MONITORING PLAN
TRIAL TITLE:
[Insert]
Short title [insert]
R&D Ref-
Chief Investigator- [insert]
Sponsor- [insert Barts Health NHS Trust/Queen Mary University of London]
Revision history:
Version / Date / Event / Changes if needed1.0 / Trial green light / N/A
Content:
1)Introduction
2)Risk adapted Strategies
3)Monitoring type
4)Scope and Schedule
5)Site initiation visits
6)On site monitoring
7)Central monitoring
8)TMF review
a)Database QC checks
9)Laboratory monitoring
10)Routine Monitoring Reports to the Sponsor (JRMO)
11)Close Out Visits
Abbreviations:
CI – Chief Investigator
CTA – Clinical Trials Assistant
CRF – Case Report Form
ISF – Investigator Site File
JRMO – Joint Research Management Office
SIV– Site Initiation Visit
TM – Trial Monitor
TMF – Trial Master File
PV – Pharmacovigilance
INSERT trial specific abbreviations as needed
- Introduction
This Monitoring plan’s objective is to clarify the process of Monitoringthat will occur for the above named trial and to ensure that:
- The rights and well-being of trial subjects are protected
- The reported data are accurate and complete
- The conduct of the trial is in compliance with the protocol, Good Clinical Practice (GCP), and applicable regulatory requirements; and the site continues to be acceptable to conduct the trial.
Monitoring procedures have been determined and based on considerations of the risk assessment which was risked as <Insert Risk here>. Refer to risk the assessment form for details of the trial’s risk and mitigations.
All Monitoring conducted within the trail should be conducted in line with Sponsor Sop 28 Monitoring and all Associated Documents (SOPs available on the JRMO website). Any modifications should be agreed in writing and documented below:
Trial Information:please complete
Trial PhaseIMP Risk Adapted Category, based on marketing status and standard medical care / Type: A/B/C (delete as appropriate – GCP Manager to complete
Sponsor’s Risk Assessment (RA)
Trial Type / CTIMP/Non-CTIMP/Radiotherapy/CE-marked device/non-CE marked device
Number of UK sites / (include any caps in place)
Number of International site (if applicable)
Total No. of Sites
Number of Patients to be recruited
Approx. start date
Planned Recruitment Period
Length of Treatment Period
Length of Follow-up Period
Trial Database to be used
IMP Storage / In-pharmacy/out-of-pharmacy storage
(delete as appropriate)
Randomisation process
Central Lab location (if applicable)
- Risk adaptedmonitoring strategies:
These may be based upon IMP risk categorisation (Type A,B and C) or the risks associated with trial conduct by examining the trial design, CI and coordinating team, population and procedures to identify specific areas of vulnerability and to determine how any risks can be mitigated.
Please insert any risk adapted strategies and mitigations that are in place or will be utilised for this trial.
- Monitoring type:
A mixture of on-site visits andcentralMonitoringwill be utilised throughout the life cycle of this trial (initiations, onsite Monitoring and close out visits).
On-site visits will be conducted by <Insert Delegates> andwill allow for the data to be verified against source documents, ensure essential documents are present in the ISF, that drug or product is delivered, stored, dispensed, and disposed of properly, and that equipment and resources are adequate and used correctly. The onsite Monitoring tool is based on the current SponsorMonitor toolsand changes have been agreed by the relevant GCP manager.
Centralised (remote)Monitoring will be conducted as per this planby a named delegate of the CI’s team, and will allow the CI and Sponsor to maintainoversight of the trial. The central Monitoringdelegate will be listed on the trial delegation log, GCP trained,and trained in the use of the centralMonitoring tool. See appendix B for the centralised Monitoringdetails (Please insert here if centralMonitoring is to be used or delete if appropriate).
The following trial oversight committees will be held: <Insert Committees – e.g. TMG, Data Monitoring Committee, and Trial Steering Committee* See protocol for mandatory committees and SOP 46 – Trial Committee for guidance and templates charters. Trial committees will be held in accordance with their charters.
