COVID-19 FAQs

Answer:

This will be determined on a case by case basis. Please contact us to discuss the projects involved.

Answer:

No. The IRB does not need to be notified of changes in Site Monitoring Visit plans (e.g. transitioning to remote). Please note that the IRB normally does not approve sponsor site monitoring plans or methods, so this is not a change from normal practice.

Answer:

No. If the site’s deviations are in line with the Change In Research that has already been approved, then the protocol is considered to have been changed and these are not deviations. Sites are still expected to report other, site-specific deviations per the Promptly Reportable Information requirements.

Answer:

Protocol deviations do not need to be reported to the WCG IRBs unless they:

• Negatively impact risks to participants, or
• Have a negative effect on study integrity

Example – DO NOT submit to IRB:

• Patient visits out of window due to self-quarantine.

Example – DO submit to IRB:

• One or more participants withdrawn from IP without tapering
• Safety labs will not conducted because facility is closed

If anticipated, submit prospectively to IRB with plan for mitigating risk.

Answer:

WCG consulted FDA on this question and the agency responded, stating: The US FDA has adopted ICH GCP E6(R2) guidelines, which states the IRB should review/approve the ICF and “… any other written information to be provided to subjects … ” Notifying subjects of changes being made to the study is considered part of the ongoing informed consent form and process.

Answer:

From a regulatory standpoint, remote consent can be done as long as there are mechanisms to manage the documentation of consent. The requirement for the documentation of consent by signature is still in place, even if the consent discussion is not conducted in person. Sites may have the informed consent discussion with individuals via telephone, FaceTime or similar systems, and can share consent materials by email. Subjects can print, sign and scan or send an image (fax or photo) of the signed signature pages to the site. Ideally, they would also send back the original wet-ink signature pages by mail or bring them to the site later to be retained in the research record, but the documentation is valid even if only the image is recorded. No research procedures should commence without the site having received documentation of consent (even if electronic). The same procedures can be used to obtain and document consent from the Legally Authorized Representative (LAR) of a potential study participant, if the participant is unable to provide consent and the LAR is not present. However, an LAR should only be asked to provide consent if the potential participant is incapable of giving valid consent because of a temporary or permanent condition; an LAR may not give consent if the participant is capable, but just inaccessible (e.g., in quarantine or isolation).

If there are specific circumstances in which this process is infeasible for a particular study, please contact us to discuss.

Answer:

No. Because the risk of acquiring COVID-19 is not specifically a research risk, it does not need to be included in the informed consent document.  However, it may be appropriate to discuss this with the research participant, especially for participants in higher-risk categories.

Answer:

Sites can use electronic signatures to obtain consent. Per FDA Draft Guidance “Use of Electronic Records and Signatures in Clinical Investigations under 21 CFR Part 11 – Questions and Answers”, the sponsor and investigator are responsible for using a risk-based approach for validating any electronic systems under 21 CFR Part 11. Please consult your internal compliance teams to determine how Part 11 requirements will be met.

Answer:

Follow CDC guidelines for healthcare professionals. You can find them here: CDC Guidelines

Answer:

It depends. Trial type, local COVID-19 situation, local and state mandates… all will influence decisions on how to proceed with on-site monitoring activities. Certain sites already are set up with eSource technology and eRegulatory binders, allowing for remote monitoring. Less-prepared sites may not be able to provide access to CRAs, either to documents or to sites. WCG currently supports several COVID-19-related trials, as well as others deemed essential. Where trials are critical, sponsors in such trials are using remote monitoring. In less critical cases, they may be placing trials on temporary hold.

Part 312 CFR, Subpart D–Responsibilities of Sponsors and Investigators Sec. 312.68 Inspection of investigator’s records and reports states that: “An investigator shall upon request from any properly authorized officer or employee of FDA, at reasonable times (emphasis added), permit such officer or employee to have access to, and copy and verify any records or reports made by the investigator pursuant to 312.62.”

Additionally, the FDA recently issued Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic. It’s worth checking out: View Guidance

Answer:

Hard questions like these arise in unprecedented times. Fortunately, sponsors have other experience that may be useful in figuring out answers. Where a study is industry-initiated, request the sponsor’s view, bearing in mind the safety and protection of everyone involved, including the research team.

In the case of local decisions on deviations, consider the following:

• Options that ensure the highest protection from risk for participants and research teams. During this pandemic, risk to community must be balanced against participant autonomy.
• Drafting an SOP or memo detailing new and/or revised processes during the pandemic.
• Documents for trial participants whose visits need to be changed that include the reason for the change (e.g., research site is closed for non-essential, non-COVID-19 clinical activities; city is on lock-down for non-essential personnel, etc.).
• Using remote technology (eConsent, phone/Skype/Webex, voice and/or video, recording, etc.) as approved by the IRB if warranted. If you must implement the process to decrease immediate risk before IRB approval, then be sure to follow up with IRB notification after the occurrence.
• Ensuring your documentation uses standard data integrity guidelines such as ALCOA (Attributable, Legible records, Contemporaneous, Original, and Accurate).
• Following normal documenting requirements such as retaining email communications with the sponsor, IRB and participant.
• Check out the FDA’s recent Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic: View Guidance.

