DMID Protocol Template Version 2.0
28 September 2005
TITLE
DMID Protocol Number:
DMID Funding Mechanism: (eg, grant #, contract #)
Pharmaceutical Support Provided by: (if applicable)
Other Identifying Numbers:
IND Sponsor: (if applicable. Do not include IND number)
Principal Investigator:
DMID Protocol Champion:
DMID Medical Monitor:
DMID Clinical Affairs Specialist:
DMID Regulatory Affairs Specialist: (if applicable)
Draft or Version Number: (Refer to DMID SOP for assigning version numbers)
Day Month Year
(Write out the month and use international date format, eg, 23 January 2004)
Statement of Compliance
Signature Page
The signature below constitutes the approval of this protocol and the attachments, and 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 US federal regulations and ICH guidelines.
Site Investigator:Signed: / Date:
Name
Title
Table of Contents
Page
Statement of Compliance ii
Signature Page iii
Table of Contents iv
List of Abbreviations vii
Protocol Summary ix
1 Key Roles 1
2 Background Information and Scientific Rationale 2
2.1 Background Information 2
2.2 Rationale 2
2.3 Potential Risks and Benefits 2
2.3.1 Potential Risks 2
2.3.2 Known Potential Benefits 2
3 Objectives 3
3.1 Study Objectives 3
3.2 Study Outcome Measures 3
3.2.1 Primary Outcome Measures 3
3.2.2 Secondary Outcome Measures 3
4 Study Design 4
4.1 Substudies (if applicable) 4
5 Study Enrollment and Withdrawal 5
5.1 Subject Inclusion Criteria 5
5.2 Subject Exclusion Criteria 5
5.3 Treatment Assignment Procedures 5
5.3.1 Randomization Procedures 5
5.3.2 Masking Procedures 5
5.3.3 Reasons for Withdrawal 5
5.3.4 Handling of Withdrawals 5
5.3.5 Termination of Study 5
6 Study Intervention/Investigational Product 6
6.1 Study Product Description 6
6.1.1 Acquisition 6
6.1.2 Formulation, Packaging, and Labeling 6
6.1.3 Product Storage and Stability 6
6.2 Dosage, Preparation and Administration of Study Intervention/Investigational Product 6
6.3 Modification of Study Intervention/Investigational Product for a Participant 6
6.4 Accountability Procedures for the Study Intervention/Investigational Product(s) 6
6.5 Assessment of Subject Compliance with Study Intervention/Investigational Product 6
6.6 Concomitant Medications/Treatments 7
7 Study Schedule 8
7.1 Screening 8
7.2 Enrollment/Baseline 8
7.3 Follow-up 8
7.4 Final Study Visit 8
7.5 Early Termination Visit 8
7.6 Unscheduled Visit 8
8 Study Procedures/Evaluations 9
8.1 Clinical Evaluations 9
8.2 Laboratory Evaluations 9
8.2.1 Clinical Laboratory Evaluations 9
8.2.2 Special Assays or Procedures 9
8.2.3 Specimen Preparation, Handling, and Shipping 9
9 Assessment of Safety 10
9.1 Specification of Safety Parameters 10
9.2 Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters 10
9.2.1 Adverse Events 10
9.2.2 Reactogenicity (for Vaccine Studies and Some Therapeutic Trials) 10
9.2.3 Serious Adverse Events 10
9.2.4 Procedures to be Followed in the Event of Abnormal Laboratory Test Values or Abnormal Clinical Findings 10
9.3 Reporting Procedures 10
9.3.1 Regulatory Reporting for Studies Conducted Under DMIDSponsored IND 10
9.3.2 Regulatory Reporting for Studies Not Conducted Under DMIDSponsored IND 10
9.3.3 Other Adverse Events (if applicable) 11
