Section Headings in the Protocol Template Should Not Be Deleted

Doc Ref 098 NCTIMP Protocol Template

Version: 3.0

Effective Date xx/xx/2017

This protocol template is intended for use in clinical studies which are notClinical 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.

MANDATORYfields/text MUST NOT be deleted.

Other sections may be adapted to suit a particular trial/study.

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

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Doc Ref 098

NCTIMP Protocol v5.0

Effective Date 09/04/2018

Trial/StudyProtocol

insert Study Title

I.P.O.C - Intervention, Population, Outcome, Comparator (ifappropriate) is a rule that helps produce a meaningful study title.

Trial/StudyAcronym
Sponsor
Sponsor R&D Number
Funder
Chief Investigator
REC Number
Clinical Trials Unit (or delete)
ISRCTN/clinicaltrials.gov Number
Version Number and Date

Doc Ref 098

NCTIMP Protocol v5.0

Effective Date 09/04/2018

<Insert Study Title>

<Insert Version number and date>

To update the table of contents, highlight the existing table of contents, click ‘Insert’, ‘Reference’, ‘Index and Tables’ and ‘OK’.

PROTOCOL APPROVAL

LIST OF ABBREVIATIONS

SUMMARY/SYNOPSIS

1INTRODUCTION

2BACKGROUND & RATIONALE

3TRIAL/STUDY OBJECTIVES & outcomes

4tRIAL/STUDY DESIGN

4.1INTERVENTION

4.2 TRIAL/STUDY DESCRIPTION

4.3 TRIAL/STUDY FLOWCHART

4.4TRIAL/STUDY MATRIX

4.5TRIAL/STUDY ASSESSMENTS

4.6 TRIAL/STUDY safety ASSESSMENTS

4.7 TISSUE

4.8INCIDENTAL FINDINGS

4.7trial/study POPULATION

4.8NUMBER OF PARTICIPANTS

4.9INCLUSION CRITERIA

4.10EXCLUSION CRITERIA

5PARTICIPANT SELECTION AND ENROLMENT

5.1IDENTIFYING PARTICIPANTS

5.2CONSENTING PARTICIPANTS

5.3SCREENING FOR ELIGIBILITY

5.4INELIGIBLE AND NON-RECRUITED PARTICIPANTS

5.5RANDOMISATION

5.5.1Randomisation

5.5.2Intervention Allocation

5.5.3Withdrawal procedures

6DATA COLLECTION & MANAGEMENT

6.1Data Collection

6.2Data Management System

7STATISTICS AND DATA ANALYSIS

7.1SAMPLE SIZE CALCULATION

7.2PROPOSED ANALYSES

7.3Missing data

7.4TRANSFER OF DATA

8TRIAL/STUDY MANAGEMENT AND OVERSIGHT ARRANGEMENTS

8.1TRIAL/STUDY MANAGEMENT GROUP

8.2TRIAL/STUDY STEERING COMMITTEE

8.3DATA MONITORING COMMITTEE

8.4INSPECTION OF RECORDS

9GOOD CLINICAL PRACTICE

9.1ETHICAL CONDUCT OF THE STUDY

9.2Confidentiality

9.3Data Protection

9.4Insurance and Indemnity

10ADVERSE EVENTS

10.1DEFINITIONS

10.2RECORDING AND REPORTING AE

11ANNUAL REPORTING REQUIREMENTS

12STUDY CONDUCT RESPONSIBILITIES

12.1PROTOCOL AMENDMENTS, deviations and breaches

12.2STUDY RECORD RETENTION

12.3END OF STUDY

13REPORTING, PUBLICATIONS AND NOTIFICATION OF RESULTS

13.1AUTHORSHIP POLICY

13.2PUBLICATION

13.3PEER REVIEW

14REFERENCES

PROTOCOL APPROVAL

Insert trial/studytitle

Signatures

The undersigned confirm that the following protocol has been agreed and approved by the Sponsor and that the Chief Investigator agrees to conduct the trial/study/study in compliance with this approved protocol and will adhere to 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

Add details of Principal or Co Investigator(s), if appropriate,

The protocol must be signed. as a minimum by the CI, before it is sent to the MHRA

All approved version(s) of the protocol must be signed by all named parties before distribution to Sponsor and Sites.

