For the attention of applicants and researchers!
The recommendations were developed on the basis of the current regulatory requirements adopted in Ukraine regarding the conduct of clinical trials of medicinal products (hereinafter – CT) under quarantine to prevent the spread of the acute respiratory disease COVID-19 and taking into account the recommendations of the European Medicines Agency (EMA, Version 3 of 28.04.2020).
1. Introduction
The actions of the sponsor, investigators and other persons involved in conducting clinical trials must comply with the requirements adopted by the authorities at the national and local levels and be based on benefit/risk assessment criteria for subjects, investigators and the quality of the data obtained during the conduct of clinical trials.
When preparing and conducting CTs, the requirements specified in the Resolution of the Cabinet of Ministers of Ukraine of July 22, 2020 No. 641 “On the Establishment of Quarantine of the Requirements of the Cabinet Resolution and the Introduction of Enhanced Anti-Epidemic Measures in the Territory with Significant Spread of the Acute Respiratory Disease COVID-19 Caused by the Coronavirus SARS-CoV-2”, as amended, must be taken into account.
In view of the need to observe social distancing, if a trial subject cannot come to the trial site (hereinafter – the TS), other measures may be taken, such as home visits, if possible, or communication by telephone or video link (telemedicine), which may be necessary to identify adverse events or reactions and to ensure continuous medical care and supervision. However, the limitations and risks of such methods and the requirements for protecting clinical trial data and the personal data of subjects must be taken into account. Such alternative methods of communication must be provided with resources and means of communication, must be duly documented and subsequently approved as substantial amendments in accordance with the established procedure.
Priority is given to any (new) applications for conducting clinical trials for the treatment or prevention of COVID-19 infection and/or applications for substantial amendments to existing clinical trials that became necessary because of COVID-19. In accordance with the Law of Ukraine “On Amendments to Certain Legislative Acts of Ukraine on Ensuring the Treatment of Coronavirus Disease (COVID-19)” of 20.03.2020 No. 539-IX, the approval of protocols of clinical trials of medicinal products for the treatment of coronavirus disease (COVID-19) and of substantial amendments to them is carried out within a period of up to five calendar days.
The impact of quarantine measures on the ability to continue ongoing CTs, open a new trial site in an approved CT, and involve staff and patients/healthy volunteers in a CT must be considered as a priority measure to ensure the health and safety of subjects. The mandatory use of personal protective equipment for doctors and subjects should be provided for.
2. Start of new clinical trials
The sponsor must critically assess the advisability of starting a new CT or including new subjects in an ongoing CT. Additional risks to subjects (patients, healthy volunteers) should be included in the protocol section on benefit/risk criteria together with risk minimization measures (see also “risk assessment” below).
When conducting CTs of medicinal products used to treat patients with coronavirus disease (COVID-19) or its complications, the CT protocol must provide for and take into account the conditions established by quarantine measures and MoH of Ukraine orders. This applies to the choice of trial sites and laboratories for polymerase chain reaction (hereinafter–PCR) tests
(https://moz.gov.ua/article/news/viznacheno-perelik-likaren-dlja-gospitalizacii-pacientiv-z-covid-19;
https://phc.org.ua/news/testuvannya-na-covid-19-v-ukraini-zdiysnyuyut-schonaymenshe-49-laboratoriy).
The State Enterprise “State Expert Center of the Ministry of Health of Ukraine” (hereinafter – the Center facilitates and prioritizes the review of clinical trial materials of medicinal products for the treatment of coronavirus disease (COVID-19) in accordance with the Law of Ukraine “On Amendments to Certain Legislative Acts of Ukraine on Ensuring the Treatment of Coronavirus Disease (COVID-19)” of 20.03.2020 No. 539-IX, which adopted “… conduct of expert evaluation of clinical trial materials of medicinal products for the treatment of coronavirus disease (COVID-19) and substantial amendments thereto, provided that such materials are submitted in Ukrainian or English, within up to five calendar days” and, for this purpose, holds relevant consultations for applicants to discuss important issues before the submission of documents.
