TASCDoc Ref_054_Protocol Template
Version: 3.0
Effective Date 13/03/2012
This protocol template is mandatory for the protocol layout to be used 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. Some sections have required fields which must be completed even if it is to confirm they are not applicable.Specific sections, where marked, MUST NOT be deleted.Other sections may be adapted to suit particular studies. Other sections may be added as required by the specific trial.
All purple and red instruction text is hidden text and will not print.Follow these instructions as appropriate.
It is strongly recommended that a Consort flow diagram is completed at the same time as the protocol.
If you are unable to see the purple instruction text on your screen, go into the Tools menu, click Options, click on the View tab, then in the section called Formatting marks, and tick the box for hidden text.
Doc Ref_054_Protocol TemplatePage 1
Version: 6.0
Effective Date 07/08/2014
Study Protocol
insert Study Title
Study Acronym / insert study acronymSponsor / insert Sponsor/Co-Sponsor and insert details as appropriate
Sponsor R&D Number
Funder / insert name of Funder
Chief Investigator / insert name of CI, including Title
EudraCT Number / insert EudraCT number before finalisation
CTA Number / insert CTA (clinical trial authorisation) number before finalisation
REC Number / insert REC number before finalisation
ISRCTN Number / insert ISRCTN number or equivalent, and amend text
Version Number and Date / insert version number and date of each version
If the trial is multi-site, or has a coordinating Trial Centre, add specific details e.g. contact names, addresses etc. on this front page or in an Appendix.
Doc Ref_054_Protocol TemplatePage 1
Version: 6.0
Effective Date 07/08/2014
<Insert Study Title>
<Insert Version number and date>
CONTENTS
To update the table of contents, highlight the existing table of contents, click ‘Insert’, ‘Reference’, ‘Index and Tables’ and ‘OK’.
CONTENTS
PROTOCOL APPROVAL
LIST OF ABBREVIATIONS
SUMMARY
1INTRODUCTION
1.1BACKGROUND
1.2RATIONALE FOR STUDY
2STUDY OBJECTIVES
2.1OBJECTIVEs
2.1.1Primary Objective
2.1.2Secondary Objectives
2.2OUTCOMES
2.2.1Primary Outcomes
2.2.2Secondary Outcomes
3STUDY DESIGN
3.1STUDY DESCRIPTION
3.2TRIAL FLOWCHART
3.3STUDY MATRIX
4STUDY POPULATION
4.1NUMBER OF PARTICIPANTS
4.2INCLUSION CRITERIA
4.3EXCLUSION 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
5.5.2Treatment Allocation
5.5.3Emergency Unblinding Procedures
5.5.4Withdrawal procedures
6INVESTIGATIONAL MEDICINAL PRODUCT
6.1STUDY DRUG
6.1.1Study Drug Identification
6.1.2Study Drug Manufacturer
6.1.3Marketing Authorisation Holder
6.1.4Labelling and Packaging
6.1.5Storage
6.1.6IMP Safety Information
6.1.7Accountability procedures
6.2STUDY COMPARATOR
6.2.1Comparator Identification
6.2.2Comparator Manufacturer
6.2.3Labelling and Packaging
6.2.4Storage
6.2.5Accountability procedures
6.3DOSING REGIME
6.4DOSE CHANGES
6.5PARTICIPANT COMPLIANCE
6.6OVERDOSE
6.7OTHER MEDICATIONS
6.7.1Permitted Medications
6.7.2Prohibited Medications
6.7.3Concomitant Medications
7STUDY ASSESSMENTS
7.1STUDY ASSESSMENTS
7.2SAFETY ASSESSMENTS
8DATA COLLECTION& MANAGEMENT
8.1Data Collection
8.2Data Management System
9STATISTICS AND DATA ANALYSIS
9.1SAMPLE SIZE CALCULATION
9.2PROPOSED ANALYSES
9.3Missing data
9.4TRANSFER OF DATA
10ADVERSE EVENTS
10.1DEFINITIONS
10.2RECORDING AND REPORTING AEs AND SAEs
10.3REGULATORY REPORTING REQUIREMENTS
10.4ANNUAL REPORTING REQUIREMENTS 10
10.5URGENT SAFETY MEASURES
11PREGNANCY
12TRIAL MANAGEMENT AND OVERSIGHT ARRANGEMENTS
12.1TRIAL MANAGEMENT GROUP
12.2TRIAL MANAGEMENT
12.3TRIAL STEERING COMMITTEE
12.4DATA MONITORING COMMITTEE
12.5INSPECTION OF RECORDS
12.6RISK ASSESSMENT
12.7STUDY MONITORING
12.7.1 PotentialRisks
12.7.2 MinimisingRisk
13GOOD CLINICAL PRACTICE
13.1ETHICAL CONDUCT OF THE STUDY
13.1.1Confidentiality
13.1.2Data Protection
13.1.3Insurance and Indemnity
14STUDY CONDUCT RESPONSIBILITIES
14.1PROTOCOL AMENDMENTS
14.2PROTOCOL DEVIATIONS, BREACHES AND WAIVERS
14.3STUDY RECORD RETENTION
14.4END OF STUDY
14.5CONTINUATION OF DRUG FOLLOWING THE END OF STUDY
15REPORTING, PUBLICATIONS AND NOTIFICATION OF RESULTS
15.1AUTHORSHIP POLICY
15.2PUBLICATION
15.3PEER REVIEW
16REFERENCES
APPENDIX:
PROTOCOL APPROVAL
Insert study title
EudraCT number
Signatures
By signing this document I am confirming that I have read, understood and approve the protocol for the above study.
