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The sponsor has overall responsibility for ensuring that this SOP is followed.

The sponsor is overall responsible for the clinical trial, from start of planning to the conclusion of the clinical trial.   Sponsor must ensure appropriate oversight throughout the trial.

This includes ensuring the trial is conducted in accordance with the protocol, applicable laws, regulations, and Good Clinical Practice guidelines. The sponsor may delegate trial-related duties to service providers but retains the overall responsibility for the quality and integrity of the trial and its data.

Trial planning

Prior to start, the Checklist Initiation for Clinical Trial – Sponsor should be used. The coordinating investigator is responsible for ensuring that all relevant tasks described in the standard operating procedures (SOPs) are completed.

Before trial start, a Trial Activity Planner (TAP) should be developed, listing major and recurring events. The TAP should include, but is not limited to:

• meeting frequency with sites, trial team, committees (e.g. steering committee, data monitoring committee (DMC))
• renewal of insurance
• ensure availability of investigational medicinal products (IMP)
• annual safety reporting
• risk assessments
• review of safety information
• review of Protocol deviation handling plan
• production and distribution of newsletters

Organisation of sponsor’s trial team

The logistics for the follow-up of the trial should be described and include assignment of staff to the following roles:

• Trial management team: Responsible for the day-to-day follow-up of trial conduct (e.g. project coordinator, coordinating investigator)
• Medical monitor: Oversees medical aspects of the trial and participant safety. The medical monitor should comply with the requirements described in the SOP Safety Reporting.
• If applicable; steering committee, data monitoring committee, scientific advisory board

The mandate, meeting frequency, requirements for meeting minutes, and confidentiality provisions should be described. The Data Monitoring Committee charter for DMCs and can be used as inspiration for other kind of committees. Relevant documentation should be prepared and maintained by the trial management group.

The coordinating investigator shall ensure that:

• Monitors have access to the protocol, trial information, investigator’s brochure (IB), investigator’s site file (ISF), case report form (CRF) and all necessary trial documents.
• Data managers, statisticians or other team members have access to the protocol, CRF and other information required to perform their assigned tasks.
• All site staff who are assigned tasks in connection with a trial receive the necessary training and information about the trial protocol, trial drug and the trial-related tasks and procedures. 

Data governance/electronic systems

The Electronic Data Capture (EDC) must be fit for purpose and approved within the sponsor organisation.  When selecting the EDC system (i.e. the eCRF) the CI should ensure the system fulfills the following criteria: 

1. The system audit trail must:
   1. be indelitable, readable and readily available for review and copying.
   2. include date, time, originator of any data creation, change or deletion, and when required the reason for change
2. There is a system and/or process to ensure that case records and any subsequent modifications are reviewed and approved by the investigator
3. There is a system and/or process to ensure the investigator has control of and continuous access to all essential records (data and documents) generated by the investigator/institution/participant before, during and after the trial
4. System uses a standard time reference so that the local time can be derived.
5. There are system features and processes to create, maintain, revoke, and document the history of user access, roles and privileges over time.
6.  System has the ability to produce a human-readable copy of data (which includes associated audit trails and any decoded data) in appropriate file formats that facilitate review, searching and analysis
7.  Process and/or system controls ensure that regulated data used for clinical research, including source data and metadata are enduring, continue to be available, readable and understandable and are retained in an archive for the legal period
8.  The development, hosting, deployment and change control of a computerised system has objective evidence that system components are traceable to requirements and have been validated based on risk, using good software lifecycle practices
9.  Signed electronic records shall contain information associated with the signing that clearly indicates all of the following:
   1. the name of the signatory
   2. the date and time when the record was signed
   3. the meaning (such as creation, confirmation or approval)
   4. electronic signatures are permanently linked to their respective record
   5. if the record is subsequently altered, then the signature no longer applies

Trial conduct

The trial management team

The trial management team is responsible for the day-to-day oversight including:

• The sites
  • Overseeing enrolment and data entry: Following up on enrolment rate and timely entering of data into the designated data acquisition tools
  • Facilitating the sites’ needs: Support and address the operational needs for smooth trial conduct.
  • Tracking personnel changes: Oversee and document any changes in personnel. Note: for drug trials change of Principal Investigator (PI) is a considered a substantial modification. Approval of a new PI may take up to three months in CTIS. Ensure all necessary documentation (e.g. CV, declaration of interests) related to changes in PI is collected, submitted and approved in CTIS before implementation. Appropriate training must be provided prior to the new PI assuming their role. For shorter vacancies, a risk assessment should be performed as to whether the site can function without a PI or not.
  • The site should also be aware that changes in other key personnel (e.g. study nurse) are relevant for the sponsor and contact lists must be updated centrally. All new personnel must receive appropriate training before undertaking trial-related duties. Training of the PI is a sponsor responsibility whereas training of other site staff is a PI responsibility. Training should be documented in the training log, or in case of a larger meeting by archiving the agenda, training material and attendance list. Trial management group will grant and remove access to electronic systems (e.g. eCRF) based on updates from sites.