All fully signed version(s) of the protocol must be kept in the SF, S/TMF and/or ISF(s)

LIST OF ABBREVIATIONS

Alphabetical Add/Delete as appropriate.

AE / Adverse Event
CI / Chief Investigator
CNORIS / Clinical Negligence and Other RisksIndemnity Scheme
CRF / Case Report Form
DMC / Data Monitoring Committee
GCP / Good Clinical Practice
ICF / Informed Consent Form
IF / Incidental Findings
ISF / Investigator Site File
PI / Principal Investigator
REC / Research Ethics Committee
SAE / Serious Adverse Event
SOP / Standard Operating Procedures
S/TMF/SMF / Trial Master File/Study Master File
T/SMG / Trial Management Group
TSC / Trial Steering Committee

SUMMARY/SYNOPSIS

All the central elements of the protocol, for example the rationale, objectives, methods, populations, time frame, and expected outcomes.

Trial/Study Title(including acronym)
Trial/Study Design
Trial/Study Population
Sample Size
Planned Trial/study Period
Clinical phase duration
Follow up phase duration or specify none
Primary / Objectives / Outcome Measures
Secondary / Objectives / Outcome Measures
Optional
Inclusion Criteria
Optional
Exclusion Criteria

1INTRODUCTION

2BACKGROUND & RATIONALE

MandatoryField

Specify the reasons for the research in light of current knowledge, need for the study, cause of the problem, possible solutions, why the research needs to be done, its relevance and a brief description of the most relevant studies published.

Include a clear explanation/justification of the research question/hypothesisusing PICOS (Participant, Intervention, Control Comparator, Outcomes, Statistical Design)

• benefits to participants, health services, relevance to current policies etc.;
• description of the disease, its diagnosis, incidence, current treatments and limitations etc.;
• description of the treatment under investigation;
• study outcomes and what evidence study may achieve this.
• summary of the known and potential risks and benefits, if any.

3TRIAL/STUDY OBJECTIVES & outcomes

Mandatory Field

A broad statement of what thestudy hopes to accomplish. Objectives should be simple and specific and stated in advance. After statement of the primary objective, secondary objectives may be specified.

Objectives: What will the results of the research be and how will they be determined/evaluated

Outcomes: What will the results of the research be and how will they be determined/evaluated

Table 1: Primary Objectives and Outcome Measures

Primary Objective: / Outcome Measure: / Timepoint of outcome measured

Table 2: Secondary Objectives and Outcome Measures

Secondary Objective: / Outcome Measure: / Timepoint of outcome measured

4tRIAL/STUDY DESIGN

4.1INTERVENTION

MANDATORY FIELD

Name and detail the interventional procedure. Participants may receive diagnostic, therapeutic, or other types of interventions, including noninvasive approaches, such as surveys, education, and interviews.

Participants can be assigned to receive one or more interventions – or to a comparator –or to no intervention.

Indicate whether there is any public involvement in the study design.

4.2 TRIAL/STUDYDESCRIPTION

MANDATORY Field

4.3 TRIAL/STUDY FLOWCHART

MANDATORY Field

4.4TRIAL/STUDY MATRIX

MANDATORY Field

Detail the specific assessments to be performed and the time points (day, week, mth, etc) required during the study - split by visit number for clarity.ie. describe the sequence of procedures at each visit. You should also include visit windows eg Visit 1, month 3 (+/-1wk)

Example Study Matrix

Screening / Baseline / Week 12(+/-1wk) / 6 months(+/-1wk) / 12 months(+/-1wk) / 24 months(+/-1wk)
Visit / V1 / V2 / V3 / V4 / V5 / V6
Vital Signs / X / X / X / X / X / X
Blood sample / X / X / X / X / X / X
Bloods / X / X / X / X / X / X
IPAQ / X / X / X / X
Adverse Events / X / X / X / X / X / X
Con Meds / X / X / X / X

4.5TRIAL/STUDY ASSESSMENTS

4.6 TRIAL/STUDY safety ASSESSMENTS

MANDATORY Field

Detail any specific safety assessments required for the IMPs.

Describe the measures that will be used to determine subject safety during the study. These may include eg physical examination, blood tests and serious adverse event reporting.

