Frequently asked questions

What clinical trial safety reports must the sponsor submit if the clinical trial is conducted in accordance with Regulation (EU) No. 536/2014 of the European Parliament and of the Council on clinical trials on medicinal products for human use and repealing Directive 2001/20/EC?

The safety reports specified in Articles 42 and 43 of the Regulation (respectively, "Reporting of suspected unexpected serious adverse reactions by the sponsor to the Agency" and "Annual reporting by the sponsor to the Agency") must be submitted electronically to the Eudravigilance database.

Is it necessary to submit a Study Progress Report to the sponsor if the clinical trial is conducted in accordance with Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC?

If a clinical trial is conducted in accordance with Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC, Study Progress Reports are not required.

Is it necessary to have the Informed Consent Form for post-authorisation safety studies of a medicinal product coordinated with the Lithuanian Bioethics Committee?

The current legislation does not require that the Informed consent form used in such studies be submitted to the Lithuanian Bioethics Committee for approval.

What language is required for the documentation of clinical trials on medicinal products?

The documents for Part II of the clinical trial application, sample forms of which are provided in the Recommendations on the list of documents and sample forms for Part II of the application for clinical trials on medicinal products submitted to the Republic of Lithuania, approved by the decision of the meeting of the Lithuanian Bioethics Committee's group of experts on biomedical research on May 17, 2022, should be submitted in Lithuanian.

Is there a state fee for the authorisation of a clinical trial of a medicinal product or a substantial modification of a clinical trial of a medicinal product?

A state fee of a fixed amount shall be charged for the authorisation of a clinical trial on a medicinal product or a substantial modification of a clinical trial of a medicinal product.

What patient facing documents must be provided by the sponsor as part of the dossier when conducting a clinical trial on a medicinal product?

In accordance with points L61 and K60 of Annex I to Regulation (EU) 536/2014, the sponsor should, when submitting an application for the approval of a clinical trial, only provide the information intended for the subjects prior to their decision to participate in the clinical trial, as well as the recruitment (promotional) material to be used in the trial (with the Part II documentation only). In accordance with Q-A 1.24(79), patient-facing documents that are relevant to the outcome of the trial should be submitted with the protocol and Part I documents.

However, it is important to note that, in accordance with the Rules of Good Clinical Practice (ICH GCP 1.2.2), which are also referred to in the Regulation, traditionally, and in most countries still, all patient-specific material was, and continues to be submitted to ethics committees.

Recognising the currently existing legal uncertainty regarding the interpretation of different documents and practices, in order to avoid unnecessarily increasing the administrative burden for business entities, the Lithuanian Bioethics Committee recommends that, until a more precise clarification of the issue can be provided, the submission of patient-specific documents should be limited to the patient-specific documents listed in Annex I, points K and L of the Regulation, and that the decision for the need for submission of other patient-specific documents should be left at the discretion of the sponsor.

What are the requirements for the sponsor in the event of Serious Breaches/deviations of the protocol during a clinical trial in Lithuania?

Serious Breaches (SB) occurring during clinical trials are reported via the EU portal in accordance with Article 52 of Regulation (EU) No 536/2014 (this applies to trials authorised under the Regulation (EU) No 536/2014 procedure).

For more information on SB notification via the EU portal, see the EMA guidelines Guideline for the notification of serious breaches of Regulation (EU) No 536/2014 or the clinical trial protocol.

Does the customer have to submit an Annual Progress Report?

Regulation (EU) No 536/2014 does not require the submission of this notification and therefore the Lithuanian Bioethics Committee does notneed to submit it.

What are the steps for a sponsor to make an amendment to a biomedical study?

In accordance with points 14 and 15 of the Order of the Minister of Health of the Republic of Lithuania of 4 January 2008 No.V-2 "On the approval of the procedure for the granting of permits for biomedical research", you are required to inform the Lithuanian Bioethics Committee in an official letter of your planned changes.

What language is required for the documentation of biomedical research (except for clinical trials of medicinal products and medical devices)?

