TITLE

(FULL PROTOCOL TITLE)

NIAID Protocol Number:

Sponsored by:

National Institute of Allergy and Infectious Diseases (NIAID)

Principal Investigator:

Draft or Version Number:

Day Month Year

Statement of Compliance

(if applicable, lift sample language from the Instruction Manual, otherwise delete and update the Table of Contents)

TITLE	1

Statement of Compliance	2

Protocol Summary	7

Précis	8

Schematic of Study Design	9

1	Key Roles	10

2	Background Information and Scientific Rationale	11

2.1	Background Information	11

2.1.1	Description of the Study	11

2.1.2	Summary of Relevant Studies	11

2.1.3	Summary of Epidemiological Data	11

2.2	Rationale	11

2.3	Potential Risks and Benefits	11

2.3.1	Potential Risks	11

2.3.2	Potential Benefits	11

3	Study Objectives	11

3.1	Primary Objective	11

3.2	Secondary Objectives	11

3.3	Exploratory Objectives (if applicable)	11

3.4	Substudy Objectives (if applicable)	11

4	Study Design	11

4.1	Description of the Study Design	11

4.2	Study Endpoints	11

4.2.1	Primary Endpoint	11

4.2.2	Secondary Endpoints	12

4.2.3	Exploratory Endpoints (if applicable)	12

4.2.4	Substudy Endpoints (if applicable)	12

5	Study Population	12

5.1	Participant Inclusion Criteria	12

5.2	Participant Exclusion Criteria	12

6	Study Procedures/Evaluations	13

6.1	Clinical Evaluations	13

6.2	Laboratory Evaluations	13

6.2.1	Clinical and Research Laboratory Evaluations and Specimen Collection	13

6.2.2	Specimen Preparation, Handling and Shipping	13

6.2.2.1	Instructions for Specimen Storage	13

6.2.2.2	Specimen Shipment	13

6.3	Substudies	13

7	Research Use of Stored Human Samples, Specimens or Data	13

7.1	Use of Stored Samples/Data	13

7.2	Disposition of Stored Samples/Data	13

8	Study Schedule	14

8.1	Screening	14

8.2	Enrollment/Baseline	14

8.3	Active Phase	14

8.4	Follow-up	14

8.5	Final Study Visit	14

8.6	Early Termination Visit	15

8.7	Recontact of Participants after Study Termination	15

9	Assessment of Safety	15

9.1	Definition of an Adverse Event (AE)	15

9.2	Definition of a Serious Adverse Event (SAE)	15

9.3	Methods and Timing for Assessing, Recording, Analyzing and Adverse Events	15

9.3.1	Methods and Timing for Assessment	15

9.3.1.1	AE/SAE Grading and Relationship Assignment	16

9.3.2	Recording/Documentation	17

9.3.3	Analysis/Management	17

9.4	Reporting Procedures	17

9.5	Type and Duration of the Follow-up of Participants after Adverse Events	18

9.6	Premature Withdrawal of a Participant	19

9.7	Replacement of a Participant Who Discontinues Study Participation	19

10	Clinical Monitoring Structure	19

10.1	Site Monitoring Plan	20

10.2	Safety Monitoring Plan	20

10.2.1	Safety Review Plan by the DSMB / SMC, (if applicable)	20

11	Statistical Considerations	20

11.1	Description of the Analyses	20

11.2	Appropriate Methods and Timing for Analyzing Outcome Measures.	20

11.3	Addressing Study Objectives	20

11.4	Sample Size Consideration	20

11.5	Participant Enrollment and Follow-Up	20

11.6	Final Analysis Plan	20

12	Quality Control and Quality Assurance	20

13	Ethics/Protection of Human Subjects	21

13.1	The Belmont Report	21

13.2	Declaration of Helsinki (if applicable)	21

13.3	Institutional Review Board	21

13.4	Informed Consent Process	22

13.4.1	Assent or Informed Consent Process (in Case of a Minor)	22

13.5	Justification for Exclusion of Women, Minorities, and Children (Special Populations)	22

13.6	Participant Confidentiality	22

13.7	Study Discontinuation	23

14	Data Handling and Record Keeping	23

14.1	Data Management Responsibilities	23

14.2	Data Capture Methods	23

14.3	Types of Data	23

14.4	Source documents and Access to Source Data/Documents	23

14.5	Timing/Reports	23

