Checklist for Clinical Trial Applications for Medicinal Products under the Directive

REPORT VIA THE COMMITTEE SYSTEM DATABASE
The documents must be submitted as independent pdf files.

1. Notification form (Both the trial responsible and the sponsor must sign)
2. Protocol in Danish or English version
   1. An international protocol must be supplemented with Danish special requirements in an appendix if the international protocol does not comply with Danish law. The appendix must refer to the original project title and have a date and version number
   2. Procedures for oral information, as part of the protocol.
3. Investigators Brochure (For marketed products, the product summary can be used)
4. Protocol summary
5. Participant information
6. Consent forms and possible power of attorney
7. Questionnaires (possibly in a single file)
8. Recruitment material
   E.g., advertisements, postings, recruitment letters, text on www.sundhed.dk or social media
9. Documentation of insurance if the Patient Compensation does not cover
   Guidelines on Insurance and Compensation
10. Danish version of relevant parts of the sponsor contract
    About publication conditions and honorarium to researcher/participants, as well as the researcher's access to data
11. Copy of the notification to the Medicines Agency (the front page) or receipt
12. Documentation of the trial responsible's experience and education
    For all trial responsibles at all Danish sites. NB! Only one responsible per site.
    1. CV
    2. Certificate of education or authorization number/id
13. Documentation of all trial responsibles and sponsors' identity
    Danish sites – NB! Only one responsible per site.
    1. For the trial responsibles e.g., copy of health card, driver's license, or passport. Possibly the last 4 digits of the social security number can be crossed out.
    2. For sponsors, the company's address and company CVR number must be included
    3. If the primary trial responsible or sponsor sends the email with a digital signature with the duly prepared application, this is considered sufficiently identified by the digital signature
14. Billing information
    A billing form must be attached at the same time as the application is submitted.
    1. Link to the form

Please note that there may be additional special requirements in some trials.

For substantive requirements for a drug protocol, please also refer to the Danish Medicines Agency's Guide to applying for permission for clinical trials with drugs in humans, section 5. The trial protocol.

THE PROTOCOL MUST CONTAIN THE FOLLOWING:

1. The original title
2. Purpose
   1. The trial's problem formulation, hypothesis, endpoints and rationale
   2. Short literature review and reference list
   3. If a previous trial is being repeated, then justify why
3. Method
   1. Including design, analysis method, and use of control group, randomization and placebo
   2. The practical implementation, examinations, and scope
   3. Possible deviations from a standard treatment
4. Statistical considerations
   1. Power calculation or other statistical consideration that justifies the number of trial subjects.
5. Trial subjects
   1. Inclusion criteria
   2. Exclusion criteria.
6. Risks, side effects and disadvantages in the short and long term
   1. Including safety measures that minimize pain, inconvenience, fear, and other risks.
   2. Risk of radioactive radiation
      The points below indicate the additional information that the committee system requires, in addition to the requirements described in The Danish Medicines Agency's guide (the requirements correspond to what a Danish protocol supplement must contain if you report an international protocol)
7. Biological material taken from trial subjects
   See also the Guide on the use of biological material in health science research projects and the Guide on genome research and IV. Special requirements: Research in genomes (if extensive mapping of the genome is carried out).
   Describe:
   1. Which and how much material is taken out
   2. To what purpose?
   3. Whether the material is destroyed after analysis
      If the material is stored in a research biobank(ie storage beyond 5-7 days after extraction):
   4. How long is the material stored?
   5. What is the purpose of the storage?
      If the material is sent abroad:
      1. Which country and what purpose?
   6. Account for compliance with the Data Protection Regulation and the Data Protection Act. When sending to third countries, supplement that the Data Protection Regulation's Chapter V is complied with (see the biobank guide section 5.4.3. Describe which country's legislation protects personal information abroad, if it is not the Data Protection Regulation and the Data Protection Act.
      If there is excess biological material at the end of the project, provide:
      1. Whether there is destruction or full anonymization of the material, or
      2. Whether the material is stored for future research, and that the data protection rules continue to be complied with
         If extra material is taken for future unspecified research:
         1. This is not the committee's jurisdiction, but is regulated by the Data Protection Regulation and the Data Protection Act. However, it can be stated in the protocol that the participants will be asked separately about this, in order to subsequently be able to document that the material in the biobank has been taken in connection with the specific research project.
8. Information from patient records
   If information from the patient record is to be used for the project, the following must be described (it is recommended that the information is collected in a clear and independent section of the protocol):
   1. It must be clear what information is needed and what the information is used for. A distinction must be made between information that is to be used before the trial subjects have consented.
   2. It should be stated that the information to be used in the project before consent is given from the trial subjects, is passed on to the researcher.
   3. It should be stated that the consent gives the trial responsible, sponsor and sponsor's representatives as well as any control authority direct access to obtain information in the patient's journal etc., including electronic journal, in order to see information about the trial subject's health conditions, which are necessary as part of the implementation of the research project and in control purposes, including self-control, quality control and monitoring, which they are obliged to perform.
9. Processing of personal data in the project
   