• Risk management
  • Ongoing risk follow-up: Supervise and manage the risks described during the risk assessment, ensuring that appropriate controls are implemented by the responsible group.
  • Regular review of risk assessments: It is recommended to review the risk assessment at least annually, before the annual safety reporting. New risks may be identified independently of planned risk assessments. These should be promptly mitigated, documented and archived together with the risk assessments.

• Protocol deviations
  • Review and document protocol deviations, ensuring implementation of appropriate corrective and preventive action (CAPA). Deviations that are considered serious breaches must be reported to the relevant authorities (CTIS in EEA). Relevant deviations should also be communicated to trial personnel to minimize the risk of recurrence.

• Monitoring reports and monitoring plan
  • Timely review and follow-up the monitoring reports according to timelines. If a site has major findings that could compromise participants safety or the quality of the data, the coordinating investigator should take appropriate measures, such as providing training, increasing the frequency of monitoring visits or as a last resort, closing the site. For sites providing high quality data and with few and minor findings, the coordinating investigator might consider reducing the frequency of monitoring.
  • Monitoring activities and frequency should be modified as necessary using gained knowledge. Consider appropriateness of monitoring plan based on feedback by monitors, data managers, medical monitors or other trial personnel, new scientific evidence, findings from the data monitoring committee etc.

• Committee meetings

• Preparing for committee meetings and ensuring the meetings have agendas and minutes, are followed up when necessary and the documentation is archived Trial master file (TMF)
  • Ensure that the trial master file is kept up to date throughout the trial, and that sites have been provided with all relevant documentation to conduct the trial in accordance with the protocol and applicable regulations.
  • A clear and consistent naming convention for documents should be established. The CTIS naming convention may not be appropriate for TMF. CTIS cannot be used as an archive.

• Agreements

Ensure all commitments outlined in agreements are fulfilled, including:

• • • Reporting requirements to pharmaceutical companies
    • Reporting to grant providers and other relevant parties
    • Payments to sites

• Authorities

Ensure any requests and obligations in Report for the Application Evaluation, Decision letters, and notifications to authorities are fulfilled.

Medical monitor review

Medical monitor should assess on a risk based basis the risk benefit balance in the study, and as a minimum in connection with the annual safety reporting. The Medical Monitor should keep the Trial management team informed.

For documentation of tasks performed Checklist Conduct for Clinical Trial – Sponsor can be used.

Trial completion

See SOP Completion, Reporting and Archiving for details.

Preparation for database lock:

• DBL meeting with trial management group, involved monitor(s), DM and STAT, recommended 6 months prior to estimated DBL
  • Determine and distribute timeline for last monitoring visit/close out visit
  • Determine and distribute timeline Final date of coding and data cleaning
  • Determine and distribute timeline Date for statistical mock report and final report
• Inform sites about DBL timelines

To prepare for trial completion, information regarding the following should be addressed in due course:

• Reporting requirements to authorities (CTIS) and Internally
• Process for informing participants of received treatment in blinded studies
• Institution policy for archiving of trial data for both sponsor and site documentation
• Inform sites about starting date for archiving period (i.e. 25 years from last patient last visit)
• Inform sites about date for deleting/anonymising data at the end of archiving period
• Process for informing trial staff and study participants of trial results
• Financial overview/outstanding payments to prepare for reporting

Authorities:

• Timelines;
  • In case of delays, be sure to apply for extension of timelines in CTIS in due time before end of study. Approval of a SM can take up to 81 days and the Desicion Letter should be received before the timelines expires.
  • Remember also to check if the "End date for research activities" provided in the "Statement of compliance with Norwegian requirements on data protection "-document is still valid or should be extended.

• For reporting to authorities see SOP Ongoing Trial Reports and Notifications. Summary of the trial results (scientific and lay person) must be reported in CTIS within 1 year after end of trial

For documentation of tasks performed the Checklist Completion of Clinical Trial Sponsor can be used.

Download: 

• Checklist Initiation of Clinical Trial Sponsor – Template
• Checklist Conduct of Clinical Trial - Sponsor - Template
• Checklist Completion of Clinical Trial - Sponsor - Template
• Data Monitoring Committee Charter - Template