**PREFACE**

*This document is a NIAID protocol template. It is provided to
investigators for developing NIAID-sponsored clinical trial protocols.
Note that instructions and explanatory text are indicated by
[italics]{.underline} and should be replaced in your protocol document
with appropriate 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 provides a general format applicable to all clinical
trials evaluating Study Agent(s)/Intervention(s). Where specific
examples are provided, they are often from the vaccine area.*

*Refer questions regarding use of this protocol template to the
appropriate NIAID Division or Branch sponsoring this clinical trial.*

**TITLE**

**NIAID Protocol Number:**

**Sponsored by:**

National Institute of Allergy and Infectious Diseases (NIAID)

**NIAID Funding Mechanism:** *(e.g., grant #, contract #)*

**Pharmaceutical Support Provided by:** *(if applicable)*

**Other Identifying Numbers:**

**IND Sponsor:** *(if applicable)*

**Principal Investigator/Protocol Chair:**

**NIAID Medical Monitor:**

**NIAID Protocol Champion**

**Draft or Version Number:**

**Day Month Year**

*(Write out the month and use international date format, e.g., 23 June
2005)*

***This template is adapted from the ICH guidance document E6 (Good
Clinical Practices), Section 6.***

**Confidentiality Statement**

**This document is confidential and is to be distributed for review only
to investigators, potential investigators, consultants, study staff, and
applicable independent ethics committees or institutional review boards.
The contents of this document shall not be disclosed to others without
written authorization from NIAID (or others, as applicable), unless it
is necessary to obtain informed consent from potential study
participants.**

[]{#__RefHeading___Toc130958042 .anchor}Statement of Compliance

*Provide a statement that the trial will be conducted in compliance with
the protocol,* *International Conference on Harmonization Good Clinical
Practice E6 (**ICH-GCP), and the applicable regulatory requirements. Use
the applicable regulations 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 under IND, 21 CFR 312).*

-   *Directive 2001/20/EC on the approximation of the laws, regulations
    and administrative provisions of the Member States relating to the
    implementation of good clinical practice in the conduct of clinical
    trials on medicinal products for human use as amended by Commission
    Directive 2005/28/EC .*

-   *Completion of Human Participants Protection Training*

    *Refer to:*

> <http://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-061.html>
>
> <http://ohrp-ed.od.nih.gov/CBTs/Assurance/login.asp>
>
> <http://www.cancer.gov/clinicaltrials/learning/page3>

-   *NIAID Clinical Terms of Award*

    []{#__RefHeading___Toc130958043 .anchor}Signature Page 1

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 U.S. federal regulations and
ICH guidelines.

The Lead Principal Investigator (Protocol Chair) should sign Signature
Page 1. A copy of this Signature Page 1 should be filed with the holder
of the Regulatory documents and a copy should be maintained at the site.

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+------+-----------------------------------------+-----+--------------+
| Sig  |                                         | Da  |              |
| ned: |                                         | te: |              |
+------+-----------------------------------------+-----+--------------+
|      | *Name/Title*                            |     |              |
+------+-----------------------------------------+-----+--------------+

[]{#__RefHeading___Toc130958044 .anchor}Signature Page 2

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 U.S. federal regulations and
ICH guidelines.

The Investigator(s) of Record (signature(s) on 1572) from each
participating clinical site should sign the Signature Page 2 as
appropriate. This Signature Page 2 should be maintained at each site.

+------+-----------------------------------------+-----+--------------+
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| gato |                                         |     |              |
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+------+-----------------------------------------+-----+--------------+
| Sig  |                                         | Da  |              |
| ned: |                                         | te: |              |
+------+-----------------------------------------+-----+--------------+
|      | *Name/Title*                            |     |              |
+------+-----------------------------------------+-----+--------------+
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+------+-----------------------------------------+-----+--------------+
| Sig  |                                         | Da  |              |
| ned: |                                         | te: |              |
+------+-----------------------------------------+-----+--------------+
|      | *Name/Title*                            |     |              |
+------+-----------------------------------------+-----+--------------+
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+------+-----------------------------------------+-----+--------------+
| Sig  |                                         | Da  |              |
| ned: |                                         | te: |              |
+------+-----------------------------------------+-----+--------------+
|      | *Name/Title*                            |     |              |
+------+-----------------------------------------+-----+--------------+

**APPENDICES**

[Statement of Compliance i](#__RefHeading___Toc130958042)

[Signature Page 1 ii](#__RefHeading___Toc130958043)

[Signature Page 2 iii](#__RefHeading___Toc130958044)

[List of Abbreviations vii](#__RefHeading___Toc130958045)

[Protocol Summary ix](#__RefHeading___Toc130958046)

[1. Key Roles 1](#key-roles)

[2. Background Information and Scientific Rationale
1](#background-information-and-scientific-rationale)

[2.1 Background Information 1](#background-information)

[2.1.1 Description of the Study Agent(s)/Intervention(s)
1](#description-of-the-study-agentsinterventions)

[2.1.2 Summary of Previous Pre-clinical Studies
1](#summary-of-previous-pre-clinical-studies)

[2.1.3 Summary of Relevant Clinical Studies
1](#summary-of-relevant-clinical-studies)

[2.1.4 Summary of Epidemiological Data
1](#summary-of-epidemiological-data)

[2.2 Rationale 1](#rationale)

[2.3 Potential Risks and Benefits 1](#potential-risks-and-benefits)

[2.3.1 Potential Risks 1](#potential-risks)

[2.3.2 Potential Benefits 1](#potential-benefits)

[3. Study Objectives 1](#study-objectives)

[3.1 Primary Objective 1](#primary-objective)

[3.2 Secondary Objectives 1](#secondary-objectives)

[3.3 Exploratory Objectives 1](#exploratory-objectives)

[4. Study Design 1](#study-design)

[4.1 Description of the Study Design
1](#description-of-the-study-design)

[4.2 Study Endpoints 1](#study-endpoints)

[4.2.1 Primary Endpoint 1](#primary-endpoint)

[4.2.2 Secondary Endpoints 1](#secondary-endpoints)

[4.2.3 Exploratory Endpoints 1](#exploratory-endpoints)

[4.2.4 Substudy Endpoints 2](#substudy-endpoints)

[5. Study Population 2](#study-population)

[5.1 Description of the Study Population
2](#description-of-the-study-population)

[5.1.1 Participant Inclusion Criteria
2](#participant-inclusion-criteria)

[5.1.2 Participant Exclusion Criteria
2](#participant-exclusion-criteria)

[*5.1.2.1* *Co-enrollment Guidelines* 2](#__RefHeading___Toc130958073)

[5.2 Strategies for Recruitment and Retention
2](#strategies-for-recruitment-and-retention)

[6. Study Agent/Interventions 2](#study-agentinterventions)

[6.1 Study Agent Acquisition 2](#study-agent-acquisition)

[6.1.1 STUDY DRUG \# 1 (Primary Study Agent for this Trial
2](#study-drug-1-primary-study-agent-for-this-trial)

[*6.1.1.1* *Formulation, Packaging, and Labeling*
2](#__RefHeading___Toc130958078)

[*6.1.1.2 Study Agent Storage and Stability*
2](#__RefHeading___Toc130958079)

[*6.1.1.3* *Preparation, Administration, and Dosage of Study
Agent(s)/Intervention(s)* 2](#__RefHeading___Toc130958080)

