trial protocol - ahspartnership.org.uk · web viewthis protocol template is mandatory for...

This protocol template is mandatory for Clinical Trials of Investigational Medicinal Products (CTIMPs) that are Sponsored or Co-Sponsored by the University of Dundee and/or NHS Tayside.

Section Headings in the protocol template should not be deleted.

MANDATORY fields/text MUST NOT be deleted.

Other sections may be adapted to suit a particular trial.

Other sections may be added as required by the specific trial.

All purple instruction text is hidden text and will not print. Follow these instructions as appropriate.

If you are unable to see the purple instruction text on your screen, the Formatting toolbar in Word has a button with the ¶ icon. If you hover your mouse over it, the ScreenTip says “Show/Hide ¶.”

Doc Ref 054 CTIMP Protocol Template v8.0Effective Date 09/04/2018

Trial Protocol

Trial Acronym

Sponsor

Sponsor R&D Number

Funder

Chief Investigator

Clinical Trials Unit

EudraCT Number

CTA Number

REC Number

IRAS number

ISRCTN/clinicaltrials.gov Number

Version Number and Date

Doc Ref 054 Page 1CTIMP Protocol Template v8.0Effective Date 09/04/2018

<Insert Trial Title> <Insert Version number and date>

CONTENTSCONTENTS.............................................................................................................................. 2PROTOCOL APPROVAL.........................................................................................................4Appendix...................................................................................Error! Bookmark not defined.LIST OF ABBREVIATIONS.......................................................................................................5SUMMARY/SYNOPSIS............................................................................................................61. INTRODUCTION.......................................................................................................72. BACKGROUND & RATIONALE...............................................................................73. TRIAL OBJECTIVES & OUTCOMES.......................................................................74. TRIAL DESIGN.........................................................................................................7

4.1 TRIAL DESCRIPTION.....................................................................................74.2 TRIAL FLOWCHART.......................................................................................74.3 TRIAL MATRIX................................................................................................74.4 STUDY ASSESSMENTS.................................................................................74.5 SAFETY ASSESSMENTS...............................................................................74.6 TISSUE............................................................................................................74.7 INCIDENTAL FINDINGS................................................................................7

5. TRIAL POPULATION................................................................................................75.1 NUMBER OF PARTICIPANTS........................................................................75.2 INCLUSION CRITERIA...................................................................................85.3 EXCLUSION CRITERIA..................................................................................85.4 CONTRACEPTIVE ADVICE............................................................................8

6. PARTICIPANT SELECTION AND ENROLMENT.....................................................86.1 IDENTIFYING PARTICIPANTS.......................................................................86.2 CONSENTING PARTICIPANTS......................................................................86.3 SCREENING FOR ELIGIBILITY......................................................................96.4 INELIGIBLE PARTICIPANTS..........................................................................96.5 WITHDRAWAL PROCEDURES......................................................................96.6 RANDOMISATION..........................................................................................9

6.6.1 Randomisation Procedure.....................................................................96.6.2 Emergency Unblinding Procedure.........................................................9

6.7 ASSOCIATED TASC POLICIES AND SOPs...................................................97. INVESTIGATIONAL MEDICINAL PRODUCTS......................................................10

7.1 TRIAL DRUG.................................................................................................107.1.1 Trial Drug Identification........................................................................107.1.2 Trial Drug Manufacturer.......................................................................107.1.3 Storage and Dispensing......................................................................107.1.4 Reference Safety Information..............................................................107.1.5 Dosing Regime....................................................................................107.1.6 Dose Changes.....................................................................................107.1.7 Withdrawal...........................................................................................107.1.8 Overdose.............................................................................................10

7.2 COMPARATOR.............................................................................................107.2.1 Comparator Identification....................................................................107.2.2 Comparator Manufacturer...................................................................107.2.3 Storage and Dispensing......................................................................107.2.4 Reference Safety Information..............................................................107.2.5 Dosing Regime....................................................................................117.2.6 Dose Changes.....................................................................................117.2.7 Withdrawal...........................................................................................117.2.8 Overdose.............................................................................................11

7.3 NON INVESTIGATIONAL MEDICINAL PRODUCTS....................................117.4 ASSOCIATED TASC POLICIES AND SOPs.................................................11

8. ACCOUNTABILITY PROCEDURES.......................................................................11



8.1 COMPLIANCE...............................................................................................118.2 OTHER MEDICATIONS................................................................................11