Answer:

Every ongoing clinical trial is managed differently depending on factors including site, location and rules mandated by local and state governments. Of course, safety of trial participants and site staff is paramount. Many sponsors, CROs and sites are moving towards virtual site visits, home visits, local laboratory testing and other study-related processes that limit face-to-face contact, although this is not possible in all cases. The patient advocacy community has greeted this development enthusiastically, given that many study participants already are compromised and the added risk of visiting a site is not attractive.

Answer:

Sponsors must have access to regulatory files, including the regulatory binder, throughout the life of a study. Technology such as a CTMS or electronic regulatory binder, that provides sponsor/designee access, could help ensure monitoring continuity for the trial.

Answer:

The FDA recently issued guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic that may be of help: View Guidance

The guidance states that, if not already in place, “Sponsors, clinical investigators, and IRBs should consider establishing and implementing policy and procedures, or revise existing policy and procedures, to describe approaches to be used to protect trial participants and manage study conduct during possible disruption of the study as a result of COVID-19 control measures at study sites. Changes to policy and procedures could address, but not be limited to, impact on the informed consent process, study visits and procedures, data collection, study monitoring, adverse event reporting, and changes in investigator(s), site staff, and/or monitor(s) secondary to travel restrictions, quarantine measures, or COVID-19 illness itself. Policy and procedures should be compliant with applicable (regional or national) policy for the management and control of COVID-19. Depending upon the nature of the changes described above, a protocol amendment may be required under the applicable regulations.”

Additionally, the Office for Civil Rights (OCR) posted FAQs on Telehealth and HIPAA, which state:  “OCR will exercise its enforcement discretion and will not pursue otherwise applicable penalties for breaches that result from the good faith provision of telehealth services during the COVID-19 nationwide public health emergency. OCR would consider all facts and circumstances when determining what constitutes a good faith provision of telehealth services.” View FAQs

Be sure to document as the site normally would, using applicable standards, GCP, regulatory requirements and site-specific SOPs/policies.

Answer:

EMRs are not under the same rules as research documents regarding 21 CFR Part 11 compliance. Certain research institutions/sites are unequipped to ensure that only specific records are viewed within the EMR. Other EMRs may be implemented with limited views of only the allowed research participants, only for a specific time, etc. The answer, therefore, depends on your individual situation. Monitors designated by the sponsor must have access to records to comply with regulatory requirements as a sponsor under 21 CFR part 312. How, where and when that occurs is determined by the research site/institution policies, regulations that apply, protocol, etc.

Answer:

The decision to conduct remote monitoring is one that sponsors weigh carefully. In order to conduct remote source data verification, study sites would have to redact source documents and provide them to the group doing the monitoring (sponsor/CRO). There are many things to consider when doing this. Proper SOPs need to be in place describing the process. The process should be as secure as possible. Additionally, the process must include a provision to handle PHI in the event a source document is not fully redacted and contains PHI.

Answer:

There are many options for the conduct of remote assessments. The type of assessments will somewhat dictate what modality is able to be employed. For clinical outcome assessments, some assessments lend themselves to being conducted via telephone or video. It is critical that the validity of the measure being conducted be assessed for the new modality. Compiled by leading scientists and supported by the literature in the field, WCG MedAvante-ProPhase has developed a listing of clinical outcome measures for which it is acceptable for the measure to be conducted by phone or video.

Other study information may be captured by multiple means, including telemedicine. Use of telemedicine is being considered by many sponsors. Considerations regarding use of telemedicine include proper modifications to consent forms and the consenting process. Many applications, such as Medocity, are HIPAA compliant. HIPAA compliance should be weighed seriously when moving to telemedicine.

Answer:

Voluntary enrollment/recruitment holds due to COVID-19 concerns do not need to be reviewed or approved by the IRB. However, if a client submits a Dear Investigator Letter or other Memo for IRB review regarding an enrollment hold, we will review the submission.

Answer:

From an IRB perspective, yes, as long as the content has been approved by the IRB, there is flexibility in allowing responses to be recorded via email, hardcopy, or phone. The change in method does not have to be reported or submitted to the IRB for approval. The IRB does recommend an Internal Memo be filed noting the protocol affected and the date the alternative method would be initiated.

However, please remember that validated instruments such as endpoint assessment tools and quality-of-life questionnaires may not be considered validated when the method of administration changes; this should be confirmed for the specific tools being used.

Answer:

Interventional studies:

WCG cannot provide a single answer applicable to all research studies and all research sites, given the many variables such as the relative risks and potential benefits of the study, the interactions necessary to perform the study procedures, and the level of protection from potential COVID-19 exposure available at sites

Clients should give appropriate consideration to the safety and welfare of their research participants and their research staff. The risks of acquiring COVID-19, including consideration of the ability to safely perform the study interventions, should be weighed against the potential benefits to the subjects. As a general matter, the more personal potential medical benefit that exists, the more likely that the risks to the subjects and research staff are warranted. Sponsors and sites should operate according to current federal, state and local policies and public health mandates

Non-interventional studies:

If the study is strictly non-interventional and limited only to internet activities, surveys, or questionnaires, then the study may continue enrolling. However, if there are interactive procedures or bodily samples (e.g. saliva) being collected that require visits to a health care facility, then the IRB may evaluate the revised risk and benefit of these studies on a case by case basis. Sponsors and sites should operate according to current federal, state, and local policies and public health mandates.