[*6.1.1.4* *Study Product Accountability Procedures*
2](#__RefHeading___Toc130958081)

[6.1.2 STUDY DRUG #2 2](#study-drug-2)

[*6.1.2.1* *Formulation, Packaging, and Labeling*
2](#__RefHeading___Toc130958083)

[*6.1.2.2* *Study Agent Storage and Stability*
2](#__RefHeading___Toc130958084)

[*6.1.2.3* *Preparation, Administration, and Dosage of Study
Agent(s)/Intervention(s)* 2](#__RefHeading___Toc130958085)

[*6.1.2.4* *Study Product Accountability Procedures*
2](#__RefHeading___Toc130958086)

[6.2 Assessment of Participant Compliance with Study
Agent(s)/Intervention(s)
2](#assessment-of-participant-compliance-with-study-agentsinterventions)

[6.3 Concomitant Medications and Procedures
2](#concomitant-medications-and-procedures)

[6.4 Precautionary and Prohibited Medications and Procedures
2](#precautionary-and-prohibited-medications-and-procedures)

[6.4.1 Prohibited Medications and Procedures
3](#prohibited-medications-and-procedures)

[6.4.2 Precautionary Medications and Procedures
3](#precautionary-medications-and-procedures)

[6.5 Prophylactic Medications and Procedures
3](#prophylactic-medications-and-procedures)

[6.6 Rescue Medications 3](#rescue-medications)

[7. Study Procedures/Evaluations 3](#study-proceduresevaluations)

[7.1 Clinical Evaluations 3](#clinical-evaluations)

[7.2 Laboratory Evaluations 3](#laboratory-evaluations)

[7.2.1 Clinical and Research Laboratory Evaluations and Specimen
Collection
3](#clinical-and-research-laboratory-evaluations-and-specimen-collection)

[7.2.2 Specimen Preparation, Handling and Shipping
3](#specimen-preparation-handling-and-shipping)

[7.2.2.1 Instructions for Specimen Storage
3](#instructions-for-specimen-storage)

[7.2.2.2 Specimen Shipment 3](#specimen-shipment)

[7.3 Substudies 3](#substudies)

[8. Study Schedule 3](#study-schedule)

[8.1 Screening 3](#screening)

[8.2 Enrollment/Baseline 3](#enrollmentbaseline)

[8.3 Follow-up 3](#follow-up)

[8.4 Final Study Visit 3](#final-study-visit)

[8.5 Early Termination Visit 3](#early-termination-visit)

[8.6 Pregnancy Visit 3](#pregnancy-visit)

[8.7 Unscheduled Visits 3](#unscheduled-visits)

[9. Assessment of Safety 3](#assessment-of-safety)

[9.1 Specification of Safety Parameters
4](#specification-of-safety-parameters)

[9.2 Definition of an Adverse Event (AE)
4](#definition-of-an-adverse-event-ae)

[9.3 Definition of a Serious Adverse Event (SAE)
4](#definition-of-a-serious-adverse-event-sae)

[9.4 Methods and Timing for Assessing, Recording, and Analyzing,
Managing Safety Parameters 4](#__RefHeading___Toc130958114)

[**9.4.1** **Methods and Timing for Assessment**
4](#__RefHeading___Toc130958115)

[*9.4.1.1* *AE/SAE Grading and Relationship Assignment*
4](#__RefHeading___Toc130958116)

[**9.4.2** **Recording/Documentation** 4](#__RefHeading___Toc130958117)

[**9.4.3** **Analysis/Management** 4](#__RefHeading___Toc130958118)

[**9.5** **Reporting Procedures** 4](#__RefHeading___Toc130958119)

[**9.5.1 Specific Serious Adverse Event Requirements**
4](#__RefHeading___Toc130958120)

[9.6 Reporting of Pregnancy 4](#reporting-of-pregnancy)

[9.7 Type and Duration of the Follow-up of Participants after Adverse
Events
4](#type-and-duration-of-the-follow-up-of-participants-after-adverse-events)

[9.8 Modification of Study Agent(s)/Intervention(s) for a Participant
4](#modification-of-study-agentsinterventions-for-a-participant)

[**9.8.1** **Dose / Schedule Modifications for a Participant**
4](#__RefHeading___Toc130958124)

[9.9 Halting Rules for the Protocol 4](#halting-rules-for-the-protocol)

[9.10 Stopping Rules for an Individual Participant/Cohort
4](#stopping-rules-for-an-individual-participantcohort)

[9.11 Premature Withdrawal of a Participant
4](#premature-withdrawal-of-a-participant)

[9.12 Replacement of a Participant Who Discontinues Study Treatment
4](#replacement-of-a-participant-who-discontinues-study-treatment)

[10. Clinical Monitoring Structure 5](#clinical-monitoring-structure)

[10.1 Site Monitoring Plan 5](#site-monitoring-plan)

[10.2 Safety Monitoring Plan 5](#safety-monitoring-plan)

[10.2.1 Safety Review Plan by the DSMB / SMC
5](#__RefHeading___Toc130958132)

[11. Statistical Considerations 5](#statistical-considerations)

[11.1 Overview and Study Objectives 5](#overview-and-study-objectives)

[11.2 Study Population 5](#study-population-1)

[11.3 Description of the Analyses 5](#description-of-the-analyses)

[11.4 Measures to Minimize Bias 5](#measures-to-minimize-bias)

[11.5 Appropriate Methods and Timing for Analyzing Outcome Measures.
5](#appropriate-methods-and-timing-for-analyzing-outcome-measures.)

[11.6 Study Hypotheses 5](#study-hypotheses)

[11.7 Sample Size Considerations 5](#sample-size-considerations)

[11.8 Maintenance of Trial Treatment Randomization Codes
5](#maintenance-of-trial-treatment-randomization-codes)

[11.9 Participant Enrollment and Follow-Up
5](#participant-enrollment-and-follow-up)

[11.10 Planned Interim Analyses (if applicable)
5](#planned-interim-analyses-if-applicable)

[11.11 Safety Review 5](#safety-review)

[11.12 Immunogenicity or Efficacy Review
5](#immunogenicity-or-efficacy-review)

[11.13 Final Analysis Plan 5](#final-analysis-plan)

[12. Quality Control and Quality Assurance
5](#quality-control-and-quality-assurance)

[13. Ethics/Protection of Human Subjects
5](#ethicsprotection-of-human-subjects)

[13.1 Declaration of Helsinki 6](#declaration-of-helsinki)

[13.2 Institutional Review Board/Ethics Committee
6](#institutional-review-boardethics-committee)

[13.3 Informed Consent Process 6](#informed-consent-process)

[13.3.1 Assent or Informed Consent Process (in Case of a Minor)
6](#assent-or-informed-consent-process-in-case-of-a-minor)

[13.4 Exclusion of Women, Minorities, and Children (Special Populations)
6](#exclusion-of-women-minorities-and-children-special-populations)

[13.5 Participant Confidentiality 6](#participant-confidentiality)

[13.6 Study Discontinuation 6](#study-discontinuation)

[14. Data Handling and Record Keeping
6](#data-handling-and-record-keeping)

[14.1 Data Management Responsibilities
6](#data-management-responsibilities)

[14.2 Data Capture Methods 6](#data-capture-methods)

[14.3 Types of Data 6](#types-of-data)

[14.4 Source documents and Access to Source Data/Documents
6](#source-documents-and-access-to-source-datadocuments)

