WMO applicable

Research proposals must meet the following technical requirements:

• The documents should be submitted through the Research Portal
• The files must be named according to the stipulations of the Standard research file, as described by the CCMO. (Please see the relevant website www.ccmo.nl for more info).
• The submission includes a cover letter which lists the files being submitted.
• Primary submissions must include a METc aanbiedingsformulier.

Any application must be listed according to the Standard Research File.

The following documents are always part of the application package:

A1   Cover letter
A1   METc submission form (Aanbiedingsformulier)-for primary submissions
B2   ABR form (via Research Portal)
C1   Clinical Trial protocol
E1   Information letter/leaflet for participants
E2   Consent form(s)
G1  Insurance certificate for WMO research with human subject insurance (when UMCG isn’t the sponsor)
G2   Proof of coverage of investigator or sponsor, for example insurance (when UMCG isn’t the sponsor)
H1   CV independent expert
I3   CV principal investigator

In case of a multicentre trial:
I1   List of participating centres and principal investigators
I2  Site Suitability Declaration (VGO) or Research Declaration per centre
I3   CV (local) investigator of [centre]

If the trial is sponsored by a profit-seeking company:
A2   Authorisation letter from the sponsor
K3   Clinical Trial Agreement/contract

Depending on the type of clinical trial, additional documents should be submitted:

• Research with medicinal product
  Please see CCMO-Clinical Trials with medicinal products 
• Research with food and/or supplement(s)
  D2   Product information functional food
  D4   Declaration of manufacturer
• Research with a medical device
  D2   IMDD (Investigational Medical Device Dossier)
  D4   CE marking (declaration of conformity )
  D4   Recommendation of Expert on Medical Devices of the UMCG
• Research with (temporary) legally incapacitated
  E1   Information letter/leaflet for legal representative
  E2   Consent form legal representative
  E1   Information letter/leaflet for participants  (when they’ve become legally competent again)
  E1   Consent form for participants  (when they’ve become legally competent again)
• Research with healthy volunteers
  E3   Recruitment material  (advertising text)

Validation phase.

After the submission, the application is automatically directed to the chosen Medical Research Ethics committee. In the validation phase the application will be assessed for completeness; the submittor will receive notification when the application is incomplete or valid.

PLEASE NOTE:
In case the UMCG is sponsor of the trial, the trial must be listed in the UMCG Research Registry.

Assessment phase.

When the application is valid, the assessment phase starts. The application is listed for a committee meeting where the proposal will be discussed. The outcome of the discussion/assessment will be communicated via email.

When you respond to the questions of the METc (rebuttal) or when you submit a substantial amendment, you only have to submit the altered documents (with red line/track changes visible) or new documents, accompanied by a cover letter. The rebuttal should include the questions of the committee and your answers.

When submitting an amendment, please describe, either in the cover letter or a separate document, such as C2 Protocol amendment, the motivation for the proposed changes.

You may submit the via Research Portal, accompanied by a (paper) cover letter:

• A point by point response (please repeat the question and then add your answer below it)
• The documents that are altered (as a consequence of the commentaries). Please highlight the changes (red line/track changes visible)
• If applicable, the additional (and new) documentation

First, we will check that the submitted documents are complete and accurate. Then we will process the rebuttal. This may take a day or two, depending on how many documents are submitted on that day.

After this, the official secretary will check whether

• The response and accompanying documents have to be discussed in a meeting or
• The response was delegated to the chair and official secretary for administrative handling.

Option 1 means that the response including documents is tabled for the first available agenda of the committee. This is done approximately 1 week before the meeting. After the rebuttal has been discussed, the applicant will be informed of the decision as soon as possible. This entire process may take 2 or 3 weeks and includes the registration of the documentation, preparing the submission for the meeting, waiting until the meeting takes place and finally making the decision letter and sending it.

Option 2 means that the chair and official secretary will check the responses with the commentaries. In some cases, a member of the METc is contacted for additional input. When the chair, and upon request a member of the METc, decides the rebuttal is adequate, the official secretary makes the approval letter to the applicant.

This process may also take up to 2/3 weeks, depending on the time available to the chair and member of the METc.

I want to submit a modification (AMENDMENT) to my approved research protocol. How do I do this?

You may submit the proposed amendment via Research Portal:

• A cover letter (A1) (including a list of the documents being submitted) and/or
• A METc submission form AMENDMENT (see our Documents page)
• A summary (C2) of the amendment including motivation for the proposed modifications
• The revised documents (track changes/red line visible)
• In some cases a new version of the ABR-form must be submitted as well

Only substantial amendments must be submitted for approval to the METc UMCG. The sponsor decides when an amendment meets those criteria. Generally, an amendment is considered ‘substantial’ when the proposed revision have significant impact on:

• The safety or physical or mental integrity of the participants;
• The scientific value of the research;
• The execution or management of the trial;
• The quality or safety of any investigational product (medicinal, device, food/supplement) used in the trial.

What is a SAE of SUSAR?

During the trial so-called Adverse Events can occur in a patiënt/participant. The research protocol should describe the procedure in case of these events.

A  Adverse Event or Adverse Reaction is any untoward medical occurance in a patient or participant but which does not necessarily have a causal relationship with this treatment.

A Serious adverse event is any untoward medical occurrence that at any dose

• results in death
• is life-threatening
• requires inpatient hospitalization or causes prolongation of existing hospitalization
• results in persistent or significant disability/incapacity,
• is a congenital anomaly/birth defect, or
• requires intervention to prevent permanent impairment or damage
• any other important medical event that did not result in any of the outcomes listed above due to medical or surgical intervention but could have been based upon appropriate judgement by the investigator

If certain SAEs do not require (expedited) reporting, these SAEs should be specified, as well as the frequency of reporting of these SAEs in line listings, or in an annual safety report or otherwise.

The sponsor (or delegated party) should report the Serious Adverse Event (SAE) or Suspected Unsuspected Serious Adverse Reaction (SUSAR) via the Research Portal.

Applicants can report the SAEs through Research Portal. The METc receives a notification of a new report. The decision on the report is filed in Research Portal.

A SAE that is fatal or life-threatening must be reported within 7 days after the sponsor was made aware. Other SAEs must be reported within 15 days.

For more information on SAEs, SUSARs and reporting thereof, please go to the website of the CCMO.

Start of the trial

You must inform the METc of the actual starting date of the study. This is the date of inclusion of the first participant. The study must commence within one year of the positive decision has been issued. The decision expires after one year.

There are additional instructions for reporting a (premature) termination for research with a medicinal product than a research without medicinal product.

Any premature termination should be motivated.

The research protocol describes the definition of the end of the trial. Usually this is the date on which the last measurement was carried out at the last subject. The ‘last patient, last visit’. This means that the involvement of the participant is concluded, the data collection completed and data analysis can commence.

The applicant notifies the METc of the end date within 56 days of the end of the trial.

The applicant notifies the METc of the end date within 90 days of the end of the study. This concerns the end date in The Netherlands. In a multinational study the start and end date for the research part outside the Netherlands may be different.

In the End of trial Form you can mention the end of trial date. In case of a premature termination of the research, please describe the reason(s) for the early termination.
Attachments, such as publications/articles or a final study report, can be included with the report PDF-files.

You are required to submit a progress report one year after the issuing of the decision, and every year thereafter via Research Portal.