Template protocol for Investigational Medicinal product(imp) <Trial Acronym> <Full Protocol Title> <Version Number and Date>

Transcription

1 Template protocol for Investigational Medicinal product(imp) <Trial Acronym> <Full Protocol Title> <Version Number and Date> Main Sponsor or list of co-sponsors :.. Trial Coordination Centre: EUDRACT Reference Number:. Protocol authorised by: Name : Date: Signature:... Role:.. Name : Date: Signature:... Role:.. Created by ICRIN (QM subgroup). Version XX. Date:. Page 1of 14

2 Trial Management : Coordinating Investigator:. Co-Investigators:... Trial Statistician:.. Trial Management:. Trial Coordinating Centre For general enquiries, supply of trial documentation, and collection of data please contact: Trial Coordinator:. Address:. Telephone Number Fax Number:. Randomisations: Web address: Clinical Queries Clinical queries should be directed to xxxxxxxxx at xxxxxxxxxxx, who will direct the query to the appropriate person. Sponsor Xxxxxxxxxxxxxxxxx is the main research sponsor for this trial. For further information, please contact: Xxxxxxxxxxxxxxxxxxxx at xxxxxxxxxxxxxxxxxxxxxxxxx Funder <who is funding the trial> Created by ICRIN (QM subgroup). Version XX. Date:. Page 2of 14

3 This protocol describes the XXXX trial and provides information regarding procedures for recruiting and enrolling subjects.the protocol should be used as a guide for the treatment of participating subjects; every care should be taken in its drafting, however, corrections or amendments may be necessary. Problems relating to this trial should be referred to the trial coordination centre. This trial will adhere to the International Conference on Harmonisation Good Clinical Practice (ICH GCP)guidelines. It will be conducted in compliance with the protocol, Data Protection regulations and other regulatory requirements as appropriate. Table of Contents 1. INTRODUCTION..Page 1.1 Background and Rationale Page Prevalence of Disease/Condition.Page Impact of Disease/Condition.....Page 2. OBJECTIVES OF THE TRIAL.Page 3. EXPERIMENTAL DESIGN AND METHODS.Page 3.1 OVERALL STUDY DESIGN.....Page 3.2 STUDY OUTCOME MEASURES..Page 3.3 TREATMENT GROUPS. Page 3.4 CENTRES...Page 3.5 NUMBER OF PATIENTS/ ASSIGNMENT TO TREATMENT GROUP. Page 3.6 DOSING REGIMEN.. Page 3.7 STUDY DURATION.. Page 4. PATIENT SELECTION CRITERIA. Page 4.1 Population Base 4.2 Pre-randomisation evaluations 4.3 Inclusion Criteria 4.4 Exclusion Criteria 4.5 Withdrawal Criteria 4.6 Concomitant Medication and Treatment 5. SCHEDULE OF ASSESSMENTS..Page 6. RANDOMISATION AND ENROLMENT PROCEDURE..Page 6.1 Randomisation or Registration practicalities 6.2 Unblinding 7. TREATMENTS. Page 7.1 Treatment Arms 7.2 Dose Modification for Toxicity 7.3 Premedication 7.4 Interaction with other drugs 7.5 Dispensing and accountability 8. DRUG SAFETY (PHARMACOVIGILANCE)...Page 8.1 Definitions 8.2 Causality 8.3 Reporting Procedures 9. ASSESSMENTS AND FOLLOW UPS. Page 9.1 Loss to Follow up Created by ICRIN (QM subgroup). Version XX. Date:. Page 3of 14

4 9.2 Trial closure 10. STATISTICS AND DATA ANALYSIS..Page 10.1 Primary and secondary Trial Parameters 10.2 Statistical and Analytical Methods 10.3 Statistical Model 10.4 Hypothesis testing 10.5 Types of analysis 10.6 Exclusion of data from analysis 10.7 Safety Data Analysis 10.8 Sample Size 10.9 Independent Safety committee, if applicable 11. MONITORING.Page 11.1 Risk Assessment 11.2 Monitoring at Trial Coordination Centre 11.3 Monitoring at Local Site 12. REGULATORY.Page 12.1 Clinical Trial Application (CTA) 12.2 Ethics Approval 12.3 Consent 12.4 Confidentiality 12.5 Indemnity 12.6 Sponsor 12.7 Funding 12.8 Audits and Inspections 13. TRIAL MANAGEMENT.Page 14. PUBLICATION POLICY.Page LIST OF APPENDICES APPENDIX1:.....Page APPENDIX 2:.. Page ETC. GLOSSARY OF ABBREVIATIONS Created by ICRIN (QM subgroup). Version XX. Date:. Page 4of 14

