Managing a NIAID Grant: a grantee experience

Dr Mina John

Centre for Clinical Immunology & Biomedical Statistics

Royal Perth Hospital & Murdoch University

Western AustralianHIV Cohort Study

Western AustralianHIV Cohort Study

The Centre for Clinical Immunology & Biomedical Statistics Royal Perth Hospital & Murdoch University

Centre research scientists, employees and visiting research fellows July 2005

WA HIV COHORT

STUDY est. 1987

BIOSTATISTICS COMPUTING

HLA GENOTYPING SERVICES

MHC RESEARCH

Simon Mallal & Ian JamesThe Centre for Clinical Immunology &

Biomedical Statistics

Royal Perth Hospital & Murdoch University

GENOMICS LAB

TECHNOLOGY

HLA & HIV co-evolution

HLA-BHLA-BCodingCoding Coding (minus Exons 1-3)Coding (minus Exons 1-3)

0.005

0.005

0.02

WA White

ACTG Hispanic

Black

ACTG White

HIV NEF (clade B)HIV NEF (clade B)

Host gene HIV gene

AcuteInfection

AIDSTIME

HLA-restricted T cell response Viral load

Escapes from current host RCReversions from previous host(s) RC

HIV adaptation to HLA in-vivo to optimise fitnessHIV adaptation to HLA in-vivo to optimise fitness

HLA associations identify sites of immune recognition & selection1

TAFTIPSI non-adapted/revertantTAFTIPSV adapted/escapedTAFTIPST adapted/escaped2

C Moore et al, Science 2002, 296; 1439

C Moore et al, Science 2002, 296; 1439

“HIV 1 adaptation to HLA-restricted immune responses: viral and host

determinants and implications for HIV-1 vaccines” 2004 - 2009

• Large, ‘representative’ national population to study• Reflect contemporary viral diversity• Pre-treatment plasmas available stored at -80• Source of DNA • Contemporaneous viral load/CD4 count• Good epidemiologic and clinical data collection &

retrieval• Centralized specimen and DNA repositories• Potential synergies with therapeutics and drug

resistance research

About the AACTG

• Largest HIV clinical trials organization in the world• Highly influential in setting standards of care for HIV/AIDS in

the US and the developed world.• Broad scientific, therapeutic, and pathogenesis-based research

agenda• Well established infrastructure for data and sample management• Directed by clinical scientists in HIV/AIDS therapeutic research. • Funded by the DHHS, NIH through the NIAID

Protocol 5142: “A phase III, Randomized, Open-Label Comparison of Lopinavir/Ritonovir Plus Efavirenz Versus Lopinavir/Ritonavir Plus 2 NRTIs Versus Efavirenz Plus 2 NRTIs as Initial Therapy for HIV-1 Infection”

Co-enrolled in

Protocol 5128: “A multi-investigator/institutional DNA bank for AIDS related human genetic studies”

Preparing the application:

The ACTG

Targeting an R01 announcement

Letter of intent

Establishing dialogue with the Scientific Review Administrator (SRA)

Preparing the application:preliminary communications

The submission

The two-stage scientific review

Just in Time Concepts

Submission

The submission: Key Ingredients

•Pressing research question – consistent with NIAID priorities

•Capability for conducting the research does not exist in the US

•Long term collaborators/research colleagues in the US or international

•Key people identified as investigators

•A dedicated administrative person within research group who can: coordinate the submission and liaise with all parties involved

•Sound understanding of the ethical principles - how to address them in the application.

•Communication with the Grants Administrator

Key Ingredients: The applicant team

Key Ingredients: the FWA

Local IRB registration with the Office of Human Research Protections (OHRP)

FWA: Federalwide Assurance Number: required for all documents pertaining to HREC processes

Ongoing communication with local IRB

NIAID Foreign Organization

System Review

These are typically under resourced and burdened by pharmaceutical trials

Provide ‘complete’ cover letters and lay descriptions using plain language

Ongoing reporting requirements – provide draft documentation especially if ‘expert’ knowledge of the grant/research is required.

Local IRB considerations

Annual reporting

Electronic submission – 1. Progress report2. Annual Financial Status Report 3. Annual Report of Possible Research Misconduct

Obtain ethics renewal documentation

Other thoughts…..

Acknowledgements• National Institutes of Health• National Health and Medical Research

Council• American AIDS Clinical Trials Group• Centre for Clinical Immunology and

Biomedical Statistics• Royal Perth Hospital Department of

Medical Illustrations: Brydon Dunstan • Royal Perth Hospital Art Collection:

Curator of Artwork, Lancelot Hyde