9.3.4 Reporting of Pregnancy 11
9.4 Type and Duration of Follow-up of Subjects after Adverse Events 11
9.5 Halting Rules 11
9.6 Safety Oversight (ISM plus SMC or DSMB) 11
10 Clinical Monitoring 12
10.1 Site Monitoring Plan 12
11 Statistical Considerations 13
11.1 Study Hypotheses 13
11.2 Sample Size Considerations 13
11.3 Planned Interim Analyses (if applicable) 13
11.3.1 Safety Review 13
11.3.2 Immunogenicity or Efficacy Review 13
11.4 Final Analysis Plan 13
12 Source Documents and Access to Source Data/Documents 14
13 Quality Control and Quality Assurance 15
14 Ethics/Protection of Human Subjects 16
14.1 Ethical Standard 16
14.2 Institutional Review Board 16
14.3 Informed Consent Process 16
14.3.1 Informed Consent/Assent Process (in Case of a Minor) 16
14.4 Exclusion of Women, Minorities, and Children (Special Populations) 16
14.5 Subject Confidentiality 16
14.6 Study Discontinuation 16
14.7 Future Use of Stored Specimens 16
15 Data Handling and Record Keeping 17
15.1 Data Management Responsibilities 17
15.2 Data Capture Methods 17
15.3 Types of Data 17
15.4 Timing/Reports 17
15.5 Study Records Retention 17
15.6 Protocol Deviations 17
16 Publication Policy 18
17 Literature References 19
Supplements/Appendices 20
Appendix A: Schedule of Events 21
List of Abbreviations
CFR / Code of Federal Regulations
CIOMS / Council for International Organizations of Medical Sciences
CONSORT / Consolidated Standards of Reporting Trials
CFR / Code of Federal Regulations
CRF / Case Report Form
CRO / Contract Research Organization
DCC / Data Coordinating Center
DHHS / Department of Health and Human Services
DMID / Division of Microbiology and Infectious Diseases, NIAID, NIH, DHHS
DSMB / Data and Safety Monitoring Board
eCRF / Electronic Case Report Form
FDA / Food and Drug Administration
FWA / Federalwide Assurance
GCP / Good Clinical Practice
HIPAA / Health Insurance Portability and Accountability Act
IB / Investigator’s Brochure
ICF / Informed Consent Form
ICH / International Conference on Harmonisation
ICMJE / International Committee of Medical Journal Editors
IDE / Investigational Device Exemption
IEC / Independent or Institutional Ethics Committee
IND / Investigational New Drug Application
IRB / Institutional Review Board
ISM / Independent Safety Monitor
JAMA / Journal of the American Medical Association
MedDRA Ò / Medical Dictionary for Regulatory Activities
MOP / Manual of Procedures
N / Number (typically refers to subjects)
NCI / National Cancer Institute, NIH, DHHS
NDA / New Drug Application
NEJM / New England Journal of Medicine
NIAID / National Institute of Allergy and Infectious Diseases, NIH, DHHS
NIH / National Institutes of Health
OCRA / Office of Clinical Research Affairs, DMID, NIAID, NIH, DHHS
OHRP / Office for Human Research Protections
OHSR / Office for Human Subjects Research
ORA / Office of Regulatory Affairs, DMID, NIAID, NIH, DHHS
PHI / Protected Health Information
PI / Principal Investigator
PK / Pharmacokinetics
QA / Quality Assurance
QC / Quality Control
SAE / Serious Adverse Event/Serious Adverse Experience
SMC / Safety Monitoring Committee
SOP / Standard Operating Procedure
US / United States
WHO / World Health Organization
Please modify list to include your protocol-specific terms.