8.2.1 Permitted Medications.........................................................................118.2.2 Prohibited Medications........................................................................118.2.3 Concomitant Medications....................................................................11

8.3 ASSOCIATED TASC POLICIES AND SOPs.................................................119. DATA COLLECTION & MANAGEMENT................................................................12

9.1 DATA COLLECTION.....................................................................................129.2 DATA MANAGEMENT SYSTEM...................................................................129.3 SOURCE DATA.............................................................................................129.4 ASSOCIATED TASC POLICIES AND SOPs.................................................12

10. STATISTICS AND DATA ANALYSIS.....................................................................1310.1 SAMPLE SIZE CALCULATION.....................................................................1310.2 PROPOSED ANALYSES..............................................................................1310.3 ASSOCIATED TASC POLICIES AND SOPs.................................................13

11. ADVERSE EVENTS................................................................................................1311.1 DEFINITIONS................................................................................................1311.2 RECORDING AND REPORTING AE............................................................14

11.2.1 Black Triangle Scheme........................................................................1411.3 REGULATORY REPORTING REQUIREMENTS..........................................1511.4 ANNUAL REPORTING REQUIREMENTS....................................................1511.5 URGENT SAFETY MEASURES...................................................................1511.6 ASSOCIATED TASC POLICIES AND SOPs.................................................15

12. PREGNANCY..........................................................................................................1513. TRIAL MANAGEMENT...........................................................................................16

13.1 TRIAL MANAGEMENT GROUP....................................................................1613.2 TRIAL STEERING COMMITTEE...................................................................1613.3 DATA MONITORING COMMITTEE..............................................................1613.4 INSPECTION OF RECORDS........................................................................1613.5 RISK..............................................................................................................16

13.5.1 Potential Risk.......................................................................................1613.5.2 Risk Assessment & Monitoring............................................................16

13.6 ASSOCIATED TASC POLICIES AND SOPs.................................................1614. TRIAL CONDUCT & RESPONSIBILITIES..............................................................16

14.1 APPROVALS.................................................................................................1714.2 CONFIDENTIALITY.......................................................................................1714.3 INSURANCE AND INDEMNITY....................................................................1714.4 PROTOCOL AMENDMENTS........................................................................1814.5 PROTOCOL DEVIATIONS, BREACHES AND WAIVERS............................1814.6 TRIAL RECORD RETENTION......................................................................1814.7 END OF TRIAL..............................................................................................1914.8 ASSOCIATED TASC POLICIES AND SOPs.................................................19

15. REPORTING, PUBLICATIONS AND DISSEMINATION OF RESULTS.................1915.1 AUTHORSHIP POLICY.................................................................................1915.2 PUBLICATION...............................................................................................1915.3 PEER REVIEW..............................................................................................2015.4 ASSOCIATED TASC POLICIES AND SOPs.................................................20

16. REFERENCES........................................................................................................20



PROTOCOL APPROVAL

Insert trial title

EudraCT number

SignaturesThe undersigned confirm that the following protocol has been agreed and approved by the Sponsor and that the Chief Investigator agrees to conduct the trial in compliance with this approved protocol and will adhere to the principles outlined in the EU Clinical Trials Directive (2001/20/EC), the EU Clinical Trials Regulation (536/2014) and any subsequent amendments of the Clinical Trials Regulation, the principles of GCP, the Sponsor SOPs, and any other applicable regulatory requirements as may be amended from time to time.

Chief Investigator Signature Date

Individual Responsible for Statistical Review

Signature Date


<Insert Trial Title><Insert Version number and date>

LIST OF ABBREVIATIONS

AE Adverse Event

AR Adverse Reaction

CNORIS Clinical Negligence and Other Risks Indemnity Scheme

CI Chief Investigator

CRF Case Report Form

GCP Good Clinical Practice

CTA Clinical Trail Authorisation

CTIMP Clinical Trial of Investigational Medicinal Product

DMC Data Monitoring Committee

DSUR Development Safety Update Report

EudraCT European Clinical Trials Database

IB Investigator’s Brochure

ICF Informed Consent Form

IF Incidental Findings

IMP Investigational Medicinal Product

ISF Investigator Site File

MA Marketing Authorisation

MHRA Medicines and Healthcare Products Regulatory Agency

NIMP Non Investigational Medicinal Product

PI Principal Investigator

PSF Pharmacy Site File

REC Research Ethics Committee

RSI Reference Safety Information

SmPC Summary of Product Characteristics

SOP Standard Operating Procedure

SAE Serious Adverse Event

SAR Serious Adverse Reaction

SUSAR Suspected Unexpected Serious Adverse ReactionTMG Trial Management Group

TSC Trial Steering Committee

TMF Trial Master File



WOCBP Women of Child Bearing Potential



SUMMARY/SYNOPSIS

.

