邢唷��>� ��欹�` ��@bjbj鎳鎳 y�勴勴�6��$�R=R=R=P�=�.>��&?��?�?�?�?(A~�:H�V�X�X�X�X�X�X�$�h儜�|��疞(A(A疞疞|��?�?4憣>袿袿袿疞��?��?V�袿疞V�袿袿j獏��Z��??惏T��R==Mv妵2矈�蠈<��紘�!�矼�!�dZ�Z�!��n�DI�鶬�袿↗�4K{III|�|�gOjIII�疞疞疞疞��.�;��;�� Note to investigators: The following protocol template was derived from Good Clinical Practice (GCP) Guidelines � an international ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human subjects. It is intended to provide a basic framework for organizing your research plan. The complete GCP guidelines can be found at: http://www.ich.org/LOB/media/MEDIA482.pdf PROTOCOL COVER PAGE PROTOCOL NAME PROTOCOL IDENTIFYING NUMBER (any amendments should bear the amendment number � clearly distinguishing each version of the protocol) PROTOCOL VERSION DATE GENERAL INFORMATION Name and address of the sponsor of the study (see GCP 1.53 for the definition of 搒ponsor�) Name and address of the person authorized to sign the protocol and amendments Name and address of study monitor (see GCP 1.38 for the definition of 搈onitoring�) Name, title, address and telephone number(s) of the medical expert for the trial Name and title of the investigator(s) and sub-investigators responsible for the trial with address and phone number(s) (see GCP 1.34 for definition of 搃nvestigator�; GCP 1.54 for definition of 搒ponsor-investigator� and GCP 1.56 for definition of 搒ub-investigator�) Name and addresses of the clinical laboratories and/or other institutions involved in the trial Study Summary TitleFull title of protocolShort TitleShortened title, if one is typically used by you or your Center/Dept.Protocol NumberThe standard protocol number used to identify this study. PhaseClinical study phase (e.g. Phase 1, 2, 3 or 4)MethodologyDesign attributes such as single blind, double blind or open label; Randomized, placebo or active placebo control; cross-over design, etc.Study DurationEstimated duration for the main protocol (e.g. from start of screening to last subject processed and finishing the study)Study Center(s)Single-center or multi-center. If multi-center, note number of projected centers to be involved.ObjectivesBrief statement of primary study objectivesNumber of SubjectsNumber of subjects projected for the entire study (e.g. not for simply one site, rather for entire study, all sites combined)Diagnosis and Main Inclusion CriteriaNote the main clinical disease state under study and the key inclusion criteria (i.e. not the entire list that will appear later in the protocol 杛ather only the key inclusion criteria)Study Product, Dose, Route, RegimenStudy drug name (generic name, though can also state marketed name if name-brand used in the study). Also dose, dose route and dose regimenDuration of administrationTotal duration of drug product administration (including any open-label lead-in, if applicable).Reference therapyNote if there is a standard reference therapy against which the study product is being compared, or if the reference is a placeboStatistical MethodologyA very brief description of the main elements of the statistical methodology to be used in the study. (As few lines as possible). Table of Contents TOC \o "1-3" 1 Background 1 1.1 Investigational Agent 1 1.2 Preclinical Data 1 1.3 Risk/Benefits 1 1.4 Dose Rationale 1 1.5 Trial Conduct 1 1.6 Population 1 1.7 Literature 1 2 Trial Objectives 2 3 Trial Design 2 3.1 Primary Study Endpoints/Secondary Endpoints 2 3.2 Study Design/Type 2 3.3 Randomization 2 3.4 Maintenance 2 3.5 Trial Treatment 2 3.6 Duration 2 3.7 Discontinuation 2 3.8 Product Accountability PAGEREF _Toc127332522 \h 3 3.9 Data Identification PAGEREF _Toc127332523 \h 3 4 Selection and Withdrawal of Subjects PAGEREF _Toc127332524 \h 3 4.1 Inclusion Criteria PAGEREF _Toc127332525 \h 3 4.2 Exclusion Criteria PAGEREF _Toc127332526 \h 3 4.3 Subject Withdrawal PAGEREF _Toc127332527 \h 3 4.4 Treatment of Subjects PAGEREF _Toc127332528 \h 3 4.5 Medication PAGEREF _Toc127332529 \h 3 4.6 Monitoring for subject compliance PAGEREF _Toc127332530 \h 3 5 Assessment of Efficacy 4 5.1 Efficacy Parameters 4 5.2 Method and Timing 4 6 Assessment of Safety 4 6.1 Safety Parameters 4 6.2 Method and Timing 4 6.3 Adverse Event Reporting 4 6.4 Definitions 4 6.5 Adverse Event Follow-up 4 7 Statistical Plan 5 7.1 Statistical Methods 5 7.2 Subject Population(s) for Analysis 5 7.3 Significance 5 7.4 Termination Criteria 5 7.5 Accountability Procedure 5 7.6 Deviation Reporting 5 8 Direct Access to Source Data/Documentation 5 9 Quality Control and Quality Assurance 5 10 Ethical Considerations 6 11 Data Handling and Record Keeping 6 12 Finance and Insurance 6 13 Publication Plan 6 14 Supplements 6 List of Abbreviations (e.g.) ICH International Conference on Harmonisation CRF Case Report Form GCP Good Clinical Practice HREB Health Research Ethics Board 1 Background Investigational Agent Insert name of investigational product(s) or test intervention Preclinical Data Insert a summary of findings from non-clinical studies that potentially have clinical significance and from clinical trials that are relevant to the trial. Risk/Benefits Insert summary of the known and potential risks and benefits, if any, to human subjects Dose Rationale Insert description of and justification for the route of administration, dosage, dosage regimen, and treatment period(s). Trial Conduct Insert a statement that the trial will be conducted in compliance with the protocol, GCP and the applicable regulatory requirement(s). For example: This study will be conducted in compliance with the protocol approved by the 黑料不打烊 Health Research Ethics Board (HREB), and according to Good Clinical Practice standards. No deviation from the protocol will be implemented without the prior review and approval of the HREB except where it may be necessary to eliminate an immediate hazard to a research subject. In such case, the deviation will be reported to the HREB as soon as possible. Population Insert a description of the population to be studied. Literature Reference any literature and data that are relevant to the trial and that provide background for the trial. Trial Objectives Insert a detailed description of the objectives and the purpose of the trial. Trial Design The scientific integrity of the trial and the credibility of the data from the trial depend substantially on the trial design. A description of the trial design includes: Primary Study Endpoints/Secondary Endpoints Insert a specific statement of the primary endpoints and the secondary endpoints, if any to be measured during the trial. Study Design/Type Insert a description of the type/design of trial to be conducted (e.g. double-blind, placebo controlled, parallel design) and a schematic diagram of trial design, procedures and stages. Randomization Insert a description of the measures taken to minimize/avoid bias, including (for example): Randomization (include a description of the method) Blinding Maintenance Insert a description of the maintenance of the randomization codes, if applicable and the procedure for breaking codes. Trial Treatment Insert a description of the trial treatment(s) or other test interventions and the dosage and dosage regimen of the investigational product(s). if any. Also include a description of the dosage form, packaging, and labeling of any investigational product(s). Duration Insert the expected duration of subject participation and a description of the sequence and duration of all trial periods, including follow-up if any. Discontinuation Insert a description of the stopping rules or discontinuation criteria for individual subjects, parts of the trial, and entire trial. Product Accountability Insert accountability procedures for the investigational product(s), including the placebo(s) and comparator(s) if any. Data Identification Insert the identification of any data to be recorded directly on the CRFs (i.e. no prior written or electronic record of data), and to be considered to be source data. (See GCP 1.11 for definition of 揷ase report forms�.) Selection and Withdrawal of Subjects Inclusion Criteria Insert subject inclusion criteria Exclusion Criteria Insert subject exclusion criteria Subject Withdrawal Insert subject withdrawal criteria (i.e. terminating investigational product treatment/trial treatment) and procedures specifying: When and how to withdraw subjects from the trial/investigational product treatment. The type and timing of the data to be collected for withdrawal of subjects. Whether and how subjects are to be replaced. The follow-up for subjects withdrawn from investigational treatment/trial treatment. Treatment of Subjects Insert how the treatment(s) is(are) to be administered, including the name(s) of all the product(s), the dose(s), the dosing schedule(s), the route/mode(s) of administration, and the treatment period(s), including follow-up period(s) for subjects for each investigational product treatment/trial treatment group/arm of the study. Medication Insert medication(s)/treatment(s) permitted (including rescue medication) and not permitted before and/or during the research, if any. Monitoring for subject compliance Insert the procedures for monitoring subject compliance Assessment of Efficacy Efficacy Parameters Insert the specifications of the efficacy parameters. Method and Timing Insert methods and timing for