[14.5 Timing/Reports 6](#timingreports)

[14.6 Study Records Retention 6](#study-records-retention)

[14.7 Protocol Deviations 6](#protocol-deviations)

[15. Publication Policy 6](#publication-policy)

[Appendix A1: Site Roster 1](#__RefHeading___Toc130958165)

[Appendix A2: Study Contacts Roster 2](#__RefHeading___Toc130958166)

[Appendix B: Schedule of Procedures/Evaluations
3](#__RefHeading___Toc130958167)

[Appendix C1: Lab Processing Flow sheet (this can be modified for each
protocol) 4](#__RefHeading___Toc130958168)

[Appendix C2: Example of Template for Specimen Collection, Processing,
and Shipment 4](#__RefHeading___Toc130958169)

[Appendix D: Optional Supplements/Appendices
6](#__RefHeading___Toc130958170)

  ----------------------------------------------------------------------------------
  []{#__RefHeading___Toc130958045   
  .anchor}List of Abbreviations     
  --------------------------------- ------------------------------------------------
  *This list should be modified to  
  include protocol-specific terms.* 

  AE                                Adverse Event/Adverse Experience

  CFR                               Code of Federal Regulations

  CIB                               Clinical Investigator's Brochure

  CIOMS                             Council for International Organizations of
                                    Medical Sciences

  CONSORT                           Consolidated Standards of Reporting Trials

  CRF                               Case Report Form

  CRO                               Contract Research Organization

  DCC                               Data Coordinating Center

  DSMB                              Data and Safety Monitoring Board

  DSMC                              Data and Safety Monitoring Committee

  FDA                               Food and Drug Administration

  FWA                               Federal-Wide Assurance

  GCP                               Good Clinical Practice

  HIPAA                             Health Insurance Portability and Accountability
                                    Act

  IB                                Investigator's Brochure

  ICF                               Informed Consent Form

  ICH                               International Conference on Harmonization

  IDE                               Investigational Device Exemption

  IEC                               Independent or Institutional Ethics Committee

  IND                               Investigational New Drug

  IRB                               Institutional Review Board

  ISM                               Independent Safety Monitor

  MedDRA ©                          Medical Dictionary for Regulatory Activities

  MOP                               Manual of Procedures

  N                                 Number (typically refers to participants)

  NCI                               National Cancer Institute, NIH

  NDA                               New Drug Application

  NIAID                             National Institute of Allergy and Infectious
                                    Diseases, NIH

  NIH                               National Institutes of Health

  OHRP                              Office for Human Research Protections

  OHSR                              Office for Human Subjects Research

  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

  WHO                               World Health Organization
  ----------------------------------------------------------------------------------

[]{#__RefHeading___Toc130958046 .anchor}Protocol Summary

*Limit Protocol Summary to 2 pages. The summary may be presented in
narrative or tabular format. See below:*

+---------------+------------------------------------------------------+
|               |                                                      |
+---------------+------------------------------------------------------+
| **Full        | *Include type of trial (e.g., dose-ranging,          |
| Title**       | observational, double blind)*                        |
+---------------+------------------------------------------------------+
| **Short       |                                                      |
| Title**       |                                                      |
+---------------+------------------------------------------------------+
| **Clinical    | *I, II, III, or IV*                                  |
| Trial Phase** |                                                      |
+---------------+------------------------------------------------------+
| **IND Sponsor | *Name of IND Sponsor (if applicable).*               |
| (if           |                                                      |
| applicable)** |                                                      |
+---------------+------------------------------------------------------+
| **Conducted   | *Name of Network or Program*                         |
| By**          |                                                      |
+---------------+------------------------------------------------------+
| **Principal   | *Name of Lead Principal Investigator (Protocol       |
| I             | Chair)*                                              |
| nvestigator** |                                                      |
+---------------+------------------------------------------------------+
| **Sample      |                                                      |
| Size**        |                                                      |
+---------------+------------------------------------------------------+
| **Study       | *Include a brief description such as health status   |
| Population**  | (e.g., healthy volunteers or HIV-positive), gender,  |
|               | age, etc.*                                           |
+---------------+------------------------------------------------------+
| **Accrual     | *Length of time to completely enroll the study*      |
| Period**      |                                                      |
+---------------+------------------------------------------------------+
| **Study       | *Provide an overview of the study design, including  |
| Design**      | 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       | *State duration per participant. Provide* the *total |
| Duration**    | length of time participants will be on study         |
|               | (intervention + follow-up)*                          |
+---------------+------------------------------------------------------+
| **Study       | *Include name, dose, duration frequency, and route   |
| Agent         | of administration, if applicable*                    |
| /Intervention |                                                      |
| Description** |                                                      |
+---------------+------------------------------------------------------+
| **Primary     | *Include primary outcome measures and method by      |
| Objective**   | which outcomes will be determined.*                  |
+---------------+------------------------------------------------------+
| **Secondary   | *Include secondary outcome measures and method by    |
| Objectives**  | which outcomes will be determined.*                  |
+---------------+------------------------------------------------------+
| **            | *(If applicable) Include exploratory outcome         |
| Exploratory** | measure(s) that may ask separate research questions  |
|               | from the parent protocol.*                           |
| *             |                                                      |
| *Objectives** |                                                      |
+---------------+------------------------------------------------------+
| **Endpoints** |                                                      |
+---------------+------------------------------------------------------+
|               |                                                      |
+---------------+------------------------------------------------------+

**Schematic of Study Design**:

***Below are examples of schematics. Choose or create a schematic that
is appropriate for a particular protocol.***

Example #1: Table format: (e.g., dose escalation)

  --------------- ----------------- ------------------- -------------------
  Cohort A        ARM 1             Sample Size         Intervention 1

                  ARM 2             Sample Size         Intervention 2
  --------------- ----------------- ------------------- -------------------

Instructions for progressing to next phase (if applicable):

  --------------- ----------------- ------------------- -------------------
  Cohort B        ARM 1             Sample Size         Intervention 1

                  ARM 2             Sample Size         Intervention 2
  --------------- ----------------- ------------------- -------------------

*Example #2: Flow diagram:*

Prior to

Enrollment

Time Point or

Study Visit 1

Time Point or

Study Visit 2

Time Point or

Study Visit 3

Time Point

or Study Visit ...

