FDA臨床方案模板

1、DMID Protocol TemplateVersion 1.008 April 2004PREFACEThis document is the DMID protocol template, which is required for developing DMID-sponsored clinical research protocols. Note that instructions and explanatory text are indicated by italics and should be replaced in your protocol document with ap

2、propriate protocol-specific text. Section headings and template text formatted in regular type should be included in your protocol document as provided in the template.This template attempts to provide a general format applicable to all clinical trials evaluating an investigational product. Where sp

3、ecific examples are provided, they are often from the vaccine area.Refer questions regarding use of this protocol template to the appropriate DMID Protocol Champion or Clinical Affairs Specialist.DMID Protocol TemplateVersion 1.008 April 2004TITLEDMID Protocol Number:DMID Funding Mechanism: (e.g., g

4、rant #, contract #)Pharmaceutical Support Provided by: (if applicable)Other Identifying Numbers:IND Sponsor: (if applicable)Principal Investigator:DMID Protocol Champion:DMID Medical Monitor:DMID Clinical Affairs Specialist:DMID Regulatory Affairs Specialist: (if applicable)Draft or Version Number:

5、(see DMID SOP for assigning version numbers)Day Month Year(Write out the month and use international date format, e.g., 23 January 2004)This template is adapted from the ICH guidance document E6 (Good Clinical Practices), Section 6.DMID Protocol TemplateVersion 1.008 April 2004 PAGE iiDMID Protocol

6、TemplateVersion 1.008 April 2004 PAGE iStatement of ComplianceProvide a statement that the trial will be conducted in compliance with the protocol, International Conference on Harmonisation Good Clinical Practice E6 (ICH-GCP) and the applicable regulatory requirements. Use the applicable regulations

7、 and requirements depending on study location and sponsor requirements. Examples of requirements that are potentially applicable include:U.S. Code of Federal Regulations applicable to clinical studies (45 CFR 46 and 21 CFR including parts 50 and 56 concerning informed consent and IRB regulations, if

8、 under IND, 21 CFR 312).Directive 9115071EEC: The Rules Governing Medicinal Products in the European Community.Completion of Human Subjects Protection TrainingRefer to: http:/NIH Clinical Terms of AwardSIGNATURE PAGEThe signature below constitutes the approval of this protocol and the attachments, a

9、nd provides the necessary assurances that this trial will be conducted according to all stipulations of the protocol, including all statements regarding confidentiality, and according to local legal and regulatory requirements and applicable U.S. federal regulations and ICH guidelines.The Lead PI, t

10、he PIs from all participating clinical sites and other key parties should sign the signature page as appropriate.Principal Investigator:Signed:Date:NameTitleDMID Protocol TemplateVersion 1.008 April 2004Table of Contents - continuedpage PAGE vDMID Protocol TemplateVersion 1.008 April 2004Table of Co

11、ntentspage PAGE iiiStatement of ComplianceiSignature PageiiList of AbbreviationsviProtocol Summaryviii TOC o 1-3 h z HYPERLINK l _Toc67800544 1Key Roles PAGEREF _Toc67800544 h 1 HYPERLINK l _Toc67800545 2Background Information and Scientific Rationale PAGEREF _Toc67800545 h 3 HYPERLINK l _Toc6780054

12、6 2.1Background Information PAGEREF _Toc67800546 h 3 HYPERLINK l _Toc67800547 2.2Rationale PAGEREF _Toc67800547 h 3 HYPERLINK l _Toc67800548 2.3Potential Risks and Benefits PAGEREF _Toc67800548 h 3 HYPERLINK l _Toc67800549 Potential Risks PAGEREF _Toc67800549 h 3 HYPERLINK l _Toc67800550 Known Poten

13、tial Benefits PAGEREF _Toc67800550 h 3 HYPERLINK l _Toc67800551 3Objectives PAGEREF _Toc67800551 h 4 HYPERLINK l _Toc67800552 4Study Design PAGEREF _Toc67800552 h 5 HYPERLINK l _Toc67800553 5Study Population PAGEREF _Toc67800553 h 7 HYPERLINK l _Toc67800554 5.1Subject Inclusion Criteria PAGEREF _Toc