Documents relating to biomedical research (except for clinical trials of medicinal products and medical devices) must be submitted in Lithuanian, but the protocol may be submitted in Lithuanian or English.

Is there a state fee for the authorisation to conduct biomedical research or for a modification to biomedical research?

If the authorisation to conduct biomedical research is issued by a regional biomedical research ethics committee, no state fee is charged.

If the authorisation to conduct biomedical research is issued by the Lithuanian Bioethics Committee, a fixed state fee is charged for issuing the authorisation.

No state fee is charged for modifications of biomedical research.

Under which conditions is research classified as a biomedical research?

To qualify as biomedical research, a research study must meet all of the following conditions:

1. it uses scientific methods of inquiry, it creates new scientific knowledge and it tests a scientific hypothesis;

2. the research belongs to the field of biomedical sciences (testing a hypothesis in one or more of the fields of medicine and health sciences);

3. the research aims to advance scientific knowledge about human health, disease, its diagnosis, treatment or prevention;

4. the subject of the research is a living or dead human being or group of human beings, a human embryo, a human foetus, a human biological sample or health information.

If a research project does not meet at least one of the four conditions, it does not fall within the scope of the Republic of Lithuania Law on Ethics of Biomedical Research.

What language is required for the documentation of clinical trials on a medical device?

The application for a clinical trial on a medical device, the Summary of the Clinical Trial and the documents to be used to obtain informed consent, including the Patient Information and Informed Consent Form(s), shall be submitted in the official language of the Republic of Lithuania. Other documents may be submitted in the national language (Lithuanian) or English.

If consent will be sought from a person or other person entitled to give consent who does not understand the Lithuanian language, the Information and Informed Consent Form(s) for participation in a clinical trial on a medical device in their native language or in another language which they understand, and the certification by the translator of the translation as to whether it is in accordance with the Lithuanian version of the documents, shall be submitted.

Is there a state fee for the authorisation of a clinical trial of a medical device / in vitro diagnostic medical device or a substantial modification of such clinical trial?

A state fee of a fixed amount shall be charged for the authorisation of a clinical trial of a medical device / in vitro diagnostic medical device or a substantial modification of such clinical trial.

What language is required for the documentation of clinical trials on in vitro diagnostic medical devices?

The application for a clinical trial on an in vitro diagnostic medical device, the Summary of the Trial and the documents to be used to obtain informed consent, including the Patient Information and Informed Consent Form(s), shall be submitted in the official language of the Republic of Lithuania. Other documents may be submitted in the national language (Lithuanian) or English.

If consent will be sought from a person or other person entitled to give consent who does not understand the Lithuanian language, the Information and Informed Consent Form(s) for participation in a clinical trial on an in vitro diagnostic medical device in their native language or in another language which they understand, and the certification by the translator of the translation as to whether it is in accordance with the Lithuanian version of the documents, shall be submitted.

What requirements apply to clinical trials with a CE-marked medical device when the device is intended to be used for its intended purpose?

If, in addition to the procedures performed under normal conditions of use of the device, the subjects participating in the trial will undergo additional procedures that are invasive or excessively burdensome, the sponsor shall notify the State Accreditation Service for Health Care Services of the trial at least 30 days before the start of the trial and shall include in the notification the documentation specified in Chapter II of Annex XV to Regulation (EU) 2017/745. Article 62(4)(b) to (k) and (m), Article 75, Article 76, Article 77, Article 80(5) and the relevant provisions of Annex XV shall apply to post-market clinical follow-up investigations.

If the subjects participating in the study will not be subjected to additional invasive or excessively burdensome procedures beyond those performed under normal conditions of use of the device, the study shall be considered a biomedical study and shall fall within the scope of the Republic of Lithuania Law on Ethics of Biomedical Research.

What requirements apply to clinical investigations of a CE-marked medical device when the device is intended to be used for an unanticipated purpose?