- Monitoring Scope and schedule:
Based on the risk assessment the trial will be monitored as follows(edit as required the text below).The Sponsor (JRMO) reserves the right to request that additional or triggeredMonitoring activity be conducted during the duration of the trial if required (Please see JRMO SOP 28 - Monitoring).
Timing and Frequency of Monitoring Visits
The frequency of monitoring visits is determined by a risk assessment of the trial (see SOP - SOP 23 - Risk assessment).
The first monitoring visit following initiation of the site and trial commencement will take place within approximately ………. weeks after the inclusion of the first patient. Subsequent Monitoring visits will take place every ………. weeks.
The interval for Monitoring visits may be longer or shorter than stated above, dependant on subject enrolment rate, quality issues, trial site compliance or other trial site issues.
Any significant deviation from the planned Monitoring timelines will be explained and documented in the monitoring visit report, reported to the JRMO and the Monitoring plan amended if appropriate.
If the site does not enrol any patients or enrolment has stopped, regular monitoring visits will not be scheduled. If there is an extended gap in trial activity the Monitor should ensure that site staff are appropriately trained when trial activities recommence.
Monitoring Schedule for Sites:
SIV / MV1 / MV2 / COVSite 01 / On-site / On-site1 / Central2 / On-site3
Site 02 / Telephone / On-site1 / Central2 / On-site3
Site 03 / Telephone / On-site1 / Central2 / On-site3
1, MV1 should be within 4 weeks of the first patient consented
2. MV2 should be within 6 months of MV1
3. COV should be within 3 months of the last patient last visit
Monitoring Schedule for Vendors:
SIV / MV1 / MV2 / COVLab* (in more than 1 lab insert line for each lab) / On-site / On-site1 / Central2 / On-site3
SMO/CRO / Telephone / On-site1 / Central2 / On-site3
eCRF Provider / Telephone / On-site1 / Central2 / On-site3
IMP Provider
(note here if IMP Provider has been delegated Pharmacovigilance)
CTU
See Conditions of Sponsorship to assess what has been delegated to the CTU
1, MV1 should be within 4 weeks of the first patient consented
2. MV2 should be within 6 months of MV1
3. COV should be within 3 months of the last patient last visit
If there are any new sites to be added, this plan will need to be amended and agreed to by the GCP Manager.
- Site Initiation Visitor Meeting:
The SIV will be conducted in line with Sponsor SOP 46 - Site selection, initiation and activation
Associated document 1: Site level feasibility assessment guidance
Associated document 2: JRMO SIV checklist template
Associated document 3: JRMO SIV presentation template
The purpose of the SIV is to ensure the investigator and site staff are familiar with trial documentation, investigational medicinal product/s, accountabilityand verification of the clinical supplies to be supplied to the site (e.g. IMP Management or tissue kits), medical device or equipment (if applicable), administrative procedures and that they are aware of the investigators responsibilities regarding compliance with the clinical protocol and the care of trial subjects. The CI/delegate will be conducting the SIV.
Evidence of the SIV and materials used will be filed in the TMF and ISF as evidence of the SIV.
The following people will be present at the SIV:INSERT HERE PI, Pharmacy, and Research Nurse Etc( NB The pharmacy SIV can if needed due to other commitments be held separately). The SIV will be in a face to face setting.
The following site/investigator training will be conducted: Detail type of initiation to be conducted (e.g. launch meeting with PowerPoint, video conference). List any training tools to be used (e.g. presentations, attendance logs)
Set out site activation procedure: List documents required by the CI from sites prior to opening to recruitment (e.g. NHS permission, fully executed contract, CVs and GCP certificates of site staff. Depending on trial classification different documentation may be required. As a rule the checklist from R&D, Ethics and MHRA CTA application forms should be used to determine what is required however it is good practice to maintain a central list as below – See SOP 46, associated document 1-3. Alternatively refer to SIV checklist that will be used)
The trial will not be allowed to commence at site until all necessary approvals have been granted and all essential documentation listed below is present in the ISF and has been verified
Note that the report is to be signed by the Monitorwho performed the SIV and also a reviewer. The reviewer(s) for this trial is <insert role and title>.