14、67800554 h 8 HYPERLINK l _Toc67800555 5.2Subject Exclusion Criteria PAGEREF _Toc67800555 h 8 HYPERLINK l _Toc67800556 6Enrollment/ Randomization/Masking Procedures PAGEREF _Toc67800556 h 9 HYPERLINK l _Toc67800557 7Study Procedures/Evaluations PAGEREF _Toc67800557 h 10 HYPERLINK l _Toc67800558 7.1Cl

15、inical Evaluations PAGEREF _Toc67800558 h 10 HYPERLINK l _Toc67800559 7.2Concomitant Medications/Treatments PAGEREF _Toc67800559 h 10 HYPERLINK l _Toc67800560 7.3Laboratory Evaluations PAGEREF _Toc67800560 h 11 HYPERLINK l _Toc67800561 Clinical Laboratory Evaluations PAGEREF _Toc67800561 h 11 HYPERL

16、INK l _Toc67800562 Special Assays or Procedures PAGEREF _Toc67800562 h 11 HYPERLINK l _Toc67800563 Specimen Preparation, Handling and Shipping PAGEREF _Toc67800563 h 11 HYPERLINK l _Toc67800564 7.4Substudies PAGEREF _Toc67800564 h 12 HYPERLINK l _Toc67800565 8Study Schedule PAGEREF _Toc67800565 h 13

17、 HYPERLINK l _Toc67800566 8.1Screening PAGEREF _Toc67800566 h 13 HYPERLINK l _Toc67800567 8.2Enrollment/Baseline PAGEREF _Toc67800567 h 13 HYPERLINK l _Toc67800568 8.3Follow-up PAGEREF _Toc67800568 h 14 HYPERLINK l _Toc67800569 8.4Final Study Visit PAGEREF _Toc67800569 h 14 HYPERLINK l _Toc67800570

18、8.5Early Termination Visit PAGEREF _Toc67800570 h 14 HYPERLINK l _Toc67800571 9Study Intervention/Investigational Product PAGEREF _Toc67800571 h 15 HYPERLINK l _Toc67800572 9.1Study Product Acquisition PAGEREF _Toc67800572 h 15 HYPERLINK l _Toc67800573 Formulation, Packaging and Labeling PAGEREF _To

19、c67800573 h 15 HYPERLINK l _Toc67800574 9.2Product Storage and Stability PAGEREF _Toc67800574 h 15 HYPERLINK l _Toc67800575 9.3Preparation, Administration and Dosage of Study Intervention/Investigational Product PAGEREF _Toc67800575 h 15 HYPERLINK l _Toc67800576 9.4Accountability Procedures for the

20、Study Intervention/Investigational Product(s) PAGEREF _Toc67800576 h 15 HYPERLINK l _Toc67800577 9.5Assessment of Subject Compliance with Study Intervention/InvestigationalProduct PAGEREF _Toc67800577 h 16 HYPERLINK l _Toc67800578 10Assessment of Scientific Objectives (e.g., Safety or Immunogenicity

21、 or Efficacy) PAGEREF _Toc67800578 h 17 HYPERLINK l _Toc67800579 10.1Specification of the Appropriate Outcome Measures PAGEREF _Toc67800579 h 17 HYPERLINK l _Toc67800580 Primary Outcome Measures PAGEREF _Toc67800580 h 17 HYPERLINK l _Toc67800581 Secondary Outcome Measures PAGEREF _Toc67800581 h 17 H

22、YPERLINK l _Toc67800582 10.2Methods and Timing for Assessing, Recording, and Analyzing Appropriate Outcome Measures PAGEREF _Toc67800582 h 17 HYPERLINK l _Toc67800583 10.3Modification and Discontinuation of Study Intervention/Investigational Product for a Participant PAGEREF _Toc67800583 h 17 HYPERL

23、INK l _Toc67800584 Dose/Schedule Modifications for a Subject PAGEREF _Toc67800584 h 17 HYPERLINK l _Toc67800585 Criteria for Discontinuation of Study Intervention/Product for Withdrawal of a Subject (or a Cohort) PAGEREF _Toc67800585 h 18 HYPERLINK l _Toc67800586 11Assessment of Safety PAGEREF _Toc6