14.6	Study Records Retention	23

15	Publication Policy	23

Appendix A: Scientific References	24

Appendix B: Schedule of Procedures/Evaluations	25

Appendix C: Lab Processing Flow Sheet/Template for Specimen Collection	26

Appendices: OPTIONAL	27

List of Abbreviations

AE	Adverse Event/Adverse Experience

CFR	Code of Federal Regulations

CIOMS	Council for International Organizations of Medical Sciences

CLIA	Clinical Laboratory Improvement Amendment of 1988

COI	Conflict of Interest

CONSORT	Consolidated Standards of Reporting Trials

CRADA	Cooperative Research and Development Agreement

CRF	Case Report Form

CRO	Contract Research Organization

CRIMSON	Clinical Research Information Management System of the NIAID

DCR	Division of Clinical Research

DHHS	Department of Health and Human Services

FWA	Federal Wide Assurance

GCP	Good Clinical Practice

HIPAA	Health Insurance Portability and Accountability Act

ICF	Informed Consent Form

ICH	International Conference on Harmonization

IEC	Independent or Institutional Ethics Committee

IRB	Institutional Review Board

ISM	Independent Safety Monitor

MedDRA ©	Medical Dictionary for Regulatory Activities

MOP	Manual of Procedures/Manual of Operations

N	Number (typically refers to participants)

NCI	National Cancer Institute, NIH

NIAID	National Institute of Allergy and Infectious Diseases

NIH	National Institutes of Health

OHRP	Office for Human Research Protections

OHSR	Office of Human Subjects Research

PHI	Protected Health Information

PI	Principal Investigator

PK	Pharmacokinetics

QA	Quality Assurance

QC	Quality Control

RCHSPB	Regulatory Compliance and Human Subjects Protection Branch

RCHSPP	Regulatory Compliance and Human Subjects Protection Program

SAE	Serious Adverse Event/Serious Adverse Experience

SMC	Safety Monitoring Committee

SOP	Standard Operating Procedure

WHO	World Health Organization

Protocol Summary

Full Title:	Enter the full title

Short Title:	Must be 30 characters or less (count must include spaces). To check count: Select “Tools” from the menu bar; Select “Word Count”; Read “Characters (with spaces)”

Conducted by:	Name of Network or Program

Principal Investigator:	Name of Principal Investigator

Sample Size:	N= If more than one cohort also indicate sample size per cohort.

Accrual Ceiling:	Include sample size plus an estimate for screening failures.

Study Population:	Include a brief description such as health status (e.g., healthy volunteers or HIV-positive), gender, age, etc.

Accrual Period:	Length of time to completely enroll the study. May include a projected start date.

Study Design:	Provide an overview of the study design, including description of study type (e.g., double-masked, placebo-controlled, open label, dose-finding, parallel or crossover design, randomized), study arms, sample size and schedule of interventions (e.g., vaccine administration), if applicable

Study Duration:	Start Date: End Date: Provide the total length of time participants will be on study (intervention + follow-up,) include a projected end date.

Primary Objective:	Include primary outcome measures and method by which outcomes will be determined.

Secondary Objectives:	Include secondary outcome measures and method by which outcomes will be determined.

Exploratory Objectives:	(If applicable) Include exploratory outcome measure(s) that may ask separate research questions from the parent protocol.

Endpoints:	Include the primary measurements and endpoints used to determine efficacy.

Précis

Schematic of Study Design

Key Roles

For questions regarding this protocol, contact [name of appropriate NIAID staff] Branch/Division/NIAID [contact information].