assessing, recording and analyzing efficacy parameters. Assessment of Safety Safety Parameters Insert specifications for safety parameters. Method and Timing Insert the methods and timing for assessing, recording and analyzing safety parameters. Adverse Event Reporting Insert a statement about compliance with the local HREB requirements and the requirements of other regulatory authorities that may apply (most commonly Health Canada). Procedures for eliciting reports of and for recording and reporting adverse event and intercurrent illnesses should be described in this section. Definitions See local HREB requirements prior to completing this section. Insert definitions for how you will apply the terms 搖nanticipated�, 搒erious�, and 搑elated� to problems that arise during the study. Adverse Event Follow-up Insert the type and duration of the follow-up of subjects after adverse events. Statistical Plan Statistical Methods Insert a description of the statistical methods to be employed including timing of any planned interim analysis(ses). Subject Population(s) for Analysis Insert the number of subjects planned to be enrolled. In multi-center studies, the number of enrolled subjects projected for each trial site should be specified. Provide a reason for choice of sample size, including reflection on (or calculations of) the power of the trial and clinical justification. Also include, here, how you will select the group of subjects for analysis (e.g., all randomized subjects, all dosed subjects, all eligible subjects, and only evaluable subjects). Significance Insert the level of significance to be used. Termination Criteria Insert the criteria for the termination of the research. Accountability Procedure Insert the procedure for accounting for missing, unused and spurious data. Deviation Reporting Insert the procedures for reporting any deviation(s) from the original statistical plan. Any deviation(s) from the original statistical plan should be described and justified in the protocol and/or in the final report. Direct Access to Source Data/Documentation It should be specified in the protocol or other written agreement the investigator(s)/institution(s) will permit trial-related monitoring, audits, IHREB review and regulatory inspection(s) by providing direct access to source data/documentation. Quality Control and Quality Assurance Insert how you will ensure that this study is conducted � and that data are generated, documented (recorded), and reported - in compliance with this protocol, with GCP, and any other applicable regulatory requirements. Ethical Considerations Describe the ethical considerations relating to this study. The following language is an example: This study will be conducted according to Canadian and international standards of Good Clinical Practice for all studies. Applicable government regulations and 黑料不打烊 research policies and procedures will also be followed. This protocol and any amendments will be submitted to the 黑料不打烊 HREB for formal approval to conduct the study. The decision of the HREB concerning the conduct of the study will be made in writing to the investigator. All subjects for this study will be provided a consent form describing this study and providing sufficient information for subjects to make an informed decision about their participation in this study. This consent form will be submitted with the protocol for review and approval by the HREB. The formal consent of a subject, using the HREB-approved consent form, will be obtained before that subject is submitted to any study procedure. This consent form must be signed by the subject or legally acceptable surrogate, and the investigator-designated research professional obtaining the consent. Data Handling and Record Keeping Insert a description of who, what, where and why Finance and Insurance Insert financing and insurance statements if not addressed in a separate agreement. Who will be responsible for paying for research related costs? Who will be responsible for paying for injuries in case of accident? (Note that this is, most commonly, addressed in a research contract�.not the protocol.) Publication Plan Where ownership of the data is not in question � this section may be omitted. Otherwise, insert a publication policy, if not addressed in a separate agreement (most commonly a contract). Supplements Insert any other documentation for the trial including copies of data capture forms (i.e. CRFs), questionnaires etc. Page PAGE 6 CONFIDENTIAL This material is the property of the University of XXXXX. Do not disclose or use except as authorized. 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