Trial Title

Trial Phase & Type

Trial Design

Trial Population

Sample Size

Planned Trial Period

Clinical phase duration

Follow up phase duration Primary Objectives Outcome Measures

Secondary Objectives Outcome Measures

Investigational Medicinal Product(s)

Inclusion Criteria

Exclusion Criteria



1. INTRODUCTION

2. BACKGROUND & RATIONALE

3. TRIAL OBJECTIVES & OUTCOMES

Table 1: Primary Objectives and Outcome MeasuresPrimary Objective: Outcome Measure: Timepoint of

outcome measured

Table 2: Secondary Objectives and Outcome MeasuresSecondary Objective: Outcome Measure: Timepoint of

outcome measured

4. TRIAL DESIGN

4.1 TRIAL DESCRIPTION

4.2 TRIAL FLOWCHART

4.3 TRIAL MATRIX

4.4 STUDY ASSESSMENTS



The identity of participants will be established at every trial visit as described in TASC SOP12: Establishing Identity of Participants in Clinical Research.

4.5 SAFETY ASSESSMENTS

4.6 TISSUE

4.7 INCIDENTAL FINDINGSAny incidental findings (IF: previously undiagnosed condition) considered to be clinically significant will be reported to the participant’s GP and/or consultant by the CI or Site PI, with the consent of the participant.

5. TRIAL POPULATION

5.1 NUMBER OF PARTICIPANTS

5.2 INCLUSION CRITERIA

5.3 EXCLUSION CRITERIA

Individuals will not be enrolled to the trial if they are participating in the clinical phase of another interventional trial or have done so within the last 30 days [amend if longer required]. Individuals who are participating in the follow-up phase of another interventional trial, or who are enrolled in an observational study, will be co-enrolled where the CIs of each study agree that it is appropriate.

5.4 CONTRACEPTIVE ADVICE

Women of child bearing potential (WOCBP) must be willing to have pregnancy testing prior to trial entry, prior to administration of trial medication and during trial treatment. A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.

In addition, WOCBP, who are sexually active, must be willing to use a form of a medically approved birth control method:

Combined Oral Contraceptive Pill Placement of an intrauterine device – ‘coil’ Barrier methods of contraception: male condom only Established use of oral, injected, transdermal or implanted hormonal methods of

contraception Male partner sterilisation

Men who are sexually active with female partners of child bearing potential will also be required to use a form of medically approved birth control method as listed above.

6.1 IDENTIFYING PARTICIPANTS



6.2 CONSENTING PARTICIPANTS

Where a participant requests to speak with a physician from the trial team the consent process will not be completed until the participant has spoken to the physician and had all their questions answered to their satisfaction.

For adults who lose capacity their previous wishes will remain legally binding and this will remain valid unless the protocol changes significantly. If this occurs and further consent is required from a participant who has lost capacity, the appropriate person will be asked for their consent.

In all cases the CI or delegate will consult with carers and take note of any signs of objection or distress from the participant – the participant will be withdrawn if they raise objection. Where appropriate the participant will be withdrawn from any further clinical intervention and agreement will be sought from a carer to allow data collection.

The informed consent process will be conducted in compliance with TASC SOP07: Obtaining Informed Consent from Potential Participants in Clinical Research

6.3 SCREENING FOR ELIGIBILITY

6.4 INELIGIBLE PARTICIPANTS

Where an individual is found to be ineligible for trial participation, will be thanked and the reasons for the ineligibility full explained. Any queries or questions will be answered by an appropriate member of the research team. If ineligibility is related to an IF which is considered to be clinically significant, it will be reported to the participant’s GP and/or consultant by the CI or Site PI, with the consent of the individual.

6.5 WITHDRAWAL PROCEDURES

Participants are free to withdraw at any time and are not obliged to give reason(s). The CI, PI or delegate will make a reasonable effort to ascertain the reason(s), both for those who express their right to withdraw and for those lost to follow up, while fully respecting the individual’s rights.

Participants may be withdrawn by the CI or PI or delegate if it is considered to be in in their best interest. A full explanation will be provided. If the trial is being conducted on an intention to treat basis, and the participant has been randomised and given one or more dose of IMP, s/he will be asked to complete trial visits as per the protocol, if the CI considers it appropriate, to allow for an intention to treat analysis - but will be censored in the per-protocol analysis. Participants are free to refuse to do so. Withdrawn participants will not be prescribed IMP.