# Key Roles

# Background Information and Scientific Rationale

## Background Information

### Description of the Study Agent(s)/Intervention(s)

### Summary of Previous Pre-clinical Studies

### Summary of Relevant Clinical Studies

### Summary of Epidemiological Data

## Rationale

## Potential Risks and Benefits

### Potential Risks

### Potential Benefits

# Study Objectives

## Primary Objective

## Secondary Objectives

## Exploratory Objectives

# Study Design

## Description of the Study Design

## Study Endpoints

### Primary Endpoint

### Secondary Endpoints

### Exploratory Endpoints

### Substudy Endpoints

# Study Population

## Description of the Study Population

### Participant Inclusion Criteria

### Participant Exclusion Criteria

[]{#__RefHeading___Toc130958073 .anchor}***5.1.2.1 Co-enrollment
Guidelines***

## Strategies for Recruitment and Retention

# Study Agent/Interventions

## Study Agent Acquisition

### STUDY DRUG \# 1 (Primary Study Agent for this Trial

[]{#__RefHeading___Toc130958078 .anchor}*6.1.1.1 Formulation, Packaging,
and Labeling*

[]{#__RefHeading___Toc130958079 .anchor}*6.1.1.2 Study Agent Storage and
Stability*

[]{#__RefHeading___Toc130958080 .anchor}*6.1.1.3 Preparation,
Administration, and Dosage of Study Agent(s)/Intervention(s)*

[]{#__RefHeading___Toc130958081 .anchor}*6.1.1.4 Study Product
Accountability Procedures*

### STUDY DRUG #2

[]{#__RefHeading___Toc130958083 .anchor}*6.1.2.1 Formulation, Packaging,
and Labeling*

[]{#__RefHeading___Toc130958084 .anchor}*6.1.2.2 Study Agent Storage and
Stability*

[]{#__RefHeading___Toc130958085 .anchor}*6.1.2.3 Preparation,
Administration, and Dosage of Study Agent(s)/Intervention(s)*

4.  []{#__RefHeading___Toc130958086 .anchor}*Study Product
    Accountability Procedures*

## Assessment of Participant Compliance with Study Agent(s)/Intervention(s) 

## Concomitant Medications and Procedures

## Precautionary and Prohibited Medications and Procedures

### Prohibited Medications and Procedures 

### Precautionary Medications and Procedures

## Prophylactic Medications and Procedures

## Rescue Medications

# Study Procedures/Evaluations

## Clinical Evaluations

## Laboratory Evaluations

### Clinical and Research Laboratory Evaluations and Specimen Collection

### Specimen Preparation, Handling and Shipping

[]{.mark}

#### Instructions for Specimen Storage

#### Specimen Shipment 

## Substudies

# Study Schedule

## Screening 

## Enrollment/Baseline 

## Follow-up 

## Final Study Visit

## Early Termination Visit

## Pregnancy Visit

## Unscheduled Visits

# Assessment of Safety

## Specification of Safety Parameters

## Definition of an Adverse Event (AE)

## Definition of a Serious Adverse Event (SAE)

[]{#__RefHeading___Toc130958114 .anchor}**9.4 Methods and Timing for
Assessing, Recording, and Analyzing, Managing Safety Parameters**

[]{#__RefHeading___Toc130958115 .anchor}***9.4.1 Methods and Timing for
Assessment***

[]{#__RefHeading___Toc130958116 .anchor}***9.4.1.1 AE/SAE Grading and
Relationship Assignment***

[]{#__RefHeading___Toc130958117 .anchor}***9.4.2
Recording/Documentation***

[]{#__RefHeading___Toc130958118 .anchor}***9.4.3 Analysis/Management***

[]{#__RefHeading___Toc130958119 .anchor}**9.5 Reporting Procedures**

[]{#__RefHeading___Toc130958120 .anchor}***9.5.1 Specific Serious
Adverse Event Requirements***

## 9.6 Reporting of Pregnancy {#reporting-of-pregnancy .unnumbered}

## 9.7 Type and Duration of the Follow-up of Participants after Adverse Events {#type-and-duration-of-the-follow-up-of-participants-after-adverse-events .unnumbered}

## 9.8 Modification of Study Agent(s)/Intervention(s) for a Participant {#modification-of-study-agentsinterventions-for-a-participant .unnumbered}

[]{#__RefHeading___Toc130958124 .anchor}**9.8.1 Dose / Schedule
Modifications for a Participant**

##  {#section .unnumbered}

## 9.9 Halting Rules for the Protocol {#halting-rules-for-the-protocol .unnumbered}

## 9.10 Stopping Rules for an Individual Participant/Cohort {#stopping-rules-for-an-individual-participantcohort .unnumbered}

## 9.11 Premature Withdrawal of a Participant {#premature-withdrawal-of-a-participant .unnumbered}

## 9.12 Replacement of a Participant Who Discontinues Study Treatment {#replacement-of-a-participant-who-discontinues-study-treatment .unnumbered}

# Clinical Monitoring Structure

##  {#section-1 .unnumbered}

## 10.1 Site Monitoring Plan {#site-monitoring-plan .unnumbered}

## 10.2 Safety Monitoring Plan {#safety-monitoring-plan .unnumbered}

[]{#__RefHeading___Toc130958132 .anchor}**10.2.1 Safety Review Plan by
the DSMB / SMC**

# Statistical Considerations

## 11.1 Overview and Study Objectives {#overview-and-study-objectives .unnumbered}

## 11.2 Study Population {#study-population-1 .unnumbered}

## 11.3 Description of the Analyses {#description-of-the-analyses .unnumbered}

## 11.4 Measures to Minimize Bias {#measures-to-minimize-bias .unnumbered}

## 11.5 Appropriate Methods and Timing for Analyzing Outcome Measures. {#appropriate-methods-and-timing-for-analyzing-outcome-measures. .unnumbered}

## 11.6 Study Hypotheses {#study-hypotheses .unnumbered}

## 11.7 Sample Size Considerations {#sample-size-considerations .unnumbered}

## 11.8 Maintenance of Trial Treatment Randomization Codes {#maintenance-of-trial-treatment-randomization-codes .unnumbered}

##  {#section-2 .unnumbered}

## 11.9 Participant Enrollment and Follow-Up {#participant-enrollment-and-follow-up .unnumbered}

## 11.10 Planned Interim Analyses (if applicable) {#planned-interim-analyses-if-applicable .unnumbered}

##  {#section-3 .unnumbered}

## 11.11 Safety Review {#safety-review .unnumbered}

##  {#section-4 .unnumbered}

## 11.12 Immunogenicity or Efficacy Review {#immunogenicity-or-efficacy-review .unnumbered}

##  {#section-5 .unnumbered}

## 11.13 Final Analysis Plan {#final-analysis-plan .unnumbered}

# Quality Control and Quality Assurance

# Ethics/Protection of Human Subjects

## Declaration of Helsinki

## Institutional Review Board/Ethics Committee

## Informed Consent Process

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

## Exclusion of Women, Minorities, and Children (Special Populations)

##  Participant Confidentiality

## Study Discontinuation

# Data Handling and Record Keeping

## Data Management Responsibilities

## Data Capture Methods

## Types of Data

## Source documents and Access to Source Data/Documents

## Timing/Reports

## Study Records Retention

## Protocol Deviations

# Publication Policy

[]{#__RefHeading___Toc130958165 .anchor}

Appendix A1: Site Roster

Example of Site Roster

If a protocol involves multi-centers, each site should have a site
specific roster including key site staff as well as NIAID and Data
Center (if used) contacts. Each of these rosters may then be placed in a
Manual of Operations for access to all site staff.

\[List participating clinical centers and any clinical laboratories
being used as central laboratories for the study.\]

Others could include: Biostatistician, Data Manager, other disciplines,
ie Virologist, Neurologist, etc.

