• NSN Law Bulletin

Further Measures Introduced in the field of Clinical Trials Due to the COVID-19 Pandemic

Since the beginning of COVID-19- outbreak, many legislative amendments had to be made and numerous measures had to be taken in the field of health in order to protect public health and to maintain the regular operation in healthcare sector.

Within this framework, on 20th of March, 2020, Guideline on Measures to be Taken in Clinical Trials Due to COVID-19 Pandemic (“Measures Guideline”) has been published by the TMMDA. Frequently Asked Questions related to the Measures Guideline (“FAQ”) has followed this publication a month later, on 20th of April, 2020. In the sequence, both publications have been updated on the 25th of July, 2020. Recently, MoH has published Measures to be Taken in Clinical Trials Due to the COVID-19 Pandemic which also updates certain provisions of the Measures Guideline. We hereby would like to share information on the most recent legislative amendments introduced concerning the clinical trials.

It has been noted that the MoH once more indicates that the sponsors should make a risk assessment continuously by considering the priorities and urgencies arising of COVID-19 situation, following the social isolation rules, trying to reduce the burden of research centers and most importantly, considering the safety of volunteers. Accordingly, MoH forms a framework for the measures to be taken in clinical trials and indicates such points under the below topics:

- Temporary Suspension or Early Termination: If deemed necessary, temporary suspension or early termination of the study shall be evaluated firstly depending on the nature of the study.

- Emergency safety measures: A researcher shall take the necessary emergency safety measures to protect the subjects, in the event that a situation arises during the conduct of the trial or related to the development of an investigational product that may affect the subject's safety. Such security measures can be applied without the approval of the Ethics Committee and the permission of TMMDA (Turkish Medicine and Medical Device Agency). The sponsor or its legal representative notifies the Ethics Committee and the Institution about the developing or possible emergency security situation and the measures taken against such. More than one security measure can be submitted in the same application.

- Protocol deviations/violations: Precautions to be taken may result in more protocol deviations/violations than usual. Such deviations/violations due to COVID-19 precautions do not need to be reported to the Ethics Committee and TMMDA. Deviations/violations should be documented according to the sponsor's SOPs. These notifications will be requested later in bulk as a list by TMMDA. Nevertheless, all procedures in the protocol should be followed and no counterattack should be taken when recruiting new volunteers. If all procedures cannot be followed, no volunteers shall be recruited.

- Monitoring Activity: Monitoring plan shall be changed as a result of a risk assessment, but such decision shall be taken by the research team. In this context;

- If it is necessary to postpone or reschedule on-site monitoring activities; the first choice should be to postpone on-site monitoring activities depending on the nature of the research in order not to increase the burden of researchers and centers. If visits must continue, visiting times should be agreed with the research center.

- If it is not possible to carry out on-site monitoring activities, remote monitoring can be performed. However, it should be verified whether the consent obtained from the volunteer allows remote monitoring.

- If the measures are reduced/removed, the frequency of on-site monitoring activities should be increased and the impact of the reduced activities should be evaluated.

- Supply of products used in research: In order to supply the research centers with the products used in the research in sufficient numbers, it is acceptable to keep the product stock more than normal - up to three times the margin of safety specified in the Import Manual; however, the expiry dates of the products should be taken into account. In this process, proforma invoices will not be physically requested in import applications. Below points should be followed where appropriate and necessary:

  • More products than normal can be given to volunteers during scheduled visits in order to reduce the frequency of volunteers' visits to research centers.

  • The products can also be delivered to a (up to a second degree) relative of the volunteer who can come to the research center instead of the volunteer.

  • Products can be transferred between research centers.

  • Products can be transferred directly to volunteers. However, in this case, as a first option, a team member responsible for the product stock at the research center should deliver the product directly to the volunteers. If this is not possible, a third-party service provider can do so.

  • No direct product supply from investigational product warehouses to volunteers will be accepted.

  • Product transfer should be carried out in accordance with Good Distribution Practices and product storage conditions, and the transfer process should be documented.

  • Except for applications related to import permit, no application/notification to the Ethics Committee and TMMDA is required. If deemed necessary, the relevant documents/applications will be requested by the TMMDA later.

- Laboratory and Imaging Services: In case the transfer of biological samples abroad cannot be carried out at all or under necessary conditions, the laboratory of the research center and/or local external laboratory facilities should be evaluated. No application/notification to the Ethics Committee and TMMDA is required. If deemed necessary, the relevant documents/applications will be requested by the TMMDA later.

- Research Center Visits: Volunteer safety being the first priority, the burden of the center and the researcher must be aimed to reduced as well. Provided that the sponsor and the principal investigator agrees;

  • If possible, volunteer visits should be postponed to a future date.

  • If possible, volunteer visits should be converted to telephone visits rather than center visits.

  • In cases where volunteers cannot reach the center, a visit to another research center or transfer of the volunteer to another research center should be considered. In such case, the principal investigators of both centers must agree on this transfer. The volunteer should be informed about the process and his/her consent should be obtained.

  • Depending on the scope of the visit, it should be considered that volunteer visits can be done at home. These visits can be done by a member of the research team or a third-party home care provider.

  • If treatment/follow-up would not be possible despite all precautions, the subject should be excluded from the study.

No application/notification to the Ethics Committee and TMMDA is required. If deemed necessary, the relevant documents/applications will be requested by the TMMDA later.

- Research center and research team changes: If the research center is not able to carry out the treatment/follow-up of their volunteers, the volunteers can be transferred to another center, provided that the principal investigator of both centers agree and that the volunteer is informed about the process and his/her consent is obtained. If the research team cannot fulfill its responsibilities in the clinical trial, changes should be made to the research team.

- Researcher meetings: Within the scope of the general measures regarding collective organizations, only online researcher meetings will be allowed. An application for a researcher meeting can also be made for studies that do not have the approval of the Ethics Committee or the permission of TMMDA. However, a cover letter sample of the first application made to the Ethics Committee is presented in the meeting applications of these studies.

- Trainings: Training or meetings on good clinical practices and clinical research will not be allowed to be held face-to-face, and they will be allowed only to be held online. The safety of the members of the Ethics Committee should be ensured, the safety of the volunteers should be considered first and the general precautions taken due to the COVID-19 outbreak should be followed. In this context, various procedures are envisaged for conducting Ethics Committee meetings online and collecting necessary signatures securely.

Although this document will remain valid until TMMDA declares otherwise, it is obvious that this most recent document will continue to be revised and updated based on evolving situations and needs.

Author: Duygu Beyazo, Gözde Şahin