If a clinical trial is to be conducted to evaluate a CE-marked medical device in accordance with Article 20(1) of Regulation (EU) 2017/745 for an unintended use, Articles 62 to 81 of the Regulation shall apply.

What is the valid period of a biomedical research authorization?

A biomedical research authorization is valid until the end of the research specified in the research application or protocol.

Is ethical committee approval required for scientific research that does not involve patients but analyzes health information or examines previously collected biological material (biological samples)?

The Law on Biomedical Research Ethics (Article 3(1)) stipulates that biomedical research may involve not only living or deceased persons, but also human embryos or fetuses, human biological samples, and health information. Therefore, the approval of an ethics committee is also required for such research.

Do student research projects require approval from the Lithuanian Bioethics Committee or a regional biomedical research ethics committee?

Student research projects are not usually considered biomedical research and are not subject to the requirement to obtain approval from a research ethics committee. This is because the purpose of most student research projects is not to develop and test new scientific hypotheses or generate new scientific knowledge, but to acquire the knowledge and skills necessary for them to conduct scientific research in the future. Also, most students have not yet acquired the right and necessary qualifications to be researchers (i.e., they do not have a higher education degree).

The requirements for patient participation in the training process are set out in Article 11(2), (3) and (4) of the Law on Patients' Rights and Compensation for Damage to Health. The law stipulates that when a patient is involved in the teaching process in healthcare institutions where healthcare professionals are trained, the patient must sign a document confirming that they have read and understood the internal rules of the healthcare institution. These rules must state that the patient is being included in the training process. A patient who has signed to confirm that they have read the internal rules of the healthcare institution where healthcare professionals are trained is deemed to have agreed to be included in the training process. A patient who does not agree to participate in the training process or does not agree to the use of information about them for scientific and training purposes shall state this in writing. His written statement must be kept in the patient's medical records. Therefore, in cases where a patient has expressed his disagreement to participate in the training process, students would not be able to use their health information (medical history or other documents), interview the patient, etc. Article 11(5) of the Law on Patients' Rights and Compensation for Damage to Health also stipulates that the use of information for scientific and educational purposes must not violate the patient's privacy. The procedure for using the information contained in the patient's medical records for teaching purposes, while ensuring the protection of personal privacy, is established by the healthcare institution where this information is stored.

Thus, students may use information about patients stored in healthcare institutions and interview patients, examine or perform certain procedures for the purposes of their research work in accordance with the procedure established by the healthcare institution and in compliance with the general ethical requirements for research involving human subjects – informing individuals, obtaining their consent, ensuring confidentiality, respecting privacy, etc.

However, if the idea and plan of a student's research work aims to generate new scientific knowledge, test new valuable hypotheses, etc., such work should be supervised by a specialist with experience in biomedical research who meets the qualification requirements for researchers set out in the Law on Science and Studies[1]. Such research requires the permission of an ethics committee and is subject to other requirements. We remind you that Article 2(7) of the Law on Biomedical Research Ethics defines biomedical research as "the testing of hypotheses in biomedical sciences using scientific research methods with the aim of developing scientific knowledge about human health, diseases, their diagnosis, treatment, or prevention." Activities that are considered biomedical research are subject to the requirements set forth in Article 5 of this law[2].

It should be noted that, according to the definition of a researcher provided in Article 4(27) of the aforementioned Law on Science and Studies, only a person (student) with at least a bachelor's degree can be a researcher. In this case, the name, surname, field of study, and course of a student participating in biomedical research and meeting this criterion could be included in the list of researchers in the application for biomedical research submitted to obtain the ethics committee's permission to conduct biomedical research.

If a student does not yet have a higher education degree, they may participate in biomedical research led by other researchers, but they cannot be granted researcher status. However, the student's name, surname, field of study, and course could also be listed in the Application for Biomedical Research in the list of other persons conducting the research.

[1] Article 4(27) of the Law on Science and Studies defines a researcher as "a person with a higher education who develops knowledge, conceptualising or creating new products, processes, methods and systems, or leading scientific research and experimental (social, cultural) development projects".

