Research

COVID-19: Guidance for researchers and study sponsors

  1. CONTEXT

Auckland District Health Board (Auckland DHB) is responding to an outbreak of a novel Coronavirus disease (COVID-19), a national 4-level alert system specifying public health and social measures needed to combat the outbreak is currently in place, and a state of national emergency was declared on 25th March 2020. Many of the usual research processes are affected, in particular non-essential healthcare interactions, and there is also an important new need for COVID-19-associated research.

This guidance covers all research being conducted at Auckland DHB, both interventional and observational, both commercial and non-commercial investigator-led studies. Where “sponsor” is used it refers to the organisation or individual responsible for the conduct of a study. The guidance is intended to minimise the adverse impacts on study participants as well as site, sponsor and vendor staff involved in studies. Key consideration is placed on managing burden and disruption to health services at this critical time. However, safety of trial participants will remain the paramount consideration for Auckland DHB.

Sponsors and researchers are asked to consider the wider impact of COVID-19 on their research portfolio, participants and staff in the situation of health system repurposing, redeployment of research staff to clinical roles, restrictions on movement, and supply chain challenges. Auckland DHB requests that any changes are designed to have minimal impact on the health system at this time.

The Ministry of Health’s Health and Disability Ethics Committees (HDEC) provide ethical oversight for all studys in New Zealand. HDEC released an emergency standard operating procedure (eSOP) on 23rd March 2020. The purpose of this eSOP is to ensure that there are practical and effective actions put in place to ensure that a robust but rapid research ethics review may be undertaken for COVID-19 research. https://ethics.health.govt.nz/operating-procedures/covid-19-emergency-response-ethical-review-operating-procedures-esop

New ethics research applications that have a COVID-19 research element and amendments to existing studies to either add or respond to a COVID-19 research element will be covered by this emergency SOP. All other research applications will continue to be reviewed under the standard HDEC SOP.

This eSOP may be updated. Users of the eSOP should pay attention to the version number on the front page of this document and check the HDEC website for updates.

COVID-19-related submissions to HDEC should be made via online forms.

 

  1. STUDIES currently in start-up phase or planned for 2020

 

The Auckland DHB Research Review Committee (RRC) will continue to carry out institutional review on its advertised schedule. However, sponsors and researchers are requested to consider their planned study portfolio for 2020 and allocate according to health system capacity, impact on infection control measures and risk assessment. Studies in start-up phase through Q2 2020 may need to be postponed depending on the developing COVID situation.

 

  1. New studies relating to COVID-19

Until further notice new research relating to COVID-19, including substantial amendments to existing research to include a COVID-19 element, will have Auckland DHB institutional review by the RRC under an expedited process.

 

  1. Active STUDIES

General Advice

Sponsors and researchers are asked to collaborate on all active studies and consider:

  • The risks to new and existing participant safety in either (i) continuing with study recruitment or (ii) discontinuing a study, in particular where there are no other treatment options. Where there is an unacceptable risk to participant safety in continuing a study, sponsors and investigators should decide whether to temporarily suspend enrolment, suspend the trial or to discontinue the trial altogether.
  • The availability of the Coordinating Investigator and delegation of responsibility should be considered in terms of current healthcare reprioritisation and the CI’s primary responsibility of the trial under ICH-GCP. Availability of clinician investigators and research nurses will be impacted as resources are diverted to essential services and Sponsors should plan for this occurrence.
  • Changes to participant visits should be considered and may include reduction in visits, increase in visit windows, establishment of satellite sites, conduct of out-of-hospital visits, remote consultations, telephone calls, emails and postal questionnaires.
  • Continuity of IP to participants – safety of participants and discontinuation of investigational product should be carefully considered, including the safety of abruptly interrupting study drug. Dispensing, shipping and storage arrangements should be reviewed:

This may include;

o dispensing to a third party

o dispensing an extended supply of study drug beyond protocol-mandated dispensing

o couriering study drug to participants’ homes,

o chain of custody and temperature monitoring requirements.

  • Changes to monitoring arrangements should be considered and may include reduction in frequency of monitoring and/or increased remote monitoring. Auckland DHB can support remote monitoring of the clinical record via Citrix. All applications for remote monitoring must be approved by the Auckland DHB COVID-19 taskforce via application to the clinical records department.
  • Quality of documentation practices by Auckland DHB and Sponsors must be maintained.
  • As this situation is unprecedented, it is acknowledged that protocol and ICH-GCP breaches are inevitable. Sponsors and research teams must make every effort to mitigate the impact of unavoidable breaches on participant safety and to the best extent possible maintain reporting requirements to HDEC under the eSOP.
  • As safety in studies is the priority, all significant safety issues, urgent safety measures and serious breaches impacting on patient safety and rights should be reported.

 

  • With respect to non-serious breaches, a post COVID-19 deviation report should be submitted to HDEC to be reviewed under the eSOP as soon as practicable.

 

Sponsor-instigated changes to existing studies

In no case may a sponsor create an amendment that creates an additional burden on Auckland DHB. If there is a possibility that this may occur, sponsors must liaise immediately with the principal investigator to discuss.

 

Studies where sponsor is adding testing for SARS-CoV-2 for safety purposes

  • This may be implemented for example where studies include taking samples, and safety checks need to be implemented so that the appropriate protection is put in place for sample handling.
  • Sponsors should treat such arrangements as urgent safety measures with subsequent notification in the usual way.
  • Sponsors and HDECs should consider agreeing to use a separate specific information sheet to provide information about additional tests rather than modifying an existing Participant Information Sheet and Consent Form.