At the same time, we inform you that the sponsor/applicant and investigators must provide in advance for, and describe in the protocol and other clinical trial materials, all possible risk minimization measures, in particular to prevent the spread of coronavirus disease (COVID-19) among trial subjects, medical staff, etc.
Also, when developing a CT protocol for a medicinal product for the treatment of coronavirus disease (COVID-19), in order to select trial sites, the sponsor / applicant must take into account those designated by the Ministry of Health of Ukraine and the National Health Service of Ukraine (directive of the Chief State Sanitary Doctor of Ukraine of 27.03.2020 No. 7) – more than 200 reference healthcare facilities (mostly infectious disease departments and infectious disease hospitals) for the hospitalization of patients with coronavirus disease (COVID-19) for the period of measures to prevent the spread of the disease (https://nszu.gov.ua/e-data/dashboard/likarni-covid).
When applying these recommendations, the sponsor / investigators should additionally take into account other regulatory acts of Ukraine that may be adopted in connection with the spread of coronavirus disease (COVID-19) and the measures taken to contain it in Ukraine.
3. Changes in ongoing clinical trials
In its risk assessment, the sponsor must decide whether the following measures may be the most appropriate during quarantine. The measures should generally be agreed with the investigators and may include:
- replacing physical visits to the trial site (reducing personal contacts of persons involved in the CT) with telephone contacts or video visits (telemedicine), postponing or canceling visits. Visits to the trial site should be made only in special cases, taking quarantine measures into account;
- temporary suspension of clinical trials at some or all trial sites, if this does not affect the condition of the trial subjects;
- suspension or slowdown of enrollment of new subjects in clinical trials;
- extension of the duration of clinical trials;
- transfer of clinical trials or involvement of new approved trial sites that have not yet been used;
- closure of the trial site. If it is not advisable at all for the trial site to continue participating, the sponsor must decide whether to close the trial site and how this can be done without harm to the safety and health of the subjects already enrolled in the clinical trial, while preserving the integrity of the clinical trial data;
- transfer of trial subjects to other trial sites, away from risk areas or closer to their homes (if this cannot be avoided, to trial sites approved for the given clinical trial, or to new trial sites that will be approved). The exceptional nature of the situation must be justified based on an assessment of the benefit/risk ratio individually for each trial subject. As a rule, putting new trial sites into operation for the quarantine period is not foreseen, unless there is no other solution for the trial subject.
If there is an urgent need for a study subject to visit a trial site (TS), the opening of a new TS may be implemented as urgent safety measures, with an application for a substantial amendment on the approval of the additional TS submitted, in accordance with the Procedure for Conducting Clinical Trials of Medicinal Products and Expert Evaluation of Clinical Trial Materials, approved by order of the Ministry of Health of Ukraine of 23.09.2009 No. 690, as amended (hereinafter, the Procedure).
An exceptional situation may arise if it is vital for the subject to remain in the clinical trial and the trial site where the subject was enrolled has been closed due to quarantine or due to the repurposing of the healthcare facility (hereinafter – HCF) for the duration of the quarantine. In such cases, transferring the subject to the nearest trial site approved for conducting the specific clinical trial is possible. It is important that the subject, as well as the investigators (the receiving ones and those transferring the subject), agree on the transfer and that the receiving trial site is able to access the previously collected information/data of the specific transferred subject and that any electronic CRF can be adjusted accordingly (the receiving investigator will have access to the CRF), which allows the receiving trial site to enter new data on this subject. Appropriate transportation of the subject must be taken into account and agreed upon. The sponsor, the ethics committees at healthcare facilities (hereinafter – EC) of both trial sites, and the Center must be informed of such measures.
Urgent laboratory, instrumental and other diagnostic tests necessary for the safety of the subject may be required. If the subject is unable to get to the clinical trial site, it is acceptable for laboratory and other diagnostic tests to be performed at a local laboratory (or an appropriate clinical facility for other tests) that is authorized to perform such tests regularly (e.g., complete blood count and blood chemistry, liver function tests, ECG, etc.), if this can be done within local restrictions and with appropriate distancing under quarantine conditions. Principal investigators must inform the sponsor of such cases. The results of such examinations may be used for safety decisions. If this is the endpoint of the CT and samples cannot be delivered to the central laboratory, analyses should be performed locally, and then explained, evaluated and stated in the CT report (the report format must comply with the ICH E3 guideline).
