug Service
The YNHHS Investigational Drug Service (IDS) is developing guidance on the proper way to get study drugs to research participants. Do not mail study drugs to research participants without receiving guidance regarding the proper way to do this.
If research participants are on investigational drugs, work with the IDS (IDS Phone: 203-688-4872, IDS Oncology: 203-200-3100, IDS Pager: 203-412-6248) to determine what the plan would be if the investigational drug could not be dispensed to your research participants. Most clinical trial protocols or sponsors prohibit the shipping of Investigational Products to participants, without written authorization from the sponsor to ship drugs. In cases where the participants are unable to come in-person for follow up visits, IDS will work with research teams to determine the best means of providing continued services to our study participants. As part of the YNHH Department of Pharmacy Services, IDS plans to stay open to support research participants. Contact IDS directly (IDS Phone: 203-688-4872, IDS Oncology: 203-200-3100, IDS Pager: 203-412-6248) or email questions to firstname.lastname@example.org.
Study-related guidance by category
Non-interventional human studies protocols carried out in non-clinical care settings:
To date, we are aware of only two studies in this category which PIs believe cannot either be paused for at least three weeks or converted to a state where the research is conducted solely by means (such as video-conferencing) that do not involve face-to-face subject encounters. The two exceptions are carried out solely in Samoa which is currently without any cases of COVID-19. However, we recognize that other such exceptions may exist. Therefore, we are establishing the following procedures:
- If your protocol currently includes no face-to-face contact and it is not otherwise affected by the current pandemic, you can continue with research without any need for changes.
- All other protocols in this category will be placed on “pause” until the end of April (April 30, 2020). At the end of the three weeks we will decide whether it is necessary to extend the pause. Study-specific IRB approval is not required to place the temporary pause on each study, see note above related to “Blanket Yale HRPP communication”.
- If you have a study that will not be placed on pause, but instead will be converted to a non-direct contact model, study-specific IRB approval is not required, see note above related to “Blanket Yale HRPP communication”. Currently, the blanket approval applies only to studies under Yale IRB purview. We will work with external IRBs on their processes (more information with be forthcoming).
- If you have a protocol in this category, but do not want the protocol placed on “pause”, the procedure is to first obtain review and approval by your Department. Each Department is establishing an internal mechanism to review the need to keep the study open. Please follow the procedure in your Department and then the Department will contact us to report approval of the exception; that approval will be re-reviewed in the Dean’s Office.
- Note that both the YNHH-based HRU and the outpatient CSRU are non-clinical care settings. Therefore, protocols that will not be “paused” that utilize these units will need to apply to the Departmental Procedure to continue the studies during this timeframe.
Non-interventional human studies protocols carried out solely in clinical care settings:
The majority of these studies see the subjects/patients concomitant with a necessary clinical care visit.
- Non-interventional (non-therapeutic) studies which fit the model above, that is, all face-to-face contact is carried out simultaneous with a clinical care required visit, should be reported to the Department Procedures, approved by the Department, and then communicated centrally.
- If a study does not conform to the model above, then the Department will review that study and, if the Department feels that this is an appropriate exception, will follow the process outlined above for central approval of an exception
- If the PI wishes to convert some of the study visits (which may in fact also be clinical care visits) to a telehealth format, study-specific IRB approval is not required, see note above related to “Blanket Yale HRPP communication”. Currently, the blanket approval applies only to studies under Yale IRB purview. We will work with external IRBs on their processes (more information with be forthcoming).
Interventional (Therapeutic) human studies protocols:
These studies may be paused at the discretion of the PI or may be closed to new patients at the discretion of the PI, but neither is required since these studies have direct potential benefit to the subjects/patients and hence the risk/benefit ratio is fundamentally different from the subject, investigator, and public health perspectives. We will assume that all of these protocols are continuing as “active”. If a protocol is to be put on “pause” or temporarily closed to accrual, study-specific IRB approval is not required, see note above related to “Blanket Yale HRPP communication”. Questions can be directed to email@example.com or Clinicalresearchresources@yale.edu.
We are developing documentation of the above plan that will cover all impacted studies. We will also provide you with a template note to file if your study is impacted. You also do not need to submit a Reportable New Information (RNI) documentation to the IRB indicating that you placed a voluntary pause on the study or enrollment. However, you will need to complete the above referenced survey.
See section “Blanket Yale HRPP communication for COVID-19”
Additional guidance on in-person sponsor monitoring visits
We have instituted two changes relevant to study sponsor visits: 1) a restriction on visitors to campus; and 2) only staff whose work is deemed essential for critical operations will be expected to report to work on the Yale University campus.
Visits March 16 through April 1, 2020 (date subject to change)
Effective immediately, all monitoring visits, including site qualification, site initiation, interim monitoring, and close out visits scheduled through April 1st, must be postponed.
Visits April 2 through May 10, 2020 (date subject to change)
Visits scheduled from April 2nd through May 10th, must be postponed or converted to one of the following virtual options: 1) email, 2) telephone, or 3) Zoom with video.
Additional guidance on Clinicaltrials.gov
If I change my study enrollment status, is an update to Clinicaltrials.gov required?
Yes. For studies subject to ClinicalTrials.gov requirements, Responsible Parties should update their records within 30 days of a change to any of the following: Recruitment Status and Overall Recruitment Status data elements on ClinicalTrials.gov. Changes to anticipated or actual Study Start Date, Primary Completion Date and Study Completion Date data elements must also be made within 30 days. In addition, it is strongly encouraged that any IRB approved protocol amendments that will reflect in public ClinicalTrials.gov protocols (e.g. inclusion/exclusion criteria) be updated within 30 days of approval.
It is recommended that the Record Verification Date be updated at least every 6 months for studies that are not yet completed, even if there were no changes to the record.
Contact the Yale CTgov Team for more information, at Yale.Ctgov@yale.edu.