PROTOCOL REGISTRATION MANUAL Office for … · 1 . PROTOCOL REGISTRATION MANUAL. Office for Policy in Clinical Research Operations Division of AIDS. DRAFT Version 3.2 . January 2018

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PROTOCOL REGISTRATION MANUAL

Office for Policy in Clinical Research Operations Division of AIDS

DRAFT Version 3.2 January 2018

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Contents I. Introduction ........................................................................................................... 4 II. Summary of Changes ........................................................................................... 4 III. Protocol Registration Required Documents by Submission Type (Concise) ......... 5

A. Submission Requirements by Submission Type ................................................... 5 IV. Document Requirements (Concise) .................................................................... 10

A. Form FDA 1572/DAIDS IoR Form ....................................................................... 10 B. Curriculum Vitae .................................................................................................. 12 C. Medical License .................................................................................................. 12 D. IRB/EC/RE/Approving Entities ............................................................................ 12 E. IBC ...................................................................................................................... 14 F. Protocol Signature Page (PSP) ........................................................................... 14 G. Site Specific Informed Consents ......................................................................... 16

V. Protocol Registration Required Documents (Detailed) ........................................ 16 A. Form FDA 1572/DAIDS IOR Form ...................................................................... 16 B. How to complete the Form FDA 1572/DAIDS IoR Form ..................................... 17

1. Section 1 - Name and Address of Investigator of Record (IoR) ........................... 18 2. Section 2 - Education, Training, and Experience (above).................................... 18 3. Section 3 - Name and Address of Location(s) Where the Study Will be

conducted (above) .............................................................................................. 19 4. Section 4 - Name and Address of Clinical Laboratory (above) ............................ 20 5. Section 5 - Institutional Review Board (IRB)/Ethics Committee (EC) and All Other

Regulatory Entity(ies) (RE)/Approving Entity(ies) and Institutional Biosafety Committees (IBCs) .............................................................................................. 20

6. Section 6 - Names of Sub-Investigators (above) ................................................. 26 7. Section 7 - Protocol Name and Protocol Number (above) ................................... 28 8. Section 8 - Clinical Protocol Information: ............................................................. 28 9. Sections 9, 10 and 11 (above) ............................................................................ 28

C. Curriculum Vitae (CV) and Medical License (above) ............................................ 29 D. Documentation Of Institutional Review Board/ Ethics Committee (IRB/EC) & Other Regulatory Entity (RE)/Approving Entity Approvals (above) ............................... 30

1. IRB/EC Approvals (above) .................................................................................. 30 2. Other RE/Approving Entity Approvals (above) .................................................... 29 3. Documentation of Pediatric Risk/Benefit Category (above) ................................ 30

E. Institutional Biosafety Committee (IBC) Approval (above) .................................. 30 F. Protocol Signature Page (PSP) ........................................................................... 31 G. Suspension or Termination of IRB/EC Approval ................................................. 33

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H. Site-Specific Informed Consent Forms (ICFs) (above) ........................................ 35 I. Types of ICFs and Protocol Registration requirements ........................................ 37

1. Health Insurance Portability and Accountability Act (HIPAA) – Privacy Rule ...... 38 2. ClinicalTrials.gov Informed Consent Requirements ............................................. 38

J. TRANSLATION REQUIREMENTS ...................................................................... 39 i. Form FDA 1572, IoR Form, CVs, and Medical Licenses ...................................... 40 ii. IRB/EC, other RE/Approving Entity, and IBC approval letters .............................. 40 iii. Site-specific ICFs ................................................................................................. 40

VI. Protocol Registration Submissions ....................................................................... 41 A. Initial Registration ................................................................................................ 41 B. Amendment Registrations (above) ....................................................................... 43 1. Full Version Protocol Amendment Registration .................................................... 43 C. Sub-Study Registration ........................................................................................ 48 D. Other Submissions............................................................................................... 48 2. Requested Materials ........................................................................................... 49 3. Disapprovals ....................................................................................................... 49 4. Registrations with Required Corrections .............................................................. 50 5. Administrative Registration ................................................................................... 51 6. Change of Investigator of Record (IoR) ............................................................... 52 7. Continuing/Annual Review .................................................................................. 53 8. Site Initiated Revisions to Site Informed Consent Forms (ICFs) .......................... 55 9. Updated Form FDA 1572 or DAIDS IoR Form ..................................................... 56 10. Deregistration ...................................................................................................... 56

VII. Definitions ........................................................................................................... 59 A. Contact Information for Questions and General Correspondence: ...................... 64 B. Appendix A - Instructions On How To Access & Submit Protocol Registration Materials Through The DAIDS Protocol Registration System (DPRS) ......................... 65 C. DPRS Access ...................................................................................................... 65 D. How do I access the New Submission screen? ................................................... 65 E. How do I complete the Site Submission process? ............................................... 65 F. How do I view the sub-study packet? .................................................................. 68 G. Still Have Questions? .......................................................................................... 69

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I. Introduction 1

The Division of AIDS (DAIDS) Office for Policy in Clinical Research Operations 2 (OPCRO) has established a protocol registration process to ensure that all clinical 3 research sites (CRSs) conducting NIAID (DAIDS)-supported and/or -sponsored clinical 4 research do so in accordance with DAIDS Clinical Research Policies and Standard 5 Procedures in addition to all applicable regulations for human subjects protection and 6 the use of investigational drugs, biologics and/or devices. 7

8 The DAIDS protocol registration process verifies that CRSs have received the 9 necessary Institutional Review Board (IRB)/Ethics Committee (EC) and other applicable 10 Regulatory Entity (RE)/Approving Entity approvals and have provided to DAIDS all 11 documentation pertaining to investigator qualifications and responsibilities that are 12 required by the U.S. federal regulations and the National Institutes of Health (NIH). 13 The DAIDS protocol registration process also verifies that site-specific informed consent 14 forms contain the necessary information to comply with U.S. federal regulations. This 15 includes the basic and additional informed consent form elements as required by U.S. 16 federal regulations at 45 CFR 46.116 and 21 CFR 50.25. 17

18 Sites cannot begin the protocol registration process until the protocol has completed 19 the DAIDS protocol development requirements. All protocols must receive final DAIDS 20 approval either after DAIDS Clinical Sciences Review Committee (CSRC) or 21 Prevention Sciences Review Committee (PSRC) or after regulatory review and DAIDS 22 Medical Officer sign-off. In addition, for those protocols conducted under a DAIDS held 23 Investigational New Drug (IND) Application, the final DAIDS approved version of the 24 protocol must be submitted to the U.S. Food and Drug Administration (FDA). Each 25 CRS will complete the protocol registration process for all clinical research supported 26 and/or sponsored by NIAID (DAIDS) that is reviewed by CSRC or PSRC. 27

28 The DAIDS Protocol Registration Manual is a reference tool to help CRSs successfully 29 complete the DAIDS protocol registration process. This manual explains the different 30 types of protocol registration submissions as well as a list of the required documents 31 for each type of submission. 32

II. Summary of Changes 33 34 This manual has been reviewed for accuracy and updated to meet 508 compliance 35 guidelines. Several sections have been updated to be consistent with current NIAID 36 (DAIDS) requirements. Key changes to note in this version of the Manual include: 37

1. DAIDS requirement of Protocol Signature Page (PSP) to document the 38 commitment of the Investigator of Record (IoR) to conduct the trial in compliance 39 with regulations/Laws 40

2. The requirement to submit translation certificate (or translation documentation) for 41 local language documents 42

3. Clarification regarding staff that must be listed on the Form FDA 1572 an/or DAIDS 43 IoR Forms in compliance with U.S. regulations and ICH E6 standards 44

4. Information regarding protocol specific Delegation of Duties logs. 45

https://www.niaid.nih.gov/research/daids-clinical-research-policies-standard-procedures

http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=50

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5. Formatting changes and hyperlinks added to improve navigation of the manual. 46 47 This Manual supersedes the version 3.0 dated April 2015. 48

III. Protocol Registration Required Documents by Submission Type (Concise) 49

DAIDS reviews and approves the last version of each protocol and Sample Informed 50 Consent (SIC) before distribution to the CRSs. CRSs are required to submit the initial 51 version and all subsequent versions of a NIAID (DAIDS) -supported and/or -sponsored 52 protocol, including the DAIDS-approved SIC and site-specific ICFs, to their local IRB/EC 53 and other applicable RE/Approving Entity (ies) for review and approval. 54

Prior to implementing the protocol and enrolling participants, a CRS must receive 55 approval from their IRB/EC and other applicable RE/Approving Entity (ies). In addition, 56 the CRS must successfully complete the DAIDS protocol registration process. 57 However, a Registration Notification from the DAIDS PRO DOES NOT authorize a 58 CRS to begin enrollment of participants. CRSs will be notified by the appropriate 59 DAIDS scientific program (i.e., Program/Contracting Officer Representative), 60 Operations Center or Data Management Center when enrollment may begin. 61

62 Detailed information on specific requirements for each required document for protocol 63 registration is included in sub-sections A-G of Section VI of the manual. 64

65 NOTE: Failure to include any required documents for protocol registration at the time 66 of submission to the DAIDS PRO will result in processing delays until all the 67 required documents are received. 68

69 A. Submission Requirements by Submission Type 70

Submission Type Submission Requirements

Document Requirement

Page Numbers

Initial Registration

Form FDA 1572 for IND studies and

DAIDS IoR Form for Non-IND studies

Form FDA 1572/DAIDS IoR

Form 10

IoR CV Curriculum Vitae 12 IoR Medical License (License equivalent) Medical License 12

IRB/EC Approval Letters and applicable

correspondence

IRB/EC/RE/Approving Entities 12

Documentation of Pediatric risk/benefit category per 45 CFR 46 & 21 CFR 50 – if

applicable


Regulatory Entity Approval Letters and


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applicable correspondence

IBC Approval Letter and applicable

correspondence (when applicable)

IBC 14

Protocol Signature Page

Protocol Signature Page (PSP) 14

Site Specific Informed Consent(s)

- all applicable languages. All ICFs

required by the protocol are required

to be submitted or justification for the

omission is required.

Site Specific Informed Consents 16

Site Specific Informed Assent(s) -

all applicable languages


Translation Confirmation

Documentation

Amendment


correspondence



applicable





Submission Letter to IRB/Regulatory

Entity/Documentation of date of submission

to the IRB/EC/RE






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- all applicable languages. All

previously approved ICFs must be submitted or

justification provided for their omission must be provided.

Any new ICFs added within the protocol

ICFs must be submitted as an

Additional ICF type or justification

provided for their omission must be

provided. Site Specific

Informed Assent(s) - all applicable languages. All

previously approved Assents must be

submitted or justification provided

for their omission must be provided. Any new Assents required must be

submitted as Additional ICF types

or justification provided for their omission must be

provided.



Documentation

Translation Requirements 39

Letter of Amendment (LoA)


correspondence



applicable


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Submission Letter to IRB/Regulatory

Entity




Administrative Registration


Form FDA 1572 or IoR Form for Non-

IND studies


Form 10



correspondence





IBC Approval Letter and applicable

correspondence (when applicable)

IBC 14



Change of Investigator



IND studies


Form 10




Continuing Review IRB/EC Approval

Letters and applicable

correspondence


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Site Initiated Revised Informed Consent Forms


correspondence






- all applicable languages


Site Specific Informed Assent(s) -

all applicable languages



Documentation

Translation Requirements 39

Updated Form FDA 1572 or DAIDS IoR Form



IND studies


Form 10

Deregistration

Memo stating that the CRS no longer

intends to participate in the protocol(s)

and/or A Copy of the IRB/EC

closure/termination letter for the protocol

if the protocol has been closed with the IRB/EC at the time of

deregistration

Deregistration 56

Suspension or Termination of IRB/EC

Approval

Documentation from the IRB/EC that

identifies the reason for suspension or

termination

Suspension or Termination of

IRB/EC Approval 33

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IV. Document Requirements (Concise) 72 A. Form FDA 1572/DAIDS IoR Form 73

Section General Requirement Detailed Requirement

Section 1 - Name and Address of Investigator of

Record (IoR)

Complete legal name (first and last name) and address of the IoR at the CRS that is responsible for

the conduct of the clinical trial. The complete legal name of the

IoR and the IoR’s complete office address (complete physical

location/street address/country)

Section 1 - Name and Address of

Investigator of Record (IoR)

Section 2 - Education, Training, and Experience

Requires the IoR to check the appropriate box on how they plan to verify their education, training

and experience that qualifies them as an expert in the clinical

investigation of the study product (drug or biologic) being tested

Section 2 - Education,

Training, and Experience

Section 3 - Name and Address of Location(s)

Where the Study Will be conducted

Complete name and address of all locations where the clinical trial

will be conducted and where clinical data will be generated or

collected. The complete name and physical address of all the locations (medical school,

hospital, clinics, satellite sites, or research facility)

Section 3 - Name and Address of Location(s) Where the

Study Will be conducted

Section 4 - Name and Address of Clinical

Laboratory

Complete name(s) and complete physical address (including

country) of ALL clinical laboratories or testing facilities

which will be used for the clinical trial to process study related

and/or study defined samples that will directly contribute to or

support the clinical trial

Section 4 - Name and Address of

Clinical Laboratory

Section 5 - Institutional Review Board (IRB)/Ethics

Committee (EC) and All Other Regulatory Entity(ies) (RE)/Approving Entity(ies) and Institutional Biosafety

Committees (IBCs)

Complete name and address of all IRBs, ECs and other applicable REs, Approving Entity(ies) and

IBCs which are responsible for the review and approval for the

conduct of clinical trials at a CRS

Section 5 - Institutional

Review Board (IRB)/Ethics Committee

(EC) and All Other

Regulatory

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Entity(ies) (RE)/Approving Entity(ies) and

Institutional Biosafety

Committees (IBCs)

Section 6 - Names of Sub-Investigators

Complete legal name (first and last name) of study staff at a CRS

responsible for making a “direct and significant contribution to

data”

Section 6 - Names of Sub-Investigators

Section 7 - Protocol Name and Protocol Number

DAIDS ES/Network protocol ID number and the complete protocol

title

Section 7 - Protocol Name and Protocol

Number

Section 8 - Clinical Protocol Information Leave blank

Section 8 - Clinical Protocol

Information:

Sections 9 – Commitments Read and understand Sections 9, 10 and 11

Section 10 – Date Date Sections 9, 10 and 11

Section 11 - Signature of Investigator

Handwritten signature or electronic signature

Sections 9, 10 and 11

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B. Curriculum Vitae 76 General Requirement Detailed

Requirement

Curriculum Vitae

Submitted (or on file and less than two years old)

Curriculum Vitae (CV)

Name on the CV matches IoR identified on current Form FDA

1572 or DAIDS IoR Form Complete (all pages submitted and the document is legible)

Signed (hand written or electronic signature is acceptable)

Dated (hand written or typed date is acceptable).

77 C. Medical License 78

Review Requirement Detailed Requirements

Medical License

Name on the ML or equivalent document matches IoR identified on current Form FDA 1572 or IoR Form Curriculum Vitae

(CV) And Medical License

The ML or equivalent document is current (not expired). Note that if the ML does not designate an expiration date, it can be accepted.

79 D. IRB/EC/RE/Approving Entities 80

IRB/EC/RE


Complete protocol title or short title for any DAIDS approved version of the protocol is listed (i.e. current or previous version, short title, IC title)

IRB/EC Approvals

DAIDS-ES and/or Network Protocol ID DAIDS Protocol Version Number from the final version of the protocol approved by DAIDS and/or the final version date of the protocol document approved by DAIDS

Other RE/Approving Entity Approvals Final approval letter

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Pediatric Risk Assessment included in the IRB approval Letter.

Documentation Of Pediatric Risk/Benefit Category

For LOAs and Amendments - The date that the amended protocol documents were submitted to the local IRB is provided in the IRB approval letter or memo/CRS note, that predates the approval is provided

Amendment Registrations

Letter of Amendment (Loa) Registration

Approval letters from all applicable IRB/EC/REs as listed on the Form FDA 1572 or DAIDS IoR Form are included or justification for their omission provided.