All planned changes must be balanced and must not create an excessive burden on the staff of clinical trial sites during the COVID-19 pandemic if investigators are involved in providing care to patients with COVID-19.
Compliance with the CT protocol must be ensured in such a way that ongoing benefit/risk assessment for the CT and study subjects remains possible. The sponsor must properly assess the impact of protocol changes on the interpretation of clinical data, and the overall data collection database can be discussed subsequently.
4. Safety reporting
Given the current situation with coronavirus infection, the Center considers it acceptable to report SUSARs and DSURs during clinical trials of medicinal products in accordance with the requirements of Section XII of the Procedure to the e-mail address of the Department of Expert Evaluation of Preclinical and Clinical Trial Materials clinic@dec.gov.ua or in paper form to the address:
03057, Kyiv, A. Tsedik St., 14.
The sponsor is expected to continue safety reporting in accordance with the requirements of Section XII of the Procedure, taking into account the recommendations of the ICH R2 and R3 guidelines. If, according to the protocol, physical visits are reduced or postponed, it is important that the investigator continues to collect adverse events/adverse reactions (hereinafter – AE/AR) from the subject by alternative means via telephone contacts or video communication (telemedicine), which must be stated in the Informed Consent. If this information was not included in the Informed Consent, a Substantial Amendment must be submitted in accordance with the established regulatory requirements.
5. Risk assessment
The safety of trial subjects is of paramount importance. Due to the issues related to COVID-19, the risks of involving trial subjects in clinical trials should be weighed against the expected benefit for them and for the population (principle 2.2 of ICH GCP).
All decisions on adjusting the conduct of clinical trials (CTs) must be based on a risk assessment by the sponsor (ICH GCP section 5.0). The sponsor is expected to perform a risk assessment of each individual ongoing CT, and the investigator of each individual trial subject, and to implement measures that prioritize the safety of the trial subject and the reliability of the data. In the event of a conflict between these two concepts, the safety of the trial subject always prevails. Such risk assessments should be based on the input of the relevant parties and documented on an ongoing basis. It is important that the sponsor, in its risk assessment, takes into account the prioritization of critical tasks in the CT and the possibility of performing them in the best way.
The sponsor must reassess the risks depending on how the situation develops. This reassessment must also be documented.
It is quite possible that as the epidemic escalates, local circumstances will lead to local changes in risk assessment, so additional measures may need to be implemented and a risk assessment focused on a specific trial site or investigator may be necessary (and this must be reported to the sponsor).
With regard to subjects participating in ongoing clinical trials (CTs) who may be identified as a risk group for COVID-19 or who are in CTs involving treatment that may increase such risk, the potential impact of COVID-19 on these groups of subjects must be taken into account when deciding whether to start or continue such CTs.
If the risk assessment leads to actions that affect the CT, the Center, the trial site and the local ethics committee (LEC) must be informed by the sponsor in accordance with the Procedure and other legislative acts. When a new event may seriously affect the benefit/risk balance of the CT, immediate action is required from the sponsor and the investigator to protect subjects from immediate hazard. These urgent safety measures may be taken without prior notification of the LEC and the Center, but immediately after these measures are implemented, as soon as possible, information must be provided to the Center and the LEC. In this notification, the sponsor must provide relevant information about the reason, the measures taken, and the plan for further action.
If the changes are likely to affect the safety or health of participants and/or the scientific value of the trial, but will not require immediate action from the sponsor or investigator, they must be submitted as applications for substantial amendments to the study materials. Such substantial amendments to clinical trial materials are made in accordance with Section X of the Procedure. The sponsor must take into account the limited capacity of experts and submit only high-quality, complete applications containing the necessary changes.
If the information relates to COVID-19, it is recommended to clearly indicate in the submitted documents any connection with COVID-19.