However, please remember that validated instruments such as endpoint assessment tools and quality-of-life questionnaires may not be considered validated when the method of administration changes; this should be confirmed for the specific tools being used.

Answer:

No, the IRB cannot extend a study’s Continuing Review period or provide a grace period around the review date.

The FDA (21 CFR 56.109(f)) and HHS (45 CFR 46.109(e)) regulations state “An IRB shall conduct continuing review of research covered by these regulations at intervals appropriate to the degree of risk, but not less than once per year.” Therefore, the IRB is required to conduct a Continuing Review at least once per year, so we cannot extend the approval period or allow for a grace period.  If this is a problem in a specific circumstance, please contact us to discuss.

Answer:

Yes.  There is a process in place for IRB transfers:

• Site must submit the Initial Review Form, IRB Transfer Form, and IRB Reliance Agreement (if the company/institution has an Master Services Agreement with WCG, the IRB Reliance Agreement is not needed; please check with your contracts group)
• For an institutional site/contact, alert institutions@wirb.com that a possible IRB Transfer from an institutional site is expected. Provide the contact name and institution name.

Answer:

The Food and Drug Administration (FDA), National Institutes of Health (NIH), and the Office for Civil Rights (OCR) in the Department of Health and Human Services have all issued guidance noting the flexibility that exists in the regulations, and additionally that they are being more flexible in certain areas.

FDA guidance on clinical trials during COVID-19: View

FDA guidance on remote monitoring devices: View

NIH guidance on clinical trials during COVID-19: View

OCR guidance on enforcement discretion in the use of telemedicine: View

Answer:

A visit with direct benefits is one where the participant expects to receive benefits immediately from participation in the clinical trial. The definition does not encompass benefits that arise from participation, such as a free physical exam, or long-term benefits to society.

Answer:

Yes. An experimental medication meets this definition in trials that offer the possibility to cure or significantly improve the well-being of the participant.

Answer:

Remote monitoring of the IP may not be feasible while local restrictions are in force. Pending lifting, sponsors may pause monitoring of clinical trials deemed non-essential or implement new/alternative methods to monitor trials. This will dependent greatly on IP type, risks, location, and COVID-19 activity within that area. Be mindful of participant worries and fears when trial routines are disrupted. Remote monitoring may stoke concerns about risks and access to the IP.

Answer:

The DEA has issued guidance for DEA-registered practitioners prescribing controlled substances without medical examination during the COVID-19 pandemic. Check with study sponsors, investigational pharmacies if applicable, and your research site’s COVID-19 policy/SOPs to determine how best to proceed.

View DEA Guidance

Answer:

WCG is currently involved with nearly every major COVID-19 trial underway and we also connect trial sites with sponsors. Please contact WCG with name, contact information and site summary for principal investigators interested in COVID-19 trials. We will forward the information to the appropriate team within WCG.

Answer:

Follow precautions defined at the CDC website: View Guidance

Note: Many trials are being placed on hold during this pandemic depending on trial type, local COVID-19 situation, and local/institutional requirements. As noted during WCG’s first COVID-19 WCG webinar, protection of human population must be balanced against individual participant needs. In-person visits may cause harm to the many individuals who support the visit (i.e. pharmacists, PIs, coordinators, registration personnel, nurses, monitors, etc.).

Answer:

Local hospital ethics committees may be overwhelmed with changes to studies that require ethical review. WCG works alongside most research institutions across the US. If the hospital is within the US, please connect us with them as we may be able to help them manage surges in reviews.

Answer:

Consent for telemedicine may be done in several ways: a) If there is an in-person visit at the beginning of the study, a normal consent process can take place with an ink hand signature on a paper consent form; b) If there is no in-person visit, then consent can be accomplished remotely as follows:

• The consent form may be sent to the subject via email, postal mail, fax, etc. The consent discussion takes place via phone or Skype; the subject then signs the printed paper copy with an ink hand signature; the signed copy is returned to the PI via email, postal mail, fax, etc.
• The consent form may be provided to the subject in electronic form, with an eSignature process in place. The consent discussion takes place via phone or Skype; the subject then signs the eCopy with a signature; the eSigned copy is returned electronically to the PI. If this method is used and the study is under FDA jurisdiction, then the study must meet Part 11 requirements.

For patients who have been quarantined and are possible subjects for a COVID-19 study, FDA has provided a model for obtaining consent in FAQ # 10, p. 15, of the Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic, available online: View Guidance

Another possibility is to use an electronic consent system. This avoids the issue of moving the paper, as noted in the guidance.

Finally, a few sponsors have proposed alternative consent models to FDA, including photographing the signature and requesting individual FDA approval.