 

Studies adding new COVID-19 related elements

  • If a sponsor wishes to add a sub-study or other component, such as enabling an epidemiological analysis of COVID-19, this should be submitted as an amendment under HDEC’s eSOP.
  • Sponsors must negotiate the proposed new research elements with the research team.

 

Monitoring arrangements

  • Monitoring or administrative arrangements to reduce the burden or physical contact with sites may be made as non-substantial amendments and will not require review by HDEC under the eSOP. They may be implemented at Auckland DHB through communication with the study team.
  • Any remote monitoring amendments must still maintain all patient confidentiality protocols already in place. Remote source data verification may be done electronically as long as appropriate security arrangements either are or can be put in place.

 

Participant visit arrangements

  • Sponsor-proposed changes to avoid exposing patients to a higher risk environment or to reduce the burden on clinical services may be implemented at Auckland DHB through communication with the research team.
  • Where an amendment may potentially increase the risk to participants (e.g. resulting in fewer participant checks), the HDEC should be notified and the amendment processed via the eSOP.
  • Sponsors should work with research teams to ensure appropriately detailed information is provided to participants to enable their informed consent to protocol amendments.

 

Study product sent directly to participants

  • Sponsors must assess the risks relating to the product and consider any shipping and storage arrangements. Participants must consent verbally to providing contact details for shipping purposes. Where participants are self-isolating or in quarantine, arrangements for a nominated person to collect the product may be implemented with the participant’s verbal consent.
  • Sponsors and research teams should consult with the Auckland DHB pharmacy about alternative access mechanisms.

 

Temporarily halting a study or extending the duration due to COVID-19

  • Temporarily halting a study is a serious consideration, as the successful completion of a study is an important ethical outcome. A study should only be suspended if there is no practical way of allowing it to achieve its primary objective in the COVID-19 world.
  • The decision to temporarily halt a study should include detailed written consideration of how the study could be usefully brought to a conclusion in the post-COVID-19 world.
  • Where a study should be temporarily halted, sponsors must issue an amendment to HDEC, who will review under the eSOP.

 

Closing a study

  • Closing a study is a serious consideration, as the successful completion of a study is an important ethical outcome. A study should only be stopped if there is no practical way of allowing it to achieve its primary objective in the COVID-19 world.
  • For any studies involving provision of treatment to participants, careful consideration should be given to post-study care. If this cannot be in line with the information provided in the participant-information sheet, a substantial amendment should be submitted to HDEC under the eSOP.
  • For any studies not involving provision of treatment to participants, a notification of conclusion of study should be made to HDEC, and an end of study report provided in due course.

 

Auckland DHB-instigated changes

 

Studies adding new COVID-19 related elements

  • If a research team wishes to add a sub-study or other component, such as enabling an epidemiological analysis of COVID-19, this should be submitted as an amendment under HDEC’s eSOP.
  • Depending on the impact of the new research element on participants and Auckland DHB resources and staff, approval of the RRC may be required.

 

Suspending recruitment

  • Auckland DHB researchers must raise such issues with the sponsor as early as possible if this is likely to occur.
  • If continuing to conduct the trial according to the protocol is judged to pose an unacceptable risk to trial participants or research personnel, and any reasonable amendment to the protocol would compromise the study results or outcome, researchers should consider the temporary suspension of participant recruitment.

 

Terminating a study due to COVID-19:

  • Researchers whose studies are affected by COVID-19 are encouraged to work with trial sponsors to the greatest extent possible to come to an arrangement so trials can continue without posing an unacceptable risk to participants or trial staff.
  • Researchers conducting their trial under a CTRA are reminded that termination provisions are contained in the Force Majeure clause of the agreements. Research teams needing to invoke a force majeure provision are reminded that they must follow the process described in the clause.

 

Moving participant visits due to staff and resources reallocated to clinical care or limiting participant contact

  • Research teams must raise such issues with the sponsor as early as possible if this is likely to occur. Where possible such arrangements should be handled prospectively as an amendment to HDEC via the eSOP. In cases where there is no time to arrange for such review, changes should be implemented as urgent safety measures and reported to HDEC as soon as practicable. In any such situation the impact on participants should be considered and arrangements made to cover this, for example additional transport.

 

  • The options are to set up as a sub-contracted site of the existing site if oversight can be maintained by the existing site, or to set up new sites, or to implement direct home care arrangements by the sponsor. For study types where addition of new sites is a substantial amendment, existing guidance for submitting a substantial amendment for new sites should be followed. In all other cases, existing guidance for non-substantial amendments and addition of new sites should be followed.

 

Withdrawing participants

  • Research teams must raise such issues with the sponsor as early as possible if this is likely to occur. For any studies involving provision of treatment to participants, careful consideration should be given to post-study care. If this cannot be in line with the information provided in the participant-information sheet, a substantial amendment should be submitted to HDEC via the eSOP.

 

Studies where the Chief Investigator (CI) is unable to carry out their duties due to COVID-19

  • Any existing arrangements covering a CI’s absence should be followed.
  • Where no such arrangements are in place HDEC should be notified.
  • If the CI will be absent for greater than three months alternative arrangements should be put in place.