Amendment Registrations

Letter of Amendment (Loa) Registration

81 82

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83 E. IBC 84


IBC

Complete protocol title or short title for the current DAIDS approved version of the

protocol is listed Institutional Biosafety

Committee (IBC) Approval

DAIDS-ES and/or Network Protocol ID is provided

DAIDS Protocol Version Number from the final version of the protocol as approved by DAIDS and/or the final version date of the protocol document

as approved by DAIDS Approval letter is the final

approval letter 85

F. Protocol Signature Page (PSP) 86 Review Requirement Detailed

Requirements

Protocol Signature Page (PSP)

Submitted for Initial, Amendment or LOA

Protocol Signature Page (PSP)

Contains the following statement verbatim: “I will

conduct the study in accordance with the provisions

of this protocol and all applicable protocol-related

documents. I agree to conduct this study in compliance with

United States (US) Health and Human Service regulations (45 CFR 46); applicable U.S. Food

and Drug Administration regulations; standards of the International Conference on Harmonization Guideline for Good Clinical Practice (E6);

Institutional Review Board/Ethics Committee

determinations; all applicable in-country, state, and local laws and regulations; and

other applicable requirements

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(e.g., US National Institutes of Health, Division of AIDS) and

institutional policies.”

Signed by the IoR (s) that is currently identified as the IoR per Form FDA 1572/DAIDS

IoR Form for the specific study site.

Lists the full DAIDS Protocol Title

Lists the DAIDS Protocol Number

Lists the correct DAIDS Protocol Version (include the

protocol and LOA version when applicable).

Lists the correct DAIDS Protocol Version Date

87 88

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G. Site Specific Informed Consents 89 Review Requirement Detailed

Requirements Site Specific Informed Consent/Assent Forms

The Complete Protocol Title is listed

Site-Specific Informed Consent

Forms (ICFs)

The DAIDS Protocol Number is listed

The DAIDS Version Number is listed

All ICs required by the Protocol version are submitted or

justification for their omission is provided

All ICs are submitted in all applicable languages or

justification for their omission is provided

Amendments only: All ICs Types previously registered are submitted or justification for their omission is provided

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V. Protocol Registration Required Documents (Detailed) 91 92

A. Form FDA 1572/DAIDS IOR Form 93 94

FORM FDA 1572/DAIDS IoR FORM: REQUIRED FOR ALL INITIAL 95 REGISTRATIONS AND WHEN THERE IS ANY MAJOR CHANGE TO THE 96 INFORMATION ON THE CURRENT FORMD FDA 1572/DAIDS IoR FORM 97 98 FORM FDA 1572 must be submitted for studies being conducted under an IND 99 application. DAIDS IOR FORM or Form FDA 1572 can be SUBMITTED FOR 100 INITIAL REGISTRATION FOR STUDIES NOT BEING CONDUCTED UNDER 101 AN IND APPLICATION 102

103 A signed Form FDA 1572/DAIDS IOR Form is required for each investigator that 104 participates in any clinical trial (drug or biologic) that is conducted under an 105 Investigational New Drug (IND) Application filed with the U.S. FDA. By signing 106 the Form FDA 1572/DAIDS IOR Form, the Investigator of Record (IoR) affirms 107 that he/she will conduct the clinical trial according to the research protocol 108 and all applicable U.S. federal regulations. Investigators at non-U.S. sites must 109 affirm to DAIDS their commitment to comply with local laws and requirements 110 throughout the course of the clinical trial by signing the Form FDA 1572/DAIDS 111 IOR Form. 112

113

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All CRSs participating in a NIAID (DAIDS)-supported and/or -sponsored clinical 114 trial conducted under an IND must submit a copy of the signed and dated Form 115 FDA 1572 to the DAIDS PRO as part of the protocol registration submission for 116 review and for submission to the U.S. FDA if DAIDS is the sponsor. 117

118 NOTE: CRSs are required to retain the original signed Form FDA 1572/DAIDS 119 IOR Form in their regulatory files at the site. Original Forms should not be sent 120 to the DAIDS PRO. 121

122 CRSs requiring more space than what is provided on the Form FDA 123 1572/DAIDS IOR Form can use a supplemental page. The supplemental page 124 provides additional space to document: additional research locations and 125 addresses; laboratory facilities and addresses; and the names of additional sub-126 investigators. The supplemental page should identify the CRS and protocol 127 number. If used, a copy of the supplemental page must also be sent to the 128 DAIDS PRO as part of the protocol registration submission. 129

130 A CRS must update and submit within 30 calendar days a revised copy of the 131 Form FDA 1572 when there is ANY major change to the information on the 132 current Form FDA1572 submitted to the DAIDS PRO. Any correction or revision 133 requires the IoR to sign and date the newly revised form. CRSs must submit 134 BOTH pages of the revised Form FDA 1572 to the DAIDS PRO even if the 135 changes only affect one page of the form. 136

137 NOTE: Examples of major changes to the Form FDA 1572 include but are not limited 138 to: 139 o Change in IoR 140 o Change in Sub-IoR 141 o Addition of a new or additional DAIDS approved location where the research 142

will be conducted 143 o Addition of a laboratory 144 o Addition or change in an IRB/EC/RE that is responsible for review and approval 145

of the clinical research protocol 146 147

NOTE: An updated Form FDA 1572 that has the same date as the original or 148 previous version will not be accepted. 149

150 The most current version of the Form FDA 1572 is available for download on the 151 RSC Web site under the “Protocol Registration” section or from the U.S. FDA 152 website (www.fda.gov). 153

154 B. How to complete the Form FDA 1572/DAIDS IoR Form 155

The Form FDA 1572 is comprised of 11 sections, 10 of which require data entry. 156 Below is detailed information to assist the CRS in completing the Form FDA 157 1572. 158

http://rsc.tech-res.com/

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1. Section 1 - Name and Address of Investigator of Record (IoR) 159 This section must contain the complete legal name (first and last name) and 160 address of the IoR at the CRS that is responsible for the conduct of the clinical 161 trial. The complete legal name of the IoR and the IoR’s complete office address 162 (complete physical location/street address) should be included in Section 1. Non- 163 U.S. CRSs should include the complete physical address, including the country. 164

165 If a CRS has more than one IoR sharing responsibilities for a clinical trial being 166 conducted under an IND, the CRS has the following options: 167

o The CRS can submit a separate Form FDA 1572 for each IoR that is 168 responsible for the study at that CRS(s) and other DAIDS approved 169 location(s). The CRS must provide documentation explaining that the 170 investigators listed on the two Form FDA 1572s are sharing 171 responsibilities for the conduct of the study at the CRS and DAIDS 172 approved satellite location(s). 173

o The CRS can submit one Form FDA 1572 that lists both investigators in 174 section 1 of the Form FDA 1572. This indicates that both investigators 175 are sharing equal responsibilities for the conduct of the study at the 176 CRS(s) and other DAIDS approved location(s). Each investigator must 177 sign and date sections 10 and 11 of the Form FDA 1572. The CRS must 178 provide documentation stating that the two investigators listed on the 179 Form FDA 1572 are sharing responsibilities for the conduct of the 180 study at the CRS(s) and other DAIDS approved location(s). 181

182 NOTE: Requirements of the documentation can be fulfilled in one of the 183 following ways: 184

o Provide a written document that specifies how responsibilities will be 185 shared and the role of each IoR at their respective location(s) 186

o Provide s tudy spec i f i c a copy of the site’s delegation of 187 responsibility log that indicates how responsibilities will be shared and 188 the roles of each IoR at their respective location(s). 189

o Provide a statement in item 1 of the Form FDA 1572 that specifies that 190 the two IoRs are Co-Investigators and how responsibilities will be 191 shared and the role of each IoR at their respective location(s). 192

193 2. Section 2 - Education, Training, and Experience (above) 194

This section requires the IoR to check the appropriate box on how they plan to 195 verify their education, training and experience that qualifies them as an expert in 196 the clinical investigation of the study product (drug or biologic) being tested. The 197 box marked “Curriculum Vitae” should be checked and a copy of the IoR’s CV 198 must be included in the registration packet that is submitted to the DAIDS PRO. 199 DAIDS does not require the submission of CVs for sub-investigators. However, 200 sites should keep a copy of all sub-investigator CVs in the regulatory files at the 201 site. DAIDS requires that all CVs be submitted in English and must be signed 202

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and dated. 203 204

3. Section 3 - Name and Address of Location(s) Where the Study Will be 205 conducted (above) 206

This section must list the complete name and address of all locations where the 207 clinical trial will be conducted and where clinical data will be generated or 208 collected. The complete name and physical address of all the locations (medical 209 school, hospital, clinics, satellite sites, or research facility) should be listed in 210 Section 3. This includes facilities where participants will be seen and study 211 procedures performed. Non-U.S. CRSs should include the country in addition to 212 the complete physical address. 213

214 If a CRS utilizes a DAIDS-approved pharmacy, it is not necessary to list the 215 pharmacy on the Form FDA 1572. If a CRS out-sources the pharmacy 216 responsibilities for the clinical trial the CRS must list the name and complete 217 physical address of the contracted pharmacy in Section 3. 218

219 If an IoR is conducting the same research protocol at more than one CRS 220 overseen by the same IRB/EC, then it is acceptable to submit one Form FDA 221 1572 which lists all locations where the clinical trial will be conducted. If more 222 than one CRS is included in Item 3, include the DAIDS site ID (if available) for each 223 CRS. 224

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4. Section 4 - Name and Address of Clinical Laboratory (above) 225

This section must list the complete name(s) and complete physical address of 226 ALL clinical laboratories or testing facilities which will be used for the clinical trial 227 to process study related and/or study defined samples that will directly contribute 228 to or support the clinical trial (i.e., diagnostic labs performing blood work, imaging 229 centers, cardiology labs, non-local labs). This may include analytical labs that 230 provide pharmacokinetic analysis, and laboratories supplying efficacy data. The 231 official name of the laboratory (i.e., Department of Pathology) should be 232 included. If multiple CRSs and/or locations are listed on the Form FDA 1572, 233 the corresponding clinical laboratories must be listed for each CRS and/or location. 234

235 Exceptions for not including ALL clinical laboratories or testing facilities include: 236

o If a primary laboratory is sending samples to a satellite or other 237 contract labs for additional testing, or 238

o If a laboratory is being used only to store study samples. 239 240

The additional labs do not need to be listed as long as the primary laboratory can 241 trace, through written records, the samples to the additional labs where the tests 242 were performed. 243

244 5. Section 5 - Institutional Review Board (IRB)/Ethics Committee (EC) and All 245 Other Regulatory Entity(ies) (RE)/Approving Entity(ies) and Institutional 246 Biosafety Committees (IBCs) 247

This section must list the complete name and address of all IRBs, ECs and other 248 applicable REs, Approving Entity(ies) and IBCs which are responsible for the 249 review and approval of clinical trials at a CRS prior to the CRS’s initiation of the 250 protocol. The official name (refer to the title provided on the IRB/EC and other 251 applicable RE/Approving Entity approval letter(s)) and complete physical 252 address of the IRBs/ECs and other applicable REs/Approving Entity(ies) which 253 reviewed the protocol should be included in Section 5. IRBs/ECs reviewing and 254 approving the clinical trial do not have to be at the same location as the research 255 being conducted. In addition to U.S. FDA requirements, DAIDS requires that all 256 sites participating in NIAID (DAIDS)-supported and/or -sponsored clinical trials 257 also list all regulatory entities that must review and approve the clinical trial 258 prior to implementation at a CRS in section5. 259

260 NOTE: The DAIDS PRO must receive an approval letter for each entity listed 261 in section 5 of the Form FDA 1572. If the other RE/Approving Entity is not 262 responsible for the review and approval of full version protocol amendments, 263 LoAs or changes to the CRS’s site-specific ICF(s), RE/Approving Entity should not 264 be removed/omitted from FORM FDA 1572. However, the CRS Leader or IoR 265 should document in a memo to the DAIDS PRO or in the comments section of 266 the IRB/EC/RE field in the DPRS when submitting registration materials if the other 267 RE/Approving Entity is not responsible for approvals. 268

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6. Section 6 - Names of Sub-Investigators (above) 269

This section must list the complete legal name (first and last name) of all study 270 staff at a CRS, and DAIDS approved additional study location(s) that are 271 responsible for making a “direct and significant contribution to the data”. A direct 272 and significant contribution includes any persons directly responsible for the 273 treatment or evaluation of research participants. This includes site personnel who 274 have more than minimal involvement with the conduct of the research 275 (performing study evaluations or procedures, conducting Informed Consent or 276 providing intervention) or more than minimal study conduct-related contact with 277 study participants or confidential study data, records, or specimens. A study 278 specific Delegation of Duties log must be maintained at the site and should 279 minimally include all persons identified as providing a direct and significant 280 contribution to the data. 281

282 Hospital staff, including nurses, residents, fellows, and office staff who provide 283 ancillary or intermittent care but who do not make a direct and significant 284 contribution to the data do not need to be listed. It is not necessary to include in 285 Section 6 a person with only an occasional role in the conduct of the research 286 (i.e., an on-call physician who temporarily dealt with a possible adverse event or 287 a temporary substitute for any research staff). If a number of residents on rotation 288 will participate in the clinical trial, a general statement regarding their planned 289 participation may be included in Section 6. 290

291 The decision about whether to list a pharmacist or research coordinator on the 292 Form FDA 1572 is the responsibility of the IoR at the CRS and should be based 293 on the contribution that the individual makes to the study. For example, a research 294 pharmacist may prepare test articles and maintain drug accountability for many 295 clinical trials that are ongoing concurrently at an institution. Because the 296 pharmacist is not making a direct and significant contribution to the data for a 297 particular study, it would not be necessary to list the pharmacist as a sub- 298 investigator in Section 6, but he/she should be listed in the investigator’s study 299 records. 300

301 CRSs are required to list, at a minimum, one sub-investigator who will be 302 responsible for fulfilling the requirements of the IoR should the IoR not be able to 303 meet his/her requirement for any given reason. The complete legal name(s) of 304 the sub-investigators who will assist the IoR in the conduct of the protocol 305 should be listed in Section 6. 306

307 The IoR is responsible for determining the sub-investigators to be included on the 308 Form FDA 1572. Individuals who will sign study medication prescriptions and 309 physicians who submit SAE/EAEs to DAIDS must be listed on the Form FDA 310 1572. The IoR must designate a physician as a sub-investigator who will be 311 responsible for backing up the IoR. 312

313 NOTE: Any physician who is responsible for the review and submission of 314 SAE/EAEs to DAIDS must be listed in Section 6 of the Form FDA 1572. Safety 315 reports cannot be submitted by a physician who is not listed in section 6 of the 316

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Form FDA 1572. 317 318

NOTE: CRSs must list the CRS Leader as a Sub-investigator in Section 6 on all 319 Form FDA 1572s if the IoR for the protocol, listed in Section 1, is not the CRS 320 Leader. If the CRS Leader is the same person listed in Section 1 on the Form 321 FDA 1572 (Protocol IoR) then the CRS Leader does NOT need to be listed again 322 as a sub-investigator. 323

324

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325 NOTE: Personnel at facilities where the study uses certain tests (e.g. cardiologist 326 reading ECG or personnel at ECG facilities) do not have to be listed if they are not 327 considered to be engaged in research activities. Per B1 of OHRP’s guidance 328 document on engagement; not all personnel are considered engaged in research 329 activities unless they have other activities, such as administering study 330 interventions being tested or evaluated or being a collaborator on the publication. 331

332 7. Section 7 - Protocol Name and Protocol Number (above) 333

The DAIDS ES/Network protocol ID number and the complete protocol title should 334 be included in Section 7. 335

336 NOTE: Short titles cannot be accepted and will result in the CRS having to 337 submit a revised Form FDA 1572 which will delay protocol registration. CRSs 338 should not include the DAIDS protocol version number, and/or protocol date in 339 Section 7. 340