24、7800586 h 19 HYPERLINK l _Toc67800587 11.1Specification of Safety Parameters PAGEREF _Toc67800587 h 19 HYPERLINK l _Toc67800588 11.2Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters PAGEREF _Toc67800588 h 19 HYPERLINK l _Toc67800589 Adverse Events, Reactogenicity (for Vacc

25、ine Studies), Serious Adverse Events. PAGEREF _Toc67800589 h 19 HYPERLINK l _Toc67800590 11.3Reporting Procedures PAGEREF _Toc67800590 h 21 HYPERLINK l _Toc67800591 Serious Adverse Event Detection and Reporting PAGEREF _Toc67800591 h 21 HYPERLINK l _Toc67800592 Reporting of Pregnancy PAGEREF _Toc678

26、00592 h 22 HYPERLINK l _Toc67800593 Procedures to be Followed in the Event of Abnormal Laboratory Test Values or Abnormal Clinical Findings PAGEREF _Toc67800593 h 22 HYPERLINK l _Toc67800594 Type and Duration of the Follow-up of Subjects After Adverse Events PAGEREF _Toc67800594 h 22 HYPERLINK l _To

27、c67800595 11.4Halting Rules PAGEREF _Toc67800595 h 23 HYPERLINK l _Toc67800596 12Clinical Monitoring Structure PAGEREF _Toc67800596 h 24 HYPERLINK l _Toc67800597 12.1Site Monitoring Plan PAGEREF _Toc67800597 h 24 HYPERLINK l _Toc67800598 13Statistical Considerations PAGEREF _Toc67800598 h 25 HYPERLI

28、NK l _Toc67800599 13.1Introduction PAGEREF _Toc67800599 h 25 HYPERLINK l _Toc67800600 13.2Overview and Study Objectives PAGEREF _Toc67800600 h 25 HYPERLINK l _Toc67800601 13.3Study Population PAGEREF _Toc67800601 h 25 HYPERLINK l _Toc67800602 13.4Study Design PAGEREF _Toc67800602 h 25 HYPERLINK l _T

29、oc67800603 13.5Study Outcome Measures PAGEREF _Toc67800603 h 26 HYPERLINK l _Toc67800604 13.6Study Hypotheses PAGEREF _Toc67800604 h 26 HYPERLINK l _Toc67800605 13.7Sample Size Considerations PAGEREF _Toc67800605 h 26 HYPERLINK l _Toc67800606 13.8Participant Enrollment and Follow-Up PAGEREF _Toc6780

30、0606 h 27 HYPERLINK l _Toc67800607 13.9Planned Interim Analyses (if planned) PAGEREF _Toc67800607 h 27 HYPERLINK l _Toc67800608 Safety Review PAGEREF _Toc67800608 h 27 HYPERLINK l _Toc67800609 Immunogenicity or Efficacy Review PAGEREF _Toc67800609 h 28 HYPERLINK l _Toc67800610 13.10Final Analysis Pl

31、an PAGEREF _Toc67800610 h 28 HYPERLINK l _Toc67800611 14Source Documents and Access to Source Data/Documents PAGEREF _Toc67800611 h 29 HYPERLINK l _Toc67800612 15Quality Control and Quality Assurance PAGEREF _Toc67800612 h 30 HYPERLINK l _Toc67800613 16Ethics/Protection of Human Subjects PAGEREF _To

32、c67800613 h 31 HYPERLINK l _Toc67800614 16.1Declaration of Helsinki PAGEREF _Toc67800614 h 31 HYPERLINK l _Toc67800615 16.2Institutional Review Board PAGEREF _Toc67800615 h 31 HYPERLINK l _Toc67800616 16.3Informed Consent Process PAGEREF _Toc67800616 h 31 HYPERLINK l _Toc67800617 Informed Consent/As

33、sent Process (in Case of a Minor) PAGEREF _Toc67800617 h 32 HYPERLINK l _Toc67800618 16.4Exclusion of Women, Minorities, and Children (Special Populations) PAGEREF _Toc67800618 h 33 HYPERLINK l _Toc67800619 16.5Subject Confidentiality PAGEREF _Toc67800619 h 33 HYPERLINK l _Toc67800620 16.6Study Disc