Those withdrawn, including those lost to follow-up, will be identified and a descriptive analysis of them provided, including the reasons for their loss, if known, and its relationship to treatment and outcome.



If a participant withdraws or is withdrawn they have the right/they do not have the right [delete as appropriate] to withdraw their data and any research tissue collected.

Details of when IMP must be withdrawn are given in Section 7.1.7

6.6 RANDOMISATION

6.6.1 Randomisation ProcedureRandomisation will be conducted in compliance with TASC SOP 40 Randomisation, Blinding and Code Breaking in Clinical Trials of Investigational Medicinal Products

6.6.2 Emergency Unblinding Procedure [delete section if open label]

Unblinding will be conducted in compliance with SOP 40 Randomisation, Blinding and Code Breaking in Clinical Trials of Investigational Medicinal Products

6.7 ASSOCIATED TASC POLICIES AND SOPS

TASC SOP07: For Obtaining Informed Consent from Potential Participants in Clinical ResearchTASC SOP12: Establishing Identity of Participants in Clinical Research TASC SOP40: Randomisation, Blinding and Code Breaking in CTIMPs

7. INVESTIGATIONAL MEDICINAL PRODUCTS

7.1 TRIAL DRUG

7.1.1 Trial Drug IdentificationInvestigational product

Dosage, form and strength

Arm 1

Arm 2

7.1.2 Trial Drug Manufacturer

7.1.3 Storage and Dispensing

7.1.4 Reference Safety Information

Version [insert date, manufacturer] of the [delete as appropriate] Summary of Product Characteristics (SmPC) or Investigator’s Brochure (IB) will be held in the Trial Master File (TMF) - specifically in Pharmacy Site File (PSF), Investigator Site File (ISF) and Sponsor File. Section 4.8 [or insert as appropriate] of the SmPC/IB contains the Reference Safety Information (RSI) for IMP and is detailed below. The SmPC/IB will be reviewed at least annually [or insert 3mthly/6mthly as appropriate] and where there have been any changes to



the RSI which may impact on the trial the protocol will be reviewed and a substantial amendment submitted for regulatory approvals.

7.1.5 Dosing Regime

7.1.6 Dose Changes7.1.7 Withdrawal

7.1.8 Overdose

7.2 COMPARATOR

7.2.1 Comparator Identification

7.2.2 Comparator Manufacturer

7.2.3 Storage and Dispensing

7.2.4 Reference Safety Information

Version [insert date, manufacturer] of the [delete as appropriate] SmPC or IB will be held in the Trial Master File - specifically in Pharmacy Site File (PSF) and Investigator Site File (ISF). Section [insert as appropriate] of the SmPC/IB specifies the RSI for the Comparator and is detailed below. The SmPC/IB will be reviewed at least annually [or insert 3mthly/6mthly as appropriate] and where there have been any changes to the RSI which may impact on the trial the protocol will be reviewed and any amendment required submitted for regulatory approvals.

7.2.5 Dosing Regime

7.2.6 Dose Changes

7.2.7 Withdrawal

7.2.8 Overdose

7.3 NON INVESTIGATIONAL MEDICINAL PRODUCTS

[delete section if no NIMPs]

Accountability Logs will also be maintained for non-IMPs (NIMPs) in the TMF and ISF(s), where appropriate.


TASC SOP 38: Manufacturing, Assembly, Packaging and Labelling of IMPS in CTIMPs



TASC SOP 39: Supply, Transport and Storage of IMP in CTIMPs

8. ACCOUNTABILITY PROCEDURESAccountability for all trial IMPs will be in compliance with TASC SOP 37: Accountability, Returns and Destruction of Investigational Medicinal Products in Clinical Trials of Investigational Medicinal Products

8.1 COMPLIANCE

8.2 OTHER MEDICATIONS

8.2.1 Permitted Medications

8.2.2 Prohibited Medications

8.2.3 Concomitant Medications

Details of all concomitant medications will be recorded on the trial Case Report Form (CRF) on a concomitant-medications log.


TASC SOP37: Accountability, Returns and Destruction of Investigational Medicinal Products in CTIMPs

9. DATA COLLECTION & MANAGEMENT

9.1 DATA COLLECTION

9.2 DATA MANAGEMENT SYSTEM

Data management will be conducted in compliance with TASC SOPs on Data Management, including TASC SOP53 Data Management Systems in Clinical Research .