5 KEYWORDS <Insert a list of Keywords> TRIAL SUMMARY TITLE DESIGN OBJECTIVES OUTCOME MEASURES POPULATION ELIGIBILITY TREATMENT DURATION REFERENCE DIAGRAM RANDOMISE ARM A ARM B Created by ICRIN (QM subgroup). Version XX. Date:. Page 5of 14

6 1. INTRODUCTION 1.1 BACKGROUND AND RATIONALE < Include review of previous studies, disease particulars, incidence, current treatment options, risks and benefits> <To include the hypothesis and research question, as well as potential risks and benefits> 2. OBJECTIVES OF THE TRIAL <List the primary, secondary and other study objectives> 3. STUDY DESIGN <Type of study: e.g. randomised double-blind, placebo controlled etc.> <Duration i.e. what constitutes the treatment phase and the follow up phase of the study> <Number and type of subjects recruited e.g. 400 participants, 200 of which are healthy> 3.1 STUDY OUTCOME MEASURES What are the endpoints of the study e.g. disease-free survival, death, toxicity etc. 4. PATIENT SELECTION CRITERIA 4.1 Population Base < Type of specific subject required in the trial e.g a certain stage of a disease etc.> 4.2 Pre-randomisation evaluations <what tests need to be performed before a subject can be included in a study e.g. CT scan LFT, biopsy etc. All screening procedures should be included> 4.3 Inclusion Criteria < with justifications, if required> 4.4 Exclusion Criteria < with justifications, if required> 4.5 Withdrawal Criteria Created by ICRIN (QM subgroup). Version XX. Date:. Page 6of 14

7 < describe the procedures for stopping the trial early. Describe the procedures for subjects should they wish to withdraw their consent, i.e. will all data to-date be held, will all data be destroyed> 4.6 Concomitant Medication and Treatment <all concomitant medication as well as any diagnostic, therapeutic or surgical procedure performed during the study period should be recorded as well allowable rescue medication for predicted events> 5. SCHEDULE OF ASSESSMENT <A schedule of assessments needs to be included, generally as a figure, for each treatment arm> 6.RANDOMISATION AND ENROLMENT PROCEDURE 6.1 RANDOMISATION OR REGISTRATION PROCEDURE <Procedure for enrolling participants and processes that require completion prior to randomisation. Include telephone numbers to call for randomisation, either through a central hub, a programmed interactive voice response system (IVRS) or a web address for an interactive web response system (IWRS)> 6.2 UNBLINDING <Unblinding is discouraged during the study unless as a response to urgent safety issues or by drug safety as a requirement for reporting. Details on the process for unbliniding a subject as a result of a safety concern needs to be described here> 7. TREATMENTS 7.1TREATMENT ARMS <Dosage, route of administration, labelling, packaging, where the study drug supply will come from, whether a supply will be delivered to the pharmacy at randomisation/registration, if the study drug is free, will need to be described 7.2 DOSE MODIFICATION FOR TOXIICITY <Tables are best for describing what dose reductions should be taken in the event of toxicity> 7.3 PREMEDICATION <A list of medications should be included, if they are to be prescribed before or during the trial e.g. antibiotics> Created by ICRIN (QM subgroup). Version XX. Date:. Page 7of 14

8 7.4INTERACTION WITH OTHER DRUGS <A list of any particular medications that the trial subjects should avoid should be included> 7.5DISPENSING AND ACOUNTABILITY < Procedures for the pharmacy on dispensing and performing drug accountability should be included> 8. DRUG SAFETY (Pharmacovigilance) The sponsor is responsible for the ongoing safety evaluation of the investigational product(s). The sponsor should promptly notify all concerned investigator(s)/institution(s) and the competent authorities (CAs) of finding(s) that could affect adversely the safety of subjects, (ICHGCP 5.16). The Sponsor should also follow ICHE2A (Guideline for Industry, Clinical Safety Data Management, Definitions and Standards for Expedited Reporting DEFINITIONS (ICH E2A) Adverse Event or Adverse Experience(AE): Any untoward medical occurrence in a patient or clinical trial subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE therefore can be any unfavourable and unintended sign, symptom( including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an Investigational Medicinal Product (IMP), whether or not considered related to the IMP. Adverse Drug Reaction (ADR): In the pre-approval clinical experience with a new medicinal product or its new usages, particularly as the therapeutic dose(s) may need to be established. All noxious and unintended responses to a medicinal product related to any dose should be considered adverse drug reactions. The phrase responses to a medicinal products means a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility i.e. the relationship cannot be ruled out. All AEs judged by either the reporting investigator or the sponsor as having a reasonable causal relationship to a medicinal product qualify as adverse drug reactions. The expression reasonable causal relationship means to convey in general that there is evidence or argument to support a causal relationship. Unexpected Adverse Drug Reaction (UAR): An adverse drug reaction, the nature and severity of which is not consistent with the applicable product information (e.g.ib or SmPC) or is more severe than described in the IB or SmPC then this should be considered as unexpected e.g (a) acute renal failure in the IB/SmPC with a subsequent report of interstitial nephritis, (b) hepatitis with a first report of fulminant hepatitis. Serious Adverse Event (SAE) or Serious Adverse Reaction: Any untoward medical occurrence or effect that at any dose: Created by ICRIN (QM subgroup). Version XX. Date:. Page 8of 14