Institutions:

Investigators:

Background Information and Scientific Rationale

Background Information

Description of the Study

Summary of Relevant Studies

Summary of Epidemiological Data

Rationale

Potential Risks and Benefits

Potential Risks

Potential Benefits

Study Objectives

Primary Objective

Secondary Objectives

Exploratory Objectives (if applicable)

(If not applicable, delete and update the Table of Contents)

Substudy Objectives (if applicable)

(If not applicable, delete and update the Table of Contents)

Study Design

Description of the Study Design

Study Endpoints

Primary Endpoint

Secondary Endpoints

Exploratory Endpoints (if applicable)

(If not applicable, delete and update the Table of Contents)

Substudy Endpoints (if applicable)

(If not applicable, delete and update the Table of Contents)

Study Population

Participant Inclusion Criteria

Participant Exclusion Criteria

Participation of Women: (if applicable)

Contraception: (if applicable)

(Sample Language)

The effects of [drugs/procedure(s)] on the developing human fetus are unknown. For this reason, women of childbearing potential and male partners must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Females of childbearing-age will have a pregnancy test prior to undergoing study procedures. Should a woman become pregnant or suspects she is pregnant while participating in this study, she should immediately inform study staff and her primary care physician.

Pregnancy: (if applicable)

(Sample Language)

Pregnant women are excluded from this study because the effects of [safety reasons related to a specific procedure].

Participation of Minorities: (if applicable)

Participation of Children: (if applicable) Participants younger than 18 years of age will be excluded from the study. Because [state rationale], the study is of “greater than minimal risk” and does not meet the criteria of 45 CFR 46, Subpart D, governing the participation of children in research.

Co-enrollment Guidelines: (if applicable) Co-enrollment in other trials is restricted, [specify types of studies the participant may be co-enrolled in, an observational study for example]. Study staff should question prospective enrollees about co-enrollment as participation in other studies may require the approval of the investigator.

Study Procedures/Evaluations

Clinical Evaluations

Laboratory Evaluations

Clinical and Research Laboratory Evaluations and Specimen Collection

Specimen Preparation, Handling and Shipping

Biohazard Containment

Because transmission of HIV and other blood-borne pathogens can occur through contact with contaminated needles, blood, blood products and body secretions; appropriate protective precautions will be employed by all personnel in the drawing of blood, shipping and handling of all specimens for this study, as currently recommended by the Centers for Disease Control and Prevention and the National Institutes of Health.

Instructions for Specimen Storage

Specimen Shipment

Transport of Infectious Agents

All specimens will be transported using packaging mandated in the Code of Federal Regulations 42 CFR Part 72 and according to individual carrier guidelines, as applicable.

Substudies

Research Use of Stored Human Samples, Specimens or Data

Use of Stored Samples/Data

Samples and data collected under this protocol may be used to study [XX]. [No] genetic testing will be performed. (If applicable) Samples and data collected under this protocol may be used to study [XX]. [No] genetic testing will be performed.

Disposition of Stored Samples/Data

Access to stored samples will be limited using [either a locked room or a locked freezer]. Samples and data will be stored using codes assigned by the investigators. Data will be kept in password-protected computers. Only investigators will have access to the samples and data.

Samples and data acquired after [date] will be tracked [describe method of tracking, such as the name of the software tracking program or other logging/tracking method].

In the future, other investigators (both at NIH and outside) may wish to study these samples and/or data. In that case, IRB approval must be sought prior to any sharing of samples. Any clinical information shared about the sample would similarly require prior IRB approval.

Any loss or unanticipated destruction of samples or data (for example, due to freezer malfunction) that meets the NIH Intramural Protocol Violation definition or results in a violation that compromises the scientific integrity of the data collected for the study; will be reported to the NIAID IRB.

At the completion of the protocol (termination), samples and data will either be destroyed, or after IRB approval, transferred to another existing protocol. [describe the disposition of the specimens, the protocol will remain open, they will be sent to a repository, etc… as applicable]

Additionally, subjects may decide at any point not to have their samples stored. In this case, the principal investigator will destroy all known remaining samples and report what was done to both the subject and to the IRB. This decision will not affect the subject’s participation in this protocol or any other protocols at NIH.