34、ontinuation PAGEREF _Toc67800620 h 33 HYPERLINK l _Toc67800621 17Data Handling and Record Keeping PAGEREF _Toc67800621 h 34 HYPERLINK l _Toc67800622 17.1Data Management Responsibilities PAGEREF _Toc67800622 h 34 HYPERLINK l _Toc67800623 17.2Data Capture Methods PAGEREF _Toc67800623 h 35 HYPERLINK l

35、_Toc67800624 17.3Types of Data PAGEREF _Toc67800624 h 35 HYPERLINK l _Toc67800625 17.4Timing/Reports PAGEREF _Toc67800625 h 35 HYPERLINK l _Toc67800626 17.5Study Records Retention PAGEREF _Toc67800626 h 35 HYPERLINK l _Toc67800627 17.6Protocol Deviations PAGEREF _Toc67800627 h 35 HYPERLINK l _Toc678

36、00628 18Publication Policy PAGEREF _Toc67800628 h 36 HYPERLINK l _Toc67800629 19Literature References PAGEREF _Toc67800629 h 37APPENDICESA: Schedule of Procedures/EvaluationsB: Site RosterDMID Protocol TemplateVersion 1.008 April 2004List of Abbreviations - continued PAGE viiDMID Protocol TemplateVe

37、rsion 1.008 April 2004List of Abbreviations PAGE viAEAdverse Event/Adverse ExperienceCFRCode of Federal RegulationsCIOMSCouncil for International Organizations of Medical SciencesCONSORTConsolidated Standards of Reporting TrialsCRFCase Report FormCROContract Research OrganizationDCCData Coordinating

38、 CenterDMIDDivision of Microbiology and Infectious Diseases, NIAID, NIHDSMBData Safety and Monitoring BoardDSMCData Safety and Monitoring CommitteeFDAFood and Drug AdministrationFWAFederal-Wide AssuranceGCPGood Clinical PracticeHIPAAHealth Insurance Portability and Accountability ActIBInvestigators

39、BrochureICFInformed Consent FormICHInternational Conference on HarmonisationIDEInvestigational Device ExemptionIECIndependent or Institutional Ethics CommitteeINDInvestigational New DrugIRBInstitutional Review BoardISMIndependent Safety MonitorJAMAJournal of the American Medical AssociationMedDRA Me

40、dical Dictionary for Regulatory ActivitiesMOPManual of ProceduresNNumber (typically refers to subjects)NCINational Cancer Institute, NIHNDANew Drug ApplicationNEJMNew England Journal of MedicineNIAIDNational Institute of Allergy and Infectious Diseases, NIHNIHNational Institutes of HealthOCRAOffice

41、of Clinical Research Affairs, DMID, NIAID, NIHOHRPOffice for Human Research ProtectionsOHSROffice for Human Subjects ResearchORAOffice of Regulatory Affairs, DMID, NIAID, NIHPHIProtected Health InformationPIPrincipal InvestigatorPKPharmacokineticsQAQuality AssuranceQCQuality ControlSAESerious Advers

42、e Event/Serious Adverse ExperienceSMCSafety Monitoring CommitteeSOPStandard Operating ProcedureWHOWorld Health OrganizationThis list can be modified to include protocol-specific terms.DMID Protocol TemplateVersion 1.008 April 2004Protocol Summary - continued PAGE ixDMID Protocol TemplateVersion 1.00

43、8 April 2004Protocol Summary PAGE viiiLimit to 1-2 pagesTitle:Include type of trial (e.g., dose-ranging, observational, double blind)Phase:I, II, III, IVPopulation:Include sample size, gender, age, general health status, geographic locationNumber of Sites:3 or fewer, list here; otherwise, list only

44、in Appendix B and in Section 1Study Duration:State duration per subjectDescription of Agent or Intervention:Include dose and route of administrationObjectives:Include primary/secondary outcome measures and method by which outcome will be determined; copy objectives and clinical/laboratory outcome me

45、asures from the appropriate sections of the protocol.Primary:Secondary:Description of Study Design: This schematic should provide an overview of the study design, including study arms, sample size and schedule of interventions (e.g., vaccine administration), if applicable; a detailed schematic descr