9 Results in Death Is Life-threatening ( Note: The term life-threatening in the definition of serious refers to an event in which the patient was at risk of death at the time of the event; it does not refer to an event which, hypothetically might have caused death if it was more severe) Requires hospitalisation or prolongation of hospitalisation Results in persistent or significant disability or incapacity Is a congenital anomaly or birth defect Medical judgement should be exercised in deciding whether expedited reporting is required in other situations, such as important medical events that may not be immediately lifethreatening or result in death or hospitalisation but may jeopardise the patient or may require intervention to prevent the other outcomes listed in the definition above. These should also be considered serious. Examples of such events are internsive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias, or convulsions that do not result in hospitalisation; or development of drug dependency or drug abuse. Suspected Unexpected Serious Adverse Reaction (SUSAR): Any suspected adverse reaction related to an IMP that is both unexpected and serious. All require expedited reporting. 8.2 CAUSALITY Causality assessment is required for clinical investigational cases, it is assumed in the case of adverse event reports associated with marketed drugs. The causality assessment and assignment should be made by the investigator responsible for the care of the subject using the definitions indicated below. Relationship Unrelated Unlikely Possible Description There is no evidence of a causal relationship There is little evidence to suggest there is a causal relationship ( e.g the event did not occur within a reasonable time after administration of trial medication). There is another reasonable explanation for the event (e.g. concomitant medications, clinical condition) There is some evidence to suggest a causal relationship (e.g. event occurs a reasonable time after administration of trial Created by ICRIN (QM subgroup). Version XX. Date:. Page 9of 14

10 medication, temporal relationship). However, the influence of other factors may have contributed to the event (e.g. concomitant medications, clinical condition) Probable Definitely Not assessable There is evidence to suggest a causal relationship and the influence of other factors is unlikely. There is clear evidence to suggest a causal relationship and other contributing factors cannot be ruled out. There is insufficient or incomplete evidence to make a clinical judgement of the causal relationship. 8.3 REPORTING PROCEDURES All adverse event require reporting. Different reporting procedures are appropriate for differing types of adverse events. 1. Non serious AR/AE All such events should be captured in the AE section of the CRF and sent to the Data Management coordinating centre on a regular basis for entry into the Clinical Database and inclusion in the Annual Safety Reports. 2. SAEs Events which fulfil the seriousness criteria, or are medically significant should be both entered into the CRF and a signed SAE form should also be completed and faxed to the coordinating centre for Drug safety within 24 hours. However, hospitalisations for elective treatment of a pre-existing condition do not require reporting as an SAE 3. SUSARs All Serious Adverse Events that are unexpected as per the IB or SmPC are SUSARs and require expedited reporting. The information for SUSARs should be entered into the Clinical database, and a signed SAE form should also be completed and faxed to the coordinating centre for Drug safety within 24 hours or alternatively the information can be provided by phone and a completed and signed SAE form sent within 24 hours as above. The drug safety coordinating centre will report to relevant CA, REC and EMEA and the Sponsor of all SUSARs occurring in the trial to the following timelines Created by ICRIN (QM subgroup). Version XX. Date:. Page 10of 14