Study Schedule

Screening

The purpose of the screening visit is to determine volunteer eligibility for study participation. Volunteers, who are diagnosed with a medical condition during the screening process, (e.g., test positive for hepatitis B, hepatitis C, HIV) will be notified and referred for medical care. The following screening evaluation must be completed in the [XX] days prior to enrollment.

Enrollment/Baseline

Day 0 is defined as the day of enrollment and initiation of the study procedure(s). Study participants must sign the protocol informed consent document to be considered enrolled into the study.

Active Phase

Follow-up

Final Study Visit

Early Termination Visit

Recontact of Participants after Study Termination

Assessment of Safety

Definition of an Adverse Event (AE)

(Sample Language)

An adverse event (AE) is any unanticipated or unintended medical occurrence or worsening of a sign or symptom (including an abnormal laboratory finding) or disease in a study participant, which does not necessarily have a causal relationship with the study condition, procedures or study agent(s), that occurs after the informed consent is obtained.

Pre-existing conditions or illnesses which are expected to exacerbate or worsen are not considered adverse events and will be accounted for in the subject’s medical history

Provide a definition, specific to this protocol, of the expected vs. unexpected AEs, based on the risk profile of the study procedures and/or disease process.

Definition of a Serious Adverse Event (SAE)

A Serious Adverse Event (SAE) is defined as an AE resulting one of the following outcomes:

Death during the period of protocol-defined surveillance

Life Threatening Event (defined as an event that places a participant at immediate risk of death)

Inpatient hospitalization or prolongation of existing hospitalization during the period of protocol-defined surveillance

Congenital anomaly or birth defect

Persistent or significant disability/incapacity

Any other condition which, in the judgment of the investigator, represents a significant hazard, such as an important medical event that does not result in one of the above outcomes, may be considered a serious adverse event when the event jeopardizes the participant or requires medical or surgical intervention to prevent one of the outcomes listed above.

Methods and Timing for Assessing, Recording, Analyzing and Adverse Events

Methods and Timing for Assessment

AE/SAE Grading and Relationship Assignment

Intensity (severity) Scale

Each adverse event, all other laboratory and clinical AEs that occur in a participant will be assessed for severity and classified into one the categories below:

Grade 1 (Mild): Event requires minimal or no treatment and does not interfere with the participant’s daily activities.

Grade 2 (Moderate): Event results in a low level of inconvenience or concern with the therapeutic measures. Moderate events may cause some interference with functioning.

Grade 3 (Severe): Event interrupts a subject’s usual daily activity or functioning and may require systemic drug therapy or other treatment. Severe events are usually incapacitating.

Grade 4 (Life threatening): Any adverse drug experience that places the participant, in the view of the investigator, at immediate risk of death from the event as it occurred.

Grade 5 (Death)

Relationship Assessment

(Sample Language)

All AEs or SAEs will be assessed for relationship to the study research procedures. A causal relationship means that the study participation caused (or is reasonably likely to have caused) the event. This usually implies an association in time between a study procedure and the event (e.g., the AE occurred shortly after the study participant had a blood draw). [If applicable, for blood draw protocols]

(Required Language)

For all collected AEs, the investigator who examines and evaluates the participant will determine the adverse event’s causality based on temporal relationship and his/her clinical judgment. The degree of certainty about causality will be graded using the categories below.

Definitely Related: There is clear evidence to suggest a causal relationship, and other possible contributing factors can be ruled out. The clinical event, including an abnormal laboratory test result, occurs within a reasonable timeframe after study procedure(s) and cannot be explained by concurrent disease or other drugs or chemicals.

Probably Related: There is evidence to suggest a causal relationship, and the influence of other factors is unlikely. The clinical event, including an abnormal laboratory test result, occurs within a reasonable time after study procedure(s), is unlikely to be attributed to concurrent disease or other drugs or chemicals, and follows a clinically reasonable response to study events.

