Managing a NIAID Grant: a grantee experience Dr Mina John Centre for Clinical Immunology & Biomedical Statistics Royal Perth Hospital & Murdoch University W estern Australian HIV Cohort Study W estern Australian HIV Cohort Study
Jan 04, 2016
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