Copies of all SIV reports will be emailed to ter report sign off,or the SIV report should be loggedin the quarterly monitoringsummary report to the JRMO.
- On-Site Monitoring at site level:
All on site Monitoring visits will includea visit to the Pharmacy,or out of pharmacy storage (delete as necessary see Risk Assessment and Sponsor’s pharmacy approval).
The Principal Investigator (PI) will be met at each visit, where possible. The PI must be sent a copy of their site’s monitoring report to ensure PI Oversight. The monitor must not send site reports only to the CI.
Monitoring visits are to cover:
(a) Source data chosen for review*
(b) Review of investigational product procedures
(c) Review of adverse event procedures
(d) Review of subject enrolment responsibilities
(e) Discussion of trial personnel, equipment and facilities
(f) Meeting with members of investigator’s team to discuss site-related issues
(g) Review of essential document maintenance (TMF/ISF/Lab or Pharmacy file)
(h)Discuss any deviations or protocol violations with investigator and take action as appropriate (e.g. amendments, inform Sponsor, CI)
Copies of all reports should be emailed to after report sign-off.
TheSource Data Verification (SDV) plan for this trial is as follows:Indicate what source data will be reviewed, the %, and list key data to be used. Reference any checklists to be used. A list of source data is found in the ISF.
Source Data Monitoring / Amount / Comment/GuidanceConsent Forms/process / 100% For all subjects on the
screening log / Request source notes from sites to review the documented consent process.
Eligibility / 100% of subjects enrolled
(not for screen fails) / Request source notes to review the documented consent process.
Phase 1 Healthy Volunteer studies only: check ID participant (i.e. passport asID not verified in the medical notes). Also check whether GP has contacted re. healthy volunteers medical history to confirm eligibility (as no medical notes)
Safety Reporting / For all / 10% SAEs and all SUSAR perform SDV to ensure presence of full and accurate source data / Ensure SAE/SUSAR forms, CRF and Source are consistent.
End point or outcome data / Insert % amount / Insert what the End Pointor Outcome data points for this trial are
Case Report Forms (CRF)/Visits ( all visits) / For 10% of the subject sample, for each subject review the complete CRF.
Specify : trials specificdocuments i.e. Quality of life questionnaires
Patient diaries
This includes all source data for identification of adverse events. Ensure all recorded events have appropriate source data. Ensure all events are recorded& assessed.
Note a minimum of 1 subject-persite. / This can be completed over a number of Monitoring visits.
(Including printed reports with clinical significance assessment.
Are any trial specific documents used as per REC approval letter / amendments?
Pharmacy will be visited at each on-site Monitoring visit.
The IMP for this trial is stored in pharmacy/out of pharmacy(delete as appropriate). The Monitor will check compliance by referring to the to the protocol, IMP Management Plan, Investigator Brochure (IB), Summary of Product Characteristics (SmPC/s), Label, IMP Management Plan)
Pharmacy/IMP monitoring / Monitoring Required / GuidanceIMP Accountability & Tracking Expiry Dates / Pharmacy will be visited at each visit to site.
100% of IMP accountability checks will be performed. / The Monitor is responsible for checking the IMP accountability and IMP reconciliation of the IMP both at individual (amount dispensed/used/returned by subject) and site level (total delivered, used, unused, and returned/destroyed by trial site).
The Monitor will also check that the IMP is being stored and handled according to the requirements of the protocol information (IB, SmPC, Label, and IMP Management Plan).
Destruction of the IMP
. / The Monitor will verify accountability and reconciliation prior to destruction.
Describe here what will be done with used / unused IMP at the site and what must be verified. If IMP is to be returned to an external partner/provider, insert terms of returns as stated in IMP agreement full instructions for IMP return / . Destruction of IMP should not occur until accountability has been completed and approval for destruction given by the Chief Investigator and the Sponsor Representative i.e. JRMO Interim accountability and destruction may be permitted.