[2] Biomedical research must have scientific and practical value; biomedical research cannot be replaced by other research that does not involve human subjects; the protection of the interests of the research subject and the confidentiality of his or her health information must be ensured; the person's consent to participate must be obtained; documents from the institutions specified by law granting the right to conduct biomedical research must be obtained.

Is an authorisation to conduct biomedical research and informed consent required for biomedical research involving health data?

The Lithuanian Bioethics Committee (LBEC) receives inquiries regarding the requirements for obtaining permission from the research ethics committee to conduct biomedical research and informed consent to participate in biomedical research when conducting research using health data that was collected prior to the application for permission to conduct biomedical research.

The question is whether researchers conducting biomedical research with health data obtained through the State Data Agency in accordance with the procedure established by the Law on the Reuse of Health Data (Pakartotinio sveikatos duomenų naudojimo įstatymas (PSDNĮ), and when exceptions to the requirement to obtain informed consent to participate in biomedical research apply.

In the opinion of the LBEC, there are two different situations in which health data collected prior to the application for permission to conduct biomedical research may be used for biomedical research:

If health data for biomedical research [1] is obtained through the State Data Agency (VDA):

a permit from the VDA is required to reuse the data (PSDNĮ Article 3(1)) and a permit from the LBEC or the Regional Biomedical Research Ethics Committee (RBTEC) is required to conduct biomedical research (Article 5(2)(9) of the Law on Biomedical Research Ethics (Biomedicininių tyrimų etikos įstatymas (BMTĮ)). The legislation does not specify the order in which these permits must be obtained, so this is decided by the applicant (researcher and/or research sponsor);

in this case, an exception to the requirement to obtain a person's consent to participate in biomedical research applies in accordance with Article 12 of the PSDNĮ and Article 5(2)(4) and Article 7(1) of the BMTĮ

If health data and samples for biomedical research are obtained directly from data controllers:

a permit from the LBEC or RBTEC is required to conduct biomedical research (Article 5(2)(9) of the BMTĮ);

in this case, when issuing a permit to conduct biomedical research, the LBEC or RBTEC shall consider the grounds for exemption from obtaining the consent of the research subject in accordance with Article 7(11) of the BMTĮ.

[1] Biomedical research is understood as the testing of hypotheses in biomedical sciences using scientific research methods, with the aim of developing scientific knowledge about human health, diseases, their diagnosis, treatment, or prevention (BMTĮ 2 str. 7 d.).

Issues related to informed consent 4

Article 2(13) of the Law on Biomedical Research Ethics stipulates that a person's consent to participate in biomedical research must be voluntary, clear, informed, and in writing. Can it be given electronically? If so, what requirements apply to such consent?

This clarification has been prepared in accordance with the legislation regulating the assurance of electronic identification and the reliability of electronic transactions and the recommendations of the European Medicines Agency on computerised systems and electronic clinical trial data [1].

According to Article 5(1) of the Law on Electronic Identification and Trust Services [2], "an electronic signature that does not meet the requirements for a qualified electronic signature set out in Regulation (EU) No. 910/2014 shall have the same legal effect as a handwritten signature, provided that the users of such electronic signatures agree in advance in writing and that it is possible to store this agreement on a durable medium." Thus, a simple electronic signature would be equivalent to a signature signed by hand by a natural person if the parties agree in advance that future agreements will be concluded electronically and/or by other means and the agreement is stored on a durable medium.

It is important to note that this agreement must be stored on a durable medium, the concept of which is explained in Directive 2011/83/EU of the European Parliament and of the Council on consumer rights [3]. A durable medium is a device that allows the consumer or trader to store information addressed personally to them in a way that allows the information to be accessed for a certain period of time and allows the stored information to be reproduced unchanged.