46、ibing all visits and assessments will be included in Appendix A.Put key words in boldface in Protocol Summary.Schematic of Study Design:Example #1: Table format: (e.g., dose escalation)Cohort AARM 1Sample SizeIntervention 1ARM 2Sample SizeIntervention 2Instructions for progressing to next phase (if

47、applicable):Cohort BARM 1Sample SizeIntervention 1ARM 2Sample SizeIntervention 2Example #2: Flow diagram:Total N: Obtain informed consent. Screen subjects by criteria; obtain history document.Prior to EnrollmentRandomizeN subjectsArm 2N subjectsArm 1N subjects Arm 3Clinical and AE assessmentPerform

48、pregnancy test; collect blood for assays;Administer Study Product/InterventionTime Point orStudy Visit 1Time Point orStudy Visit 2Clinical and AE assessmentTime Point orStudy Visit 3Time PointAssessment of Final Study Outcome Measuresor Study Visit DMID Protocol TemplateVersion 1.008 April 2004 PAGE

49、 37Key RolesSee ICH E6 GCP, Section 6.1.For questions regarding this protocol, contact (insert name of appropriate DMID staff) at NIAID/DMID (insert contact information).Required:Institutions:Sponsor(s), Monitor (if other than Sponsor), Study sites, Clinical laboratory(ies) and other medical or tech

50、nical departments and/or institutionsProvide the following information for each organization or institution:InstitutionAddressContact PersonPhone NumberFax NumberE-mailIndividuals:Sponsor: Individual authorized to sign the protocol and protocol amendments for the Sponsor and the Sponsors medical exp

51、ert for the trialInvestigators: Lead investigator(s) responsible for conducting the trial and the qualified physician who is responsible for all trial-site related medical decisionsProvide the following information for each individual:Name, degree, titleInstitutionAddressPhone NumberFax NumberE-mail

52、Optional: (consider listing, for example):Major International Collaborators, if not included as site investigatorsProtocol Data ManagerProtocol EpidemiologistProtocol PharmacologistDMID Clinical Trials SpecialistPharmaceutical Company Representative(s)Protocol Statistician(s)Collaborating Investigat

53、orsMedical Monitor (Pharmaceutical Company)Independent Safety MonitorOther individuals should be listed in a separate document (e.g., the Manual of Procedures) as a contact list.Background Information and Scientific RationaleBackground InformationSee ICH E6 GCP, Section 6.2.Include:The name and desc

54、ription of the study intervention/investigational products(s)A summary of findings from non-clinical in vitro studies that have potential clinical significanceA summary from relevant clinical trialsDiscussion of important literature and data that are relevant to the trial and that provide background

55、 for the trial (reference citations are listed in Section 19)Applicable clinical, epidemiological or public health background or context of the studyImportance of the study and any relevant treatment issues or controversiesRationaleInclude a description of and justification for the route of administ

56、ration, dosage, dosage regimen, intervention periods, and selection of study population. Include a statement of the hypothesis.Potential Risks and BenefitsInclude a discussion of known potential benefits, if any, and risks to human subjectsPotential RisksKnown Potential BenefitsObjectivesA detailed

57、description of the primary and secondary objectives of the study is included in this section. These typically include:Statement of purpose: e.g., to assess, to determine, to compare, to evaluateGeneral purpose, e.g., efficacy, safety, immunogenicity, pharmacokineticsSpecific purpose, e.g., dose-resp

58、onse, superiority to placeboName(s) of intervention (e.g., vaccine, drug, biologic) being evaluated, specification of doses or dose ranges to be studied, dose regimensMethod of assessing how the objective is met, i.e., the study outcome measuresStudy DesignSee ICH E6 GCP, Section 6.4.The scientific

59、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 should include:A description of the type/design of trial to be conducted (e.g., placebo-controlled, double-mask, parallel design, open-label, dose escalat

60、ion, dose-ranging)The rationale for design features should be discussedPhase of trialThe number of study groups/armsDescription of study groups/arms including sample size (including a table, if appropriate)Approximate time to complete study enrollmentThe expected duration of subject participationA d