- Central Monitoring [delete if not relevant to the trial]
See appendix B for the centralised monitoringdetails.The results of central monitoring of the clinical data will be included in the central monitoring report. Copies of all central Monitoring reports will be emailed to after report sign off, or the central Monitoring report should be logged in quarterly monitoring summary reports to the JRMO (see section).The purpose of centralised monitoring is to maintain oversight of site activity.
The CI must inform the JRMO of any concerns in trial management when submitting reports (refer to central monitoring report template within SOP 26 – associate docs).
Type of Central Monitoring / Monitoring Activity and Frequency / ResponsibilityChecks for missing or inconsistent or invalid data / Specify key data to be
checked and frequency
Raise discrepancy and
chase resolutions
Track timely completion of CRFs
Periodic review of SAE Reporting / Specify key data to be
check and frequency
Indicate whether cross site checks of SAE data is to be performed
IMP accountability / Indicate whether IMP accountability records are to be collected sites and frequency at which this is to be done
Detail checks to be
performed
- TMF review
Single Centre Trials (delete as appropriate)
The Trial Master File TMF will be checked for completeness by the Monitor at least once a yearthroughout the trial. Single centre studies will have both TMF and Investigator Site File which must be monitored.*
Multi-centre Trials (delete as appropriate)
The Trial Master File (TMF) will be maintained by the Chief Investigator, or delegated member or staff and checked for completeness by the Monitor or independent delegate at least once a yearthroughout the trial..
TMF and ISFs will be set up and a maintained in line with Sponsor SOP 45 Essential documentation.
.
- Database and Computer Systems
Databases and Computer systems must comply with the following Sponsor SOPs:
SOP – 38A Use of computerized computerised equipment, software and systems in clinical a research projects
SOP - 38B Trial Data Management Systems
Computer System/data management system / Monitoring Required / GuidanceTrial Database / Is the Trial Database being updated in a timely manner? / *See SOP 38B for required Trial Database approvals
CRFs / A data base check for accuracy of data entry will be performed at………. (Insert time points agreed withChief Investigator).
The X% of CRFs will be checked and the following data points to be checked:
- End point data
- Insert others as applicable
All CRFs monitored during a visit will be detailed in the Monitoring Visit Report.
Computer Systems / List computer systems here: / Consider if there are any support department (imaging/pharmacy/pathology)
Computer systems have been verified that are central for primary end points, data integrity or patient safety.
Systems used to transfer images or data across sites.
- Monitoring for vendors
- LaboratoryMonitoring
All non-commercial UK based central laboratories will receive
NHS labs that are performing tests that fall within their CPA accreditation will require minimal Monitoring oversight. However, if they are performing test that are outside of the CPA these will be monitored.
Samples will be transferred to (insert lab) from each site / X site. At the end of the trial the participants have consented for their samples to be used in future ethically approved research/transferred to a HTA lab/destroyed (delete as appropriate – see protocol and REC approved docs.) Further details on sample management can be found (insert sample management plan and location i.e. TMF/Lab file). Where possible the monitor will meet with the lab manager and will send a copy of the monitoring report will be sent to them to ensure their oversight of the labs compliance and performance. The Monitor will verify that the protocol requirements have been met regarding timing, storage, shipping and documentation of biological samplesDetail here what checks of samples records are to be made that are critical to the protocol (i.e. samples that are critical to eligibility, end points or safety). See Lab Monitoring form for guidance.
- Insert other central facilities
- Routine Monitoring Reports to the Sponsor (JRMO)
CTIMPs that are Monitored by other parties i.e. not by the JRMO must provide the Sponsor with quarterly/6-monthly.* Timelines are to be agreed with the GCP Manager.
Quarterly/6-monthly monitoring reports will be reported to the . These reports will be submitted by the JRMO to the Sponsor Oversight Group as part of Sponsor oversight of the trials performance and compliance.
N.B – this is N/A for CTIMPs where all sites are monitored by the JRMO
- Close Out Visit (COV):
The monitoring of trial closure will comply with the following Sponsor SOPs:
SOP 18a - Project closure: guidance for research staff of sponsored studies