Reporting study progress

  • WMO

Implementation

During the study, it will be necessary to monitor several aspects in addition to the visits of the subjects. For example, in its primary letter of approval, the MREC always request that they be kept informed about the study progress. They also expect to be notified of any adverse events according to the timelines, as well as of any changes to the protocol (e.g. by means of amendments). In addition, the TMF/ISF must be maintained, all data collected must be entered into the (e)CRF and a monitor will make regular visits to ensure that the study is being performed according to the guidelines for GCP and the approved protocol

Annual progress and safety reports

Progress report

Beginning one year after the date on which the research was approved by the reviewing MREC and until the end of the study, annual progress reports must be sent to the reviewing MREC. The month and year in which the study was approved are taken as the starting point. The first report must be sent no later than 12 months after approval.

  • If the reviewing MREC is MREC Amsterdam UMC the progress report should be used (see the MREC report page). It should be completed, signed and sent through Research Manager.

Progress reports need not be submitted to the competent authority (CCMO/VWS).

Safety report

For a drug trial, in addition to a progress report, a safety report on the investigational medicinal product must be provided each year to the assessment committee (MREC Amsterdam UMC or CCMO) and to the competent authority. For further details see the site of the CMC.  

The annual progress report must contain at least the following:

  • A list of all suspicions (expected and unexpected) of serious side effects
  • A report on the safety of the subjects, comprising a risk analysis, a statement of the safety measures that have been/are being taken and an evaluation of the balance between the efficacy and harmfulness of the investigational medicinal product and the possible consequences for the continuation of the trial.

The annual safety report is often combined with the progress report.

Investigator Brochure/SPC evaluation

For drug trials, the Investigator’s Brochure (IB) must be reviewed at least annually for any revised and/or additional safety information (clinical or pre-clinical) or other relevant information. More frequent revision may be necessary, depending on the stage of development of the drug and the availability of new information. New information may even be so important that it must be provided immediately to the reviewing committee (via CTIS) to the principal investigators of the participating sites and to participating subjects before including it in a revised IB and subject information form.

In the case of a registered medicinal product as well, an annual check must be made to identify any determine whether there are any changes to the SPC and whether the possible changes should lead to the adjustment of the subject information form.

If new data have been included in the IB or SPC, the new document must be submitted to the reviewing committee as a substantial amendment. 

Requirement notification for the temporary suspension of inclusion or premature suspension of the study.

Protocol Deviations / Serious Breaches

If the procedures and actions that should have been performed according to the protocol are deviated, this is referred to as a protocol deviation. In Amsterdam UMC a GCT SOP02 'Reporting and escalating important deviations / serious breaches in research involving human subjects' is in place. A flowchart is available to determine how, when and to whom deviations should be reported.

> Non-important (minor) deviations are recorded in the (electronic) Case Report Form (CRF) or on a 'study specific deviation log'. Examples are administrative deviations that do not have a direct impact on the safety of the participant, such as a study visit or questionnaire 'out of window' or a participant accidentally skipping a study procedure.

> An important (major) protocol deviation or serious breache (in clinical trials involding medicinal products) is a deviation from the research protocol or legislation and regulations that have an sgnificant effect on the safety and/or well-being of the participant or on the integrity of the research data collected. Whether a situation has a significant impact depends on various factors and is assessed by the reporter (in the case of a clinical trial involving medicinal products, this is the Principal Investigator). This assessment is made on an individual basis in the context of the incident in question.

Important deviations and/or serious breaches (in clinical trials involving medicinal products) are reported as soon as possible after knowledge, using the appropriate forms (GCT T38a Important deviation / serious breach form or GCT T38b Important deviation form – participating site )

    Note: Adverse events in research can at the same time meet the criteria for (near) incidents or calamities in
    Amsterdam UMC. For definitions, instructions on reporting undesirable events, (near) incidents, see manual K2 meldingen: incident/melding invoeren in K2 – instructie Amsterdam UMC(versie 3) (iprova.nl)

    Temporary suspension

    If a study is suspended (at least temporarily) due to suspicion of safety reasons, the following actions must be taken immediately:

    • Notify the reviewing MREC immediately of the reason for the temporary and unexpected suspension of inclusion and/or the temporary suspension of the study. Such notification must be made by both telephone and email (for the MREC Amsterdam UMC: metc@amsterdamumc.nl).
    • For trials involving medicinal products: Notification to the reviewing committee will assign through CTIS. See the ECTR regulation for more information.
    • Notify the Medical Directorate and the Executive Board immediately.
    • If applicable, block the randomisation system for the study (at least temporarily).
    • For multi-centre research, notify the other centres/researchers that inclusion has been suspended (at least temporarily).
    • Prior to re-starting (if applicable), submit an amendment to the MREC if study documents have been revised.

    The inclusion/implementation of the study cannot be resumed until after the reviewing assessment committee (and if applicable, the competent authority) has ruled in favour of the submitted amendment.

    If the suspension of the study is for a reason other than the safety of the subject, the temporary suspension of inclusion need not be reported immediately, but within no more than 15 days.

    Based on GCT SOP 02 reporting deviations and escalations in research involving human subjects

    Premature termination of the study

    If the study is terminated earlier than planned (premature termination), the following actions must be taken:

    1. Notify the reviewing MREC within 15 calendar days after the decision is taken. Send the ‘final report’ form to the MREC Amsterdam UMC or the CCMO ‘Study termination form’ if the CCMO has been the reviewing assessment committee. Within the same period (15 calendar days), notify the Executive Board (indienenmetc@amsterdamumc.nl).
    2. For drug trials, notify the reviewing committee via CTIS, see the site of the CMC for more details
    3. For medical-device trials that have been reported to the CCMO: notify the manufacturer of the premature termination. The manufacturer is obliged to report premature termination immediately, stating the reasons to the CCMO.

      Notify the subjects promptly of the premature termination. If the premature termination is due to a safety reason, this should always be done in consultation with the Executive Board.
      In the case of an international study, the MREC must be informed of the termination of the study in the Netherlands, but also if the study has been terminated worldwide.

      The MREC must also be informed if the study is terminated as expected and described in the protocol.

      Based on GCT SOP 02 reporting deviations and escalations in research involving human subjects