In summary, it can be concluded that a person's consent may be given electronically and/or by other means, by signing with a non-qualified electronic signature, if the parties have previously agreed on these conditions in writing, i.e., the initial contract must be signed with a physical signature (on paper) or a qualified electronic signature. In biomedical research, this agreement could be expressed when the subject first signs the informed consent form for participation in biomedical research, which would provide for the possibility of signing subsequent consents with a simple electronic signature.

Regarding the possibility for a person to sign consent on a tablet computer

Article 25 of Regulation (EU) No. 910/2014 of the European Parliament and of the Council on electronic identification and trust services for electronic transactions in the internal market provides that " the legal validity of an electronic signature and its admissibility as evidence in legal proceedings may not be denied solely on the grounds that it is an electronic signature or that it does not meet the requirements for a qualified electronic signature." Pursuant to Article 1.73(2) of the Civil Code, "documents signed by the parties and transmitted by telecommunications terminal equipment shall be deemed equivalent to documents in written form, provided that the text is protected and the signature can be identified."[5]

According to the explanation of the Chief Archivist of Lithuania [6], in order for digitized signatures on a tablet to be suitable for expert identification of the signatory, the established requirements for equipment must be met. It should be noted that the signatory must be provided with conditions as close as possible to normal writing, using a special writing tool adapted for this purpose. It is important to assess whether the equipment used for the digitized signature captures the biometric information required for expert examination – the position of the signature in the X and Y coordinate system, the duration and speed of signing, and pressure data. The image of the signature recorded on the device, usually saved in *.pdf format, is not sufficient for expert analysis of handwriting – the aforementioned biometric data is also necessary.

If the tablet computer had the ability to ensure text protection and the ability to identify the signature (person) if necessary, such a signature would be considered valid consent to participate in biomedical research. However, if the parties cannot ensure the two necessary requirements, in the event of a future dispute, the parties would have to prove the fact of consent by other means. If a dispute arises between the parties regarding the fact of signing the relevant consent and it is examined in court, the evidence would be assessed in accordance with the rules laid down in procedural law.

In summary, it can be said that a written signature on a tablet screen could have the same legal force as a handwritten signature on a paper document, provided that the above-mentioned requirements for signing on a tablet screen are met, suitable for expert handwriting analysis, and a reliable link between the signature and the content of the document.

We remind you that when signing informed consent forms with an electronic signature, all requirements set out in the Law on Biomedical Research Ethics, Regulation (EU) No. 536/2014 [7] and GCP rules [8] relating to patient information and obtaining informed consent apply, as well as the requirement set out in Article 58 of Regulation (EU) No. 536/2014 and point 8.3.12 of the GCP rules that the sponsor and principal investigator must ensure that the signed consent forms are stored at the trial site for 25 years after the end of the clinical trial.

REFERENCES:

1. EMA Guideline on computerised systems and electronic data in clinical trials {accessed at https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/guideline-computerised-systems-electronic-data-clinical-trials_en.pdf}

2. Law on Electronic Identification and Trust Services for Electronic Transactions of the Republic of Lithuania

3. Directive 2011/ 83/EU on consumer rights, amending Council Directive 93/13/EEC and Directive 1999/44/EC of the European Parliament and of the Council and repealing Council Directive 85/577/EEC and Directive 97/7/EC of the European Parliament and of the Council

4. Regulation (EU) No 910/2014 of the European Parliament and of the Council of 23 July 2014 on electronic identification and trust services for electronic transactions in the internal market and repealing Directive 1999/93/EC

5. Civil Code of the Republic of Lithuania

6. Explanation by the Chief Archivist of Lithuania: "Could a written signature on a tablet screen have the same legal force as a handwritten signature on a paper document?" "Is it possible to sign an electronic document with a signature that does not meet the requirements for a qualified signature, and what is the legal validity of such a document?" {accessed at https://archyvai.lt/lt/klausimai---atsakymai.html}

7. Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use and repealing Directive 2001/20/EC

8. ICH E6 (R2) Good clinical practice - Scientific guideline {accessed at https://www.ema.europa.eu/en/ich-e6-r2-good-clinical-practice-scientific-guideline}

Is the patient's consent required if a doctor wants to describe a specific patient's case in a scientific journal or present it at a conference?