341 8. Section 8 - Clinical Protocol Information: 342 NOTE: The DAIDS IoR Form does not include a Clinical Protocol Information 343 Section 344 345 As the IND sponsor, DAIDS submits the protocol and all relevant information to 346 the FDA on behalf of investigator. This section should be left blank for both 347 boxes. If DAIDS is not the IND sponsor for a trial, the IND sponsor is responsible 348 for submitting the protocol and all relevant information including the Form FDA 349 1572 to the FDA and can determine the appropriate information for this section. 350

351 9. Sections 9, 10 and 11 (above) 352 Note: These sections are numbered 8, 9, and 10 on the DAIDS IoR Form 353 354 The IoR must read Section 9, date Section 10 and sign Section 11. The complete 355 legal handwritten or electronic signature of the IoR should be included in Section 356 11 and should correspond with the name in Section 1 of the Form FDA 357 1572.NOTE: If more than one IoR is listed in section 1 of the Form FDA 1572, 358 both IoR’s must sign and date this section. 359 360 Note: Electronic Signature are permissible using the Adobe Acrobat Self-Sign 361 plug-in to insert your signature on fillable FDA forms. Security certificates 362 associated with your digital signatures should be maintained at the site in 363 compliance with 21 CFR 11.1(a) 364

365 NOTE: If a CRS updates their Form FDA 1572, the IoR(s) is responsible 366 for signing and dating the new document even if the change(s) only affect page 367 1. 368

369 NOTE: An updated Form FDA 1572 that is dated the same as the original or 370 previous version will not be accepted. 371 372

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373 C. Curriculum Vitae (CV) and Medical License (above) 374 375 REQUIRED FOR ALL INITIAL REGISTRATIONS AND WHEN THERE IS ANY 376 MAJOR CHANGE TO THE CURRENT CV ON FILE WITH THE DAIDS PRO 377 OR EVERY TWO YEARS. 378

379 The Investigator of Record (IoR) overseeing DAIDS-supported and/or sponsored 380 clinical research must provide evidence of qualifications (experience, training and 381 education) to assume responsibility for the conduct of clinical trials. CRSs must 382 submit to the DAIDS PRO, a CV for the IoR for all initial protocol registrations. 383 All CVs must provide sufficient documentation for DAIDS to verify the IoR(s) 384 qualifications to conduct a clinical trial. 385

386 All investigators must sign and date their CV prior to submission to the DAIDS 387 PRO. All IoRs are required to submit an updated, newly signed and dated CV 388 when there is ANY major change to the current CV on file with the DAIDS PRO 389 or at a minimum of every 2 years. 390

391 In addition, if the IoR is a physician, a copy of the IoR’s current medical license 392 documentation or equivalent (i.e., documentation of good standing in the country 393 where they are practicing) must be submitted with all CVs. 394

395 NOTE: Examples of major changes to the IoR CV include but are not limited to: 396 o Change in contact information 397 o Change in education, Change in experience, New trainings 398 o New publications 399

400 U.S. federal regulations require that the IoR’s CV be submitted to the U.S. FDA 401 for all studies being conducted under an IND. DAIDS, as the IND sponsor, 402 submits the IoR CV to the U.S. FDA. Sub-investigators are not required to submit 403 CVs to the DAIDS PRO. However, sites should keep a copy of all sub- 404 investigator CVs in the regulatory files at the site. 405

DAIDS accepts a NIH Bio-Sketch formatted CV that includes education/training, 406 current employment, past relevant employment, licensures/memberships, and any 407 relevant publications. 408

409 The NIH Bio-Sketch formatted CV template is available here.410

http://grants.nih.gov/grants/funding/424/index.htm

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D. Documentation Of Institutional Review Board/ Ethics Committee 411 (IRB/EC) & Other Regulatory Entity (RE)/Approving Entity Approvals 412 (above) 413

414 REQUIRED FOR ALL INITIAL, AMENDMENT and LoA REGISTRATIONS, 415 CONTINUING/ ANNUAL REVIEW SUBMISSIONS, SITE INITIATED 416 REVISIONS TO SITE- SPECIFIC ICFs, ADMINSTRATIVE REGISTRATIONS, 417 AND SUBMISSION OF REVISED SITE ICF(s) IN RESPONSE TO A 418 DISAPPROVAL NOTIFICATION 419

420 1. IRB/EC Approvals (above) 421 CRSs are required to submit the current version and all subsequent versions 422 of NIAID (DAIDS)-supported and/or sponsored clinical trials and observational 423 studies, including the DAIDS-approved sample informed consent (SIC) and site- 424 specific ICFs, to their IRB/EC and other applicable REs/Approving Entity(ies) for 425 review and approval. CRSs must submit a copy of ALL appropriate documentation 426 to and from the IRB/EC/RE/Approving Entity along with a copy of all the final 427 approval letter(s) to the DAIDS PRO as part of the protocol registration submission. 428 Original documents should be kept in the regulatory files at the CRS. The 429 IRB/EC/RE/Approving Entity approval letter(s) accompanying all initial, 430 amendment, and LoA registrations must be a final approval not requiring any 431 modifications to the site-specific ICF(s). 432

433 NOTE: Appropriate documentation includes but is not limited to: 434

o the submission letter from the site to the IRB/EC 435 o the letter(s) from the IRB/EC documenting queries and changes required 436

to the site-specific ICFs 437 o site response to the queries 438 o final approval letter(s) 439

440 All IRB/EC/RE/Approving Entity approval letter(s) must be able to be linked 441 to the current DAIDS-approved version of the protocol. If an 442 IRB/EC/RE/Approving Entity does not include the DAIDS required identifying 443 information in their approval letters, CRSs can submit a memo with their 444 IRB/EC/RE/Approving Entity submission that includes: identifying information 445 corresponding to the protocol, lists all the documents submitted for 446 IRB/EC/RE/Approving Entity review as well as the date of submission to the 447 IRB/EC/RE/Approving Entity. The required identifying information is: 448

o Complete Protocol Title for the current DAIDS-approved version of the 449 protocol. The DAIDS PRO will accept a long or short title for those 450 protocols which include both on the DAIDS-approved SIC. 451

o DAIDS ES and/or Network Protocol ID Number 452 o DAIDS Protocol Version Number from the final version of the protocol 453

approved by DAIDS AND/OR the final version date of the protocol 454 document approved by DAIDS. 455

The CRS's memo can be used to document that the IRB/EC/RE/Approving 456 entity received the correct version of the protocol and may be included with 457 the IRB/EC/RE/Approving entity approval letters that are submitted to the DAIDS 458 PRO. 459

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NOTE: The CRS’s memo to the IRB/EC/RE/Approving entity requesting review 460 must pre-date the date on the final IRB/EC/RE/Approving entity approval letter(s). 461

462 NOTE: Sites are strongly advised to document the date the CRS receives each 463 final IRB/EC/RE/Approving Entity approval letter to ensure compliance with the 464 DAIDS protocol registration policy regarding submission of amendment and 465 LoA registration materials to the DAIDS PRO within 14 calendar days of receipt 466 of all final IRB/EC/RE approval letters. This documentation should be kept in 467 the site’s regulatory files for verification by monitors. 468 469 NOTE: If the reviewing IRB transferred the responsibility to another IRB, a site 470 needs to provide documentation of the delegation of authority to the other IRB 471

472 NOTE: If any of the IRB/EC/RE/Approving Entity approval letter(s) or CRS's 473 memo do not contain enough information to be linked to the most current DAIDS- 474 approved version of the protocol, designated site personnel (i.e., CRS coordinator, 475 IoR) and/or additional personnel listed in the DPRS will be sent a Requested 476 Materials notice that details the missing and/or corrected information/materials 477 that must be submitted to the DAIDS PRO for registration processing to 478 continue. The review process will not continue until the requested materials are 479 received at the DAIDS PRO. For information on how to submit requested 480 materials refer to Section VII, Sub Section D. i.- “Requested Materials” of this 481 manual. 482

483 2. Other RE/Approving Entity Approvals (above) 484

When other approvals are required in addition to the local IRB/EC at a CRS prior 485 to implementation at a CRS, copies of those approval letters and any other 486 appropriate correspondence (as noted in Section i above) must be submitted 487 to the DAIDS PRO with registration materials. 488

489

NOTE: If a given RE/Approving Entity requires review/approval of initial versions 490 of protocols but does not review and approve full version amendments and LoAs, 491 the CRS Leader or IoR should document this fact in the comments section of the 492 IRB/EC/RE approval field in the DPRS or with a memo to the DAIDS PRO when 493 submitting registration materials. 494

495 NOTE: DAIDS requires that each site participating in DAIDS supported and/or 496 sponsored clinical trials, list all entities that must review and approve a clinical 497 trial prior to implementation at a CRS on their Form FDA 1572 and/or DAIDs IoR 498 Form. For information on completing the Form FDA 1572 and/or DAIDS IoR 499 Form, refer to Section IV, Sub Sections A and B – “Section 5 - Institutional 500 Review Board (IRB)/Ethics Committee (EC) and All Other Regulatory Entity(ies). 501 502 If a regulatory reviewing entity reviews the clinical trial at some point during the 503 course of the trial but not required for the initiation of the clinical trial, a site must 504 provide documentation from that entity that confirms such requirement. 505 RE)/Approving Entity (ies) and Institutional Biosafety Committees (IBCs)” of this 506

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manual. 507 508

3. Documentation of Pediatric Risk/Benefit Category (above) 509

Per the DAIDS Policy for Enrolling Children (including Adolescents) in NIAID 510 (DAIDS)-supported and/or -sponsored Human Subject Clinical Research, for 511 research studies including children or adolescents, DAIDS requires 512 documentation of the IRB/EC designation of the pediatric risk/benefit category 513 from the U. S. Federal regulations, 45 CFR 46, 404-407 & 21 CFR 50.51-54 514 and IRB /EC approval for involvement of children based on the determination 515 specified by that category. This requirement applies to the initial and 516 continuing/annual reviews of research protocols and to any subsequent reviews 517 of full version protocol amendments and LoAs involving potential study risks or 518 benefits. The documentation may be in the IRB/EC approval letter(s) or in 519 other official correspondence from the IRB/EC to the site Investigator. 520

521 NOTE: Failure to submit documentation of the IRB/EC designation of the 522 pediatric risk/benefit category or documentation that the CRS will not enroll 523 children or adolescents at the time of registration submission to the DAIDS PRO 524 will result in delays in protocol registration. 525

526 E. Institutional Biosafety Committee (IBC) Approval (above) 527 528 REQUIRED FOR ALL INITIAL REGISTRATIONS FOR RESEARCH THAT 529 INVOLVES RECOMBINANT DNA 530

Research supported by NIH funding that involves recombinant DNA is subject 531 to special regulatory oversight by an IBC. In addition, clinical trials testing 532 products containing recombinant DNA must be submitted to the NIH Office for 533 Biotechnology Activities (OBA) for review by the NIH Recombinant DNA Advisory 534 Committee (RAC). Detailed information regarding the requirements for NIAID 535 (DAIDS) -sponsored and/or -supported research involving recombinant DNA 536 is available on the RSC website under the “Protocol Registration” section. 537

538 Once IBC approval is received, a copy of the final approval letter and any other 539 appropriate correspondence (as noted in section i above) must be submitted 540 to the DAIDS PRO with the initial registration submission. Failure to submit 541 documentation of IBC approval at the time of initial registration submission to the 542 DAIDS PRO will result in delays in protocol registration. 543

544 If an IBC must review and approve all full version protocol amendments and 545 LoAs prior to the implementation at a CRS, documentation of the IBC approval 546 should be submitted to the DAIDS PRO at the time of amendment or LoA 547 registration. 548


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All IBC approval letter(s) must be able to be linked to the current DAIDS- approved 549 version of the protocol at the time of initial protocol registration. Since not all 550 IBCs include the DAIDS-required identifying information in their approval letters, 551 a CRS can submit a memo with their IBC submission which lists identifying 552 information corresponding to the protocol, all the documents submitted for review 553 as well as the date of submission to the IBC. The required identifying information 554 is: 555

o Complete Protocol Title for the current DAIDS-approved version of the 556 protocol. The DAIDS PRO will accept a long or short title for those 557 protocols which include both on the DAIDS sample informed consent 558 forms. 559



The CRS's memo can be used to document that the IBC received the correct 564 version of the protocol and may be included with the IBC approval letter that is 565 submitted to DAIDS PRO. 566

567 NOTE: The CRS’s memo to the IBC requesting review must pre-date the date on 568 the final IRB/EC approval letter(s). 569

NOTE: If the IBC approval letter or CRS's memo does not contain enough 570 information to be linked to the most current DAIDS-approved version of the 571 protocol, designated site personnel (i.e., CRS coordinator, IoR) and/or additional 572 personnel listed in the DPRS will be sent a Materials Request notice that details 573 the missing and/or corrected information/materials that must be submitted to the 574 DAIDS PRO for registration processing to continue. The review process will not 575 continue until the requested materials are received at the DAIDS PRO. For 576 information on how to submit requested materials refer to Section VII, Sub Section 577 D. of this manual. 578 579 F. Protocol Signature Page (PSP) 580 581 REQUIRED FOR ALL INITIAL, AMENDMENT, LOA AND CHANGE OF IOR 582 SUBMISSIONS 583 584 The Division of AIDS (DADS) has implemented a new regulatory requirement, a 585 Protocol Signature Page (PSP), to document the commitment of the Investigator 586 of Record (IOR) to conduct the trial in compliance with the trial as agreed to by 587 the sponsor and in compliance with United States (US) Health and Human 588 Service regulations (45 CFR 46); applicable U.S. Food and Drug Administration 589 regulations; standards of the International Conference on Harmonization (ICH) 590 Guideline for Good Clinical Practice (E6); Institutional Review Board/Ethics 591 Committee determinations; all applicable in-country, state, and local laws and 592 regulations; and other applicable requirements and institutional policies. 593 594

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Note: DAIDS does not require submission of the PSP to an IRB/IEC or 595 regulatory authority, unless required by the regulatory authority. 596

597 598

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The following language must be included in all PSPs: 599

“I will conduct the study in accordance with the provisions of this protocol 600 and all applicable protocol-related documents. I agree to conduct this study 601 in compliance with United States (US) Health and Human Service 602 regulations (45 CFR 46); applicable U.S. Food and Drug Administration 603 regulations; standards of the International Conference on Harmonization 604 Guideline for Good Clinical Practice (E6); Institutional Review Board/Ethics 605 Committee determinations; all applicable in-country, state, and local laws 606 and regulations; and other applicable requirements (e.g., US National 607 Institutes of Health, Division of AIDS) and institutional policies.” 608

A site should not alter the above template language but may add required 609 language (e.g. institutional requirement) for the IoRs commitment to conduct the 610 trial in accordance with applicable regulations. 611

All PSPs must be able to be linked to the current DAIDS- approved version of the 612 protocol at the time of protocol registration. The required identifying information 613 are: 614

o Complete Protocol Title for the current DAIDS-approved version of the 615 protocol. The DAIDS PRO will accept a long or short title for those 616 protocols which include both on the DAIDS sample informed consent 617 forms. 618

o DAIDS ES and/or Network Protocol ID Number 619 o DAIDS Protocol Version Number ( including LOA version when 620

applicable) for the version being registered 621 o DAIDS Protocol Version Date for the version being registered 622

623 All PSPs must be signed by the DAIDS approved IoR. The PSP is protocol-624 specific, and must be signed by the IOR at each participating site. This 625 responsibility may not be delegated. If there are more than one IoR, a PSP is 626 required for each IoR or a Single PSP can be submitted that is independently 627 signed and dated by each IoR. Note that if there is changes of IoR, an updated 628 PSP is required as part of the Change of IoR submission. 629

630 All original PSPs must be maintained in the site's regulatory binder. 631 632 NOTE: Failure to include any required documents for protocol registration at the 633 time of submission to the DAIDS PRO will result in processing delays until all 634 the required documents are received. 635