   1. You must inform that the Data Protection Regulation and the Data Protection Act are complied with. Note that it is the responsibility of the sponsor or the trial responsible to ensure that the data protection rules are complied with in connection with the processing of personal data in the project. There may be a requirement in the region or at the university for registration of the project on an internal list.
      Describe if personal data is sent abroad:
   2. Which country and what purpose?
   3. That the Data Protection Regulation and the Data Protection Act are complied with. When sending to third countries, supplement that Chapter V of the Data Protection Act is complied with (see The Danish Data Protection Agency website for further guidance on securing the level of protection when transferring personal data to third countries).
   4. Which country's legislation protects personal information abroad, if it is not the Data Protection Regulation and the Data Protection Act.
10. Economy
    
    1. Describe who initiated the trial
       If there are supporters, describe:
       1. Name of supporters, including the amount for each supporter (fixed sum and/or per trial person)
       2. How the support is included in the trial, eg remuneration of staff, laboratory examinations etc. (possibly attach budget)
       3. Whether the support is paid directly to the researcher, his/her department/institute, research fund or other
       4. Whether the researcher has financial ties to the supporter or other stakeholders in the trial.
11. Possible remuneration and/or other benefits to the trial subjects
    See also Appendix 1.pdf
    1. The size of the remuneration, including possible transportation allowance, lost earnings and/or inconvenience compensation
    2. How much will the participants be paid proportionally if they withdraw early
    3. Other benefits - financial value
    4. For trial patients, you must explain that the requirements in Appendix 1.pdf are met.
12. Recruitment of trial subjects and informed consent
    See the standard Guidelines for giving oral participant information
    If children and young people are included see: I. Special requirements: Drug trials with persons without legal capacity.
    If acute trial see: II. Special requirements: Drug trials in acute situations
    Beskriv rekrutteringen samt proceduren for mundtlig information og modtagelse af samtykket:
    1. How trial subjects are found and identified (posting, advertisement, recruitment letter, internet, social media, via treating doctor or via posting in patient records - see also item 8)
    2. How the first contact with the trial person takes place.
    3. The process of obtaining informed consent.
       
       1. Where, when and by whom the oral and written information is given.
          
          1. If it is exceptionally not the trial responsible doctor who informs, this must be justified separately, and the requirements for the informant must be stated (eg GCP experience, experience with the disease area, etc.).
       2. How it is ensured that the conversation takes place undisturbed.
       3. How the right to an assessor is ensured.
       4. What reflection time there will be between giving oral and written information and obtaining informed consent.
       5. When consent is sought to be obtained.
          The template Guidelines for giving oral information can be used

13. Publication of results

    1. State that positive, negative as well as inconclusive results are published, for example via www.clinicaltrials.gov or www.clinicaltrialsregister.eu

14. Scientific ethics

    Describe:

    1. Why risks, neither in themselves nor in relation to the trial's benefits, are indefensible, and
    2. Why the therapeutic gain for trial subjects or future patients justifies the trial.
       