Chief Investigator / Signature / DateIndividual Responsible for Statistical Review / Signature / Date
Add details of Chief Investigator, the Principal Investigator, if appropriate and the statistician),
Approved version(s) of the protocol should be signed off before distribution
Doc Ref_054_Protocol TemplatePage 1
Version: 6.0
Effective Date 07/08/2014
<Insert Study Title>
<Insert Version number and date>
LIST OF ABBREVIATIONS
(including Study abbreviations)
Compile a list of abbreviations as appropriate.
GCP / Good Clinical PracticeIMP / Investigational Medicinal Product
ISF / Investigator Site File
TMF / Trial Master File
SOP / Standard Operating Procedure
CRF / Case Report Form
AE / Adverse Event
SAE / Serious Adverse Event
AR / Adverse Reaction
UAR / Unexpected Adverse Reaction
SUSAR / Suspected Unexpected Serious Adverse Reaction
CNORIS / Clinical Negligence and Other Risks Scheme
SmPC / Summary of Product Characteristics
NRES / National Research Ethics Service
REC / Research Ethics Committee
MHRA / Medicines and Healthcare Products Regulatory Agency
SUMMARY
Detail rationale for the study, objectives, and methods. Two summaries may be appropriate - a Professional Summary and a Lay Summary (Lay Summary is optional).
Brief information to be provided on:
The problem to be addressed
What is the hypothesis to be tested?
Why is a trial needed now?
Study design
Planned interventions
Proposed outcome measures
What is the participant group and where will they be recruited from?
How will the results of the trial be used (e.g. inform clinical decision making, improve understanding)
Duration of treatment period and follow up
Proposed type of analysis
1INTRODUCTION
1.1BACKGROUND
Required Field
Should include any reviews, for example a systematic review such as Cochrane, of previous studies, disease particulars, incidence, current treatment options, risks and benefits.
1.2RATIONALE FOR STUDY
Required Field
This section should include a clear explanation of the research question and hypothesis, justification for the study, including e.g. using the PICOS format (Patient, Intervention, Control Comparator, Outcomes, Study/Statistical Design)
- an explanation of why the study is appropriate, benefits to participants, health services, relevance to current policies etc.;
- description of the disease under investigation, its diagnosis, incidence, current treatments, their limitations etc.;
- description of the treatment under investigation;
- statement of what would be a worthwhile improvement in study outcomes and what
evidence there is that the treatment under investigation may achieve this.
- summary of findings from non-clinical studies that potentially have clinical significance and from clinical trials that are relevant to the trial.
- summary of the known and potential risks and benefits, if any, to human subjects.
- description of and clarification for the route of administration, dosage, dosage regimen, and treatment period(s)
2STUDY OBJECTIVES
2.1OBJECTIVEs
2.1.1Primary Objective
Required Field
2.1.2Secondary Objectives
Required Field
2.2OUTCOMES
Consideration should be given to the number ofOutcomes identified.Only sufficient data should be collected to answer the research question, supported by the Trial Statistician and the Statistical Analysis Plan.
2.2.1Primary Outcomes
Required Field
2.2.2Secondary Outcomes
Required Field
3STUDY DESIGN
3.1STUDY DESCRIPTION
Required Field
3.2TRIAL FLOWCHART
Provide a schematic diagram, such as a Consort diagram, of the study design including participant time line (
Detail:
- type of and length of study e.g. 24 week, multi-centre, randomised, double-blind, placebo controlled etc.;
- duration e.g. what constitutes the treatment phase and the follow up phase;
- points in trial for measurement of outcomes;
- location or setting of the study e.gsingle site within Tayside or refer to use of external sites .