636 G. Suspension or Termination of IRB/EC Approval 637 638 Per U.S. federal regulations, 45 CFR 46.113 the IRB/EC has the authority to 639 suspend or terminate approval of research that is not being conducted in 640 accordance with the IRB’s/EC’s requirements or that has been associated with 641 unexpected serious harms to participants. The regulations mandate that when the 642 reviewing IRB/EC suspends or terminates its approval of research, this information 643


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be reported to, among others, the investigator and sponsor. 644

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Per the DAIDS Critical Events Manual, for any studies that are protocol registered 645 through the DAIDS PRO, the CRS must submit documentation of the suspension 646 or termination of IRB/EC approval to DAIDS as soon as possible, but in no later 647 than 3 reporting days through the DPRS. If a study is not registered through the 648 DAIDS PRO, the CRS must notify the appropriate DAIDS Program Officer (PO) 649 or Contracting Officer Representative (COR) of the IRB/EC actions to suspend or 650 terminate IRB/EC approval. 651

652 H. Site-Specific Informed Consent Forms (ICFs) (above) 653 654 REQUIRED FOR: 655 - ALL INITIAL, AMENDMENT & LoA REGISTRATIONS IF THERE WAS A 656

CHANGE TO THE SITE-SPECIFIC ICFs, 657 - CONTINUING /ANNUAL REVIEW SUBMISSIONS IF THERE WAS A 658

CHANGE TO THE SITE-SPECIFIC ICFs, SITE-INITIATED REVISIONS TO 659 SITE-SPECIFIC ICFs, & 660

- SUBMISSION OF REVISED SITE ICFs IN RESPONSE TO A 661 DISAPPROVAL NOTIFICATION 662

663 Site-specific ICF(s) must contain all information necessary to comply with U.S. 664 federal regulations, local laws and regulations, and DAIDS policies. This includes 665 all the basic and additional elements, as appropriate, as outlined in U.S. federal 666 regulations, 45 CFR 46.116 & 21 CFR 50.25. It is recommended that sites develop 667 their own site-specific ICF(s). To assist sites with developing their site-specific 668 ICF(s), DAIDS works with the Protocol Teams to create sample informed 669 consents (SIC) that contain all the specific elements required by the U.S. federal 670 regulations, 45 CFR 46.116 & 21 CFR 50.25. 671

672

A CRS must submit to the DAIDS PRO a copy of all site-specific ICF(s) that will 673 be used during the consent process at the site after review and approval by the 674 IRB/EC and other applicable REs/Approving Entity (ies), and retain the original(s) 675 on file at the site. 676

All materials that are used in the consent process (e.g. ICFs, questionnaires etc..) 677 that are given to participants should be submitted to DAIDS for sponsor files along 678 with any approvals (if any) IRB/EC/RE of these documents. 679

680 If some SIC forms provided with the protocol will not be needed at a CRS, (i.e., if 681 a pregnancy ICF is not needed because pregnant women will not be enrolled), 682 the CRS should document this either in the comments section of the ICF field of 683 the DPRS or with a memo to the DAIDS PRO with the registration submission. 684 685 If an SIC is removed as part of an Amended protocol and the site will no longer be 686 using the consent form, a memo or note must be included with the Amendment 687 registration submission declaring that the specific consent form will no longer be 688 utilized at the site. 689

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690 When an IRB/EC/RE/Approving Entity approves a site-specific ICF and the site 691 contact information is left blank, the CRS must include a memo with their 692 registration submission explaining that the CRS will insert the site-specific 693 contact information prior to consenting participants. 694 695 If an IRB/EC/RE requires language in a site-specific ICF specific to the institution 696 or based on local regulations/requirements, the site should include that information 697 in the site-specific ICF and must provide documentation from IRB/EC/RE regarding 698 the required language in the site-specific ICF. However, even though an 699 IRB/EC/RE requires language in site-specific ICF, none of the basic and additional 700 elements found in the Sample IC (SIC) or required by DAIDS policy should be 701 removed. Refer to the Frequently Asked Questions on the DAIDS RSC website for 702 additional information regarding the development of site-specific ICFs. 703 704 If a CRS deletes or makes any substantive change to basic and/or additional 705 elements as presented in the DAIDS-approved SIC, the IoR or designee for the 706 clinical trial must provide written documentation to explain the deletions/change(s) 707 at the time of registration submission to the DAIDS PRO. 708

709 All site-specific ICF(s) must be able to be linked to the current DAIDS approved 710 version of the protocol. The DAIDS-required identifying information is: 711

o Complete Protocol Title for the current DAIDS-approved version of the 712 protocol. The DAIDS PRO will accept a long or short title for those 713 protocols which include both on the DAIDS-approved SIC forms. 714



719 NOTE: For version tracking purposes at the CRS (i.e., at the request of an 720 IRB/EC and other applicable REs/approving entity (ies)), CRSs can specify the 721 site (local) version number or version date of the site-specific ICF(s) in the header 722 or footer of their site-specific ICF(s). However, the DAIDS protocol version 723 number and/or the final version date of the DAIDS-approved protocol should 724 remain on all site-specific ICFs as well. 725

726 NOTE: If any of the site-specific ICF(s) do not contain enough information to be 727 linked to the most current DAIDS-approved version of the protocol, designated 728 site personnel (i.e., CRS coordinator, IoR) and/or additional personnel listed in 729 the DPRS will be sent a Materials Request notice that details the missing and/or 730 corrected information/materials that must be submitted to the DAIDS PRO for 731 registration processing to continue. The review process will not continue until 732 the requested materials are received at the DAIDS PRO. For information on 733 how to submit requested materials refer to Section VII, Sub Section D. i. - 734 “Requested Materials” of this manual. 735

37

736 I. Types of ICFs and Protocol Registration requirements 737 Main ICF: The Main ICF issued for enrollment of participants into the protocol. 738 The Main ICF should include all of the basic and appropriate additional elements 739 as outlined in U.S. federal regulations, 45 CFR 46.116 & 21 CFR 50.25. The link 740 to OHRP’s guidance on informed consent form required elements can be found 741 here. 742

743 Screening and Stored Specimen ICFs: The following are DAIDS requirements 744 regarding generic screening and stored specimen consent forms and protocol- 745 specific screening consent forms: 746

Generic screening and stored specimen ICF: A generic screening and/or stored 747 specimen ICF is an ICF that is developed by a CRS for its own purposes and not 748 related to any DAIDS requirement and should NOT be submitted to the DAIDS 749 PRO. The DAIDS PRO will NOT review or approve any such generic screening 750 and/or stored specimen ICFs if they are submitted with registration materials. 751

752 Protocol-specific screening and stored specimen ICF: A protocol-specific 753 screening and/or stored specimen ICF is an ICF developed for a specific protocol 754 that is approved by DAIDS and is included as part of the final protocol and 755 DAIDS-approved SICs. If the DAIDS-approved Main ICF includes screening 756 procedures and stored specimen information and a CRS chooses to develop a 757 separate protocol-specific screening and/or stored specimen ICF to be used at 758 the site, then the screening and eligibility and/or stored specimen information can 759 be removed from the site-specific main ICF. In this instance, the CRS must 760 submit BOTH the protocol-specific screening and/or stored specimen ICF and 761 the site-specific main ICF to the DAIDS PRO for review and approval. 762

763 Short ICFs: If a CRS elects to use a short ICF in addition to the main ICF, the 764 CRS must have a main ICF OR written summary that includes all of the required 765 basic and appropriate additional elements which have been approved by the 766 IRB/EC and has been submitted to the DAIDS PRO for registration. A CRS must 767 receive a Registration Notification from the DAIDS PRO for all short form ICFs 768 prior to implementation. 769

770 Sub-study ICFs: If a NIAID (DAIDS)-supported and/or-sponsored protocol 771 includes a separate DAIDS-approved SIC for a sub-study that is part of the main 772 protocol and the CRS anticipates participating in the sub-study, the CRS must 773 include the sub-study site-specific ICF in their protocol registration submission. A 774 CRS must receive a Registration Notification from the DAIDS PRO for all sub- 775 study ICFs prior to implementation. 776

777 Pregnancy ICF: If a DAIDS-supported and/or sponsored protocol includes a 778 DAIDS-approved SIC for women who become pregnant while on study and the 779 CRS anticipates that some pregnant women may be included or followed on the 780


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study, the CRS must submit the site-specific pregnancy ICF to the DAIDS PRO. 781 Sites have the flexibility to combine the pregnancy ICF and the main ICF into one 782 ICF, as long as the required information is still present and this approach is 783 approved by the IRB/EC. If one or more ICFs are combined, there should be a 784 note to the DAIDS PRO documenting why one of the original consents is not 785 included in the registration submission. 786 If the site will not follow or enroll pregnant women, the pregnancy ICF does not 787 need to be submitted, and the site should document the plan not to include 788 pregnant women with a note to the DAIDS PRO. A CRS must receive a 789 Registration Notification from the DAIDS PRO for any pregnancy ICF prior to 790 implementation. 791

Assents: The IRB/EC must determine that adequate provisions are made for 792 soliciting the assent of children and/or adolescents when in the judgment of the 793 IRB/EC the children and/or adolescents are capable of providing it, 45 CFR 794 46.408. The IRB/EC is responsible for determining the age of assent and for 795 determining whether the use of an assent form is appropriate. A CRS must 796 receive a Registration Notification from the DAIDS PRO for all assents prior to 797 implementation. 798

799 1. Health Insurance Portability and Accountability Act (HIPAA) – Privacy Rule 800

The Privacy Rule is a U.S. federal regulation under the Health Insurance 801 Portability and Accountability Act (HIPAA) of 1996 that governs the protection of 802 individually identifiable health information. 803

804 The DAIDS PRO does not review site-specific ICFs for information related to 805 HIPAA. If the site-specific ICF(s) contains language pertaining to HIPAA 806 authorization, the DAIDS PRO will NOT assess this language for Privacy Rule 807 compliance. In addition, it is very important that confidentiality language included 808 in the DAIDS-approved sample informed consent remain in the site-specific ICF 809 even if this information is included in a separate HIPAA authorization form. 810

811 NOTE: The HIPAA regulations do not apply to non-U.S. CRSs. 812

813 Information related to the Privacy Rule can be found at the following HHS website. 814

815 2. ClinicalTrials.gov Informed Consent Requirements 816

817 ClinicalTrials.gov is the clinical trial registry databank maintained by the NIH 818 National Library of Medicine (NLM) which was created by statute outlined in the 819 Food and Drug Administration Amendments Act of 2007 (FDAAA). Through 820 FDAAA, the U.S. Food & Drug Administration (FDA) amended current informed 821 consent regulations (21 CFR 50.25) to now require that all informed consent 822 documents for applicable drug (including biological products) and device clinical 823 trials include a specific statement that clinical trial information will be entered into 824 ClinicalTrials.gov. As of December 1, 2011, for new protocols, the following 825



http://www.hhs.gov/ocr/privacy/

https://clinicaltrials.gov/ct2/manage-recs/fdaaa

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language MUST be included in the DAIDS-approved sample informed consent 826 (SIC) ONLY for applicable trials: 827

828 “A description of this clinical trial will be available on www.C l i n i c a l Tr ials. g o v, 829 as required by U.S. law. This Web site will not include information that can 830 identify you. At most, the Web site will include a summary of the results. 831 You can search this Web site at any time.” 832

833 The DAIDS PRO will review site-specific ICFs for information related to 834 clinicaltrials.gov. If the DAIDS-approved SIC contains the clinicaltrials.gov 835 language, then the language MUST be in all site-specific informed consents for 836 that study. Failure to include this language in applicable site-specific informed 837 consents will result in a required corrections notification. 838

839 NOTE: Per U.S. federal regulations, this language cannot be modified. 840

841 NOTE: Participants do not need to be re-consented for existing or ongoing studies 842 unless the IRB/EC determines otherwise. 843

844 NOTE: The required language can be translated into local language. 845

846 NOTE: If the inclusion of the ClinicalTrials.gov language is mandated by the 847 IRB/EC/RE (for non-applicable trial), documentation from the IRB mandating the 848 statement inclusion must be provided. 849

850 Information related to the informed consent requirement for clinicaltrials.gov can 851 be found on the following HHS website. 852

853 J. TRANSLATION REQUIREMENTS 854

For all documents that require translation to a language other than Spanish, a 855 CRS must submit to the DAIDS PRO a copy of the DAIDS Protocol Registration 856 Translation Confirmation Document, attesting that the translation is a true and 857 accurate reflection of the local language documents that have been reviewed and 858 approved by the IRB/EC and other REs/Approving Entity. 859

In addition, sites must submit translation certificate or equivalent (i.e. a signed and 860 dated documentation by the translator/translators attesting that the translation is 861 a true and accurate interpretation of the local language document) 862

863

NOTE: CRSs ARE NOT required to complete the DAIDS Protocol Registration 864 Translation Confirmation Document for any protocol registration documents in 865 Spanish. 866 867 An electronic copy of the DAIDS Translation Confirmation Document can be 868 found on the DAIDS RSC web site under the “Protocol Registration” section. 869

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870 i. Form FDA 1572, IoR Form, CVs, and Medical Licenses 871

All Form FDA 1572s, DAIDS IoR Forms, CVs and Medical L icenses must be 872 prepared in English. Non-English versions of these documents will not be 873 accepted by the DAIDS PRO. 874

875 ii. IRB/EC, other RE/Approving Entity, and IBC approval letters 876

All non-English IRB/EC, other applicable RE/Approving Entity, and IBC approval 877 letter(s) must be translated into English, except for Spanish. CRSs must submit 878 copies of both the local language and translated English approval letter(s) to 879 the DAIDS PRO. 880

881 NOTE: CRSs should provide an English translation of any other appropriate 882 IRB/EC/RE/IBC documentation that explains changes/deletions in the site 883 specific ICFs or that could assist the DAIDS PRO when reviewing registration 884 materials. 885 886 iii. Site-specific ICFs 887

CRSs must prepare site-specific ICFs in all languages in which they will conduct 888 informed consent discussions for each study. If CRSs elect to use short ICFs in 889 addition to the Main ICF, the short ICF must also be prepared in all languages in 890 which the informed consent discussions will be conducted. After approval by all 891 applicable IRBs/ECs and REs, copies of the approved site-specific ICFs must be 892 submitted to the DAIDS PRO. 893

894 If informed consent discussions will be conducted in English and another local 895 language, including Spanish, the site-specific English and local language ICFs 896 must be submitted to the DAIDS PRO. No back-translations are required by 897 DAIDS. 898

899 If informed consent discussions will be conducted in a local language other than 900 English or Spanish, site-specific local language ICFs must be submitted to the 901 DAIDS PRO. Back-translations (into English) of the site-specific local language 902 ICFs for which discussion will be conducted also must be submitted to the DAIDS 903 PRO. 904

905 NOTE: If a DAIDS Clinical Trials Network has specific requirements regarding 906 translation of site-specific ICFs, the CRS should follow those requirements as 907 well as any applicable translation and back-translation requirements specified in 908 institutional policies, the study protocol, and/or the network Manual of Operations. 909 NOTE: Site specific ICFs in languages that were not submitted with the original 910 initial registration should be submitted as additional ICF language type within 911 DPRS and will be considered initial registration in the newly submitted language 912 type. 913

41

VI. Protocol Registration Submissions 914 915

Prior to implementing a protocol and enrolling participants, a CRS must receive 916 final approval for the site-specific ICFs from the IRB/EC and other applicable 917 REs/Approving Entity(ies). In addition, the CRS must successfully complete the 918 DAIDS initial protocol registration process. However, successfully completing the 919 DAIDS initial protocol registration process does not authorize a CRS to begin 920 enrollment of participants. CRSs will be notified by the appropriate DAIDS scientific 921 program (i.e., Program Officer), Operations Center or Data Management Center 922 when enrollment may begin for a protocol. 923

924 Each CRS will complete the protocol registration process for all clinical research 925 supported and/or sponsored by DAIDS that is reviewed by DAIDS Scientific Review 926 Committees, namely the Prevention Sciences Review Committee (PSRC) and the 927 Clinical Sciences Review Committee (CSRC) and if it is determined protocol 928 Registration is required. Upon receiving final IRB/EC and other applicable 929 RE/Approving Entity approval(s), the CRS will submit all required registration 930 documents to the DAIDS PRO via the DAIDS DPRS. 931