The data management system (DMS) will be [delete as appropriate] OpenClinica/Excel/ or [insert as appropriate], as approved by Sponsor.

The DMS will be based on the protocol and CRF for the trial and individual requirements of the investigators. The CRF will collect only information that is required to meet the aims of the trial and to ensure the eligibility and safety of the participant. The trial database will be compliant with TASC SOP53 For Data Management Systems in Clinical Research. The database is managed in line with all applicable principles of medical confidentiality and UK law on data protection, namely, the Data Protection Act 1998, which brought UK law into line with the EU Data Protection Directive. The Data Controller will be the University of Dundee [or insert as appropriate] and the Data Custodian will be [insert as appropriate eg CI/TCTU/HIC/Other].



The CI may delegate CRF completion but is responsible for completeness, plausibility and consistency of the CRF. Any queries will be resolved by the CI or delegated member of the trial team.

[delete if not using OpenClinica] Development and validation of the trial database, QC and extraction of data will be done according to Tayside Clinical Trials Unit (TCTU) procedures and TASC SOP53 Extracts for analysis will be managed by TCTU and based on the dummy data tables provided by the trial team.

Database lock will be conducted in compliance with TASC SOP32 Locking Clinical Study Databases.

9.3 SOURCE DATA

Medical case notes/the CRF/trial questionnaires/GP records/other [insert as appropriate] will be used as source data. All trial data relevant to a participant’s general medical history will be recorded in the case note. Essential information regarding trial participation will also be recorded in the case note.


TASC SOP19: Preparing and Maintaining Case Report Forms (CRFs) for Use in CTIMPsTASC SOP32: Locking Clinical Study Databases.TASC SOP53: For Data Management Systems in Clinical Research TASC SOP48: Data Management in CTIMPs using Excel [delete if DMS is not Excel]

10. STATISTICS AND DATA ANALYSIS10.1 SAMPLE SIZE CALCULATION

10.2 PROPOSED ANALYSES

Statistical analysis will be conducted in compliance with TASC SOP05: Statistical Analysis Plans for Clinical Trials of Investigational Medicinal Products.

A statistical analysis plan (SAP) will be prepared for analysis of primary and secondary outcomes and will include a plan for handling missing data. [delete and insert SAP below if SAP is to be specified in the protocol]


TASC SOP05: For Statistical Analysis Plans for CTIMPs

11. ADVERSE EVENTS

11.1 DEFINITIONS

Safety reporting will be conducted in compliance with TASC SOP 11 “Identifying, Recording and Reporting Adverse Events for CTIMPs”.



Adverse Event (AE) Any untoward medical occurrence in a clinical trial participant administered a medicinal product and which does not necessarily have a causal relationship with this product.

Adverse Reaction (AR) An untoward and unintended response in a participant to an investigational medicinal product which is related to any dose administered to that participant.

Serious Adverse Event (SAE)

A serious adverse event is any untoward medical occurrence that:

results in death is life threatening requires hospitalisation or prolongation of existing

hospitalisation results in persistent or significant disability or incapacity is a congenital anomaly or birth defect Or is otherwise considered serious

Serious Adverse Reaction (SAR)

An adverse reaction, defined in the RSI, which is serious, as defined above.

Suspected Unexpected Serious Adverse Reaction (SUSAR)

A serious adverse reaction, the nature and severity of which is not consistent with the information about the medicinal product in question set out in the Reference Safety Information.

11.2 RECORDING AND REPORTING AE

All AEs will be recorded on the AE Log in the CRF and will be assessed for severity by the CI or PI. AEs will be recorded from the time a participant consents to join the trial until the participant’s last trial visit. An AE may be classified as a serious adverse event (SAE) or adverse reaction (AR). An initial assessment of expectedness/listedness for SAEs will be conducted by the Investigator.

The Investigator will make a clinical judgment as to whether or not an AE is of sufficient severity to require the participant’s removal from treatment. A participant may also voluntarily withdraw from treatment due to what he or she perceives as an intolerable AE. If either of these occurs, the participant should, if required, be offered an end of trial assessment and be given appropriate care under medical supervision until symptoms cease, or the condition becomes stable.

AEs will be followed up until (recovered/recovered with sequelae/death/five times of the elimination half-life after the last IMP dose/ 30 days after participant’s last visit/other) [delete as appropriate].