Protocol Summary
Phase:
Population:
Number of Sites:
Study Duration:
Subject Participation Duration:
Description of Agent or Intervention:
Objectives: / Primary:
·
Secondary:
·
Description of Study Design:
Estimated Time to Complete Enrollment:
Schematic of Study Design:
i
DMID Protocol Template Version 2.0
28 September 2005
1 Key Roles
Individuals:Protocol Champion:
Principal Investigator:
Medical Monitor: (if applicable)
Institutions:
Optional:
2 Background Information and Scientific Rationale
2.1 Background Information
2.2 Rationale
2.3 Potential Risks and Benefits
2.3.1 Potential Risks
2.3.2 Known Potential Benefits
3 Objectives
3.1 Study Objectives
3.2 Study Outcome Measures
3.2.1 Primary Outcome Measures
3.2.2 Secondary Outcome Measures
4 Study Design
4.1 Substudies (if applicable)
5 Study Enrollment and Withdrawal
5.1 Subject Inclusion Criteria
5.2 Subject Exclusion Criteria
5.3 Treatment Assignment Procedures
5.3.1 Randomization Procedures
5.3.2 Masking Procedures
5.3.3 Reasons for Withdrawal
5.3.4 Handling of Withdrawals
5.3.5 Termination of Study
6 Study Intervention/Investigational Product
6.1 Study Product Description
6.1.1 Acquisition
6.1.2 Formulation, Packaging, and Labeling
6.1.3 Product Storage and Stability
6.2 Dosage, Preparation and Administration of Study Intervention/Investigational Product
6.3 Modification of Study Intervention/Investigational Product for a Participant
6.4 Accountability Procedures for the Study Intervention/Investigational Product(s)
6.5 Assessment of Subject Compliance with Study Intervention/Investigational Product
6.6 Concomitant Medications/Treatments
7 Study Schedule
7.1 Screening
7.2 Enrollment/Baseline
7.3 Follow-up
7.4 Final Study Visit
7.5 Early Termination Visit
7.6 Unscheduled Visit
8 Study Procedures/Evaluations
8.1 Clinical Evaluations
8.2 Laboratory Evaluations
8.2.1 Clinical Laboratory Evaluations
8.2.2 Special Assays or Procedures
8.2.3 Specimen Preparation, Handling, and Shipping
8.2.3.1 Instructions for Specimen Preparation, Handling, and Storage
8.2.3.2 Specimen Shipment
9 Assessment of Safety
9.1 Specification of Safety Parameters
9.2 Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters
9.2.1 Adverse Events
9.2.2 Reactogenicity (for Vaccine Studies and Some Therapeutic Trials)
9.2.3 Serious Adverse Events
9.2.4 Procedures to be Followed in the Event of Abnormal Laboratory Test Values or Abnormal Clinical Findings
9.3 Reporting Procedures
9.3.1 Regulatory Reporting for Studies Conducted Under DMIDSponsored IND
9.3.2 Regulatory Reporting for Studies Not Conducted Under DMIDSponsored IND
9.3.3 Other Adverse Events (if applicable)
9.3.4 Reporting of Pregnancy
9.4 Type and Duration of Follow-up of Subjects after Adverse Events
9.5 Halting Rules
9.6 Safety Oversight (ISM plus SMC or DSMB)
10 Clinical Monitoring
10.1 Site Monitoring Plan
11 Statistical Considerations
11.1 Study Hypotheses
11.2 Sample Size Considerations
11.3 Planned Interim Analyses (if applicable)
11.3.1 Safety Review
11.3.2 Immunogenicity or Efficacy Review
11.4 Final Analysis Plan
12 Source Documents and Access to Source Data/Documents
13 Quality Control and Quality Assurance
14 Ethics/Protection of Human Subjects
14.1 Ethical Standard
14.2 Institutional Review Board
14.3 Informed Consent Process
14.3.1 Informed Consent/Assent Process (in Case of a Minor)
14.4 Exclusion of Women, Minorities, and Children (Special Populations)
14.5 Subject Confidentiality
14.6 Study Discontinuation
14.7 Future Use of Stored Specimens
15 Data Handling and Record Keeping
15.1 Data Management Responsibilities
15.2 Data Capture Methods
15.3 Types of Data
15.4 Timing/Reports
15.5 Study Records Retention
15.6 Protocol Deviations
16 Publication Policy
17 Literature References
1
DMID Protocol Template Version 2.0
28 September 2005
SupplementS/Appendices
20
DMID Protocol Template Version 2.0
28 September 2005
Appendix A: Schedule of Events
21