932 Upon making ANY submission to the DAIDS PRO, a CRS will receive a Confirmation 933 of Submission notice that indicates successful submission of materials to the DAIDS 934 PRO. If a CRS does not receive a Confirmation of Submission notice within 24 - 935 48 hours of submitting materials, the CRS should contact the DAIDS PRO. 936

937 The CRS must place a copy of all final Protocol Registration notifications from 938 the DAIDS PRO in the site's regulatory files. Refer to Section II - Definitions of this 939 manual for a list of final registration notifications. 940

941 A. Initial Registration 942

A CRS that has NOT PREVIOUSLY received a Registration Notification from the 943 DAIDS PRO for any version of the protocol must complete the initial protocol 944 registration process. 945

If a CRS has previously received a DAIDS PRO Registration Notification for one 946 language (i.e., English) and later submits registration documents for a new language 947 (i.e., Spanish), the new language should be submitted as an Additional IC Language 948 submission type but will be considered an initial registration as this is the first time the 949 specific language has been submitted to the DAIDS PRO for review. 950

951 If a CRS has previously received a Registration Notification from the DAIDS PRO 952 for one informed consent type (i.e., main, pregnancy) and later submits registration 953 documents for a new informed consent type (i.e., stored specimen, short form), the 954 new informed consent type should b e s u b m i t t e d a s a n Additional I C Type 955 but is considered an initial registration as this is the first time the informed consent 956 form has been submitted to the DAIDS PRO for review. 957

958 NOTE: If a CRS has previously received a Registration Notification from the DAIDS 959

42

PRO and is only submitting an additional language or informed consent type, the site 960 is NOT required to resubmit the Form FDA 1572/DAIDS IoR Form and the IoR CV with 961 the protocol registration submission. 962

The following documents must be submitted to the DAIDS PRO for all initial 963 registration submissions: 964

o A copy of the Form FDA 1572 signed and dated by the IoR (for studies 965 conducted under an IND) OR a copy of the DAIDS IoR Form signed and 966 dated by the IoR (for non-IND studies) 967

o Investigator of Record CV and other required documentation (current 968 medical license or equivalent) 969

o A copy of the CRS’s IRB/EC and other applicable RE/Approving Entity 970 approval letter(s) and any other appropriate documentation from the 971 IRB/EC and other applicable REs/Approving Entity(ies). NOTE: For 972 examples of other appropriate IRB/EC/RE/Approving Entity documentation 973 refer to section D, sub-section i - “IRB/EC/RE/Approving Entity approvals” 974 of this manual. 975

o A copy of the IRB/EC and other applicable RE/Approving Entity approved 976 site-specific ICFs (all languages including English translations, if 977 applicable). Refer to section V, “Translation Requirements” of this manual. 978

o A copy of the CRS's IBC approval letter, if applicable 979 980 NOTE: If an initial registration submission is missing any required documents or 981 is incomplete, designated site personnel (i.e., CRS coordinator, IoR) and/or 982 additional personnel listed in the DPRS will be sent a Requested Materials notice that 983 details the missing and/or corrected information/materials that must be submitted to 984 the DAIDS PRO for registration processing to continue. The review process will not 985 continue until the requested materials are received at the DAIDS PRO. For 986 information on how to submit requested materials refer to Section VII, Sub Section D. 987 i. “Requested Materials” of this manual. Not submitting all documentation may delay 988 registration. 989

990 When all required documents have been received and reviewed, a CRS will receive 991 a Registration Notification from the DAIDS PRO that will include all languages and 992 informed consent types that have been submitted. The Registration Notification from 993 the DAIDS PRO indicates successful completion of the initial protocol registration 994 process. 995

996 If a CRS receives a Registration with Required Corrections Notification, a CRS must 997 make the required corrections and submit them to their IRB/EC for review and approval 998 OR must submit justification for why the required correction(s) will not be made to 999 the DAIDS PRO within 120 calendar days of the date the Registration with Required 1000 Corrections Notification was issued. For information on how to submit required 1001 corrections refer to Section VI, Subsection D. iii. - “Registrations with Required 1002 Corrections” of this manual. 1003

1004 NOTE: The 120 calendar days is for submission of IRB/EC approved corrections OR 1005

43

justifications for why the corrections will not be made to the DAIDS PRO. 1006 1007 Upon successful completion of the DAIDS PRO initial registration process, indicated 1008 when a CRS receives a Registration Notification or a Registration with Required 1009 Corrections Notification, a CRS will begin receiving safety information for the protocol 1010 (i.e., safety reports, safety memos, investigator’s brochures, etc.) from the DAIDS RSC 1011 Safety Information Center. 1012

1013 If a site-specific ICF(s) does not include all the required basic and appropriate additional 1014 elements to comply with U.S. Federal Regulations and DAIDS policies, designated CRS 1015 personnel (i.e., CRS Coordinator, IoR) will be notified via a Disapproval Notification from 1016 the DAIDS PRO regarding the deficiencies. The Disapproval Notification will outline 1017 the deficiencies in the site-specific ICF(s) that must be revised/corrected before a 1018 final Registration Notification can be issued. 1019

1020

NOTE: A Disapproval Notification is not a final notification and DOES NOT 1021 indicate successful completion of the protocol registration process. 1022

1023 For information on the options a CRS has upon receipt of a Disapproval Notification 1024 from the DAIDS PRO, refer to Section VII, Sub Section D. ii.- “Disapprovals” of this 1025 manual. 1026 1027 B. Amendment Registrations (above) 1028

1. Full Version Protocol Amendment Registration 1029

A full version “Protocol Amendment” is a revision to a protocol made by the Protocol 1030 Team/Chair/Awardee that requires DAIDS review and final approval/sign-off before 1031 implementation. The changes to the protocol are incorporated into the protocol 1032 document and will result in a change to the DAIDS protocol version number (i.e., 1033 2.0, 3.0, etc.). Sites should refer to the protocol document for information on the 1034 protocol registration process for full version protocol amendments. 1035

1036 CRSs should submit the amended protocol, DAIDS-approved SIC(s), and the 1037 amended site-specific ICF(s) to their IRBs/ECs and other applicable REs/Approving 1038 Entity(ies) for review and approval as soon as possible. Per the DAIDS Protocol 1039 Registration policy, submission to the local IRB/EC must take place within 45 calendar 1040 days for U.S. sites and 75 calendar days for non-U.S. sites of the date the amendment 1041 was approved by DAIDS and distributed to the sites. 1042

NOTE: The 45 or 75 calendar day requirement for submission of full version protocol 1043 amendment registration materials is for local IRB/EC only. 1044

1045 Amendments including any revised site-specific ICF(s) must be implemented 1046 immediately upon CRS receipt of all required IRB/EC and RE approvals unless the 1047 amendment specifies otherwise. A CRS can implement the IRB approved revised 1048 ICF(s) immediately and DAIDS PRO approval notification is not required for 1049 amendments unless specified in the amendment. 1050

1051

44

The CRS may delay implementing an amendment when the IRB/EC/RE/Approving 1052 Entity approved amendment states the protocol changes will be implemented once 1053 specific operational issues (i.e., training on new procedures added in the amendment) 1054 are addressed. The IRB/EC/RE/Approving Entity documentation must be kept in the 1055 site’s regulatory files for verification by monitors. 1056

1057 When the IRB/EC/RE/Approving Entity approved amendment and revised site-specific 1058 ICFs are not implemented immediately after final IRB/EC/RE/Approving Entity 1059 approval, sites may continue conducting protocol related interactions and interventions 1060 with already enrolled study participants under the previously approved version as long 1061 as the IoR has determined that this is in the participant’s best interest. After receiving 1062 final IRB/EC/RE/Approving Entity approval and while operational issues are being 1063 addressed, new participants may only be enrolled under the previously approved 1064 version of the site-specific ICFs when the IRB/EC/RE/Approving Entity has determined 1065 this is acceptable. The IRB/EC/RE/Approving Entity determination should be 1066 documented in writing and filed in the site’s regulatory files. 1067

A CRS must submit full version protocol amendment registration documents to 1068 the DAIDS PRO within 14 calendar days of the CRS's receipt of all the required final 1069 written IRB/EC approval documentation for the amendment. The submitted documents 1070 must include documentation of the date the amended protocol and any revised site-1071 specific. 1072

ICF(s) were submitted to the local IRB/EC. The DAIDS PRO will not review any revised 1073 site-specific ICF(s) unless otherwise noted in the protocol. 1074

1075 NOTE: Sites are strongly advised to document the date the CRS receives each 1076 final IRB/EC/RE/Approving Entity approval letter. Documenting this information 1077 supports the CRS’s action to comply with the DAIDS protocol registration policy 1078 regarding submission of amendment and LoA registration materials to the DAIDS 1079 PRO within 14 calendar days of receipt of all final IRB/EC/RE/Approving Entity 1080 approval letters. This documentation should be kept in the site’s regulatory files for 1081 verification by monitors. 1082

1083 If a CRS has received a Registration Notification from the DAIDS PRO for an earlier 1084 version of the protocol including all informed consent types and specific language(s), 1085 then the registration to a new version of the protocol would be a full version protocol 1086 amendment. A CRS that has never received a Registration Notification from the 1087 DAIDS PRO for any version of the protocol, language or informed consent type must 1088 follow the instructions for Initial Protocol Registration detailed in Section VI, sub-1089 section A of this manual. 1090

1091

NOTE: If a CRS has submitted a registration packet for a previous version of a protocol 1092 prior to a new version being approved by DAIDS and distribution to the sites, the DAIDS 1093 PRO will continue to process the registration for the earlier version. 1094

1095 The following documentation must be submitted to the DAIDS PRO for all full version 1096 protocol amendment registration submissions: 1097

o A copy of the site’s IRB/EC and other applicable RE/Approving Entity 1098

45

approval letter(s) and any other appropriate documentation from the 1099 IRB/EC and other applicable REs/Approving Entity(ies) listed on the FDA 1100 Form 1572/DAIDs IoR Form. NOTE: For examples of other appropriate 1101 IRB/EC/RE documentation refer to section D, sub-section i - 1102 “IRB/EC/RE/Approving Entity approvals” of this manual. 1103

o Documentation of the date the amended protocol and any revised site- 1104 specific ICF(s) were submitted to the local IRB/EC. 1105

o A copy of the IRB/EC and other applicable RE/Approving Entity approved 1106 site ICF(s) (all languages including English translations, if applicable). Refer 1107 to section V, “Translation Requirements” of this manual. 1108

o A copy of the CRS's IBC approval letter, if applicable 1109

NOTE: If any ICFs registered in the previous version will no longer be utilized at the 1110 site, documentation must be submitted that states that the ICFs will no longer be 1111 utilized at the site. 1112

1113 NOTE: Examples of appropriate documentation of the date the amended protocol 1114 and any revised site-specific ICF(s) were submitted to the local IRB/EC includes but 1115 is not limited to: 1116

o the submission letter from the site to the IRB/EC, a memo from the IoR 1117 or designee specifying the date of submission to the IRB/EC 1118

1119 NOTE: If the IRB/EC determines that a full version protocol amendment does not 1120 require changes to the site-specific ICF(s), the CRS should document this either in 1121 the comments section of the ICF field of the DPRS or with a memo to the DAIDS 1122 PRO with the full version protocol amendment registration submission. Otherwise, all 1123 previously registered ICF types must be submitted with the amended version or 1124 Justification for the omission of ICF type must be provided. Documentation of approval 1125 of the amended protocol is still required from of the site’s IRB/EC and other applicable 1126 RE/Approving Entity approval letter(s) and any other appropriate documentation from 1127 the IRB/EC and other applicable REs/Approving Entity(ies) regardless of whether the 1128 site ICFs were revised. 1129

1130 NOTE: Re-consenting participants as a result of amendment (Change or new 1131 information that may affect subject participation) is the decision of the CRS’s IRB/EC. 1132 CRSs should follow their IRB/EC/RE/Approving Entity instructions for re- consenting 1133 participants as a result of the amendment. 1134

1135 NOTE: If a full version protocol amendment registration submission is missing any 1136 required documents or is incomplete, designated site personnel (i.e., CRS coordinator, 1137 IoR) and/or additional personnel listed in the DPRS will be sent a Requested Materials 1138 notice that details the missing and/or corrected information/materials that must be 1139 submitted to the DAIDS PRO. For information on how to submit requested materials 1140 refer to Section VI, Sub Section D. i. - “Requested Materials” of this manual. 1141

1142 When all required documents have been received and approved, a CRS will receive 1143 a Registration Notification from the DAIDS PRO that will include all languages and 1144 informed consent types that have been submitted. The Registration Notification from 1145

46

the DAIDS PRO indicates successful completion of the full version protocol amendment 1146 registration process. 1147

1148 NOTE - A Registration Notification from the DAIDS PRO is NOT required prior to 1149 implementing a full version protocol amendment at a CRS. 1150

1151 NOTE: Once a new version of a protocol is approved by DAIDS and has been distributed 1152 to the sites, a CRS will no longer be able to register for a previous version. 1153

1154 i. Letter of Amendment (LoA) Registration 1155

1156 CRSs should submit the LoA and any amended site-specific ICF(s) to their IRBs/ECs 1157 and other applicable REs/Approving Entity(ies) for review and approval as soon 1158 as possible. Per the DAIDS Protocol Registration policy, submission to the local 1159 IRB/EC must take place within 45 calendar days for U.S. sites and 75 calendar days 1160 for non- 1161 U.S. sites of the date the LoA was approved by DAIDS and distributed to the sites. 1162

NOTE: The 45 or 75 calendar day requirement for submission of LoA materials is 1163 for local IRB/EC only. 1164

1165 NOTE: Protocol revisions resulting from LoAs DO NOT affect the DAIDS protocol 1166 version. For version tracking purposes at the CRS (i.e., at the request of an IRB/EC 1167 and other applicable REs/Approving Entity(ies)), CRSs can specify the site (local 1168 version number or version date of the site-specific ICF(s) in the header or footer of their 1169 site-specific ICF(s). However, the DAIDS protocol version number and/or the final 1170 version date of the DAIDS- approved protocol should remain on all site-specific ICFs 1171 as well. 1172 LoAs including any revised site-specific ICF(s) must be implemented immediately upon 1173 CRS receipt of all required IRB/EC and RE/Approving Entity approvals unless the LoA 1174 specifies otherwise and DAIDS PRO approval notification is not required for LoA unless 1175 specified in the LoA. 1176

1177 The CRS may delay implementing a LoA when the IRB/EC/RE/Approving Entity 1178 approved LoA states the protocol changes will be implemented once specific 1179 operational issues (i.e., training on new procedures added in the LoA) are addressed. 1180 The IRB/EC/RE documentation must be kept in the site’s regulatory files for verification 1181 by monitors. 1182

1183 When the IRB/EC/RE/Approving Entity approved LoA and revised site-specific ICFs are 1184 not implemented immediately after final IRB/EC/RE approval, sites may continue 1185 conducting protocol related interactions and interventions with already enrolled study 1186 participants under the previously approved version as long as the IoR has determined 1187 that this is in the participant’s best interest. After receiving final IRB/EC/RE/Approving 1188 Entity approval and while operational issues are being addressed, new participants may 1189 only be enrolled under the previously approved version of the site-specific ICFs when 1190 the IRB/EC/RE has determined this is acceptable. The IRB/EC/RE/Approving Entity 1191 determination should be documented in writing and filed in the site’s regulatory files. 1192

1193

47

A CRS must submit LoA registration documents to the DAIDS PRO within 14 calendar 1194 days of the CRS’s receipt of all the required final written IRB/EC approval 1195 documentation for the LoA. The submitted documents must include documentation 1196 of the date the LoA and any revised site-specific ICF(s) were submitted to the local 1197 IRB/EC. The DAIDS PRO will not review any revised site-specific ICF(s) unless 1198 otherwise noted in the protocol. 1199