Possibly Related: There is some evidence to suggest a causal relationship (e.g., the event occurred within a reasonable time after study procedure(s)). However, the influence of other factors may have contributed to the event (e.g., the subject’s clinical condition, other concomitant events). Although an adverse event may be judged only as “possibly related” soon after discovery, it can be flagged as requiring more information and later be upgraded to “probably related” or “definitely related”, as appropriate.

Unlikely: A clinical event, including an abnormal laboratory test result, whose temporal relationship to study procedure(s) makes a causal relationship improbable (e.g., the event did not occur within a reasonable time after study procedure(s)) and in which other drugs or chemicals or underlying disease provides plausible explanations (e.g., the participant’s clinical condition, other concomitant treatments).

Unrelated: The AE is completely independent of study procedure(s), and/or evidence exists that the event is definitely related to another cause. There must be an alternative, definitive cause documented by the clinician.

Expected Events Related to Disease Process: Expectedness refers to the awareness of adverse events previously observed, not on the basis of what might be anticipated from the study procedure(s).

Recording/Documentation

At each contact with the subject, information regarding adverse events will be elicited by appropriate questioning and examinations and will be immediately recorded on a source document. Source documents will include: progress notes, laboratory reports, consult notes, phone call summaries, survey tools and data collection tools. Source documents will be reviewed in a timely manner by the research team. All reportable adverse events that are identified will be recorded on an appropriate [case report form (CRF)/CRIMSON]. The start date, the stop date, the severity of each reportable event, and the Investigator’s judgment of the AEs relationship to the [procedure/intervention] will also be recorded [on the CRF/in CRIMSON].

Analysis/Management

Reporting Procedures

(Sample Language)

Stable chronic conditions which are present prior to study entry, and do not worsen, are not considered adverse events and will be accounted for in the subject’s medical history.

Or

Since participants on this study have [illness/condition] and are likely to be ill at baseline, many will have adverse events by the above criteria. Medical management for [illness/condition] and its complications, will be standard of care and not part of the research process. The research process is related to [blood drawing/ or describe procedure and its intent here]. Therefore, we intend to report as adverse events only those due to research-related activities. Adverse events related to treatment or the underlying disease will be reported in aggregate at time of the annual review. However, all serious adverse events will be reported as described below. [If applicable]

(Required Language)

Adverse event reporting requirements to the NIAID Institutional Review Board (IRB) for this protocol are as follows:

Investigators will submit a completed serious adverse event report to the NIAID IRB within 7 days after becoming aware of a participant death, a potentially life-threatening (grade 4) serious adverse event that is possibly, probably or definitely related to study procedure(s), an urgent inpatient hospitalization or transfer to the ICU.

Investigators will submit a completed serious adverse event report to the NIAID IRB within 15 days after becoming aware of any Grade 3 (severe) adverse event that is possibly, probably or definitely related to study procedure(s), or an inpatient hospitalization (other than elective), a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.

Investigators will report within 15 days on any other event or condition regardless of grade, which in their judgment represents an event reportable to the IRB.

Investigators will forward all safety reports and related communications to the IRB within 15 days of receipt.

A summary of all adverse events will be reported to the NIAID IRB with a continuing review submission.

All subjects will be instructed to alert the study clinician if any adverse event occurs within 48-hours after the blood draw. Any AEs that occur within 48-hours of and are related to the blood draw will be recorded in the participant’s clinic file and captured on the AE CRF and reported in aggregate at time of annual review. Any SAEs that occur within 48-hours of and are related to the blood draw will be reported according to the requirements below. [If applicable]

Type and Duration of the Follow-up of Participants after Adverse Events

Monitoring of Participants

(Sample Language)

At each contact with the participant, the investigator must seek information on adverse events by specific questioning and, as appropriate, by examination.

AEs may be observed by the Investigator and/or study staff, elicited from the participant and/or family member, reported on diary cards [if applicable], or volunteered by the study participant. Adverse events that had previously been reported by a study participant will also be reassessed for duration, intensity and possible reoccurrence. Assessment of safety will include clinical observation and monitoring of hematological, chemical, and immunologic parameters [modify as appropriate].