SAEs will be followed up until (recovered/recovered with sequelae/death/five times of the elimination half-life after the last IMP dose/ 30 days after participant’s last visit/other) [delete as appropriate].

Participants with unresolved AEs/SAEs at end of trial will be followed up until (recovered/recovered with sequelae/death/five times of the elimination half-life after the last IMP l dose/ 30 days after participant’s last visit/other) [delete as appropriate]. Suspected Unexpected Serious Adverse Reaction (SUSARS) will be followed until resolution.

The CI, PI or delegate will ask about the occurrence of AEs and hospitalisations at every visit during the trial. Serious AEs (SAEs) will be submitted on an SAE form to the Sponsor Pharmacovigilance Section [email protected] within 24 hours of becoming aware of the SAE. Site PIs will also notify the CI when submitting an SAE.

Worsening of a pre-existingcondition during the trial will not be classed as an AE, but may be defined as an outcome. Pre-specified outcome(s) will not be classed as an AE but as an outcome. Elective admissions and hospitalisations for treatment planned prior to randomisation will not be considered as an AE. However any AEs occurring during such hospitalisations will be recorded.

The evaluation of expectedness will be made based on the knowledge of the reaction and the relevant safety information (RSI) in the SmPC/IB [delete as appropriate] (see section 7), as described in TASC SOP 11 Identifying, Recording and Reporting Adverse Events for CTIMPs. The Sponsor will make the definitive assessment on expectedness for the purposes of SUSAR reporting.

11.2.1Black Triangle Scheme As [insert as appropriate] is defined under the Medicines and Healthcare Products Regulatory Agency MHRA Black Triangle Scheme as a drug requiring additional monitoring all adverse reactions will also be reported though the MHRA yellow card scheme: www.mhra.gov.uk/yellowcard

11.3 REGULATORY REPORTING REQUIREMENTS

The Sponsor is responsible for reporting SUSARs to the UK competent authority, the MHRA, and the Research Ethics Committee (REC). Fatal or life threatening SUSARs will be reported within 7 days and non-fatal and non-life threatening SUSARs within 15 days.

11.4 ANNUAL REPORTING REQUIREMENTS

Annual reporting will be conducted in compliance with TASC SOP 15: Preparing and Submitting Progress and Safety Reports in CTIMPs and Non-CTIMPs.The following reports will be submitted each year as a condition of the regulatory authorisation to undertake a clinical trial or as a condition of a favourable opinion from a REC. The Development Safety Update Report (DSUR) will be prepared jointly by the Sponsor Pharmacovigilance Section and CI and submitted by the Sponsor to the MHRA on the anniversary of date of Clinical Trial Authorisation (CTA) [insert CTN if appropriate].


mailto:[email protected]


The DSUR and reports of SUSARs in the UK, with an HRA CTIMP Safety Report Form, will be sent to REC by the Sponsor Pharmacovigilance Section. Any other safety reports, for example, reports of a data monitoring committee (DMC), will be sent by the CI to REC, with a Safety Report Form, and to the Sponsor.

An HRA Annual Progress Report for CTIMPs will be prepared and submitted by the CI to REC, and copied to the Sponsor, on the anniversary date of the REC favourable opinion.

11.5 URGENT SAFETY MEASURES

The CI or other trial physician will take appropriate immediate urgent safety measures in order to protect the participants against any immediate hazard to their health or safety. The MHRA, REC and Sponsor will be notified in writing within three days.


TASC SOP 11: Identifying, Recording and Reporting Adverse Events for CTIMPsTASC SOP 15: Preparing and Submitting Progress and Safety Reports in CTIMPS and Non-CTIMPS

12. PREGNANCYPregnancy is not considered an AE or SAE, unless there is a congenital abnormality or birth defect. Any unexpected pregnancy occurring during the trial and the outcome of the pregnancy, will be recorded on a TASC Pregnancy Notification Form and submitted to the Sponsor Pharmacovigilance Section [email protected] within 24 hours of becoming aware of the pregnancy. The pregnancy will be followed up until the end of the pregnancy. If the trial participant is a male, informed consent for follow up will be sought from his female partner.

13. TRIAL MANAGEMENT13.1 TRIAL MANAGEMENT GROUP

The trial will be co-ordinated by a Trial Management Group (TMG), consisting of the [insert as appropriate] the CI and PI(s), TM, PM, RN. Minutes of the TMG will be maintained in the TMF.