When deciding whether patient consent is required to describe a specific patient's case in a scientific journal or present it at a conference, the first thing to consider is whether the patient can be identified from the description or presentation. It is important to note that "personal data" or data that "identifies" a person is understood more broadly than just the mention of a name and surname. Personal data, as defined by the GDPR, is any information that can directly or indirectly help to identify a physical person. This can include audio, visual data, genetic information, or one or more characteristics specific to a person of a physical, physiological, psychological, economic, cultural, or social nature. Therefore, if the patient's case is presented at the conference in such a way that it does not allow the identity of the person in question to be determined either directly or indirectly, the law does not require the patient's consent. However, it is important to note that when a patient agrees to treatment and disclosure of information about themselves, they cannot foresee that this information may be used in a scientific journal or conference. Therefore, it is reasonable to assume that requesting consent would meet patients' expectations. This is one of the reasons why well-known medical journals require patient consent when publishing case reports (e.g., The Lancet, Journal of Medical Case Reports, Journal of the American Medical Association, and others).

Is a person's consent required for a retrospective study involving previously collected health information or human biological material (biological samples)?

According to Article 7 of the Law on Biomedical Research Ethics, biomedical research may only be conducted with the written consent of the person (or their legal representative). However, when the subject of biomedical research is human biological material and/or health information collected previously for healthcare, statistical, or other purposes, the ethics committee issuing the approval shall decide on the need to obtain the person's consent. In such a case, the researcher (research sponsor) must submit, together with other research documents, a request for exemption from the requirement to obtain the informed consent of the person, stating and explaining the reasons for such a request.

What information should be provided in the Informed Consent Form when the sponsor intends to use biological samples and/or health information collected during a particular clinical trial for future research?

The information on the use of samples and coded data for purposes other than those directly related to the trial provided in the main Informed Consent Form may not be sufficiently clear or even misleading to the trial participant, as the use of biological samples and coded data remaining after the end of the clinical trial for future research is not mandatory for participation in the primary clinical trial and not necessary for the fulfilment of the objectives of a given clinical trial.

In view of this, we recommend:

(a) developing a separate Informed Consent Form on the use of biological samples and coded data collected during the trial for future research, which clearly specifies the purposes for which the collected samples or coded data will be used, for how long and where they will be stored, and discusses the personal data issues and other relevant information.

(b) in the Consent section of the Informed Consent Form, include a box for the subject to agree or not to agree to the use of personal data for the additional purposes of research, diagnostics or the development of other medical devices, preceded by a statement in the text of the consent form to this effect.

Issues related to vulnerable persons 3

When can vulnerable persons be included in a clinical trial (i.e., a trial involving living human beings)?

Clinical trials involving vulnerable persons are permitted if at least one of the following three conditions is met:

1) when the clinical trial can only be conducted with vulnerable persons and there is scientific reason to believe that participation in the clinical trial will provide the subject with direct benefits that outweigh the risks and inconveniences associated with the clinical trial;

2) when the clinical trial can only be conducted with vulnerable persons and the clinical trial is directly related to the health condition of the subject and there is scientific reason to expect that participation in the clinical trial will be beneficial to the group of persons not participating in the trial to which the subject belongs, and the interventional research methods used for the purpose of the clinical trial have a minor undesirable temporary effect on the subject's health;

3) when the clinical trial is directly related to a life-threatening or debilitating health condition of the subject, for which there is no adequate healthcare available, and there are scientific grounds to expect that participation in the clinical trial will provide the subject with direct benefits that outweigh the risks and inconveniences associated with the clinical trial.

Who are considered vulnerable persons?