(Additional Sample Language as appropriate)

Any AE that occurs between the times a study participant signs the informed consent form and the time s/he departs the study at the end of the final follow-up visit (or at the time of early discontinuation of the participant from the study for any reason) will be captured and recorded.

Follow-up of participants after Adverse Events

All SAEs and non-serious AEs reported in this study will be followed until resolution or [until the investigator and the clinical monitor are in agreement that] the AE/SAE has stabilized and no more follow-up is required. This requirement indicates that follow-up may be required for some events after the participant discontinues participation from the study. These events will be reported to the IRB annually.

(Additional Sample Language as appropriate)

Primary care of the participant’s initial medical condition will continue to be under the auspices of his/her local medical provider. A letter describing the study will be sent to the participant’s medical provider. The local medical provider will be instructed verbally and with written guidelines to contact the NIH investigators immediately to report any adverse event. A toll-free number will be available to provide 24-hour access to the Principal Investigator (PI) or designee. The participant’s primary medical provider will be encouraged to call the PI should any change in condition be noted as compared to the participant’s baseline status. Should the occasion arise, participants may also be treated at the NIH Clinical Center.

Premature Withdrawal of a Participant

Replacement of a Participant Who Discontinues Study Participation

Clinical Monitoring Structure

Site Monitoring Plan

Safety Monitoring Plan

Safety Review Plan by the DSMB / SMC, (if applicable)

(If not applicable, remove this subsection and update the Table of Contents. However, if a DSMB is required, sample language is available in the DCR Intramural NH Template Instructions document.)

Statistical Considerations

Description of the Analyses

Appropriate Methods and Timing for Analyzing Outcome Measures.

Addressing Study Objectives

Sample Size Consideration

Participant Enrollment and Follow-Up

Final Analysis Plan

Description of the Statistical Methods to Be Employed:

Level of Significance to be Used:

Accrual and Sample Size Considerations:

Relationship(s) of Endpoints to Calculations:

Analysis Plan:

Analysis of Variables:

Exploratory Analyses:

Handling of Missing and Spurious Data:

Quality Control and Quality Assurance

Definitions:

Quality assurance (QA): the systematic and independent examination of all study-related activities and documents. These audits determine whether the evaluated activities were appropriately conducted and that the data were generated, recorded, analyzed, and accurately reported according to protocol, standard operating procedures (SOPs), and good clinical practices (GCPs). (ICH E6 1.46).

Quality control (QC): periodic operational checks within each functional department to verify that clinical data are generated, collected, handled, analyzed, and reported according to protocol, SOPs, and GCPs. (ICH E6 1.47).

Following written standard operating procedures, the monitors will verify that the protocol is conducted and data are generated, documented (recorded), and reported in compliance with the protocol and the applicable regulatory requirements.

The study will provide direct access to all study related sites, source data/documents, and reports for the purpose of monitoring and auditing by the sponsor, and inspection by local and regulatory authorities.

Quality control procedures will be implemented on the data entry system. Data quality control checks will be run on the database and reports will be generated. Any missing data or data anomalies will be communicated to the site(s) for clarification/resolution.

Ethics/Protection of Human Subjects

The Belmont Report

In accordance with the FWA00005897: “This institution assures that all of its activities related to human subject research, regardless of funding source, will be guided by the ethical principles of The Belmont Report.” Additionally, the investigator assures that all activities of this protocol will be guided by the ethical principles of The Belmont Report, 45 CFR 46 and all of its subparts (A, B, C and D).

Declaration of Helsinki (if applicable)

(if applicable, lift sample language from the Instruction Manual, otherwise delete this section and update the Table of Contents)

Institutional Review Board

A copy of the protocol, informed consent forms, other information to be completed by participants, such as survey instruments or questionnaires, and any proposed advertising/ recruitment materials will be submitted to the IRB for written approval.

The investigator must submit and obtain approval from the IRB for all subsequent amendments to the protocol, informed consent documents and other study documentation referenced above. The investigator will be responsible for obtaining IRB approval of the annual Continuing Review throughout the duration of the study.