6. Communications between the sponsor, the trial site, and trial subjects
Changes to the conduct of the clinical trial must be agreed with the investigators at the trial sites. It is important that the changes and the consequences of their impact are clear, including marking of the changed documents with tracked changes to support their implementation at the trial sites. Agreements may be documented as email correspondence.
In addition, the investigator must promptly notify trial subjects of changes in the conduct of the clinical trial that affect them (e.g., cancellation of visits, changes in laboratory tests and in the delivery of investigational medicinal products (hereinafter – IMPs), etc.).
7. Changes to the informed consent procedure
The procedure for obtaining informed consent (hereinafter – IC) in all clinical trials must comply with the terms of the clinical trial protocol, the provisions of the Declaration of Helsinki, and the Procedure.
The sponsor must keep in mind the current burden on healthcare professionals and carefully assess the appropriateness of enrolling new subjects in ongoing clinical trials. Absolute priority should be given to conducting clinical trials on the prevention or treatment of coronavirus disease (COVID-19) and diseases associated with COVID-19, or clinical trials on serious diseases that have no satisfactory treatment. If the sponsor plans to initiate a clinical trial to test a new treatment for COVID-19, alternative procedures for obtaining informed consent should be sought, since it is quite likely that a potential subject cannot leave the isolation ward and give consent in the usual way (personally signing and dating). The use of personal protective equipment must be ensured when carrying out the procedure for obtaining informed consent and storing the informed consent form document.
However, the following specific approaches regarding patients with COVID-19 must be taken into account.
If it is impossible to obtain written consent from a potential subject (for example, due to physical isolation, owing to illness with COVID-19), the trial participant may give oral consent in the presence of an impartial witness. In such cases, the witness is obliged to sign and date the informed consent document, and the investigator must indicate in the source documentation how the impartial witness was selected (Section IV, paragraph 1.2 of the Procedure).
In addition, a situation is possible in which the subject and the person obtaining consent sign and date separate informed consent forms. In any case, all relevant records of such a procedure must be kept in the investigator's file at the clinical trial site. Then, when it becomes possible, a signed and dated informed consent form should be obtained from the subject in the usual manner as soon as possible.
If potential subjects with COVID-19 are unable to give consent because of the severity of their condition, or when minors are included in the trial, consent must be obtained from the legal representative(s) in accordance with the Procedure (Section IV, paragraphs 1.2 and 3.1).
In acutely life-threatening situations where it is impossible to obtain in advance the informed consent of the subject (or her/his legally authorized representative(s)), it will need to be obtained later, as permitted under the Procedure (Section IV, paragraph 1.3.2 of the Procedure). In these cases, the investigator must record in the source documentation why it was not possible to obtain the subject’s consent before inclusion in the clinical trial, stating the reason and the subsequent steps for obtaining informed consent and informing the patient about the clinical trial.
For other ongoing CTs, re-consent may be needed from subjects already enrolled in the CT. However, the need for subjects to visit the trial site solely to provide repeat informed consent (IC) should be avoided. If re-consent is needed to implement new urgent changes in the conduct of the CT (primarily those introduced for reasons related to COVID-19), alternative ways of obtaining such repeat IC during the pandemic should be considered: contact the subject by telephone or video call (telemedicine), obtain verbal consent, and supplement it with confirmation by e-mail. The approved updated information letter and IC form must be provided to subjects by e-mail or regular mail. The procedure for obtaining IC in this way must be documented in the source documentation and confirmed through the usual IC procedures at the first opportunity when the subjects return to the trial site.
8. Changes in the distribution of the investigational medicinal product
The recommendations concern investigational medicinal products (IMPs), concomitant and background therapy products, and accompanying materials usually provided at visits and specified in the clinical trial protocol. Changes in their distribution may be necessary to avoid unnecessary visits to the trial site, as well as to provide subjects with the necessary treatment. The sponsor should assess the risks related to IMPs and consider any alternative mechanisms for organizing their delivery and storage conditions.
Such measures raise various practical considerations, in particular, whether the IMP can be stored at the participant's home, how the stability of the IMP during transportation will be ensured (especially the temperature regime and maintenance of the “cold chain”), and how its accountability and the assessment of adherence to the prescribed use (as defined in the CT protocol) will be organized.