1200 NOTE: Sites are strongly advised to document the date the CRS receives each final 1201 IRB/EC/RE approval letter. Documenting this information supports the CRS’s action 1202 to comply with the DAIDS protocol registration policy regarding submission of 1203 amendment and LoA registration materials to the DAIDS PRO within 14 calendar days 1204 of receipt of all final IRB/EC/RE/Approving Entity approval letters. This 1205 documentation should be kept in the site’s regulatory files for verification by monitors. 1206

1207 The following documentation must be submitted to the DAIDS PRO for all LoA 1208 registration submissions: 1209

o A copy of the site’s IRB/EC and other applicable RE/approving entity 1210 approval letter(s) and any other appropriate documentation from the 1211 IRB/EC and other 1212 applicable REs/Approving Entity(ies) listed on the FDA Form 1572/DAIDs IoR 1213 Form. NOTE: For examples of other appropriate IRB/EC/RE documentation 1214 refer to section D, sub-section i. - “IRB/EC/RE/Approving Entity approvals” 1215 of this manual. Documentation of the date the LoA and any revised site-1216 specific ICF(s) were submitted to the local IRB/EC 1217

o A copy of the IRB/EC and other applicable RE/Approving Entity approved 1218 site ICF(s) (all languages including English translations, if applicable). 1219 Refer to section v, “Translation Requirements” of this manual. 1220

o A copy of the CRS's IBC approval letter, if applicable. 1221 1222

NOTE: Examples of appropriate documentation of the date the LoA and any 1223 revised site-specific ICF(s) were submitted to the local IRB/EC includes but is not 1224 limited to: 1225

1226 o the submission letter from the site to the IRB/EC 1227 o a memo from the IoR or designee specifying the date of submission to 1228

the IRB/EC 1229 1230 NOTE: Re-consenting participants as a result of LoA (Change or new information that may 1231 affect subject participation) is the decision of the CRS’s IRB/EC. CRSs should follow their 1232 IRB/EC/RE/Approving Entity instructions for re- consenting participants as a result of 1233 the LoA. 1234

1235

48

1236 NOTE: If a LoA registration submission is missing any required documents or is 1237 incomplete, designated site personnel (i.e., CRS coordinator, IoR) and/or additional 1238 personnel listed in the DPRS will be sent a Requested Materials notice that details the 1239 missing and/or corrected information/materials that must be submitted to the DAIDS 1240 PRO. For information on how to submit requested materials refer to Section VII, Sub 1241 Section D. i. - “Requested Materials” of this manual. 1242

1243 When all required documents have been received, a CRS will receive a Registration 1244 Notification from the DAIDS PRO for each LoA registration submission. The 1245 Registration Notification from the DAIDS PRO indicates successful completion of the 1246 LoA registration process. 1247

1248 NOTE: LoAs are considered individual amendments to a protocol. Thus, sites must 1249 protocol register to all LoAs independent of initial and amendment registrations. If a site 1250 elects to include a LoA as part of another submission to the IRB/EC/RE/Approving 1251 Entity (i.e., continuing review, amendment review, and initial review) the site must 1252 clearly document all the materials that are being submitted to the IRB/EC/RE/Approving 1253 Entity for review and approval. It is a CRS’s responsibility to inform the DAIDS PRO 1254 regarding all registrations (i.e., LoA, amendment, initial, continuing review) the site 1255 is requesting at the time of submission. Failure to register to a LoA may result in a 1256 CRS being out of compliance with DAIDS policies and may result in delays in 1257 implementing operational changes triggered by LoA registrations. 1258

1259 NOTE: All submission types (Initial, Amendment, LoA) must be submitted independently. 1260

1261 NOTE: A Registration Notification from the DAIDS PRO is NOT required prior to 1262 implementing a LoA at a CRS. 1263

C. Sub-Study Registration 1264 1265

A CRS must protocol register to all sub-studies that have a protocol number and/or 1266 DAIDS protocol identification number if a site anticipates enrolling participants. A 1267 CRS will receive a registration notification for each sub-study that is submitted for 1268 protocol registration. CRSs must register to embedded sub-studies as part of the 1269 main study registrations. Registration for embedded sub-studies is required for all 1270 versions of the main study unless the site informs the DAIDS PRO that they are no 1271 longer participating in the embedded sub-study and request deregistration. CRSs 1272 should register to stand alone sub-studies as separate registrations and can be 1273 done independently from the main study registration. A CRS registering to a 1274 stand-alone sub-study is required to submit all required documents (i.e., IRB/EC 1275 approval letter(s), site-specific consent(s), Form FDA 1572 and/or DAIDS IoR 1276 Form, and IoR CV) when registering to a stand- alone sub-study. 1277

1278 NOTE: For an explanation of embedded and stand-alone sub-studies refer to 1279 Section II, “Definitions” of this manual. 1280

1281 D. Other Submissions 1282

Other submissions are ANY submissions made to the DAIDS PRO that are not 1283

49

Initial, Amendment or LoA registrations. Below is detailed information on 1284 requirements related to “other submissions” a CRS may submit to the DAIDS PRO. 1285

1286 2. Requested Materials 1287

Requested materials are additional and/or corrected materials requested by the 1288 DAIDS PRO as a result of an incomplete submission to the DAIDS PRO. If 1289 any required documents are missing, incomplete, or are inaccurate, the DAIDS 1290 PRO will issue a Requested Materials notice to designated CRS personnel (i.e. 1291 CRS Coordinator, IoR). This request will stop the registration review process. 1292

1293 NOTE: The Protocol Registration review process will not continue until all 1294 Requested Materials have been received by the DAIDS PRO. 1295

1296 The following documentation must be submitted to the DAIDS PRO in response 1297 to a Materials Request Notification as a “materials Request” type submission 1298

1299 o A copy of the requested materials 1300 1301 A CRS will receive a Confirmation of Submission notice once the requested materials 1302 have been received by the DAIDS PRO. 1303

1304 3. Disapprovals 1305

If it is determined during the DAIDS PRO review process that a site-specific ICF(s) does 1306 not include all the required basic and appropriate additional elements to comply with 1307 U.S. Federal Regulations and DAIDS policies, designated CRS personnel (i.e., CRS 1308 Coordinator, IoR) will be notified via a Disapproval Notification from the DAIDS PRO 1309 regarding the deficiencies. The disapproval notification will outline the deficiencies in 1310 the site-specific ICF(s) that must be revised or corrected before a final Registration 1311 Notification can be issued. 1312

1313 Upon receipt of a Disapproval Notification from the DAIDS PRO a CRS has two options: 1314

1315 1. Make the necessary revisions/corrections and submit the revised document(s) 1316

to their IRB/EC and other applicable RE approval(s) for review and approval. 1317 Upon receiving final IRB/EC/RE approval for the revised document(s) the 1318 CRS must make a "Corrected Materials" submission to the DAIDS PRO. 1319

1320 OR 1321

2. Submit justification for the omission/changes to the DAIDS PRO via a request 1322 for Disapproval Reversal 1323

1324 Under Option 1 - The following documentation must be submitted to the DAIDS PRO 1325 as “Corrected Materials” once a CRS receives final IRB/EC and other applicable 1326 RE/Approving Entity approval for the revised document(s): 1327

o A copy of the site’s IRB/EC and other applicable RE approval letter(s) and 1328 any other appropriate documentation from the IRB/EC other applicable 1329

50

REs/Approving Entity(ies). NOTE: For examples of other appropriate 1330 IRB/EC/RE documentation refer to section D, sub-section i. “IRB/EC 1331 approvals” of this manual. 1332

o A copy of the IRB/EC and other applicable RE/Approving Entity approved 1333 revised site-specific ICF(s) 1334

1335 When ALL required documents have been received and it is confirmed that the required 1336 corrections have been made, the DAIDS PRO will issue a Registration Notification. 1337

1338 Under Option 2 - If a CRS believes that a Disapproval Notification has been issued 1339 in error, the CRS can submit a request for Disapproval Reversal. A CRS must 1340 provide justification and/or documentation explaining why the disapproval should be 1341 reversed. 1342 1343 The following documentation must be submitted to the DAIDS PRO to request a 1344 disapproval reversal: 1345

o Written justification and/or a copy of any documentation supporting 1346 the CRS’s request for the disapproval reversal 1347

1348 A CRS will be notified within 4 business working days as to whether or not the disapproval 1349 will be reversed via e-mail from the DAIDS PRO. 1350 1351

4. Registrations with Required Corrections 1352 1353

If a CRS receives a Registration with Required Corrections Notification, a CRS must 1354 make the required corrections and submit them to their IRB/EC/RE/Approving Entity 1355 for review and approval OR must submit justification for why the required corrections 1356 will not be made within 120 calendar days of the date the Registration with 1357 Required Corrections Notification was issued. 1358

1359 A Registration with Required Corrections Notification indicates that a CRS may begin 1360 using the site-specific ICFs after protocol activation by the appropriate Operations Center, 1361 Data Management/Statistical Center or DAIDS Program. 1362

1363 Upon receipt of a Registration with Required Correction Notification from the DAIDS 1364 PRO a CRS has two options: 1365

1366 1. Make the necessary required corrections and submit them to their IRB/EC 1367

for review and approval. Upon receiving final IRB/EC and other applicable 1368 RE/Approving Entity approval for the corrected document(s) the CRS must 1369 make a "Corrected Materials" submission to the DAIDS PRO. 1370

1371 OR 1372

1373 2. Submit justification for the omission/changes via a "Corrected Materials" 1374

submission to the DAIDS PRO. 1375 1376

51

1377 Under Option 1 - The following documentation must be submitted to the DAIDS PRO 1378 as “Corrected Materials”, once a CRS receives final IRB/EC and other applicable RE 1379 approval for the corrected document(s): 1380

o A copy of the site’s IRB/EC and other applicable RE/Approving Entity 1381 approval letter(s) and any other appropriate documentation from the IRB/EC 1382 other applicable REs/Approving Entity(ies). 1383

o A copy of the IRB/EC and other applicable RE/Approving Entity approved 1384 revised/corrected site-specific ICF(s) 1385

1386 1387 NOTE: For examples of other appropriate IRB/EC/RE/Approving Entity 1388 documentation refer to section D, sub-section i “IRB/EC approvals” of this manual. 1389 1390 1391 Under Option 2 - If a CRS has believed that a Registration with Required Corrections 1392 Notification has been issued in error, the CRS can submit justification and /or 1393 documentation explaining why the Registration with Required Corrections Notification 1394 should be reversed. 1395

1396 1397 The following documentation must be submitted to the DAIDS PRO as “Corrected 1398 Materials”: 1399

o Written justification and/or a copy of any documentation supporting 1400 the CRS’s request for the Registration with Required Corrections 1401 reversal. 1402

1403 1404 For Option 1 and 2, a CRS will receive an Approval of Required Corrections Notification 1405 from the DAIDS PRO when all the required corrections have been reviewed and 1406 approved. The official registration date will remain the date the Registration with Required 1407 Correction Notification was issued. 1408 1409

5. Administrative Registration 1410 1411

Administrative registrations should occur when a site is not recruiting participants in 1412 a NIAID (DAIDS)-supported and/or -sponsored clinical trial but has administrative 1413 functions only. Protocol/Grant PI/Protocol Chair/Co-Chair’s routinely make substantial 1414 study interventions (decisions and interpretations) that affect study participants even 1415 though participants may not be enrolled or seen at the Protocol/Grant PI/Protocol 1416 Chair/Co-Chair’s CRS. As a result, the Protocol/Grant PI/ Protocol Chair/Co-Chair’s 1417 institutions are considered engaged with the research and must assure compliance with 1418 applicable Department of Health and Human Services (DHHS) regulations. For more 1419 information on engagement refer to the OHRP guidance document. 1420

1421 Based on U.S. federal regulation 45 CFR 46.103(a), “each institution engaged" in human 1422

http://www.hhs.gov/ohrp/policy/engage08.html


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subject research that is supported and/or sponsored by the DHHS must provide the 1423 OHRP with a satisfactory Assurance of Compliance with the regulations, unless the 1424 research is exempt under U.S. federal regulation 45 CFR 46.101(b). 1425 1426 For all administrative registrations, DAIDS requires that that the Protocol/Grant 1427 PI/Protocol Chair/Co-Chair consults with their IRB/EC and receive documentation in 1428 writing of the IRB/EC’s decision concerning their protocol review and approval. At least 1429 two different kinds of decisions can be made: 1430

1431 1432

1) IRB/EC wants to be involved in reviewing and approving the protocol. 1433

2) IRB/EC does not want to be involved in reviewing and approving the 1434 protocol and will rely on another IRB/EC, designated on the Federal Wide 1435 Assurance (FWA), for review and approval. 1436

1437 1438 DAIDS will honor the decision of the IRB/EC. The Protocol/Grant PI/ Protocol Chair/Co- 1439 Chair (s) need to consult with their IRB/EC and obtain written documentation of the 1440 IRB/EC’s decision regarding their review and approval of the protocol in order to comply 1441 with U.S. federal regulations. 1442

Upon receipt of final approval and/or documentation from the IRB/EC, an administrative 1443 registration submission should be made to the DAIDS PRO. 1444

The following documentation must be submitted to the DAIDS PRO for all Administrative 1445 Registrations: 1446

o A copy of the IRB/EC approval letter AND any other appropriate 1447 documentation from the IRB/EC including the IRB/EC decision regarding 1448 protocol review and approval. NOTE: For examples of other appropriate 1449 IRB/EC/RE/Approving Entity documentation refer to section D, sub-section 1450 i “IRB/EC approvals” of this manual. 1451

o A copy of the Form FDA 1572 signed and dated by the Protocol/Grant 1452 PI/Protocol Chair/Co-Chair (for studies conducted under an IND) OR a copy 1453 of the DAIDS IoR Form signed and dated by the Protocol Protocol/Grant 1454 PI/ Protocol Chair/Co-Chair (for non-IND studies) 1455

o A copy of the Protocol/Grant PI/Protocol Chair/Co-Chair CV and 1456 corresponding Medical license/equivalent 1457

1458 A CRS will receive a Registration Notification from the DAIDS PRO for each 1459 administrative registration submission when all required documents have been 1460 received. The Registration Notification from the DAIDS PRO indicates successful 1461 completion of the administrative registration process. 1462

1463 6. Change of Investigator of Record (IoR) 1464

1465 When there is a change in the IoR listed in Section 1 on the Form FDA 1572 or DAIDS 1466 IoR Form, a CRS should submit a copy of the revised Form FDA 1572 or the revised 1467 DAIDS IoR Form to the DAIDS PRO. To officially change the IoR for a protocol(s), 1468


53

the CRS must submit the documentation within 30 calendar days of the CRS’s 1469 notification that the current IoR will no longer serve as the IoR for the study. The 1470 following documentation should be submitted to the DAIDS PRO for all Change of IoR 1471 requests: 1472

o Memo requesting a change of IoR 1473 o A copy of the new Form FDA 1572 signed and dated by the new IoR 1474

(for studies conducted under an IND) OR a copy of the new DAIDS IoR 1475 Form signed and dated by the new IoR (for non-IND studies) 1476

o CV for the new IoR and other required documentation (current medical license 1477 or equivalent) 1478

o A Protocol Signature Page for each Investigator of Record 1479 1480 A CRS will receive a Change of IoR Approval Notification from the DAIDS PRO when 1481 the change of IoR has been reviewed and approved by the DAIDS PRT. 1482

1483 NOTE: The Change of IoR is NOT official until the CRS receives a Change of IoR 1484 Approval Notification from the DAIDS PRO. 1485