3.3STUDY MATRIX
Required Field
Example Study Matrix
Time / Screening / Baseline / Week 12 / 6 months / 12 months / 24 monthsVital Signs / X / X / X / X / X / X
Blood sample / X / X / X / X / X / X
Waist / X / X / X / X / X / X
Hip / X / X / X / X
BMI / X / X / X / X / X / X
Bloods / X / X / X / X
IPAQ / X / X / X
4STUDY POPULATION
4.1NUMBER OF PARTICIPANTS
Required Field
Detail:
- Number of participants, participant populationlength of recruitment period, where recruiting from e.g. cluster trial.As appropriate provide either the definite number of collaborating sites or alternatively provide an indication of the expected number of sites, e.g. We expect to recruit from between 100-110 GP practices.
- Detail anticipated dropout rate and whether you will be able to recruit to replace drop outs
4.2INCLUSION CRITERIA
Required Field
4.3EXCLUSION CRITERIA
Required Field
Always include at least 30 days since participating in a drug trial or interventional study to ensure participants are given a sufficient recovery period between participating in trials; the wash out period is usually a minimum of 30 days between drug trials or interventional studies, but can be longer if appropriate depending on the IMP half-life.
5PARTICIPANT SELECTION AND ENROLMENT
5.1IDENTIFYING PARTICIPANTS
Required Field
Where will participants be recruited from (e.g. clinic, GP, SPCRN), who will identify participants, who will contact participants and how, what will potential participants receive (e.g. PIS etc.) and will advertising be used etc.
5.2CONSENTING PARTICIPANTS
Required Field
Refer to TASC SOP07: Obtaining Informed Consent from Potential Participants in Clinical Research
Who consents (trial roles rather than individual names), where and what time period is given between participant receiving PIS to consenting.
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 had spoken to the physician and had all their questions answered to their satisfaction.
5.3SCREENING FOR ELIGIBILITY
Required Field
Detail and clarifyany study-specific pre-randomisation tests and assessments e.g. tolerance to study medication, ECG, bloods, screening tests, to be performed.
5.4INELIGIBLE AND NON-RECRUITED PARTICIPANTS
Required Field
Detail procedures for participants who are not subsequently randomised to the study e.g. will GPs be notified of any abnormal findings via routine procedure.
5.5RANDOMISATION
5.5.1Randomisation
Required Field
Refer to TAC SOP 40 Randomisation, Blinding and Code Breaking in Clinical Trials of Investigational Medicinal Productsand ICH Topic E 9, Statistical Principles for Clinical Trials ()
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 trial 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.
5.5.2Treatment Allocation
Required Field
Detail procedures for dispensing of drug/comparator (who, where, when), instructions participants will receive etc.
5.5.3Emergency Unblinding Procedures
Required Field
Refer to TASC SOP40: Randomisation, Blinding and Code Breaking in Clinical Trials of Investigational Medicinal Products.
If study is blinded, detail procedures for breaking of the study blind, who can perform this, where details of contacts for unblinding can be found etc.
Include information on how 24 hour emergency unblinding will be provided
5.5.4Withdrawal 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 trial/ investigational product treatment.
- 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 investigational product treatment/trial treatment
- 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
- those lost to follow-up
Although a participant is not obliged to give reason(s) for withdrawing prematurely, if the participant appears lost to follow up, the CI will make a reasonable effort to ascertain the reason(s), while fully respecting the individual’s rights, and will demonstrate that everything possible was done in an attempt to find any participant lost to follow-up.Those lost to follow-up or withdrawn will be identified and a descriptive analysis of them provided, including
the reasons for their loss and its relationship to treatment and outcome.
6INVESTIGATIONAL MEDICINAL PRODUCT
6.1STUDY DRUGAll sections under 6.1 are Required Fields
6.1.1Study Drug Identification
Detail:
- full name, generic name and UK trade name, if appropriate;
- form e.g. tablet, capsule etc.
6.1.2Study Drug Manufacturer
Detail name and address of the company or other organisation that will supply the study drug.
6.1.3Marketing Authorisation Holder
Detail name, address and MA number of the company manufacturing the study drug (if appropriate)
6.1.4Labelling and Packaging
Detail name and address of the company or pharmacy or research group performing any additional packaging and study labelling that may be necessary (if appropriate).
If appropriate, also detail specifics such as the number of tablets in a bottle to be given to the participants.
6.1.5Storage
Detail storage conditions and location
Detail dispensing site location and any special arrangements e.g. delivery to participants’ home.