       1. For placebo: State whether there is an effective treatment already, or that placebo is necessary for methodological reasons. How is it ensured that trial subjects are not exposed to risk or harm?
15. Relevant clauses in the contract

    1. This is about clauses in the contract between the sponsor and the trial site about publication, honorarium to researcher, and researcher's access to data. The clauses must be translated into Danish.

16. Information about compensation scheme
    

    Describe:

    1. Whether the trial is covered by patient compensation or separate insurance is taken out. See insurance guide 

You must submit a summary of the protocol, which should be a true and comprehensive description that can be understood by people without a healthcare education. It should be generally understandable Danish, where clinical professional terms are explained or rewritten.

THE PROTOCOL SUMMARY MUST CONTAIN THE FOLLOWING:

1. The project's original title (title as stated in the reporting database)
2. The trial manager/sponsor's name and trial site
3. The purpose of the trial
4. The trial's method, design and investigation procedures, including information on any research biobank
5. Trial subjects, including inclusion and exclusion criteria
6. Side effects, risks and disadvantages
7. Financial conditions
8. Recruitment of trial subjects
   Same requirements as for protocol point 12
9. Publication of trial results
10. Scientific ethical statement

The date and version number must be added to the document, and updated every time changes are made.

THE WRITTEN PARTICIPANT INFORMATION MUST DESCRIBE THE FOLLOWING:

1. The original title of the experiment (title as it appears in the clinical trial database)
2. Inquiry to participate in a research project
3. The purpose of the experiment, its significance, and scope
4. Method and practical organization of the experiment
5. Use of approved and non-approved medications
   
   1. Including names, dosage, and use of randomization, placebo, treatment-free periods, and possible interactions with other drugs
6. Risks of the experiment
   
   1. What risks, side effects, complications, disadvantages, and burdens can be anticipated in the short or long term - including radiation risks
   2. Possible safety measures
   3. It must be informed that there may be unforeseen risks and burdens associated with the experiment
7. Extraction of biological material from test subjects
   See Guide to the use of biological material in biomedical research projects
   Describe:
   1. Which material and how much material is taken out
   2. What is the purpose of the extraction?
   3. Whether the material is destroyed after analysis
      If the material is stored in a research biobank (i.e., storage beyond 5-7 days after it has been taken out):
   4. How long the material is stored
   5. What is the purpose of storage
      If the material is sent abroad:
   6. Which country and for what purpose?
   7. Account for the compliance with the General Data Protection Regulation and Data Protection Act. When sending to third countries, also inform about the country and recipient, and that Chapter V of the General Data Protection Regulation is complied with
   8. Describe, which country's legislation protects personal data abroad, if it is not the General Data Protection Regulation that applies
      If there is excess biological material at the end of the project:
   9. Whether the material will be destroyed or completely anonymized, or
   10. Whether the material will be stored for future research, and that the data protection rules continue to be complied with in that case. It must be clear that new research in the biological material must be approved by an ethics committee and that new consent must generally be obtained, but the committee can grant dispensation (see section 5.2.2. in the biobank guide).
8. Journal information
   If patient journal information is to be used in the project, it must be stated:
   
   1. What information is used, and the purpose of it
   2. That the test subject's consent gives the person responsible for the experiment, the sponsor and its representative direct access to relevant health information in the journal in order to carry out, monitor, and control the experiment
   3. That the Medicines Agency's inspectors have access to obtain journal information, also electronically, as part of the Agency's statutory inspection of clinical trials (if foreign control authorities also need access, a power of attorney is used)
9. Personal information
   
