The document discusses collaboration between the National Institutes of Health (NIH) and the Food and Drug Administration (FDA) to develop a standardized clinical trial protocol template. In 2015, the NIH-FDA Joint Leadership Council agreed to jointly create a template to improve protocol quality. A working group from both agencies reviewed existing NIH templates and drafted a phase 2 and 3 template, which was posted for public comments. The template was further revised based on feedback and aligned with TransCelerate's template. The finalized NIH-FDA template was released in 2017.

1. December 2017
Collaboration with FDA and
NIH

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NIH Enhancing Stewardship of Clinical Trials

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NIH-FDA Protocol Template Initiative
March 2015: NIH–FDA Joint Leadership Council agreed to jointly develop a
clinical trial protocol template to improve quality of protocols received for
review
Goal of the template
Provide a standard protocol format
Provide instructions for writing a complete protocol
Working group consisted of NIH and FDA staff
NIH Program staff, FDA reviewers, IRB members, Statisticians, clinical operations, etc.
Reviewed over 13 NIH protocol templates
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NIH-FDA Protocol Template Development
February 2016: Draft phase 2 and 3 clinical trial protocol template posted for
public comment.
Numerous comments received from over 60 respondents and incorporated into
revised template
NIH-FDA Working Group met regularly with TransCelerate to harmonize format
of templates
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Benefit of a harmonized protocol template
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Patients
Burden
Time
Clarity
Quality
Sites
Workflows
Planning
Time
Regulators
Consistency
Automation
Traceability
Streamlined Review
Sponsors
Reduce human error
Automation
Traceability
IRBs
Consistency
Automation
Traceability
Streamlined Review

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CPT NIH-FDA
CPT and NIH-FDA Templates: Where we started

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Review of TransCelerate CPT and NIH-FDA templates
• Reviewed TOC and instructional content
• Found many similarities
• Used “best of” from each template
• Learned from comments from public, IRBs and FDA
• Agreed on flexibility within the template (2nd & 3rd level headings)
• Resulted in significant updates from previous versions
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How did we do this and what did we find?

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CPT NIH-FDA
Off to a good start?
12 Section Headers,
including Appendices
17 Section Headers,
plus Appendices

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A closer look
TransCelerate CPT
1.0 Synopsis
2.0 Schedule of Activities
3.0 Introduction
4.0 Objectives and Endpoints
5.0 Study Design
6.0 Study Population
7.0 Treatments
8.0 Discontinuation Criteria
9.0 Study Assessments &
Procedures
10 Statistical Considerations
NIH-FDA
Protocol Summary & Schematic
1.0 Key Roles
2.0 Introduction
3.0 Objectives and Purpose
4.0 Study Design & Endpoints
5.0 Study Enrollment & Withdrawal
6.0 Study Agent
7.0 Study Procedures and Schedule
8.0 Assessment of Safety
9.0 Clinical Monitoring
10 Statistical Considerations

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• Simplified TOC
• Moved sections and sub-sections:
– Prioritized sections for the user:
investigator & reviewers
• Moved Schedule of Activities to Protocol
Summary
• Harmonized Heading Titles
– Treatment v. Study Agent = Study
Intervention
• Harmonized subsections
– Introduction: Study Rationale,
Background, Benefit/Risk
Assessment
Alignment = Organization + Prioritization + Semantics
Harmonized Templates
1.0 Protocol Summary
2.0 Introduction
3.0 Objectives and Endpoints
4.0 Study Design
5.0 Study Population
6.0 Study Intervention
7.0 Discontinuation of SI & Ppt DC/Wd
8.0 Study Assessments & Procedures
9.0 Statistical Considerations
10 Supporting Doc & Oper. Consid.
11 References

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Best practices for intended users
• Quality in protocol development
• Site staff have one format
• FDA & IRB reviewers have one format
• Standards reduce error
• Facilitates automation and re-use
• Standard template supports a better INDs application
• FDA modernizes workflow, extract data elements
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Released
May 2017
NIH-FDA Phase 2 and 3 IND/IDE Clinical Trial Protocol
Template

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NIH Clinical e-Protocol Writing Tool

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Future Plans for NIH-FDA Template
• Develop behavioral intervention and phase 1 protocol templates using NIH-
FDA protocol format
• Add behavioral and phase 1 protocol templates and instructions to electronic
writing tool
• Consider developing ability to integrate with ClinicalTrials.gov registration,
IRB submissions, etc.
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Work Group Members From Several Offices
• Office of New Drugs (OND)
• Office of Strategic Programs (OSP)
• Office of Translational Sciences (OTS)
• Office of Biostatistics (OB)
• Office of Clinical Pharmacology (OCP)
• Office of Computational Sciences (OCS)
• Office of the Director (OD)/ Center for Biological Evaluation and Research
(CBER)
• Office of Cellular, Tissue and Gene Therapies (OCTGT)/ CBER
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NIH-FDA Joint Protocol
NIH
Michelle Culp
Cynthia Boucher
Christine Cutillo
Daniel Falk
Shanda Finnigan
Adam Haim
Barbara Karp
Petra Kaufmann
Lynette Nieman
Sarah Read
Megan Ryan
Galia Siegel
Steven
Sparenborg
Betty Tai
Aynur Unalp-Arida
James Witter
Anne Zajicek
FDA
Melissa Robb
David Cho
Owen Faris
Peter Kim
Peter Marks
Eileen Navarro-
Almario
Vaishali Popat
Rachel Sherman
TransCelerate CPT
Mitzi Allred, Merck
Ralf Bilke, BI
TK Booker, Amgen
Elizabeth Bygate, GSK
Susan Colby, BMS
Vivian Combs, Lilly
Rob DiCicco, GSK
Robert Ferendo
Nareen Katta, AbbVie
Diane Klatzman, J&J
Bill Lander, GSK
Amy Leishman, Lilly
Mark Makurath, Merck
Frederik Malfait
Virginia Nido, Roche
Nils Schlote, Roche
Cathy Stein-Izsak, Allergan
Stacy Tegan, Accenture
FDA CPT Working Group
Vaishali Popat, OND IO
Peter Kim, OND/OAP/DAIP
Lisa Soule, OND/ODEIII/ DBRUP
Martin Rose, OND/ODEI/DCRP
Bob Temple, CDER/OCD
Milena Lolic, CDER/OCD/PASE
Ray Chiang, CDER/OMP
Stephanie Shapley, CDER/OMP
Melissa Robb, CDER/OMP
Steve Wilson, OTS/OB
Robert ONeill, CDER/OTS
Sirisha Mushti, OTS/OB
Che Smith, OTS/OB
David Petullo, OTS/OB
Lili Garrard, OTS/OB
Ron Fitzmartin, CDER/OSP
Ta-Jen Chen, CDER/OSP
Jeff Florian, OTS/OCP
Eileen Navarro Almario, OTS/OCS
Daniela Vanco, CBER/OD
Robert Sokolic, CBER/ OCTGT
Provided comment separately on CPT:
OSI, CDRH offices,
OND/DPP (Mitchell Mathis)

18. Thank you