+---------------------+----------------------+------------------------+
| Site                | Site                 | NIAID Medical Monitor  |
| Inv                 | In                   |                        |
| estigator-Principal | vestigator-Associate | \[Name\]               |
|                     |                      |                        |
| \[Name\]            | \[Name\]             | \[Title\]              |
|                     |                      |                        |
| \[Title\]           | \[Title\]            | \[Institution\]        |
|                     |                      |                        |
| \[Institution\]     | \[Institution\]      | \[Address\]            |
|                     |                      |                        |
| \[Address\]         | \[Address\]          | \[City/State/Zip\]     |
|                     |                      |                        |
| \[City/State/Zip\]  | \[City/State/Zip\]   | Phone:                 |
|                     |                      |                        |
| Phone:              | Phone:               | Fax:                   |
|                     |                      |                        |
| Fax:                | Fax:                 | Email:                 |
|                     |                      |                        |
| Email:              | Email:               |                        |
+---------------------+----------------------+------------------------+
|                     |                      |                        |
+---------------------+----------------------+------------------------+
| *NIAID Program      | *Project Manager*    | *Laboratory Study      |
| Officer*            |                      | Contact*               |
|                     | \[Name\]             |                        |
| \[Name\]            |                      | \[Name\]               |
|                     | \[Title\]            |                        |
| \[Title\]           |                      | \[Title\]              |
|                     | \[Institution\]      |                        |
| \[Institution\]     |                      | \[Institution\]        |
|                     | \[Address\]          |                        |
| \[Address\]         |                      | \[Address\]            |
|                     | \[City/State/Zip\]   |                        |
| \[City/State/Zip\]  |                      | \[City/State/Zip\]     |
|                     | Phone:               |                        |
| Phone:              |                      | Phone:                 |
|                     | Fax:                 |                        |
| Fax:                |                      | Fax:                   |
|                     | Email:               |                        |
| Email:              |                      | Email:                 |
+---------------------+----------------------+------------------------+
| ***Site             | ***Site Study        | ***Data Coordinating   |
| Pharmacist***       | Coordinator***       | Center Contact         |
|                     |                      | (example,***           |
| \[Name\]            | \[Name\]             |                        |
|                     |                      | ***data manager,       |
| \[Title\]           | \[Title\]            | biostatistician)***    |
|                     |                      |                        |
| \[Institution\]     | \[Institution\]      | \[Name\]               |
|                     |                      |                        |
| \[Address\]         | \[Address\]          | \[Title\]              |
|                     |                      |                        |
| \[City/State/Zip\]  | \[City/State/Zip\]   | \[Institution\]        |
|                     |                      |                        |
| Phone:              | Phone:               | \[Address\]            |
|                     |                      |                        |
| Fax:                | Fax:                 | \[City/State/Zip\]     |
|                     |                      |                        |
| Email:              | Email:               | Phone:                 |
|                     |                      |                        |
|                     |                      | Fax:                   |
|                     |                      |                        |
|                     |                      | Email:                 |
+---------------------+----------------------+------------------------+

[]{#__RefHeading___Toc130958166 .anchor}Appendix A2: Study Contacts
Roster

Example of Study Contacts Roster

*The purpose of the study contacts sheet is to provide a centralized
list of the key disciplines involved in the study in order to facilitate
centralized communication. Depending on the structure of the study, the
data center is often responsible for filtering all questions to the
appropriate contacts and then disseminating the information to the
appropriate person(s). In the event another system of communication is
used, a detailed study contacts sheet is essential.*

+---------------------+---------------------+--------------------------+
| Principal           | Drug Company        | NIAID Medical Monitor    |
| Investigator        | Representative (if  |                          |
| (Protocol Chair)    | involved)           | \[Name\]                 |
|                     |                     |                          |
| \[Name\]            | \[Name\]            | \[Title\]                |
|                     |                     |                          |
| \[Title\]           | \[Title\]           | \[Institution\]          |
|                     |                     |                          |
| \[Institution\]     | \[Institution\]     | \[Address\]              |
|                     |                     |                          |
| \[Address\]         | \[Address\]         | \[City/State/Zip\]       |
|                     |                     |                          |
| \[City/State/Zip\]  | \[City/State/Zip\]  | Phone:                   |
|                     |                     |                          |
| Phone:              | Phone:              | Fax:                     |
|                     |                     |                          |
| Fax:                | Fax:                | Email:                   |
|                     |                     |                          |
| Email:              | Email:              |                          |
+---------------------+---------------------+--------------------------+
|                     |                     |                          |
+---------------------+---------------------+--------------------------+
| *NIAID Program      | *NIAID Project      | *Laboratory main Study   |
| Officer*            | Manager*            | Contact*                 |
|                     |                     |                          |
| \[Name\]            | \[Name\]            | \[Name\]                 |
|                     |                     |                          |
| \[Title\]           | \[Title\]           | \[Title\]                |
|                     |                     |                          |
| \[Institution\]     | \[Institution\]     | \[Institution\]          |
|                     |                     |                          |
| \[Address\]         | \[Address\]         | \[Address\]              |
|                     |                     |                          |
| \[City/State/Zip\]  | \[City/State/Zip\]  | \[City/State/Zip\]       |
|                     |                     |                          |
| Phone:              | Phone:              | Phone:                   |
|                     |                     |                          |
| Fax:                | Fax:                | Fax:                     |
|                     |                     |                          |
| Email:              | Email:              | Email:                   |
+---------------------+---------------------+--------------------------+
| ***NIAID Study      | ***BIOSTATICIAN***  | ***DATA COORDINATING     |
| Pharmacist***       |                     | CENTER CONTACT***        |
|                     | \[Name\]            |                          |
| \[Name\]            |                     | \[Name\]                 |
|                     | \[Title\]           |                          |
| \[Title\]           |                     | \[Title\]                |
|                     | \[Institution\]     |                          |
| \[Institution\]     |                     | \[Institution\]          |
|                     | \[Address\]         |                          |
| \[Address\]         |                     | \[Address\]              |
|                     | \[City/State/Zip\]  |                          |
| \[City/State/Zip\]  |                     | \[City/State/Zip\]       |
|                     | Phone:              |                          |
| Phone:              |                     | Phone:                   |
|                     | Fax:                |                          |
| Fax:                |                     | Fax:                     |
|                     | Email:              |                          |
| Email:              |                     | Email:                   |
+---------------------+---------------------+--------------------------+
| ***DATA             | ***VIROLOGIST,      | ***Additional            |
| COORDINATING CENTER | NEUROLOGIST, OR     | Participating Clinical   |
| DATA MANAGER***     | OTHER REQUIRED      | Sites-***                |
|                     | DISCIPLINES***      |                          |
| ***\[Name\]***      |                     | ***\[Contact Name\]***   |
|                     | ***\[Name\]***      |                          |
| ***\[Title\]***     |                     | ***\[Title\]***          |
|                     | ***\[Title\]***     |                          |
| **                  |                     | ***\[Contact             |
| *\[Institution\]*** | **                  | Institution\]***         |
|                     | *\[Institution\]*** |                          |
| ***\[Address\]***   |                     | ***\[Address\]***        |
|                     | ***\[Address\]***   |                          |
| ***\[               |                     | ***\[City/State/Zip\]*** |
| City/State/Zip\]*** | ***\[               |                          |
|                     | City/State/Zip\]*** | ***Phone:***             |
| ***Phone:***        |                     |                          |
|                     | ***Phone:***        | ***Fax:***               |
| ***Fax:***          |                     |                          |
|                     | ***Fax:***          | ***Email:***             |
| ***Email:***        |                     |                          |
|                     | ***Email:***        | ***\*\*\*This may be     |
|                     |                     | listed on a separate     |
|                     |                     | page***                  |
+---------------------+---------------------+--------------------------+

[]{#__RefHeading___Toc130958167 .anchor}Appendix B: Schedule of
Procedures/Evaluations