The primary purpose of all changes in distribution is to provide trial participants
IMPs, concomitant and/or background therapy medicines, and ancillary materials as needed, in accordance with the clinical trial protocol and in order to avoid interruptions in IMP intake and treatment, to maintain a positive benefit/risk balance and to protect the rights, safety, and well-being of trial subjects, as well as the integrity of the data collected during the clinical trial. Continuation of IMP intake must be carried out under appropriate supervision of the responsible investigator.
Changes in the distribution of investigational medicinal products (IMPs) may include providing the subject with a greater quantity of IMP than is normally provided at a visit. The aim is to supply the subject with the necessary IMP for a longer period and to avoid the subject’s visits to the trial site. This may be done provided that the use of the IMP continues under the appropriate supervision of the responsible investigator. When conducting a clinical trial, it is recommended to maintain the necessary stock of all IMPs and other medicinal products to ensure continuity of their use in the event of their failed distribution. In case of an urgent shortage of IMP at some trial sites or as a result of moving subjects from one trial site to another, it may be necessary to redistribute IMP between trial sites in accordance with GMP Annex 13 (section 47). This should be considered only in cases where direct distribution of IMP to the trial site by the usual distributor is not possible or, in exceptional circumstances, when a subject is moved from one trial site to another. The sponsor should assess whether the trial sites can handle and control such a redistribution process, especially in the case of limited storage conditions. Redistribution should follow a written procedure established in cooperation with a qualified person or the person responsible for IMP distribution, and the trial sites need to be provided with sufficient information to ensure that this process can be carried out safely.
Adequate accompanying documentation on the transfer of the IMP must be kept in the trial file of the parties involved.
Along with the reduction in the number of physical visits to trial sites, the need may arise to deliver investigational medicinal products directly to the trial participant during the COVID-19 pandemic, in order to avoid the risk of spread/infection.
To ensure delivery of the IMP to the subject directly from the trial site, it is advisable to use the capacities of healthcare facilities/investigators/sub-investigators.
If, due to the COVID-19 pandemic, the trial site is unable to cope with the additional burden of shipping investigational medicinal products (IMPs) to subjects, then, as an exception, the IMP may be delivered to subjects by an independent distributor under an agreement concluded with the sponsor. In this case, it is necessary to conclude additional agreements and to make changes to the informed consent in the established procedure (a substantial amendment is required in accordance with Section X of the Procedure). Such methods of IMP delivery must not jeopardize the disclosure of subjects' personal data, confidential data, and the blinding of data processing. Responsibility for controlling the dispensing of the IMP remains with the principal investigator and the sponsor. Additional personnel involved in IMP delivery must undergo appropriate training, taking into account the storage and administration requirements. Their duties must be specified in the contract and/or the delegation log. Delivery of the IMP involving any courier service without a contract (under the above conditions) between it and the sponsor is prohibited.
All delivery procedures must ensure timely receipt of the IMP directly by the subject or their legal representative. Transfer of the IMP to a third party (a neighbor, etc.) is prohibited. The investigator must receive confirmation of all deliveries of the IMP and confirmation of their receipt by the subject by telephone/video contact or e-mail. The investigator remains
9. Specifics of conducting monitoring
Certain sponsor responsibilities – monitoring of clinical trials to ensure the quality of clinical trials – should be reassessed. Alternative proportionate monitoring arrangements may be temporarily required. The first priority when considering any changes is to protect the rights, safety, and well-being of clinical trial participants.
The scope of monitoring at the trial sites, if it remains possible, should take into account nationwide and local restrictions, urgency (e.g., source data verification can often be postponed) and the availability of trial site staff, and should be carried out only with the approval of the principal investigator and the administration of the healthcare facility. The overload of staff and trial sites resulting from the introduction of any alternative measures must also be taken into account to ensure an acceptable balance between appropriate monitoring and the potential and capabilities of the trial sites.
Adjustment of monitoring measures may include a combination of the following:
a). Monitoring at the trial site (On-site monitoring).