1486 NOTE: A CRS must notify their DAIDS Office for Clinical Site Oversight (OCSO) 1487 representative and/or DAIDS Program Officer when there is a change in CRS Leader 1488 or other key CRS site personnel and/or contact information. 1489 7. Continuing/Annual Review 1490 The DHHS regulations, 45 CFR 46.109(e) require that all DHHS supported research 1491 undergo continuing IRB/EC review at intervals appropriate to the degree of risk, but 1492 NOT LESS than once per year. Continuing review must be performed prior to the 1493 expiration date specified on the IRB/EC approval letter(s) and/or site-specific ICFs. 1494 The frequency of ongoing reviews should be documented in IRB/EC policies and 1495 procedures and may be protocol/study specific. CRSs can visit the OHRP website for 1496 additional guidance related to continuing review. 1497 1498 CRSs participating in NIAID (DAIDS)-supported and/or -sponsored clinical trials, 1499 reviewed by the DAIDS Scientific Review Committees and are protocol registered are 1500 required to submit documentation of IRB/EC Continuing/Annual review approval to the 1501 DAIDS PRO. Continuing/Annual review documentation must be submitted to the DAIDS 1502 PRO within 14 days of the CRS receiving final written documentation of IRB/EC 1503 Continuing/Annual review approval. The IRB/EC approval of continuing review must 1504 be a final approval and not require any modifications or further input by the CRS. 1505 The following documents must be submitted to the DAIDS PRO for all continuing/annual 1506 review submissions: 1507

o A copy of the IRB/EC Continuing/Annual review approval letter AND any 1508 other appropriate documentation from the IRB/EC. NOTE: For examples of 1509 other appropriate IRB/EC/RE/Approving Entity documentation refer to 1510 section D, sub-section i “IRB/EC approvals” of this manual. 1511

o A copy of the IRB/EC approved site-specific ICF(s) if revised at the time 1512 of Continuing/Annual review 1513

1514


54

NOTE: All IRB/EC approval letters for Continuing/Annual review must state that the 1515 approval is for continuing review (i.e., similar terminology is acceptable: yearly review, 1516 annual review) 1517

1518 NOTE: Documentation of IRB/EC receipt of continuing review request alone does not 1519 satisfy the DHHS requirement regarding documentation of Continuing/Annual review 1520 and approval by the IRB/EC. 1521

1522 NOTE: The DAIDS PRO will not review any revised site-specific ICF(s) submitted with 1523 the continuing/annual review registration submission. 1524

1525 CRSs will only be sent a Confirmation of Submission notice that indicates 1526 continuing/annual review materials have been received by the DAIDS PRO. CRSs 1527 will NOT receive any additional notifications from the DAIDS PRO for 1528 Continuing/Annual review documentation unless there is a problem with the 1529 documentation submitted (i.e., incomplete packet or inappropriate review by the 1530 IRB/EC). If problems are noted, the DAIDs PRO will follow-up via e-mail to inform 1531 the CRS about the deficiencies and to request corrected continuing/annual review 1532 documentation. 1533

1534 If a CRS’s IRB/EC procedures for expedited review deviate from those as specified 1535 in OHRP guidance (i.e., specific pre-approved country procedures), then the CRS 1536 must provide documentation of the IRB/EC procedures to the DAIDS PRO at the 1537 same time the CRS submits their IRB/EC Continuing/Annual review approval 1538 documents. In addition, documentation of any change in timing of the IRB/EC review 1539 procedure for Continuing /Annual reviews for the CRS must be submitted to the 1540 DAIDS PRO along with the final IRB/EC Continuing/Annual review approval letter(s). 1541

1542

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Lapses in Continuing Review 1543

Per the DHHS regulations 45 CFR 46.103(b) & 46.109(e) and OHRP guidance on 1544 continuing review, if there is a lapse in continuing review (i.e., If an investigator has 1545 failed to provide continuing review information to their IRB/EC or the IRB/EC has not 1546 reviewed and approved a research study by the Continuing/Annual review date 1547 specified by the IRB/EC), the research at the CRS must stop, unless the IRB/EC finds 1548 that it is in the best interest of individual participants to continue participating in the 1549 research interventions or interaction. Enrollment of new participants cannot occur after 1550 the expiration of IRB/EC approval(s). 1551

1552 CRSs should contact their DAIDS Office for Clinical Site Oversight (OCSO) 1553 representative and/or DAIDS Program Officer when there is any lapse and for 1554 additional guidance and information. 1555

1556 CRSs should submit IRB/EC lapse documentation (i.e., the site's documentation of 1557 the lapse to the IRB/EC and the IRB/EC's response) to the DAIDS PRO. 1558

1559 8. Site Initiated Revisions to Site Informed Consent Forms (ICFs) 1560

Modifications to a CRS’s site-specific ICFs are considered site initiated when the 1561 changes are made as a result of new information or at the request of the IRB/EC and 1562 other applicable REs/Approving Entity(ies). 1563

1564 Revisions to a CRS's site-specific ICFs are only considered site-initiated when revisions 1565 have been made after the CRS has received a Registration Notification from the DAIDS 1566 PRO for the most current DAIDS-approved protocol version. Any changes made to 1567 a CRS’s ICF(s) prior to receiving a Registration Notification from the DAIDS will 1568 be considered part of the CRS’s initial or amendment registration. For additional 1569 information on initial and amendment registration submissions refer to Section VI, Sub- 1570 Sections A - “Initial Registration” and B - “Amendment Registration” of this manual. 1571

1572 Site-initiated revisions DO NOT affect the final DAIDS protocol version number and 1573 CRSs must be sure that the correct DAIDS protocol version number, remains on all 1574 site ICF(s). For version tracking purposes at the CRS, CRSs can specify the site 1575 (local) version number or version date of the site-specific ICF(s) in the header or footer 1576 of their site-specific ICF(s). However, the final DAIDS protocol version number and/or 1577 final version date of the protocol document approved by DAIDS should remain on 1578 all site- specific ICFs as well. 1579 1580 The following documentation must be submitted to the DAIDS PRO for all site-initiated 1581 revised ICFs: 1582

o A copy of the site-initiated revised ICF(s) 1583 o A copy of the site’s IRB/EC and other applicable RE/Approving Entity 1584

approval letter(s) and any other appropriate documentation from the IRB/EC 1585 other applicable REs/Approving Entity(ies). 1586

1587 1588

http://www.hhs.gov/ohrp/policy/continuingreview2010.html



mailto:[email protected]



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NOTE: For examples of other appropriate IRB/EC/RE/Approving Entity 1589 documentation refer to section D, sub-section i “IRB/EC approvals” of this manual. 1590

1591 1592 NOTE: If a site initiated revised ICF submission is missing any required documents or 1593 is incomplete, designated site personnel (i.e., CRS coordinator, IoR) and/or 1594 additional personnel listed in the DPRS will be sent a Requested Materials notice that 1595 details the missing and/or corrected information/materials that must be submitted to 1596 the DAIDS PRO. For information on how to submit requested materials refer to 1597 Section VII, Sub Section D .i. - “Requested Materials” of this manual. 1598

1599 Once the CRS receives approval from their IRB/EC and other applicable REs/Approving 1600 Entity(ies), the CRS may implement the revised site-specific ICFs immediately. The 1601 DAIDS PRO will not review the site initiated revisions to CRS’s ICFs. 1602

1603 CRSs will be sent a Confirmation of Submission notice that indicates materials have 1604 been received by the DAIDS PRO. CRSs will NOT receive any additional notifications 1605 from the DAIDS PRO for site initiated revisions to site-specific ICFs. 1606

1607 9. Updated Form FDA 1572 or DAIDS IoR Form 1608

1609 When there is ANY major change to the information listed on the Form FDA 1610 1572/DAIDS IoR Form submitted to the DAIDS PRO, a CRS should submit an updated 1611 Form FDA 1572 (IND studies) or DAIDS IoR Form (Non-IND studies) to the DAIDS 1612 PRO within 30 calendar days. 1613

1614 The following documentation should be submitted to the DAIDS PRO for all Updated 1615 Form FDA 1572s/DAIDS IoR Forms: 1616

o A copy of the updated Form FDA 1572 signed and dated by the IoR 1617 (for studies conducted under an IND) 1618

OR 1619

o A copy of the updated DAIDS IoR Form signed and dated by the IoR (for 1620 non- IND studies) 1621

NOTE: If there is a Change of IoR (listed in Section 1 of either form), refer to Section 1622 VI, Sub-Section D. v - “Change of Investigator of Record" of this manual. 1623

1624 NOTE: CRSs should submit a copy of the signed and dated Form FDA 1572/DAIDS 1625 IoR Form to the DAIDS PRO and retain the original version in their regulatory files 1626 at the site. 1627

1628 CRSs will be sent a Confirmation of Submission notice that indicates materials have 1629 been received by the DAIDS PRO. CRSs will NOT receive any additional notifications 1630 from the DAIDS PRO for updated Form FDA 1572s or DAIDS IoR Form unless 1631 the updated document(s) results in a Change of IoR at the CRS. 1632

1633 10. Deregistration 1634

Any CRS that has completed the DAIDS protocol registration process for a protocol 1635

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(main or sub-study), must complete the DAIDS deregistration process for each protocol 1636 to which it is registered. 1637

1638 NOTE: Deregistration is NOT automatic when a study is completed. 1639 1640 Deregistration can occur when: 1641

o The CRS no longer has participants on study (all follow-up has been 1642 completed) and does not plan to enroll additional subjects 1643

o If no participants were ever enrolled at the CRS and the study has closed 1644 to accrual. 1645

1646 In addition, a CRS should check with their DAIDS Clinical Trials Network or DAIDS 1647 Program Officer to confirm i f t h e r e a r e any protocol, network and/or DAIDS 1648 specific requirements prior to deregistering with the DAIDS PRO and/or 1649 closing/terminating the study with the IRB/EC. 1650 1651 The DAIDS deregistration process is independent of a CRS’s closure/termination of 1652 a study at their IRB/EC. The IRB/EC’s determination to close or terminate a study is 1653 NOT required for a CRS to deregister with DAIDS. Completion of the DAIDS 1654 deregistration process indicates that a CRS’s participation in a study is complete but 1655 does not reflect the closure of a multi-center study at all CRSs participating in the study. 1656 1657 If a CRS plans to complete the DAIDS deregistration process for a study but will not 1658 be closing/terminating the study at their IRB/EC, the CRS should consult its IRB/EC 1659 to confirm any requirements and/or standard operating procedures that must be met 1660 prior to deregistration. A CRS’s IRB/EC may require the continued submission of 1661 safety information and/or other data for the study. In this case, deregistration with 1662 DAIDS PRO should NOT be done until the study has been completed at all participating 1663 sites. 1664

1665 The following documentation must be submitted to the DAIDS PRO for all deregistration 1666 requests: 1667

o Memo stating that the CRS no longer intends to participate in the protocol(s) 1668 1669

AND/OR 1670

o A Copy of the IRB/EC closure/termination letter for the protocol if the 1671 protocol has been closed with the IRB/EC at the time of deregistration 1672

1673 A CRS will receive a Deregistration Notification from the DAIDS PRO when 1674 deregistration has been reviewed and approved by the DAIDS PRO. 1675

1676 NOTE: A CRS is not considered deregistered until a Deregistration Notification has 1677 been issued by the DAIDS PRO. 1678

1679 Once a CRS receives a Deregistration Notification for a protocol, the CRS is no longer 1680 required to submit any additional protocol registration documents to the DAIDS PRO 1681 if the protocol amends. A CRS must continue to follow their IRB/EC requirements 1682

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for submission of documents if the protocol has not been closed/terminated with the 1683 IRB/EC. 1684

Upon completion of the DAIDS deregistration process, a CRS will no longer receive 1685 safety information (i.e., safety reports, safety memos, investigator’s brochures) from the 1686 DAIDS RSC Safety Information Center. 1687

Additional guidance is available regarding the DAIDS registration process along with 1688 a summary of site responsibilities once deregistration is complete. This information 1689 is located on the RSC web site under the “Protocol Registration” section. 1690


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1691

VII. Definitions 1692 1693 Approving Entity: Any organization whose approval is required prior to a CRS’s 1694 participation in DAIDS trial that is not an IRB/EC, Regulatory Entity or an IBC. Includes 1695 but is not limited to approvals from state health systems and administrative bodies. 1696 1697 Clinical research: Research conducted on participants, material, or data of human 1698 origin with an identifiable person as the source. Clinical research includes exploratory, 1699 behavioral and observational studies. All clinical trials are a subset of clinical research. 1700 (DAIDS) 1701

Clinical Research Site (CRS): Distinct locations (i.e., hospitals, outpatient clinics, 1702 health maintenance organizations, community health centers, private practices, clinics) 1703 supported and/or sponsored by NIAID (DAIDS) where qualified professionals conduct 1704 clinical research in accordance with good clinical practice (GCP) and applicable 1705 regulations. (DAIDS) 1706

Clinical Research Site (CRS) Leader: The onsite senior research scientist responsible 1707 for the administrative and scientific components of the CRS. The CRS leader is 1708 responsible for overall site activities, including day-to-day operations, performance, and 1709 compliance at the site level. (DAIDS) 1710

Clinical Sciences Review Committee (CSRC): The Division of AIDS internal scientific 1711 review committee responsible for the programmatic review of therapeutic protocols 1712 sponsored by DAIDS. The review will include careful assessment of the scientific 1713 objectives, design, safety, ethics, and feasibility of proposed research protocols. 1714 Scientific representatives from collaborating NIH Institutes and Centers participate as 1715 appropriate. (DAIDS) 1716

Clinical trial: A research study in which one or more human subjects are prospectively 1717 assigned to one or more interventions (which may include placebo or other control) 1718 to evaluate the effects of those interventions on health-related biomedical or 1719 behavioral outcomes (NIAID) 1720

Code of Federal Regulations (CFR): Published by the U.S. Office of the Federal 1721 Register National Archives and Records Administration, these are detailed procedures 1722 for meeting requirements authorized by law: 1723

Title 21: Food and Drugs (covers regulations administered by FDA as authorized 1724 by the Food, Drug and Cosmetic Act). 1725 Title 45: Public Welfare (includes regulations administered by Office for Human 1726 Research Protections (OHRP) relating to the protection of human subjects). 1727 (DAIDS) 1728

Curriculum Vitae (CV): A statement of investigator’s qualifications including 1729 professional experience accomplishments, educational background, and any 1730 publications. This document is required for all initial protocol registrations. (DAIDS) 1731

Division of AIDS (DAIDS): One of six divisions within the National Institute of Allergy 1732 and Infectious Diseases. DAIDS is responsible for the initiation, management, and 1733 oversight for the clinical trials and research that is sponsored and/or supported by 1734 NIAID (DAIDS). (DAIDS) 1735

DAIDS Protocol Registration Office (PRO): An office within the DAIDS Regulatory 1736

60

Support Contract (RSC) that receives and processes all protocol registration materials 1737 for DAIDS. (DAIDS) 1738

DAIDS Protocol Registration System (DPRS):An internet-based system that allows 1739 DAIDS Clinical Research Sites (CRS) to submit and track all documents submitted to the 1740 DAIDS Protocol Registration Office (PRO).(DAIDS) 1741

DAIDS Regulatory Support Contract (RSC): A contract that provides clinical, regulatory 1742 and technical support services for NIAID (DAIDS)-supported and/or - sponsored clinical 1743 trials. (DAIDS) 1744

DAIDS-sponsored: DAIDS is responsible for the management (including submission of 1745 the Investigational New Drug Application (IND) and Investigational Device Exemption 1746 (IDE) Application to FDA, and initiation of the study) and oversight for the trial. (DAIDS) 1747

DAIDS-supported: Clinical research activities would be considered to be supported by 1748 NIAID (DAIDS) under one or more of the following circumstances: 1749

1750

1. DAIDS provides direct funding to an institution via a grant, contract or 1751 cooperative agreement for the clinical research activities; or indirect funding via 1752 a subcontract executed under a DAIDS-supported award to another institution 1753

2. DAIDS provides other tangible support for the clinical research activities which 1754 includes, but is not limited to, regulatory support, site monitoring services, study 1755 product supply, management and distribution services. 1756

3. DAIDS-supported central laboratory or data management center receives from 1757 other organizations specimens or data for processing or analysis and the 1758 results or analyses, will be used to direct involvement of participants in clinical 1759 research activities. (DAIDS) 1760