<table>
<colgroup>
<col style="width: 16%" />
<col style="width: 24%" />
<col style="width: 7%" />
<col style="width: 6%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 8%" />
</colgroup>
<thead>
<tr class="header">
<th colspan="4"></th>
<th colspan="4">Follow-Up Schedule</th>
<th colspan="2"></th>
</tr>
<tr class="odd">
<th colspan="2">Procedures</th>
<th><blockquote>
<p>Screening</p>
</blockquote></th>
<th><blockquote>
<p>Baseline</p>
</blockquote></th>
<th><blockquote>
<p>Time Point or Study Visit 1</p>
</blockquote></th>
<th><blockquote>
<p>Time Point or Study Visit 2</p>
</blockquote></th>
<th><blockquote>
<p>Time Point or Study Visit 3</p>
</blockquote></th>
<th><blockquote>
<p>Time Point or Study Visit 4, etc.</p>
</blockquote></th>
<th><blockquote>
<p>Study Completion</p>
</blockquote></th>
<th><blockquote>
<p>Premature Discontinuation</p>
</blockquote></th>
</tr>
</thead>
<tbody>
<tr class="odd">
<td colspan="2">Signed Consent Form</td>
<td>X</td>
<td>X</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="even">
<td colspan="2">Assessment of Eligibility Criteria</td>
<td>X</td>
<td>X</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td colspan="2">Review of Medical History</td>
<td>X</td>
<td>X</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="even">
<td colspan="2">Review of Concomitant Medications</td>
<td>X</td>
<td>X</td>
<td>X</td>
<td>X</td>
<td>X</td>
<td>X</td>
<td>X</td>
<td>X</td>
</tr>
<tr class="odd">
<td colspan="2">Study Intervention</td>
<td></td>
<td>X</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="even">
<td rowspan="3"><blockquote>
<p>Physical Exam</p>
</blockquote></td>
<td>Complete</td>
<td>X</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td>X</td>
<td>X</td>
</tr>
<tr class="odd">
<td>Symptom-Directed</td>
<td></td>
<td>X</td>
<td>(X)</td>
<td>(X)</td>
<td>(X)</td>
<td>(X)</td>
<td></td>
<td></td>
</tr>
<tr class="even">
<td>Vital Signs</td>
<td></td>
<td>(X)</td>
<td>(X)</td>
<td>(X)</td>
<td>(X)</td>
<td>(X)</td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td colspan="2">Assessment of Adverse Events</td>
<td></td>
<td></td>
<td>(X)</td>
<td>(X)</td>
<td>(X)</td>
<td>(X)</td>
<td>X</td>
<td>X</td>
</tr>
<tr class="even">
<td rowspan="3"><blockquote>
<p>Clinical Laboratory</p>
</blockquote></td>
<td>Chemistry</td>
<td>X</td>
<td>X</td>
<td>(X)</td>
<td>(X)</td>
<td>(X)</td>
<td>(X)</td>
<td>X</td>
<td>X</td>
</tr>
<tr class="odd">
<td>Hematology</td>
<td>X</td>
<td>X</td>
<td>(X)</td>
<td>(X)</td>
<td>(X)</td>
<td>(X)</td>
<td>X</td>
<td>X</td>
</tr>
<tr class="even">
<td>Urinalysis</td>
<td>X</td>
<td>X</td>
<td>(X)</td>
<td>(X)</td>
<td>(X)</td>
<td>(X)</td>
<td>X</td>
<td>X</td>
</tr>
<tr class="odd">
<td><blockquote>
<p>Research Laboratory</p>
</blockquote></td>
<td>Immunology<br />
__mL whole blood</td>
<td></td>
<td>X</td>
<td></td>
<td>(X)</td>
<td></td>
<td>(X)</td>
<td>X</td>
<td>X</td>
</tr>
<tr class="even">
<td><blockquote>
<p>Other Procedures</p>
</blockquote></td>
<td></td>
<td></td>
<td>(X)</td>
<td></td>
<td>(X)</td>
<td></td>
<td>(X)</td>
<td>(X)</td>
<td>(X)</td>
</tr>
</tbody>
</table>

+-----------------------------------------------------------------------+
| *(X) -- As indicated/appropriate.*                                    |
|                                                                       |
| *Provide a list of tests to be done, e.g.:*                           |
|                                                                       |
| *Hematology -- Hemoglobin, hematocrit, WBC and differential count,    |
| platelet count\                                                       |
| Biochemistry -- Sodium, potassium, chloride, urea, creatinine,        |
| glucose, uric acid, bicarbonate, amylase, lipase, albumin, total      |
| bilirubin, cholesterol, triglycerides, and CPK, as appropriate for    |
| the study. Note that this list is an example; specify list of tests   |
| applicable for the protocol.*                                         |
|                                                                       |
| *Urinalysis -- Protein and glucose, as appropriate for the study*     |
|                                                                       |
| *Immunology -- Specify specimen types for non-standard laboratory     |
| assays*                                                               |
|                                                                       |
| *Other -- Other procedures that are done to evaluate outcome measures |
| (e.g., photographs, X-rays)*                                          |
|                                                                       |
| *Study Intervention -- Modify as appropriate if intervention is       |
| administered more than once throughout the study*                     |
|                                                                       |
| *Specify time points for follow-up in days, weeks, or months, as      |
| appropriate for protocol.*                                            |
|                                                                       |
| *At baseline, all procedures should be done before study              |
| intervention.*                                                        |
|                                                                       |
| *Indicate volume of blood if frequent or large phlebotomies are part  |
| of the protocol over two months.*                                     |
+-----------------------------------------------------------------------+

[]{#__RefHeading___Toc130958168 .anchor}Appendix C1: Lab Processing Flow
sheet (this can be modified for each protocol)

**Example of Lab Processing Chart for NIAID Protocol Assays**

[Protocol \# Version \# Date created or revised .]{.underline}

[Lab
Technologist\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_E-mail
address\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_Phone\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_]{.underline}

[Data Handling- All specimens must be logged into the specimen
management module and all aliquots must be entered into the storage
module and exported weekly. Volumes must be accurate and the \# of
aliquots entered must be adjusted to match the \# of aliquots actually
prepared.]{.underline}