   1. Describe that personal data will be processed in the experiment. Account for compliance with the Data Protection Act and the General Data Protection Regulation (Be aware of the duty to inform (about the registered person's rights), which applies after the General Data Protection Regulation, see The Danish Data Protection Agency's guide to this (Danish))
      If the material is sent abroad:
   2. Which country and for what purpose?
   3. Account for the compliance with the General Data Protection Regulation and Data Protection Act. When sending to third countries, also inform about the country and recipient, and that Chapter V of the General Data Protection Regulation is complied with
   4. Describe, which country's legislation protects personal data abroad, if it is not the General Data Protection Regulation that applies
10. Economy
    Describe:
    
    1. Who initiated the experiment
    2. Names of supporters
    3. Who supports the experiment - the size of the amount for each supporter, and how the support is included in the experiment
    4. Whether the person responsible for the experiment has a financial connection to companies or funds with interests in the experiment
11. Possible remuneration and/or other benefits to the test subjects
    Describe:
    
    1. The size of the remuneration, including possible travel reimbursement, lost earnings, and/or inconvenience allowance
    2. How much will the participants be paid proportionally if they withdraw early?
    3. Other benefits - economic value
    4. Taxation/deduction
12. What is the standard treatment, and are there other treatment options?
13. The benefit of the experiment
    
    1. What benefit there is for the test subject, for others, and for the research.
14. If the experiment must be terminated
    
    1. What can lead to the test subject being taken out of the experiment, or the experiment being completely terminated.
15. Contact person
    
    1. How the test subject can get more information
    2. Name, address, email address, and phone number of a contact person in the experiment
16. The test subject's general rights
    
    1. If you hand out the pamphlet Your rights as a research participant in clinical trials on medicinal products, you must inform that it is enclosed and encourage to read it.
    2. If you do not hand out the pamphlet, you must write the information that appears in "Your rights as a research participant in clinical trials on medicinal products"  in the participant information. 

DRUG TRIALS WITH CHILDREN

1. The protocol/Danish supplement (ethics section) should be supplemented with the following:
   
   1. Specifically justify why it is necessary to carry out the trial with children. The age of the children should be stated and justified specifically, as older children should be included rather than younger children.
   2. You must be able to justify specifically that the trial deals with the child's clinical condition, that the patient group benefits and that you are testing data from research with capable individuals or from other trial methods.
   3. Describe any measures that can minimize pain, fear or discomfort in relation to the child's development.
2. The procedures for oral information to trial subjects and representatives should be supplemented with:
   
   1. State that consent will be obtained from both parents in case of joint custody. See also the Consent declarations.
   2. What prerequisites the informing health professional has, i.e., knowledge of the area and educational prerequisites for informing the age group.
   3. The information to the child should be adapted to the child's ability to understand the trial as well as the child's age and maturity in both language and content.
   4. State that separate consent will also be obtained from children over 15 years of age (see the consent declarations), and that separate information will be prepared for the 15-17 year old.
   5. That separate consent will be obtained from the young person when the young person becomes of age, if there are young trial subjects who become of age during the trial.
   6. Written participant information should be prepared for the parents. It should be stated that the holder of parental custody receives the same information as the young person and is involved in deciding on the trial.
      Note that the trial subject must always be consulted. The trial subject's expressions must be taken into account, insofar as the expressions are current and relevant. In that the substitute consent must express the interest of the trial subject.
3. Consent forms
   
   1. Consent declaration for use in obtaining substitute consent from the holder of parental custody (p.5 and p.6).
   2. Possible use of power of attorney (from one parent to the other). Get foraeldrefuldmagt.doc.
4. Indicate if consent is obtained electronically with digital signature
   
   1. The security level must correspond to the OCES standard, e.g., NemID.
5. If standard consent form is not used, see Forskertjekliste - samtykkeerklæringer endelig januar 2023.pdf.