13.2 TRIAL STEERING COMMITTEE

A Trial Steering Committee (TSC) will be established to oversee the conduct and progress of the trial. The terms of reference of the TSC are detailed in the TMF. Minutes of the TSC will be maintained in the TMF.

13.3 DATA MONITORING COMMITTEE

An independent DMC will be established to oversee the safety of trial participants. The terms of reference of the DMC are detailed in the TMF. Minutes of the DMC will be maintained in the TMF.


mailto:[email protected]


13.4 INSPECTION OF RECORDS

The CI, PIs and all institutions involved in the trial will permit trial related monitoring, audits, REC review, and regulatory inspection. In the event of an audit, the CI will allow the Sponsor, representatives of the Sponsor or regulatory authorities direct access to all trial records and source documentation.

13.5 RISK

13.5.1 Potential Risk

Potential risks to participants are described below.

Potential risks to the trial are described below.

13.5.2Risk Assessment & MonitoringA trial risk assessment was carried out by the Sponsor prior to Sponsorship approval being granted. The Sponsor has determined the appropriate extent and nature of monitoring for the trial and will appoint appropriately qualified and trained monitors. A trial monitoring plan will be prepared and reviewed regularly throughout the trial.


TASC POLICY 04: GCP Monitoring PolicyTASC SOP03: Monitoring CTIMPs

14. TRIAL CONDUCT & RESPONSIBILITIESThe CI will be responsible for the conduct of the trial. Site delegate(s) will oversee the trial and will be accountable to the CI. A trial-specific Delegation of Duties & Signature Log will be prepared for each Site, detailing the duties of each member of staff working on the trial.

14.1 APPROVALS

The trial will be conducted in accordance with the principles of Good Clinical Practice (GCP).In addition to Sponsorship approval, a favorable ethical opinion will be obtained from an appropriate NHS REC. Authorisation from the MHRA, and appropriate NHS R&D permission(s) will be obtained prior to commencement of the trial.

14.2 CONFIDENTIALITY

The CI and trial staff will comply with the requirements of the EU Data Protection Directive (Directive 95/46/EC) or any subsequent amendment or replacement thereof with regard to the collection, storage, processing and disclosure of personal information and will uphold the Directive’s core principles.

The CI and trial staff will also adhere to the NHS Scotland Code of Practice on Protecting Participant Confidentiality or equivalent.

All trial records and data will be managed in a manner designed to maintain participant confidentiality. All records, electronic or paper, will be kept in a secure storage area with



access limited to appropriate trial staff only. Computers used to collate data will have limited access measures via user names and passwords.

Personal clinical information will not be released without the written permission of the participant, except as necessary for monitoring and auditing by the Sponsor, its designee or regulatory authorities.

The CI and trial staff will not disclose or use for any purpose other than performance of the trial, any data, record, or other unpublished, confidential information disclosed to those individuals for the purpose of the trial. Prior written agreement from the Sponsor will be required for the disclosure of any said confidential information to other parties.

Access to collated participant data will be restricted to the CI and appropriate delegated trial staff.

Where data requires to be transferred, an appropriate Data Transfer Agreement will be put in place.

Published results will not contain any personal data that could allow identification of individual participants.

14.3 INSURANCE AND INDEMNITY

[delete as appropriate] [The University of Dundee] [and] [Tayside Health Board] [is] [are] [Sponsoring] [Co-Sponsoring] the trial.

Insurance. – [include if UoD sponsoring/co-sponsoring;delete if NHST only Sponsor] The University of Dundee will obtain and hold Professional Negligence Clinical Trials Insurance cover for legal liabilities arising from the trial.

[include if NHST sponsoring/co-sponsoring] Tayside Health Board will maintain its membership of the Clinical Negligence and Other Risks Insurance Scheme (“CNORIS”) which covers the legal liability of Tayside in relation to the trial.

[include if University staff involved and NHS participants involved] Where the trial involves University of Dundee staff undertaking clinical research on NHS participants, such staff will hold honorary contracts with Tayside Health Board which means they will have cover under Tayside’s membership of the CNORIS scheme.

Indemnity. [delete as appropriate] The [Sponsor] [Co-Sponsors] [does not] [do not] provide trial participants with indemnity in relation to participation in the Trial but [has] [have] insurance for legal liability as described above.

[delete as appropriate] Where other Scottish Health Boards are participating as trial sites, those other Scottish Health Boards will maintain membership of CNORIS to cover their liability in relation to their conduct of the trial.