+-----+------+---+--------------------+--------+-------------------------+
| Vi  | S    | P |                    | Tests  | Processing              |
| sit | tudy | r |                    |        |                         |
|     | or   | i |                    |        |                         |
|     | Subs | m |                    |        |                         |
|     | tudy | a |                    |        |                         |
|     | #/   | r |                    |        |                         |
|     | Pat  | y |                    |        |                         |
|     | ient | S |                    |        |                         |
|     | Su   | p |                    |        |                         |
|     | bset | e |                    |        |                         |
|     |      | c |                    |        |                         |
|     |      | . |                    |        |                         |
|     |      | C |                    |        |                         |
|     |      | o |                    |        |                         |
|     |      | l |                    |        |                         |
|     |      | l |                    |        |                         |
|     |      | e |                    |        |                         |
|     |      | c |                    |        |                         |
|     |      | t |                    |        |                         |
|     |      | i |                    |        |                         |
|     |      | o |                    |        |                         |
|     |      | n |                    |        |                         |
|     |      | a |                    |        |                         |
|     |      | n |                    |        |                         |
|     |      | d |                    |        |                         |
|     |      | H |                    |        |                         |
|     |      | a |                    |        |                         |
|     |      | n |                    |        |                         |
|     |      | d |                    |        |                         |
|     |      | l |                    |        |                         |
|     |      | i |                    |        |                         |
|     |      | n |                    |        |                         |
|     |      | g |                    |        |                         |
+-----+------+---+--------------------+--------+-------------------------+
| *   | E    | E |                    | Full   | None or                 |
| *Bl | nter | n |                    | name   |                         |
| ank | prot | t |                    | of     | Spin speeds, time of    |
| t   | ocol | e |                    | test   | spin, temp. of spin,    |
| emp | #,   | r |                    | then   | aliquots and volume,    |
| lat | s    | b |                    | abbrev | special processing      |
| e** | tep, | l |                    | iation | (within x time of       |
|     | arm, | o |                    |        | collection, refer to    |
| En  | S    | o |                    | Test   | Appendix or Protocol    |
| ter | ub-s | d |                    | Code:  | Specific Information    |
|     | tudy | v |                    | \_\_   | Sheet/MOP) where to     |
| VID | \#   | o |                    | \_\_\_ | ship(lab code, not      |
| and |      | l |                    | \_\_\_ | whole address, ), when  |
|     |      | u |                    |        | to ship (monthly,       |
| t   |      | m |                    |        | real-time, batch until  |
| ime |      | e |                    |        | week x)                 |
| poi |      | , |                    |        |                         |
| nts |      | t |                    |        | spec. code:             |
|     |      | u |                    |        |                         |
| (   |      | b |                    |        |                         |
| pre |      | e |                    |        |                         |
| do  |      | a |                    |        |                         |
| se, |      | d |                    |        |                         |
| 1   |      | d |                    |        |                         |
| hr, |      | i |                    |        |                         |
| et  |      | t |                    |        |                         |
| c.) |      | i |                    |        |                         |
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|     |      | \ |                    |        |                         |
|     |      | # |                    |        |                         |
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|     |      | \ |                    |        |                         |
|     |      | # |                    |        |                         |
+-----+------+---+--------------------+--------+-------------------------+
| [   |      |   |                    |        |                         |
| SPE |      |   |                    |        |                         |
| CIM |      |   |                    |        |                         |
| ENS |      |   |                    |        |                         |
| COL |      |   |                    |        |                         |
| LEC |      |   |                    |        |                         |
| TED |      |   |                    |        |                         |
| FOR |      |   |                    |        |                         |
| NI  |      |   |                    |        |                         |
| AID |      |   |                    |        |                         |
| PRO |      |   |                    |        |                         |
| TOC |      |   |                    |        |                         |
| OLS |      |   |                    |        |                         |
| (Ad |      |   |                    |        |                         |
| ult |      |   |                    |        |                         |
| /Pe |      |   |                    |        |                         |
| dia |      |   |                    |        |                         |
| tri |      |   |                    |        |                         |
| c)] |      |   |                    |        |                         |
| {.u |      |   |                    |        |                         |
| nde |      |   |                    |        |                         |
| rli |      |   |                    |        |                         |
| ne} |      |   |                    |        |                         |
|     |      |   |                    |        |                         |
| Ad  |      |   |                    |        |                         |
| ult |      |   |                    |        |                         |
| bl  |      |   |                    |        |                         |
| ood |      |   |                    |        |                         |
| c   |      |   |                    |        |                         |
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| ect |      |   |                    |        |                         |
| ion |      |   |                    |        |                         |
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| 45  |      |   |                    |        |                         |
| 0mL |      |   |                    |        |                         |
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| ery |      |   |                    |        |                         |
| 56  |      |   |                    |        |                         |
| d   |      |   |                    |        |                         |
| ays |      |   |                    |        |                         |
| (8  |      |   |                    |        |                         |
| wee |      |   |                    |        |                         |
| ks) |      |   |                    |        |                         |
|     |      |   |                    |        |                         |
| Ped |      |   |                    |        |                         |
| iat |      |   |                    |        |                         |
| ric |      |   |                    |        |                         |
| bl  |      |   |                    |        |                         |
| ood |      |   |                    |        |                         |
| c   |      |   |                    |        |                         |
| oll |      |   |                    |        |                         |
| ect |      |   |                    |        |                         |
| ion |      |   |                    |        |                         |
| li  |      |   |                    |        |                         |
| mit |      |   |                    |        |                         |
| is  |      |   |                    |        |                         |
| \_\ |      |   |                    |        |                         |
| _\_ |      |   |                    |        |                         |
| \_\ |      |   |                    |        |                         |
| _\_ |      |   |                    |        |                         |
| \_\ |      |   |                    |        |                         |
| _\_ |      |   |                    |        |                         |
| \_\ |      |   |                    |        |                         |
| _\_ |      |   |                    |        |                         |
| \_\ |      |   |                    |        |                         |
| _\_ |      |   |                    |        |                         |
+-----+------+---+--------------------+--------+-------------------------+
| CL  |      |   |                    |        |                         |
| INI |      |   |                    |        |                         |
| CAL |      |   |                    |        |                         |
| LAB |      |   |                    |        |                         |
| TE  |      |   |                    |        |                         |
| STS |      |   |                    |        |                         |
| /   |      |   |                    |        |                         |
| SAF |      |   |                    |        |                         |
| ETY |      |   |                    |        |                         |
| L   |      |   |                    |        |                         |
| ABS |      |   |                    |        |                         |
| (Lo |      |   |                    |        |                         |
| cal |      |   |                    |        |                         |
| l   |      |   |                    |        |                         |
| abo |      |   |                    |        |                         |
| rat |      |   |                    |        |                         |
| ory |      |   |                    |        |                         |
| req |      |   |                    |        |                         |
| uir |      |   |                    |        |                         |
| eme |      |   |                    |        |                         |
| nts |      |   |                    |        |                         |
| may |      |   |                    |        |                         |
| dif |      |   |                    |        |                         |
| fer |      |   |                    |        |                         |
| and |      |   |                    |        |                         |
| sup |      |   |                    |        |                         |
| erc |      |   |                    |        |                         |
| ede |      |   |                    |        |                         |
| sug |      |   |                    |        |                         |
| ges |      |   |                    |        |                         |
| ted |      |   |                    |        |                         |
| sp  |      |   |                    |        |                         |
| eci |      |   |                    |        |                         |
| men |      |   |                    |        |                         |
| c   |      |   |                    |        |                         |
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| ion |      |   |                    |        |                         |
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| ng) |      |   |                    |        |                         |
| E   |      |   |                    |        |                         |
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| of  |      |   |                    |        |                         |
| th  |      |   |                    |        |                         |
| ese |      |   |                    |        |                         |
| wo  |      |   |                    |        |                         |
| uld |      |   |                    |        |                         |
| be  |      |   |                    |        |                         |
| mo  |      |   |                    |        |                         |
| dif |      |   |                    |        |                         |
| ied |      |   |                    |        |                         |
| for |      |   |                    |        |                         |
| the |      |   |                    |        |                         |
| sp  |      |   |                    |        |                         |
| eci |      |   |                    |        |                         |
| fic |      |   |                    |        |                         |
| ne  |      |   |                    |        |                         |
| eds |      |   |                    |        |                         |
| of  |      |   |                    |        |                         |
| the |      |   |                    |        |                         |
| pro |      |   |                    |        |                         |
| toc |      |   |                    |        |                         |
| ol. |      |   |                    |        |                         |
+-----+------+---+--------------------+--------+-------------------------+
|     |      |   | 5mL SST or red top | fetop  | None                    |
|     |      |   | tube (no           | rotein |                         |
|     |      |   | additive) - Send   |        |                         |
|     |      |   | to local clinical  |        |                         |
|     |      |   | lab ambient.       |        |                         |
|     |      |   |                    |        |                         |
|     |      |   | Complete CRF       |        |                         |
|     |      |   | #\_\_\_            |        |                         |
+-----+------+---+--------------------+--------+-------------------------+
|     |      |   | Serum (from 10mL   | HCG    | None                    |
|     |      |   | SST or red top     | (pre   |                         |
|     |      |   | tube (no           | gnancy |                         |
|     |      |   | additive)) or      | test)  |                         |
|     |      |   | urine (1mL) - Send |        |                         |
|     |      |   | to local clinical  | (urine |                         |
|     |      |   | lab ambient.       | test   |                         |
|     |      |   |                    | must   |                         |
|     |      |   | Complete CRF \#    | have a |                         |
|     |      |   | \_\_\_             | sensi  |                         |
|     |      |   |                    | tivity |                         |
|     |      |   |                    | of     |                         |
|     |      |   |                    | 25-50  |                         |
|     |      |   |                    | mIU/mL |                         |
+-----+------+---+--------------------+--------+-------------------------+
|     |      |   | No extra blood     | A      | None                    |
|     |      |   | needed. Use        | lbumin |                         |
|     |      |   | 10mLSST tube or    |        |                         |
|     |      |   | red top tube (no   |        |                         |
|     |      |   | additive). Send to |        |                         |
|     |      |   | local clinical lab |        |                         |
|     |      |   | ambient.           |        |                         |
|     |      |   |                    |        |                         |
|     |      |   | Complete CRF \#    |        |                         |
|     |      |   | \_\_\_             |        |                         |
+-----+------+---+--------------------+--------+-------------------------+
|     |      |   | Tonsil biopsy +/or | Biopsy | Process immediately in  |
|     |      |   | excisional lymph   | exami  | operating room, 50-75%  |
|     |      |   | node biopsy        | nation | of biopsy to be cut     |
|     |      |   | (non-inguinal) -   |        | into 2mm slices in      |
|     |      |   | Send to local      |        | aluminum foil cups      |
|     |      |   | Pathology lab.     |        | covered in OCT, ship to |
|     |      |   |                    |        | \_\_\_. A single cell   |
|     |      |   | Complete CRF \#    |        | suspension( from lymph  |
|     |      |   | \_\_\_             |        | node biopsies only)of   |
|     |      |   |                    |        | 5-40x10^6^ cells will   |
|     |      |   |                    |        | be teased from the      |
|     |      |   |                    |        | biopsy; send            |
+-----+------+---+--------------------+--------+-------------------------+