6.1.6IMP Safety Information
The most up to date version of the Summary of ProductCharacteristics (SmPC)or Investigator’s Brochure (IB) will be heldin the Pharmacy Site File (PSF), Trial Master File (TMF) and Investigator Site File(s) (ISF).
Detail licensed indications, if study drug will be used outside its licensed indications, contraindications and expected side effects.It may be useful to list known side effects in a table for clarity.
If more than one IMP will be administered in the study, add additional sections for each IMP as appropriate.
6.1.7Accountability procedures
REFER TO TASC POLICY 37: Accountability, Returns and Destruction of Investigational Medicinal Products in Clinical Trials of Investigational Medicinal Products
Describe accountability procedures for the investigational product(s), including the placebo(s) and comparator(s), if any.
6.2STUDY COMPARATOR
All sections under 6.2 are Required Fields if a comparator is to be used as part of the study
Detail, where appropriate,comparator form e.g. tablet, capsule etc., composition, who will manufacture the comparatoretc.e.g. placebo or active MP giving consideration to the fact that the comparator may be an alternative active MP.
6.2.1Comparator IdentificationDetailform e.g. tablet, capsule etc.
6.2.2Comparator Manufacturer
Detail name and address of the company or other organisation that will supply the study drug.
6.2.3Labelling and Packaging
Detail name and address of the company or pharmacy performing any additional packaging that may be necessary and study labelling.
If appropriate, also detail specifics such as the number of tablets in a bottle to be given to the participants etc.
6.2.4Storage
Detail storage conditions and location.
6.2.5Accountability procedures
REFER TO TASC POLICY 37: Accountability, Returns and Destruction of Investigational Medicinal Products in Clinical Trials of Investigational Medicinal Products
Describe accountability procedures for the investigational product(s), including the comparators(s).
6.3DOSING REGIME
Required Field
Detailroute of administrationdosage, including if per body weight, duration of treatment period, when participants will receive IMP/comparator.
Describe the sequence and duration of trial periods (e.g. wash-out, treatment, follow-up etc.)
Define any dietary requirements, or life style requirements that will be imposed (i.e. no smoking)
6.4DOSE CHANGES
Required Field
Detail if any changes in dose will be implemented and in what circumstances.Refer to Study diagram/Study assessments if simpler
6.5PARTICIPANT COMPLIANCE
Required Field
Detail howcompliance will be monitored e.g. drug accountability at each visit, participant diary.Also clarify what, if any, measures will be taken if compliance is found to be poor e.g. meet with patient to train incompliance.
6.6OVERDOSE
Detail any expected effects of overdose (based on available study drug(s) information), and what action is to be taken in the event of overdose.
6.7OTHER MEDICATIONS
6.7.1Permitted Medications
Required Field
Detail other drugs that may be taken during the study.
6.7.2Prohibited Medications
Required Field
Detail other drugs that are not allowed during the study due to e.g. interaction with the study drug, an effect on study outcome etc.Provide a specific list of prohibited drugs for clarity.Also comment on what will happen if a prohibited medication is taken during the study.
Provide details of how use of prohibited medication will be monitored.
6.7.3Concomitant Medications
Required Field
Details of all con-meds should be recorded on the CRF on a con-meds log.
7STUDY ASSESSMENTS
7.1STUDY ASSESSMENTS
Required Field
Detail the specific study assessments to be performed and the timepoints during the study - split by visit number if appropriate for clarity.It is recommended that a table of assessments or study matrix by visit is prepared, e.g.describe the sequenceof procedures at each visit as detailed in the table.i.e. – Informed Consent ,Screening Visit
Time / Screening / Baseline / Week 12 / 6 months / 12 months / 24 monthsHeight / X / X / X / X / X / X
Weight / X / X / X / X / X / X
Waist / X / X / X / X / X / X
Hip / X / X / X / X
BMI / X / X / X / X / X / X
Bloods / X / X / X / X
IPAQ / X / X / X
7.2SAFETY ASSESSMENTS
Required Field
Detail any specific safety assessments required for the study drug.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. 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
8DATA COLLECTION& MANAGEMENT
8.1Data Collection
Required Field
Detail data to be collected, including:
- the data 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 or study specific 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)
8.2Data Management SysteMREQUIRED FIELDProvide details of the data management system to be used and who is providing it.:
The data management system will be [provided by TCTU using OpenClinica]or [another GCP compliant system –specify - approved by the Sponsor.] The study system will be based on the protocol and case report form (CRF) for the study and individual requirements of the investigators. The CRF will not collect more information than is required to meet the aims of the study and to ensure the eligibility and safety of the participant. The CRF will be used as source data but data relevant to a participant’s general medical history will be be recorded also in the casenote.