According to Article 6 of the Law on Ethics of Biomedical Research of the Republic of Lithuania, vulnerable persons whose consent to participate in biomedical research may be influenced by external circumstances or who are partially or completely unable to defend their interests are considered to be:

persons who, due to their state of health, cannot be considered capable of reasonably assessing their interests;
children;
students, if their participation in biomedical research is related to their studies;
persons living in social care institutions;
soldiers during their actual military service;
employees of healthcare institutions where biomedical research is conducted who are subordinate to the researcher;
persons in prisons or other places of deprivation of freedom.

Please note that the Lithuanian Bioethics Committee or the regional biomedical research ethics committee, when evaluating documents for the issuance of a permit to conduct biomedical research, and the Lithuanian Bioethics Committee, when evaluating documents, may, by a reasoned decision, recognize other groups of persons as vulnerable persons.

Is the consent of both parents always required when conducting biomedical research involving children?

Article 7(3) of the Law on Ethics of Biomedical Research of the Republic of Lithuania stipulates that the consent of a child to participate in biomedical research is given by the child's legal representatives.

Given that the father and mother, even if they do not live with the child, have the right and duty to communicate with the child and participate in his or her upbringing (Article 3.170 of the Civil Code of the Republic of Lithuania), the consent of both parents is required for the child to be included in a biomedical study, except in cases where 1) it cannot be obtained for objective reasons, or 2) one of the parents authorizes the other to act on their behalf and this is formalized in a notarized form, or 3) the right to make decisions relating to the child's health and/or representation in healthcare institutions is granted to only one of the parents by a court decision.

1) The following circumstances are considered objective: one of the parents is deceased, incapacitated, declared dead or missing by a court, or one of the parents has had their parental rights restricted.

2) There may also be cases where one parent could act on behalf of both parents. For example, when the child's mother and father sign a power of attorney at a notary's office, which provides that that one parent (the principal) authorises the other parent to represent the child in healthcare institutions and to make decisions relating to the child's health on his or her behalf (the represented parent). In this case, one parent would act on behalf of both parents (the principal and the representative), thus expressing the will of both parents regarding the clinical trial.

3) The exclusive right of one of the parents to make decisions related to the child's health and/or representation in healthcare institutions may also be established by a court decision (ruling) (Article 18 of the Civil Procedure Code of the Republic of Lithuania).

Please note that a child who is capable of understanding the information provided to them has the right to express their wish not to participate or to withdraw from participation in a biomedical trial. In such cases, the child's wishes must be respected, regardless of the parents' consent. However, this provision does not apply when non-participation or withdrawal from participation is contrary to the interests of the child. The child's representatives shall decide whether the child's wish not to participate in the research is contrary to the child's interests, taking into account the opinion of the researcher.

How to find out which insurers provide mandatory civil liability insurance for principal investigators and sponsors of biomedical research?

Article 12(2) of the Law on Biomedical Research Ethics obliges the sponsor of a biomedical study and the principal investigator when conducting a clinical trial of a medicinal product or any other biomedical study in which the intervention methods used for the purposes of the biomedical research pose a risk to the health of the participant, insure their civil liability for damage that may occur to the subject during the biomedical research by concluding compulsory civil liability insurance contracts with insurers for the sponsor and principal investigator of the biomedical research, in accordance with the procedure established by law, have the right to carry out compulsory civil liability insurance for the sponsor of the biomedical research and the principal investigator.

According to Article 3 of the Insurance Law of the Republic of Lithuania, the following entities have the right to carry out insurance activities in the Republic of Lithuania:

1) Insurance companies established in accordance with the procedure laid down by the laws of the Republic of Lithuania: public limited companies, private limited companies, and European companies (Societas Europaea) that have obtained an insurance activity license.

Please note that the license grants the right to carry out compulsory insurance risk insurance activities only if this is specifically indicated in the license itself, therefore, the license must specify that the insurance company has the right to carry out compulsory insurance of the civil liability of principal investigators and sponsors of biomedical research.

2) Insurance companies from other European Economic Area (EEA) countries that exercise the right of establishment and/or the right to provide insurance or reinsurance, insurance or reinsurance intermediary services.