[delete as appropriate] Where other UK NHS organisations are participating as trial sites, those other UK NHS organisations will maintain membership of a scheme similar to CNORIS.



[delete as appropriate] Where organisations within the EU are participating as trial sites, the co-sponsors shall put in place appropriate agreements with those organisations which shall contain provision for suitable insurance cover for the liability of those organisations in relation to their conduct of the trial.

14.4 PROTOCOL AMENDMENTS

Amendments to protocol will be conducted in compliance with TASC SOP26 Amendments to CTIMPs.The CI will seek Sponsor approval for any amendments to the Protocol or other approved trial documents. Amendments to the protocol or other trial documents will not be implemented without approval from the Sponsor and subsequent approval from the appropriate REC and/or MHRA, as appropriate, and NHS R&D Office(s).

14.5 PROTOCOL DEVIATIONS, BREACHES AND WAIVERS

Management of deviations and breaches to protocol or GCP will be conducted in compliance with TASC SOP25 Escalation and Notification of Serious Breaches of GCP or the Trial Protocol for CTIMPs.

The CI will not implement any deviation from the protocol without agreement from the Sponsor, except where necessary to eliminate an immediate hazard to trial participants.

In the event that there is a deviation from the protocol, the nature of and reasons for the deviation will be recorded in the CRF/TMF and documented in the trial TASC Deviation & Breach Log.

If a serious breach of the protocol or GCP is suspected, this will be reported to the Sponsor immediately using the TASC Potential Breach Reporting Form and will be recorded in the CRF and documented in the trial TASC Deviation & Breach Log.

If a breach necessitates a subsequent protocol amendment, this will be submitted to the Sponsor for approval and then to the appropriate REC, MHRA and NHS R&D for review and approvals as appropriate.

It is Sponsor policy that waivers to the Protocol will not be approved.

14.6 TRIAL RECORD RETENTION

Archiving of trial documents will be carried out as specified in TASC SOP13: Archiving Clinical Research Data for Clinical Trials of Investigational Medicinal Products. For studies where the data will not form part of an application for a Marketing Authorisation (MA) all trial documentation, electronic and paper, will be kept for 5 years. For studies where the data does form part of an application for an MA all trial documentation will be kept for 15 years. Case notes will be maintained in compliance with local NHS Policy on Retention of Medical Case notes.

14.7 END OF TRIAL

The end of trial at all Sites is defined as last participant last visit (LPLV)/database lock/other [insert as appropriate]. The Sponsor, CI and/or the TSC [delete if appropriate] have the right at any time to terminate the trial for clinical or administrative reasons.



The end of the trial will be reported to the Sponsor, REC, MHRA and NHS R&D Office(s) within 90 days, or 15 days if the trial is terminated prematurely. The CI will ensure that any appropriate follow up is arranged for all participants.

A final clinical trial report will be submitted to the MHRA via EudraCT within 1 year [or insert 6 months for paediatric trials] of the end of the trial and will also be provided to the Sponsor and REC.


TASC SOP13: Archiving Clinical Research Documentation and DataTASC SOP16: Closure of CTIMPsTASC SOP18: Study Start Up in CTIMPsTASC SOP23: Completion of Delegation LogsTASC SOP25: Escalation and Notification of Serious Breaches of GCP or the Trial Protocol for CTIMPSTASC SOP26: Amendments in CTIMPsTASC SOP 28: For Approvals for CTIMPs

15. REPORTING, PUBLICATIONS AND DISSEMINATION OF RESULTS15.1 AUTHORSHIP POLICY

The data arising from this trial resides with the trial team and ownership with the University of Dundee. On completion of the trial, the trial data will be analysed and tabulated, and a clinical trial final report will be prepared.

15.2 PUBLICATION

Details of the trial and clinical trial final report will be published on the EudraCT database, the latter no later than 12 months [or insert 6 months for paediatric trials] after the end of trial, and will be available to the public via the EU Clinical Trial Register. The report will be made available to the Funder. The report can be used for publication and presentation at scientific meetings. Trial investigators have the right to publish orally or in writing the results of the trial. The criteria for authorship will follow the criteria of the The International Committee of Medical Journal Editors as described in the TASC Publication Policy.

15.3 PEER REVIEW


TASC POLICY 06: TASC Publication Policy: Guidance for Trialists

16. REFERENCES



APPENDIXAmendment No.

Protocol Version No.

Protocol Date

Author(s) of changes Brief Details of Changes made


trial protocol - ahspartnership.org.uk · web viewthis protocol template is mandatory for...

Documents