11 Fatal and Life Threatening SAEs within 7 calendar days with a follow up complete report within a further 8 calendar days. Non- Fatal or life threatening SUSARs within 15 calendar days All investigators will be informed of all SUSARs occurring throughout the study, in a blinded fashion, for blinded trial designs. 9. ASSESSMENTS AND FOLLOW UP < How long will the subject be followed up for? When and what will their assessments consist of> 9.1 Loss to follow up <List procedures for subjects lost to follow up> 9.2 Trial Closure <include definition of end of trial, include a list of the procedures for closing a trial, whether early of after recruitment. 10. Statistics and Data Analysis < include details on the statistical plan for the study including; sample size calculation, trial parameters for analysis, the statistical methods and models to be employed, any rules for data exclusion, any interim analyses, interaction with any safety committees, data management etc.> < Data and all appropriate documentation for the trial will be held for a minimum of xx years after completion of the trial, including follow up> 11. Monitoring 11.1 RISK ASSESSMENT < Describe the level of risk associated with the trial i.e. low,med,high, a level of monitoring and a justification of the proposed level of monitoring> 11.2 MONITORING AT THE TRIAL COORDINATION CENTRE <Details of the Data Management of the data> 11.3 MONITORING AT THE LOCAL SITE <Based on the risk assessment, the frequency ( number) of site monitoring visit and the % Source Document Verification (SDV)> Created by ICRIN (QM subgroup). Version XX. Date:. Page 11of 14

12 12 REGULATORY 12.1 CTA <This trial has/is pending a Clinical Trials Authorisation from the Irish Competent Authority IMB Reference XXXXXXXXX, may require updating depending on whether or not is an international trial> 12.2 ETHICS APPROVAL <The trial coordination centre has received/expect to receive approval from XXX Research Ethics Committee. The trial must be submitted for Site Specific Assessment (SSA) at each participating site and signed before recruiting subjects into the trial.> <This trial will be conducted in accordance with the recommendations for physicians in the Declaration of Helsinki 1964 and later revisions> 12.3 CONSENT <Consent to enter a trial must be sought from each subject only after a full explanation of the trial, its objectives, the risks and potential benefits, the assessments and timing of these assessments etc has been given, an information leaflet given and time allowed for consideration. Signed subject consent forms must be obtained. The right of the subject to refuse to participate without giving reasons must be respected. See INSTITUTION Patient Information Leaflet Template> 12.4 CONFIDENTIALITY <Patients identification data will be required for the recruitment process. The data generated and the Trial coordination centre will preserve the confidentiality of subjects taking part in the Trial and follow all procedures detailed in the Data Protection Act> 12.5 INDEMNITY <XXXXXX holds Public Liability( negligent harm ) and Clinical Trial ( non-negligent harm ) insurance policies which apply to this trial.> 12.6 SPONSOR <XXXXXXXXXXXXXXX will act as the main Sponsor for this trial. Delegated responsibilities will be assigned to XXXXXXXXXXXXXX taking part in this trial.> 12.7 FUNDING <Xxxx is funding this trial.> < Any per patient payments, investigator payments should be detailed here> Created by ICRIN (QM subgroup). Version XX. Date:. Page 12of 14

13 12.8 AUDITS AND INSPECTIONS <This trial may be subject to an audit by XXXXXXXXXXXX under its remit as Sponsor, the Trial Coordination Centre and other Regulatory bodies to ensure adherence to GCP.> 13 TRIAL MANAGEMENT < A trial management group (TMG) will be appointed and will be responsible for overseeing the progress on the trial. The day to day management of the trial will be coordinated through the XXXX Trial Coordination Centre> <Include if a Trial Steering Committee or Independent Data Monoting Committee will be convened for this trial> 14 PUBLICATION POLICY < The trials publication policy should be described in full. E.g. All publications and presentations relating to the trial will be authorised by the Trial Management Group. The first publication of the trial results will be in the name of the Trial Management Group, if this does not conflict with the Journal s policy. If there are named authors, these will include at least the trials Chief Investigator, Statistician and Trial Coordinator. Members of the TMG and the Data Monitoring Committee will be listed and contributors will be cited by name if published in a journal where this does not conflict with the journal s policy. Authorship of parallel trials initiated outside the Trial Management Group will be according to the individuals involved in the trial but must acknowledge the contribution of the Trial Management Group and the Trial Coordination Centre> 15 REFERENCES <List of useful references for the trial> EXAMPLE APPENDICES < Appendices should be additional information to the protocol and can consist of: Drug information from SmPC PIS, Consent form, GP letter Performance Scales Criteria definitions Detail on processes Common Terminology Summary of Dose Modifications Expected side effects Created by ICRIN (QM subgroup). Version XX. Date:. Page 13of 14

14 Schedule of events table Copy of the Declaration of Helsinki EXAM VISITS Screening Randomisation Visit 1 Visit 2 Visit3 Visit 4 Visit 5 Visit n ECG X X X X X X X MRI X X X X X-Ray Medical History Informed Consent Laboratory samples Performance Status Efficacy scales Safety measures X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X Created by ICRIN (QM subgroup). Version XX. Date:. Page 14of 14