These companies may provide compulsory civil liability insurance for the sponsor of a biomedical study and the principal investigator if they are authorized to carry out general civil liability insurance activities in Lithuania.

3) Branches of third-country insurance companies established in the Republic of Lithuania that have obtained authorisation to carry out insurance activities as branches.

The list of insurance companies and insurance activity licences can be found on the website of the Bank of Lithuania: http://www.lb.lt/draudimo_imones

What are the liability insurance requirements for biomedical research where subjects may only experience temporary, minor adverse effects?

If the biomedical research involves interventional techniques that cause only minor and temporary adverse health effects in the subjects, a copy of the health care institution's third party liability insurance contract must be submitted with the study documentation (if the contract provides for indemnification for damage that may occur in this type of research and if the health care institution or its employee is the sponsor or investigator of the research).

The list of biomedical research methods with minor adverse temporary effects on the subject's health to which this requirement applies is set out in Order No V-1483 of the Minister of Health of the Republic of Lithuania of 31 December 2014.

Will investigators need to obtain a new Good Clinical Practice training certificate when the new version of the ICH Guideline for Good Clinical Practice E6(R3) comes into effect on July 23, 2025?

All investigators, including those with clinical trial experience, must complete training on the new version of the ICH Guideline for GCP E6 R3. Investigators are not required to have certificates confirming their participation in this training; it is sufficient to document the fact that they have completed the training in a training log or similar document. For new (inexperienced) investigators, the usual procedure applies – a GCP training certificate is mandatory.

In which cases is it necessary for an investigator of a clinical trial to have a certificate of training in Good Clinical Practice (GCP)?

The GCP certificate must be obtained by investigators who have not participated as an investigator in clinical trials on medicinal products within the last five years.

How long is the Good Clinical Practice (GCP) certificate valid for?

The GCP certificate has no expiry date unless otherwise stated on the certificate. The GCP training is designed to update the knowledge on conducting clinical trials.

What are the requirements for indicating in the patient-facing documents that health checks/the investigational medicinal product are free of charge?

In accordance with point 2.7 of the Lithuanian Bioethics Committee's Recommendations on advertisements inviting subjects to participate in clinical trials of medicinal products, we recommend that the information provided to the subject should state that the subject will receive the investigational medicinal product/health checks free of charge, as in all clinical trials of medicinal products in which investigational medicinal products/health checks are provided free of charge. health checks free of charge, as in all clinical trials of medicinal products in which the investigational medicinal products/health checks are provided free of charge.

Advertising material will be used to recruit subjects into the clinical trial. What are the requirements in Lithuania?

The Lithuanian Bioethics Committee's guidelines on advertisements when inviting subjects to participate in clinical trials on medicinal products are available in Lithuanian here (link: https://bioetika.lrv.lt/media/viesa/saugykla/2024/1/wRHxo9ygzTU.pdf).

Advertising material will be used to recruit subjects into the clinical trial. When submitting the clinical trial dossier, what information, in addition to the promotional material itself, should be submitted for evaluation?

When various advertising materials (printed trial information material, flyers, posters, advertisements, email invitations, etc.) are to be used in the clinical trial, the following information should be submitted for evaluation:

A reasoned explanation of why it is necessary to invite subjects to the study̨ by means of promotional advertisements;
how patients who prove to be ineligible for the trial at the first visit will be treated (whether they will be given qualified help or advice in the same facility, whether information on where to go for help, etc.);
an explanation of where (e.g. in which health care institutions, health-related or other publications) it is intended to place the advertisement to be submitted, and whether this will be a one-off placement of an advertisement;
whether travel (or other) reimbursement is foreseen for those who will and will not meet the inclusion criteria;
if the data of respondents̨ will be collected, an explanation of what personal data will be collected, how long it will be kept, justification for the duration of the storage and confirmation that the collected personal data will be kept in accordance with the requirements for the protection of personal datą.