[]{#__RefHeading___Toc130958169 .anchor}Appendix C2: Example of Template
for Specimen Collection, Processing, and Shipment

OVERVIEW

> All specimens will be collected per Section 6.0, Schedule of
> Evaluations. Collection requirements are below. Processing details are
> located in the relevant appendix listed below. All specimens generated
> from this protocol must be labeled, stored and shipped according to
> the specific laboratory and Data Management System guidelines for the
> protocol unless otherwise specified.

TABLE

+------------+-------------+------+-----------+-------------+-------+
| **Assay/P  | **Tube Type | **   | **P       | **Aliquot   | **Shi |
| rocedure** | or Specimen | Deri | rocessing | s/Storage** | pping |
|            | Type and    | vati | Instr     |             | Ad    |
| *          | Quantity**  | ve** | uctions** | ***(Specify | dress |
| **(Specify |             |      |           | the number  | and   |
| the assay  | ***(Specify | ***( | **        | and volume  | F     |
| name, use  | tube type,  | e.g. | *(Specify | of aliquots | reque |
| the same   | size,       | pla  | where     | and any     | ncy** |
| name as in | additive    | sma, | specific  | i           |       |
| Section    | required    | PB   | ins       | nstructions | **    |
| 6.0)***    | for blood   | MCs, | tructions | for         | *(Use |
|            | draw (or    | se   | are       | freez       | shi   |
|            | indicate    | rum, | (e.g.,    | ing/storage | pping |
|            | specimen    | etc. | PSIS) or  | on site)*** | links |
|            | type and    | )*** | if sent   |             | where |
|            | amount,     |      | to a      |             | appro |
|            | e.g. lymph  |      | local lab |             | priat |
|            | node tissue |      | for       |             | e)*** |
|            | or CSF)***  |      | proce     |             |       |
|            |             |      | ssing)*** |             |       |
+============+=============+======+===========+=============+=======+
| **         |             |      |           |             |       |
| VIROLOGY** |             |      |           |             |       |
+------------+-------------+------+-----------+-------------+-------+
|            |             |      |           |             |       |
+------------+-------------+------+-----------+-------------+-------+
|            |             |      |           |             |       |
+------------+-------------+------+-----------+-------------+-------+
|            |             |      |           |             |       |
+------------+-------------+------+-----------+-------------+-------+
| **IM       |             |      |           |             |       |
| MUNOLOGY** |             |      |           |             |       |
+------------+-------------+------+-----------+-------------+-------+
|            |             |      |           |             |       |
+------------+-------------+------+-----------+-------------+-------+
|            |             |      |           |             |       |
+------------+-------------+------+-----------+-------------+-------+
|            |             |      |           |             |       |
+------------+-------------+------+-----------+-------------+-------+
| **M        |             |      |           |             |       |
| ETABOLIC** |             |      |           |             |       |
+------------+-------------+------+-----------+-------------+-------+
|            |             |      |           |             |       |
+------------+-------------+------+-----------+-------------+-------+
|            |             |      |           |             |       |
+------------+-------------+------+-----------+-------------+-------+
|            |             |      |           |             |       |
+------------+-------------+------+-----------+-------------+-------+
| **PHAR     |             |      |           |             |       |
| MACOLOGY** |             |      |           |             |       |
+------------+-------------+------+-----------+-------------+-------+
|            |             |      |           |             |       |
+------------+-------------+------+-----------+-------------+-------+
|            |             |      |           |             |       |
+------------+-------------+------+-----------+-------------+-------+
|            |             |      |           |             |       |
+------------+-------------+------+-----------+-------------+-------+

[]{#__RefHeading___Toc130958170 .anchor}Appendix D: Optional
Supplements/Appendices

*(NOTE: Since the protocol and the clinical trial/study report are
closely related, further relevant information can be found in the ICH
Guideline for Structure and Content of Clinical Study Reports. These
materials may be included as part of the protocol.)*

*Appendices may include:*

-   *Schedule of Events*

-   *Substudies*

-   *Biosafety Precautions*

-   *Repository Instructions*

-   *Toxicity Grading Scales*

-   *Laboratory Handling*

-   *Investigator Brochure*

*Optional accompanying documents may include:*

-   *Conflict of Interest Statement*

-   *Financial Disclosure*

-   *Sample Consent Form(s)*

-   *Site and Safety Monitoring Plans*

-   *Monitoring Plan*

-   *CRF copies*

-   *Manual of Procedures*

-   *Package Inserts*

    *Note: Other materials that may need to be submitted to the IRB
    include:*

    *Advertisements*

    *Study Questionnaires*

    *CRF copies*

    *Patient Education Materials*

#  {#section-6 .unnumbered}