DRUG TRIALS WITH ADULTS LACKING CAPACITY TO CONSENT

1. The protocol/Danish supplement (ethics section) should be supplemented with:
   
   1. Describe why the trial subjects are without capacity to consent (are incapable of taking care of their own affairs)
      
      1. Does it concern severe dementia, mental retardation or mental illness of a permanent nature or other forms of serious impaired health of a temporary nature?
   2. Justify why it is necessary to carry out the trial with trial subjects without capacity to consent
   3. Justify that the trial concerns the trial subject's clinical condition, that the patient group benefits, and that you are testing data from research with capable individuals or from other trial methods
   4. For persons covered by the Guardianship Act § 5, you must state that consent is obtained from the guardian when participating persons under guardianship, if the guardianship authorizes consent to trial participation. Get templates for consent declarations
2. The procedures for information and consent should be supplemented with information about:
   
   1. That substitute consent will be obtained from the nearest relative and trial guardian. See also the consent forms.
   2. How the Trial guardian is appointed - this person must use his/her professional knowledge to assess whether the trial subject can participate in a trial of this nature.
   3. What prerequisites the informing health professional has to involve the trial subject
   4. That the information to the trial subject is adapted to the trial subject's ability to understand the trial
   5. That written participant information has been prepared for the representative
   6. That a separate consent will be obtained from the trial subject if the subject regains his/her capacity during the trial. This only applies to trials of a nature where capacity can be regained.
3. Consent form
   Attach
   
   1. Consent form for use for subsequent consent for the trial subject: p. 1 - p. 2- p. 3 - p. 4
   2. Consent form for use for subsequent consent from representative (relative and trial guardian): p. 7 and p. 8
4. Indicate if consent is obtained electronically with digital signature
   
   1. The security level must correspond to the OCES standard, e.g., NemID
5. If standard consent form is not used, see Forskertjekliste - samtykkeerklæringer endelig januar 2023.pdf

See also Guidelines for Emergency Trials outside of the CTR and the MDR.

1. The protocol/Danish addendum should be supplemented with:
   
   1. What patient group is involved?
      
      1. How will you describe the temporary incapacity, i.e., what mental or physical condition are the trial subjects in?
      2. Capable trial subjects with a different underlying disease can exceptionally be included as a control group, but then you need to justify the need for it.
   2. Describe why the trial can only be carried out without informed or surrogate consent?
      
      1. I.e., why can the intervention not be postponed.
   3. It must be specifically justified that there is a presumption that the trial can improve the trial subject's health in the long term.
2. The procedures for information and consent should be supplemented with information about:
   
   1. You must account for the fact that you will obtain consent from a trial guardian prior to inclusion.
   2. You must account for the fact that you will obtain informed consent or substitute consent (from the nearest relative and a trial guardian) as soon as possible after the trial has been initiated.
   3. There should be a description of how the trial guardian is appointed in both of the above situations (the trial guardian must be independent of the project and have professional insight). Read more about consent conditions in acute drug trials.
   4. Description of the information given to the trial guardian (see Guidelines for Emergency Trials outside of the CTR and the MDR).
      The following should be attached:
   5. Written participant information to the trial subject (when he/she becomes capable).
   6. Written participant information to relatives and a description of the information given to the trial guardian who is to give surrogate consent (if the trial subject does not gain capacity during the implementation of the trial).
3. Consent forms
   Attach
   
   1. Consent form intended for surrogate consent from the trial guardian: p. 9.
   2. Consent form for use for subsequent consent for the trial subject: p. 1 - p. 2 - p. 3 - p. 4
   3. Consent form for use for subsequent consent from a representative (relative and trial guardian):
   4. Consent form for use for subsequent consent from representative (relative and trial guardian): p. 7 and p. 8.
4. Indicate if consent is obtained electronically with digital signature.
   
   1. The security level must correspond to the OCES standard, e.g., NemID.
5. If the standard consent form is not used, see Forskertjekliste - samtykkeerklæringer endelig januar 2023.pdf.