Cancellation or postponement of monitoring visits at trial sites and extension of the period between them will likely be required. Researchers must be informed of this in advance.
Additional monitoring measures at clinical trial sites may include limited, targeted on-site monitoring identifying clinical trial sites with a higher risk.
The monitoring plan at the trial site must be adapted and include alternative measures (such as those specified in items b), c) and d) below);
b). Centralized monitoring and central review of the collected data (Centralised monitoring and central review of data collected).
Centralized monitoring of data obtained by electronic data capture systems (for example, e-RF, central laboratory or ECG/CT/MRI, e-PRO, etc.) can supplement and temporarily replace monitoring at trial sites through remote evaluation of current and/or accumulated data collected in a timely manner from trial sites;
c) Remote (off–site) monitoring.
Additional off-site monitoring measures may include telephone/video visits, e-mails, or other online tools to discuss the status of the clinical trial with the investigator and the investigator's team. This activity can be used to obtain information on the progress of the clinical trial, to exchange information on resolving specific problems, to review procedures and the status of subjects, and also to facilitate remote selection of trial sites and training of investigators;
d) Remote verification of source data (Remote source data verification).
At present, remote source data verification (SDV) is justified only in individual cases, in particular, during clinical trials for the treatment or prevention of COVID-19 or at the final stages of data processing before database lock in key (pivotal) trials investigating serious and life-threatening conditions with no existing satisfactory treatment. The focus should be on quality control of critical data, such as primary efficacy data and important safety data. Important secondary efficacy data may be monitored at the same time, provided that this does not result in the need to access additional documents and does not increase the burden on trial site staff.
The sponsor must determine the volume, extent and nature of remote verification of source data that it considers necessary for each CT in this exceptional situation and must carefully weigh the possible additional burden on staff and technical resources during alternative monitoring options.
In these few cases, the responsible investigators should themselves determine whether the situation at their trial sites allows the following options for remote verification of source data:
- providing the monitor with anonymized (de-identified) copies of source documentation (this may be done electronically if performed by members of the research team);
- direct, appropriately managed remote access to the electronic medical records of trial subjects;
- video review of medical records with the support of research team members. In this case, no copy is sent to the monitor and no images are recorded during the review.
For clinical trials of medicinal products for the treatment of COVID-19 that are planned to be submitted for expert evaluation to the Center, remote verification of source data must be described in the protocol, the informed consent form, and, if necessary, other related documents.
It is extremely important that follow-up measures are planned and ready for implementation when the situation normalizes. This should probably include enhanced on-site monitoring for a period sufficient to ensure that the effect of reduced monitoring can be eliminated and problems resolved or properly documented for reporting in the CT report. Maintaining the blinding of the trial and data confidentiality is also very important.
All these measures should not create an additional excessive burden on the research team. Investigators should not be put under undue pressure to carry out remote verification of source data. The priority for investigators remains the medical care and attention that must be provided to study participants and other patients.
10. Changes in the conduct of the clinical trial audit
It is recommended to postpone sponsor audits. In extreme cases, with the agreement of the principal investigator and the administration of the healthcare facility, an audit may be conducted directly at the trial site, as well as a remote audit, if this inspection is critically important for investigating serious violations during the conduct of clinical trials, serious adverse reactions, etc.
11. Deviations from the clinical trial protocol
Due to the inevitable increase in deviations from the CT protocol, the sponsor needs to analyze their number and types to assess the need for appropriate amendments to the CT protocol. All protocol deviations must be urgently documented in the source documents, and information about such deviations (for example, by an information letter) is provided to the Center. In the case of deviations from the CT protocol that require substantial amendments, the relevant documents must be submitted to the Center and the local ethics committee (LEC) (Section X of the Procedure). If the relevant substantial amendments are not submitted and approved in the established manner, the CTs will be considered to have been conducted not in accordance with the CT protocol.
12. Reimbursement of expenses
For the implementation of urgent measures to protect trial subjects participating in clinical trials in connection with the spread of coronavirus disease (COVID-19) and the measures taken to prevent its spread in Ukraine, additional unforeseen costs may arise, which must be compensated by the clinical trial sponsor. All additional financial compensation to healthcare facilities/investigators/sub-investigators must be documented and made in accordance with the current regulatory legal acts of Ukraine.