The tests performed should be appropriate to the treatment, e.g. U&Es if there is a risk of renal problems. Stipulate the times at which safety evaluations will be conducted

4.7 TISSUE

MANDATORY Field

Detail which types of tissue will be collected, when, if they will be destroyed at study end or if they will be stored for potential future use with consent, for how long, where they will be stored and if there is an intention to share +/-any associated data with other researchers. Specify clearly if there is any intention to conduct genetic diagnostic/therapeutic analysis now or in the future.

4.8INCIDENTAL FINDINGS

MANDATORY TEXT

Any 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.

4.9 trial/studyPOPULATION

4.10NUMBER OF PARTICIPANTS

MANDATORYField

Detail: Number of participants expected to be recruited, number required to complete, expected dropout rate and/or replacement, time each on trial/study, length of recruitment period,

4.11INCLUSION CRITERIA

MANDATORYField

4.12EXCLUSION CRITERIA

MANDATORY TEXT

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

Where appropriate, insert contraceptive advice ‘women of child-bearing potential (WOCBP), who do not abstain from sex, must be willing to have pregnancy testing prior to study entry. In addition, women of child bearing potential, who are sexually active, must be willing to use a form of a medically approved birth control method eg; · Combined Oral Contraceptive Pill or Placement of a intrauterine device - ‘coil’or Barrier methods of contraception: male condom only or Established use of oral, injected, transdermal or implanted hormonal methods of contraception or Male partner sterilisation .

5PARTICIPANT SELECTION AND ENROLMENT

MANDATORY FIELD

5.1IDENTIFYING PARTICIPANTS

MANDATORYField

Where will participants be recruited from e.g. clinic, GP, community, database, Network; who will identify, who will contact and how willstudy informationbe provided eg PIS, letter, advertising.

.

5.2CONSENTING PARTICIPANTS

MANDATORYField

Who consents,when,where. Provide a minimum of 24h from participant receiving PIS to consent or justify if <24h.

MANDATORY TEXT

Where a participant requests to speak with a physician from the study 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 capacitytheir previous wishes will remain legally binding and this will remain valid unless the protocolchanges 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

5.3SCREENING FOR ELIGIBILITY

MANDATORY FIELD

Detail anystudy-specific pre-consent and post-consent but pre-randomisation activities e.g. ECG, bloods.

Specify if re-screening is to be considered. If yes, add criteria, timelines etc.,new identifier re-consent etc

5.4INELIGIBLE AND NON-RECRUITED PARTICIPANTS

5.5RANDOMISATION[delete IF STUDY IS NOT RANDOMISED

5.5.1Randomisation

REQUIRED FIELD

Detail:

• who created the randomisation code e.g. TCTU, research team, or external third party, define role of individual(s) not their name;
• provide evidence that the randomisation code is GCP compliant e.g. can the randomisation list be recreated from seed.
• who within the study personnel is responsible for randomisation of participants;
• type of randomisation, e.g. simple, block, stratified, minimisation (define stratification variables or block sizes where appropriate);
• procedures for randomisation, location(s) of randomisation list, use of equal or unequal allocation between treatment arms;
• if blinded, detail the level of blinding, how it will be implemented etc.

5.5.2Intervention Allocation

Required Field if appropriate

5.5.3Withdrawal procedures

Required Field

Detail:

• reasons and procedures for withdrawing participants (either at their own request or for other reasons) should be detailed if possible.
• Withdrawal procedures should consider:
• when and how to withdraw subjects from the study.
• the type and timing of the data to be collected for withdrawn participants.
• whether participants are to be replaced (if applicable)
• the follow-up for subjects withdrawn from a study intervention
• if the participant’s data is to be included and how consent for this is obtained
• if data from any follow-up or safety visit may be included

Required Field

Detail any specific safety assessments required for the study. Describe the measures that will be used to determine subject safety during the study. These may include physical examination, blood tests and adverse event reporting. Stipulate the times at which safety evaluations will be conducted

6DATA COLLECTION& MANAGEMENT

6.1Data Collection

Required Field

Detail data to be collected, including:

• the source (e.g. CRF, questionnaire, medical notes, electronic data collection procedures);
• time points for collection (e.g. baseline, during treatment phase, during follow-up phase, unscheduled visits up)
• who will collect the data
• details of any standardised tools (e.g. pain scores)
• describe any methods to maximise completeness of data collection (e.g. telephoning participants who have not returned questionnaires)
• note any data that is to be recorded directly on the case report forms (CRFs) (i.e. no prior written or electronic record of data)

6.2Data Management System

REQUIRED FIELD

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

If external third party SOPs are in use, it/they must be specified here

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

If data and/or personal information is to be held/processed by an external third party, it must be specified here

The DMS will be based on the protocol and CRF for the trial/study and individual requirements of the investigators. The CRF will collect only information that is required to meet the aims of the trial/studyand to ensure the eligibility and safety of the participant. The trial/study database will be compliant with TASC SOP53Data Management Systems in Clinical Research.

If Excel as DMS refer also to TASC SOP48: Data Management In CTIMPS Using Excel.

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].

This information on DPA and EU DPD must be in the PIS also

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/study team.

[delete if not using TCTU OpenClinica] Development and validation of the trial/study database, QC and extraction of data will be done according to Tayside Clinical Trial 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/study team.

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

7 STATISTICS AND DATA ANALYSIS

7.1SAMPLE SIZE CALCULATION

Require Field

Detail the sample size, precision or power calculation, dropout rates, relevant assumptions and justifications.Comment on an estimate of the recruitment period with justification that the required sample size will be achievable.

Confirm who carried out the sample size calculation.

7.2PROPOSED ANALYSES

Required Field

Refer for guidance to TASC SOP05: Statistical Analysis Plans for Clinical Trial/study/studys of Investigational Medicinal Products

Detail the variables to be used for assessment and how these will be reported (e.g. means, standard deviations, medians etc.).

Write detailed statistical analysis plans for analyses of primary and secondary outcomes including:

• how the outcomes will be measured
• any transformations on the data likely to be required before analysis
• appropriate statistical tests which will be used to analyse the data e.g. per protocol, intention to treat
• methods for handling more than two treatment groups and multiple comparison methods (if appropriate)
• plans for pre-defined subgroup analyses
• details of any interim analysis
• who will be performing the statistical analysis e.g. TCTU statistician, DEBU statistician, trial/study/study team statistician

7.3Missing data

Detail plans for handling missing data, non-compliers and withdrawals or refer to Statistical Analysis Plan.

7.4TRANSFER OF DATADetail procedures in place to ensure patient confidentiality if patient data is to be transferred between sites.

8 TRIAL/STUDYMANAGEMENT AND OVERSIGHT ARRANGEMENTS

8.1 TRIAL/STUDYMANAGEMENT GROUP

Required Field

Each study, no matter the number of participants or number of collaborating sites, should establish a trial/study management group (T/SMG) to set and review the day to day management of the study. The T/SMG should include the CI, PI, study manager or equivalent, , research nurse if appropriate. Other grant holders can be included but not all of the co-applicants need to be included. A TCTU member of staff can be included if the CI feels it appropriate.

Suggested text only - delete or amend as appropriate.

A Delegation Log must be in place at each site.

The trial/study will be co-ordinated by a Trial/Study Management Group (T/SMG), consisting of e.g. the grant holderChief Investigator (CI), external Principal Investigators (PIs), Study Manager, research nurse[insert as appropriate].

8.2TRIAL/STUDY STEERING COMMITTEE

[delete if appropriate] Suggested text only - amend as appropriate. If no SC will be established, the reason for not having a SC should be included in this section instead e.g. remit will be carried out as part of the T/SMG.

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

8.3DATA MONITORING COMMITTEE

[delete if appropriate] Suggested text only - amend as appropriate. If no DMC will be established, the reason for not having a DMC should be included in this section instead

An independent Data Monitoring Committee (DMC) will be established to oversee studyprogress.The terms of reference of the DMC are detailed in the S/TMF.Minutes of the DMC will be maintained in the S/TMF

8.4INSPECTION OF RECORDS

MANDATORY TEXT

The CI, PIs and all institutions involved in the study will permit study related monitoring, audits, and REC review. The CI agrees to allow the Sponsor or, representatives of the Sponsor, direct access to all study records and source documentation.