The investigator will notify the IRB of serious adverse events and protocol violations.

Informed Consent Process

Informed consent is an ongoing, interactive process that is initiated when the discussion regarding participation on the study begins and continues throughout study participation. The research team will discuss the study’s purpose, procedures, risks, potential benefits, and the rights of participants with the participant/[legal guardian], to help him/her make educated decisions about whether to begin or continue participation in the trial. Ample opportunity will be made for the investigator and the participant to exchange information and ask questions. Participants will sign and date the informed consent document prior to undergoing any protocol specific procedures. Participants may withdraw consent at any time throughout the course of the study.

The acquisition of informed consent will be documented in the participant’s medical record. The original signed informed consent form will be retained in the medical chart and a copy will be provided to the participant.

Assent or Informed Consent Process (in Case of a Minor)

Justification for Exclusion of Women, Minorities, and Children (Special Populations)

Exclusion of Women: (if applicable)

Exclusion of Minorities: (if applicable)

Exclusion of Children: (if applicable)

Participant Confidentiality

The investigator will ensure that the participant’s privacy and confidentiality is maintained. Participants will not be identified in any published reports of this study. All records will be kept confidential to the extent provided by federal, state and local law. In addition, the investigator shall inform participants that study monitors and other representatives of the Sponsor may inspect documents and records required to be maintained by the investigator. The investigator will inform the participants that Sponsor representatives are bound by agreement and the law to maintain subject privacy and confidentiality. All laboratory specimens, evaluation forms, reports, and other records that leave the collection site will be [identified only by a coded number/ de-identified] in order to maintain participant confidentiality. Personally identifiable information in electronic data management systems will be protected compliant with regulatory requirements and federal computing security requirements to preserve privacy and confidentiality. Clinical information will not be released without written permission of the participant, except as necessary for monitoring by the IRB/EC, NIAID, and OHRP.

Study Discontinuation

Data Handling and Record Keeping

Data Management Responsibilities

Data Capture Methods

Types of Data

Source documents and Access to Source Data/Documents

Study data will be collected on case report forms (CRF) designed for the study [or in an electronic data system (CRIMSON)]. The Principal Investigator is responsible for assuring that the data collected is complete, accurate, and recorded in a timely manner. Source documentation (the point of initial recording of a piece of data) should support the data collected on the case report form [in CRIMSON], and in the case of CRFs, be signed and dated by the person recording and/or reviewing the data. Source documents include recordings of observations or notations of clinical activities and all reports and records necessary for the evaluation and reconstruction of the clinical trial. Data for CRFs will be collected during visits and phone calls with subjects and health care providers, participant diaries and abstracted from the medical record. The CRF form may act as the source document for the following study procedures: [Specific procedures]. It is not acceptable for the CRF to be the only record of a subject’s participation in the study. This is to ensure that anyone who would access the medical record has adequate knowledge that the subject is participating in a research study.

Timing/Reports

Study Records Retention

Publication Policy

This protocol will be registered on ClinicalTrials.gov, as sponsored by the National Library of Medicine, to meet publication requirements by the ICMJE.

Appendix A: Scientific References

Appendix B: Schedule of Procedures/Evaluations

Evaluation	Screening

(-# days)	Baseline

(-# days)	Day 0	4	8	12	16	20	24	32	40	48	Prem. Disc. Evals.
Medical/Medication History
Clinical Assessment
[Complete/Targeted] Physical Exam
[Other Clin. Assess. components if on a different schedule]

Appendix C: Lab Processing Flow Sheet/Template for Specimen Collection

Appendices: OPTIONAL

Protocol Version X.0

January 31, 2008

Page 5 of 27

NIAID Natural History Protocol Template Version 1.0

TABLE OF CONTENTS

Page 3 of 27

1 August, 2006

APPENDICES

Natural History Template -SL-Intra V.1.1 1-2008

DHHS/NIH/NIAID/NCRS, Natural History, Template

Heather Bridge

2008-04-01

Charles Hollman

NIH/NIAID