13. Conducting bioequivalence studies involving healthy volunteers amid the spread of the coronavirus infection COVID-19
The sponsor / applicant / investigators, when conducting bioequivalence studies and in the context of the spread of COVID-19, must apply, but not limit themselves to, the following measures:
- determine the sites for conducting bioequivalence studies and the conditions for their conduct taking into account the requirements of the Resolution of the Cabinet of Ministers of Ukraine of 22 July 2020 No. 641 “On the establishment of quarantine and the introduction of enhanced anti-epidemic measures in the territory with significant spread of acute respiratory disease COVID-19 caused by the coronavirus SARS-CoV-2”, as amended (if a “red” or “orange” level of epidemic danger is established in the territory of the region where the study is planned, such studies must be postponed until the level of epidemic danger decreases;
- to admit to screening procedures potential trial participants who have a negative result of a SARS-CoV-2 test performed by PCR analysis of nasopharyngeal biomaterial to confirm the absence of infection with the SARS-CoV-2 virus within 48 hours before screening and the next stage of the study, in which, after the informed consent form is signed, contactless thermometry and a questionnaire regarding the sanitary and epidemiological environment over the last 14-21 calendar day will be carried out;
- only those subjects are allowed to participate in each subsequent study period (“day 0”) who have negative results of testing of nasopharyngeal biomaterial by the PCR method confirming the absence of infection with the SARS-CoV-2 virus within 48 hours before the start of each study period (hospitalization for all necessary procedures in accordance with the requirements of the study protocol), and who have undergone non-contact thermometry and a physical examination;
- conducting PCR testing of medical staff of trial sites who take part in clinical trials and have contact with volunteers, as well as of sponsor representatives (monitors of the clinical stage of the study), in accordance with internal procedures.
All measures taken that deviate from the CT protocol must be indicated in the source documents and explained, of which the sponsor/applicant informs the Center and subsequently must submit substantial amendments to the CT materials in accordance with Section X of the Procedure. Such changes may be part of a consolidated amendment.
The sponsor / applicant and investigators must anticipate in advance and describe in the protocol and other clinical trial materials all possible risk minimization measures, in particular to prevent the spread of COVID-19 among trial subjects and medical personnel, if a clinical trial of medicinal products is planned in order to demonstrate their bioequivalence, as well as for clinical trials of medicinal products for the treatment of coronavirus disease (COVID-19).
14. On the work of Ethics Committees at treatment and preventive institutions
The Law of Ukraine “On Amendments to Certain Legislative Acts of Ukraine Regarding the Provision of Treatment of Coronavirus Disease COVID-19” of 20.03.2020 No. 539-IX adopted the following: “… conducting expert evaluation of clinical trial materials of medicinal products for the treatment of coronavirus disease (COVID-19) and substantial amendments thereto, provided that such materials are submitted in Ukrainian or English, within up to five calendar days”. The local ethics committee (LEC) must also be guided by this provision.
In view of the above, local ethics committees (LECs) are recommended to take all possible appropriate measures to ensure uninterrupted operation, in accordance with their Regulations, in the conditions of the COVID-19 outbreak and compliance with the quarantine regime in order to prevent the spread of COVID-19, but taking into account and using personal protective equipment for LEC members.
At the same time, the work of local ethics committees during the quarantine period should be continued, taking into account the recommendations:
and regulatory agencies:
(https://www.gov.uk/guidance/managing-clinical-trials-during-coronavirus- covid-19).
Local ethics committees (LECs) must adapt their standard operating procedures in terms of taking appropriate measures for conducting clinical trials of medicinal products and reviewing clinical trial materials in the context of the coronavirus disease outbreak (COVID-19).
Thus, the safety and rights of trial subjects are the top priority during their participation in clinical trials.
Due to the quarantine measures introduced in the country, it is necessary to take into account the recommendations on conducting clinical trials published on the Center's website (https://dec.gov.ua/announcement/do-uvagy-zayavnykiv-ta-doslidnykiv/).