1761 Electronic Protocol Registration (EPR): An alternate way CRSs can submit 1762 registration materials via email to the DAIDS PRO if they encounter problems 1763 when trying to submit registration materials through the DPRS. (DAIDS) 1764

Food and Drug Administration (FDA): A public health agency within the United 1765 States (U.S.) Department of Health and Human Services. FDA’s mission is to 1766 promote and protect public health by helping safe and effective products reach 1767 the market in a timely way and monitoring products for continued safety after 1768 they are in use as authorized by The Federal Food, Drug and Cosmetic Act. 1769 (DAIDS) 1770

Form FDA 1572: FDA required document in which clinical investigators agree 1771 to conduct the clinical trials according to U.S. federal regulations. The Form FDA 1772 1572 is signed and a copy submitted to the IND sponsor. (DAIDS) 1773 Full Version Protocol Amendment: Protocol modifications that result in a 1774 change in protocol version number. This new protocol version incorporates any 1775 currently proposed changes in addition to those made in all Clarification Memos 1776 (CMs) and Letter of Amendments (LOAs) that have been approved since the 1777 finalization of the previous protocol version. (DAIDS) 1778 Institutional Biosafety Committee (IBC): Committee set up by an institution 1779 under NIH guidelines to review recombinant DNA research and ensure its 1780 appropriate use. IBCs may also review other bio hazardous research, including 1781 select agents. (NIAID) 1782

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Institutional Review Board/Ethics Committee (IRB/EC): Committee used by an 1783 institution to ensure the protection of human subjects by independently 1784 approving, modifying, or disapproving research protocols. (NIAID) 1785

Investigational New Drug (IND) Application: A request for authorization from 1786 the FDA to administer an investigational drug or biological product to humans. 1787 Such authorization must be secured prior to interstate shipment and 1788 administration of any new drug or biological product that is not the subject of 1789 an approved New Drug Application or Biologics/Product License Application. 1790 (FDA) An IND application is required by the FDA before clinical trials of an 1791 investigational drug or biological agent may be initiated. An IND is also generally 1792 required if the U.S. FDA has not approved the route of administration, dosage 1793 level, or patient population for the drug or biological agent. (DAIDS) 1794

Investigator of Record (IoR): The individual at the CRS responsible for ensuring 1795 that a clinical trial is conducted in accordance with the protocol, applicable 1796 U.S. federal regulations, in-country regulations and any provisions imposed by 1797 the reviewing IRB/EC/other regulatory entity. This person is the signatory for the 1798 Form FDA 1572 for studies conducted under an IND or the DAIDS Investigator of 1799 Record Form for non-IND studies. 1800

Investigator of Record (IoR) Form: A document required by DAIDS for non-1801 IND studies. By signing the document, the IoR accepts full responsibility for 1802 conduct of the trial at their CRS. (DAIDS) 1803

Letter of Amendment (LoA): A revision to a protocol made by the Protocol 1804 Team/Chair/Awardee through a letter that requires DAIDS final approval/sign-off 1805 before implementation. Changes described in a LoA are listed in a document that 1806 is separate from the protocol document itself and will NOT result in the 1807 change to the DAIDS protocol version number. (DAIDS) 1808

National Institute of Allergy and Infectious Diseases (NIAID): NIH institute 1809 that conducts and supports research to understand, treat, and prevent 1810 infectious, immunologic, and allergic diseases. (NIAID) 1811

National Institutes of Health (NIH): A Federal agency whose mission is to 1812 improve the health of the people of the United States. NIH is a part of the Public 1813 Health Service, which is part of the U.S. Department of Health and Human 1814 Services. (NIH) 1815

Observational Study: A type of study in which individuals are observed or 1816 certain outcomes are measured, but no treatments or interventions are assigned 1817 by the study. (DAIDS) 1818

Office for Human Research Protections (OHRP): U.S. Department of Health 1819 and Human Services (DHHS) office overseeing human subject protection 1820 regulations for HHS-supported research. (NIH) 1821 Office for Policy in Clinical Research Operations (OPCRO): An office in DAIDS 1822 that provides a variety of clinical research management resources and 1823 oversight to the DAIDS clinical research portfolio. This includes overseeing the 1824 development, standardization, implementation and execution of policies, 1825 procedures and standards of conduct for all of DAIDS domestic and international 1826 clinical research. (DAIDS) 1827

Prevention Sciences Review Committee (PSRC): The Division of AIDS internal 1828 scientific review committee responsible for the programmatic review of vaccine 1829

https://www.niaid.nih.gov/research/daids-clinical-research-glossary

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and prevention protocols sponsored by DAIDS. The review will include careful 1830 assessment of the scientific objectives, design, safety, ethics, and feasibility of 1831 proposed research protocols. Scientific representatives from collaborating NIH 1832 Institutes and Centers participate as appropriate. (DAIDS) 1833

Protocol Registration Notifications: The following are notifications that a CRS 1834 may receive from the DAIDS PRO: 1835

1. Confirmation of Submission - A notification sent out to the CRS 1836 Coordinator and IoR confirming that registration materials have been 1837 successfully submitted to the DAIDS PRO. If a CRS does not receive 1838 a Confirmation of Submission Notification within 24-48 hours of 1839 submitting registration documents to the DAIDS PRO, the CRS should 1840 contact the DAIDSPRO to find out how to proceed. 1841

2. Registration Notification - A final notification from the DAIDS PRO 1842 indicating that a CRS has successfully completed the protocol 1843 registration process. 1844

3. Registration with Required Corrections Notification -A notification from 1845 the DAIDS PRO indicating that a CRS must make required 1846 corrections and submit them to their IRB/EC for review and approval 1847 OR must submit justification for why the required correction will not 1848 be made within 120 calendar days of the date the Registration with 1849 Required Corrections Notification was issued. A Registration with 1850 Required Corrections Notification indicates that a CRS may begin using 1851 the site- specific informed consent forms (ICFs) after protocol activation 1852 by the appropriate Operations Center, Data Management/Statistical 1853 Center or DAIDS Program. 1854

4. Disapproval Notification - A notification from the DAIDS PRO indicating 1855 that the site-specific informed consent forms (ICFs) do not include all the 1856 required basic and additional elements to comply with U.S. federal 1857 regulations and DAIDS policy. The Disapproval Notification will outline 1858 the deficiencies that must be revised/corrected before a final 1859 Registration Notification can be issued. All revised site-specific ICFs 1860 must be approved by the IRB/EC prior to submission to the DAIDS PRO. 1861 A disapproval notification is NOT a final notification since corrective 1862 materials must be resubmitted. 1863

5. Deregistration Notification - A final notification from the DAIDS PRO 1864 indicating that a CRS is no longer registered to a study and all 1865 associated sub-studies. 1866

6. Change of IoR Approval Notification – A final notification from the 1867 DAIDS PRO indicating that DAIDS has approved the change of IoR for 1868 a protocol at a CRS. 1869

7. Requested Materials Notice - A message from the DAIDS PRO 1870 indicating that additional/corrected materials are required as a result 1871 of an incomplete or inaccurate submission to the DAIDS PRO. 1872

1873 A Materials Request Notification stops the registration review process until the 1874 requested materials have been received at the DAIDS PRO. (DAIDS) 1875 1876 Protocol Registration Team (PRT): A team within OPCRO responsible for 1877 managing the Protocol Registration (PR) process, which includes oversight of 1878 the DAIDS PRO. (DAIDS) 1879

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Regulatory Entity (RE)/Approving Entity - Any group other than the local 1880 IRB/EC responsible, for reviewing and/or approving a clinical research protocol and 1881 site- specific ICFs prior to implementation at a site. For example, in some 1882 states within the U.S., institutional approvals are required since these states 1883 have research regulations in addition to the federal human subjects protection 1884 regulations detailed in U.S. federal regulations (45 CFR 46).In addition, at many 1885 non-U.S. sites, other approvals may be required in addition to the local IRB/EC 1886 approval, which include but are not limited to approvals from ministry of health, 1887 national regulatory agency, in-country drug control council, national IRB/EC, or 1888 other government agency. (DAIDS) 1889

Sub-Investigator: Any member of the clinical research team designated and 1890 supervised by the CRS Leader/IoR of a protocol at a CRS to perform critical 1891 trial related procedures and/or to make important clinical trial-related decisions. 1892 (DAIDS) 1893

Sub-Study: A sub-study asks a separate research question from the parent 1894 protocol and may or may not contribute to the parent protocol’s objectives but 1895 uses all or a subset of study participants or specimens. A sub-study can be 1896 included as part of the main/parent protocol document or may not be included in 1897 the main protocol but requires current or previous participation in the main protocol. 1898 (NIAID) 1899

1900

The following are different types of sub-studies that a site may protocol register: 1901

1. Embedded Sub-study - A sub-study that is part of a main protocol 1902 that may or may not have a separate ICF. Embedded sub-studies 1903 have the same protocol version number as the main study and 1904 have a separate protocol number and/or DAIDS protocol ID number. 1905 If there is a full version Amendment to the main study , when protocol 1906 registering to the amendment, sites are required to protocol register 1907 to all embedded sub-studies. A CRS will receive a registration 1908 notification for each embedded sub-study that is submitted for 1909 protocol registration. LOA registrations are only completed under the 1910 Main study however if the LOA requires revision to the sub-study IC, 1911 than the site IC should be submitted under the sub-study as a Site 1912 Revised IC. 1913

2. Stand Alone Sub-study - A sub-study that is not part of the main 1914 protocol but requires participants to be enrolled in the main study 1915 or have previously participated in the main study. A stand-alone 1916 sub-study is an independent protocol that may or may not have the 1917 same protocol version number/date as the main study and will 1918 always have a separate protocol number and/or DAIDS protocol 1919 ID number. A CRS should submit all required documents (i.e. 1920 IRB/EC approval letter[s], site-specific informed consent form[s], 1921 Form FDA 1572 and/or DAIDS IoR Form, and IoR CV) when 1922 registering to a stand- alone sub-study. A CRS will receive a 1923 registration notification for each stand-alone sub-study that is 1924 submitted for protocol registration. (DAIDS). Amendment and LOA 1925 registrations should be submitted independently from the main study. 1926

1927

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VIII. DAIDS Protocol Registration Office Contact Information and DPRS Access 1928

The DAIDS Protocol Registration Office (PRO) has two different e-mail addresses: 1929 one for submission of protocol registration documents and a second for 1930 questions and general correspondence. 1931

1932 A. Contact Information for Questions and General 1933 Correspondence: 1934

EMAIL: [email protected] PHONE: 301-897-1707 1935 OFFICE HOURS: Monday through Friday 8:30 AM to 5:00 PM (U.S. Eastern 1936 Standard Time) 1937

1938 Effective January 2012, all sites participating in NIAID (DAIDS)-supported and/or 1939 - sponsored clinical research that requires protocol registration, are required to 1940 submit protocol registration materials to the DAIDS PRO through the DAIDS 1941 Protocol Registration System (DPRS). Information on the DPRS and how to access 1942 the system is available on the DPRS website or information on how to submit 1943 protocol registration materials through the DPRS once a CRS has received a 1944 user name and password, refer to Appendix A of this manual. 1945

1946 In order to gain access to the DPRS, site personnel must complete the DPRS 1947 training that’s available online at DAIDS Learning Portal. 1948 First, log in to the DAIDS Learning Management System (LMS) with your user 1949 name and password. Then enter DPRS into the search field, and select the DPRS 1950 training course. If you do not have a DAIDS LMS account click to request account 1951 access. 1952 At the time of completion of the DPRS training, a username and password will 1953 be provided to the person who completed the training. If DPRS login details have 1954 not been received, contact DAIDS-ES Support at [email protected] 1955

1956 If a CRS encounters problems when submitting protocol registration materials 1957 through the DPRS, a CRS can submit protocol registration materials via e-mail 1958 to the DAIDS Electronic Protocol Registration (EPR) mailbox. If a CRS submits 1959 materials through the EPR mailbox, the email message must outline the details 1960 of what is being submitted, and the kind of registration that is being submitted. 1961

1962


https://ncrms.niaid.nih.gov/NCRMS/Main/Login.aspx

https://daidslearningportal.niaid.nih.gov/

https://www.daidslearningportal.com/user/register



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1963 1964

Information on protocol registration timelines is available on the RSC web site under 1965 the “Protocol Registration” section. 1966

1967 B. Appendix A - Instructions On How To Access & Submit Protocol 1968 Registration Materials Through The DAIDS Protocol Registration 1969 System (DPRS) 1970

1971 How do I gain access to DPRS? 1972

C. DPRS Access 1973 1. DPRS can be accessed via the DAIDS Learning Portal. DPRS Training 1974 completion is required to gain DPRS access. Log into the DAIDS Learning 1975 Management System (LMS) with your user name and password. Then enter 1976 DPRS into the search field, and select the DPRS training course. If you do 1977 not have a DAIDS LMS account click here to request account access. 1978 1979 2. Once the DPRS training has been completed, DPRS user log-in and 1980 password will be sent to the trainee. If the training has been completed, but 1981 have not received DPRS login details yet, contact DAIDS-ES Support at 1982 [email protected]. 1983

1984 D. How do I access the New Submission screen? 1985

1986 1. Go to the DAIDS Protocol Registration Page. Enter your user name and 1987 password and click Login. 1988

1989 2. From the Home Page, click Submission on the main navigation bar 1990 and then click New Submission from the drop-down menu, which takes you 1991 to the New Submission page. 1992

1993 Figure 1: New Submission Option 1994 1995 1996

1997 1998 1999

E. How do I complete the Site Submission process? 2000 2001

1. Enter the Submission Details: Enter the appropriate information under the 2002 Site & Protocol details heading. Click the LOV icon to select the Site, IoR and 2003 Protocol No. Click the list of values to select the version/LOA. 2004





https://ncrms.niaid.nih.gov/NCRMS/Main/Login.aspx

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2005 2. Select Sub-Studies: This list of values displays all embedded sub-studies 2006

associated with the study. Select a sub-study displayed to submit materials 2007 for the sub-study along with the study. The packet will be created when the 2008 main study is submitted. 2009

2010 3. Submissions: Select the appropriate checkboxes under the Submissions 2011 heading. 2012

Note: The system selects the same submission type for the sub-study as on 2013 the main study. 2014 2015

4. Next: Click Next. If the save is successful, the Upload Documents heading 2016 appears in the lower half of the screen. 2017 2018

5. Upload Documents: Click the upload icon to upload the appropriate documents. 2019 Enter notes to provide additional clarification. Click Save. 2020 2021 2022 2023

Figure 2: Enter details in the New Submission screen 2024

2025

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Figure 3: Upload documents in the New Submission screen and add notes 2026

2027 2028 2029 2030

6. Confirm Submission Details: When finished, click Submit. At the pop-up 2031 confirmation window, confirm the Site, IoR Name and Protocol No. Select the 2032 version and again click Submit. 2033

2034 The system confirms whether the submission was successful. 2035

2036 Figure 4: Confirm Submission Details 2037

2038 2039 2040 2041 2042 2043

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7. Optional: System will provide option to submit sub-study packets that have 2044 not yet been submitted by selecting a packet number at the top of the 2045 Notification screen. 2046

2047 2048 2049 Figure 5: Navigate to associated packets yet to be submitted 2050

2051 2052 2053 2054 2055 2056

F. How do I view the sub-study packet? 2057 2058

1. Select a packet number at the top of the screen to view any other associated 2059 packets for this study. The Sub-Study screen appears similar to the main 2060 submission except the Protocol Number is changed to the sub-study number. 2061 The submission type remains the same. 2062

2063 Note: You can use this feature to toggle between the sub-study packets. You 2064 also can copy person information to sub- study packets. 2065

2066 2. Click the Upload Documents hyperlink in the associated packets to copy 2067

documents from the main packet. 2068 2069

2070 2071 2072

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2073 2074 2075 Figure 6: Viewing the sub-study packet 2076

2077 2078 2079

G. Still Have Questions? 2080 2081

Email: [email protected] 2082 Phone: 1 (240) 778-2517 2083 2084


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