CPTR RDST Data Platform Concept September 22, 2014
Outline • C-Path overview and examples of data projects • Knowledge sharing concept • RDST approach • Examples of RDST data types • Database architecture • Next steps – timeline CPTR-RDST Data Platform 2014 Workshop Slides 2
C-Path Consortia Seven global consortia developing novel drug development tools Coalition Against Major Diseases UNDERSTANDING DISEASES OF THE BRAIN Critical Path to TB Drug Regimens Biomarkers TESTING DRUG COMBINATIONS Clinical Outcome Multiple Sclerosis Outcome Assessments Consortium Assessment DRUG EFFECTIVENESS IN MS Instruments Polycystic Kidney Disease Consortium Clinical Trial NEW IMAGING BIOMARKERS Simulation Tools Patient-Reported Outcome Consortium In vitro tools DRUG EFFECTIVENESS Data Standards Electronic Patient-Reported Outcome Consortium DRUG EFFECTIVENESS Predictive Safety Testing Consortium DRUG SAFETY 3
C-Path Online Data Repository CDC TB study data now available MSOAC Current C-Path examples CAMD – AD Clinical Trial Simulation Tool PKD - Biomarker Qualification Project MSOAC – New Outcome Assessment Instrument for MS 4
Datasets contributed to C-Path for consortia projects Number of # of Total Number Consortium Therapeutic Area Data Studies of Subjects Contributors Coalition Against Alzheimer's disease 27 7340 11 Major Diseases Parkinson's disease 7 2597 2 Critical Path to Tuberculosis 10 2495 5 TB drug Regimens MS Outcome Multiple sclerosis 6 4700 4 Assessments Consortium Polycystic kidney Polycystic Kidney Disease 5 2941 4 disease Normal healthy 1 172 1 volunteer-kidney Skeletal-muscular Predictive 38 1766 6 (non- clinical) Safety Testing Hepato-toxicity 43 2340 7 Consortium (non-clinical) Nephro-toxicity 14 941 8 (non-clinical) 5
Value of data sharing, data standards & data pooling Start Point Nine member companies agreed to share data from 24 Alzheimer’s disease (AD) trials The data were not in a common format The data were remapped to the CDISC AD standard and pooled Result A new clinical trial simulation tool was created and has been the first model endorsed by the FDA and EMA 24 studies, >6500 patients Researchers utilizing database to advance research 6
Access to AD Model endorsed data available to by FDA and EMA qualified researchers 7
Future TB model 8
Rapid DST TB Data Sharing Platform Architecture Concept 9
Data Platform to Inform Assay Development How do we build this system? CPTR TB Drug Resistance DB Linking Global TB Sequence Researchers Validated DR biomarkers • TB sequence community inputs • Expert review to advance investigational biomarkers to validated status Analysis files Analysis files Analysis files • Can use separate or generated generated generated consolidated DBs • FDA compliant CDISC architecture Investigational DB for regulatory submission DB Sequence repository Approved members Anonymized sequence data • Academic labs Expert Clinical annotation • Reference labs Approved Phenotypic methods Panel • Commercial companies biomarkers Review User friendly cloud interface • Others… Analysis files Analysis files Analysis files generated generated generated CPTR-RDST Data Platform 2014 Workshop Slides 10
How do we accomplish this? • Clear objective – Improved research resource to enable development of new rapid diagnostics for TB • Future objective – With sustainability funding: resource for clinicians • Build on previous efforts for TB and for data sharing – Apply technology product development discipline – Design to handle wide range of data types – Quality criteria and defined process for incoming data – Lean, efficient and well managed implementation – Expandable / adaptable / flexible – Great usability • Strong alignment with anticipated analysis use cases CPTR-RDST Data Platform 2014 Workshop Slides 11
Related efforts: TBDReamDB http://www.tbdreamdb.com/index.html CPTR-RDST Data Platform 2014 Workshop Slides 12
Example of future objective: Stanford HIV database http://hivdb.stanford.edu/ CPTR-RDST Data Platform 2014 Workshop Slides 13
Product development discipline • Detailed, documented requirements Requirements • Early prototyping Prototype • Design to requirements • Staged development with clear milestones Design • Extensive testing Build – Verification of all features and function – Usability Test – Performance – Scalability Deploy • Phased rollout – RDST members Support and enhance – Qualified external researchers • Ongoing support and enhancements based on user feedback CPTR-RDST Data Platform 2014 Workshop Slides 14
RDST Data: multiple data types Need to incorporate multiple types of data • sequence data • SNP reports • resistance test data • clinical trial/study/registry data • external information resources • any other data that may be necessary Which need to be analyzed to find and validate correlations CPTR-RDST Data Platform 2014 Workshop Slides 15
RDST Data: genotypic data example TB FASTQ file – 650 MB uncompressed @M00347:61:000000000-A9B8J:1:1101:15324:1677 1:N:0:1 TCTTGATCGCGAGTTCGCGGCCCGGGGTGAGCACCCAGGTGAGCGGGAAATGCGTGGTGTCGTGGTAGCTGACGTCGACGATGCCGTGGCG + 11>>1@BF1>>11AEF00000AA////A//A1AB/?/GAEC1GBE??///FFG/?E?EFHF/F?A?EG1BDBC/FCGGCC<FACHCCG/>CC-.<>10<<-< @M00347:61:000000000-A9B8J:1:1101:15765:1689 1:N:0:1 TGCGATTGCAGCGCGTCGGCGTCGGTGGTGTAACCGGTCTTGGTCTTCTTGGTCTTCGGCATCTCCAGCTCGTCGAACAGAACGGCCTGCA sequence data with quality info + 11111>A1D31B1A0EE00A/EA//E//EAFGHHFGCEEGHDBHHHHHHHBDHHHHFG/E?EHHHGFFGHHGEFG?FHGEEHHEGGGGGHGGH @M00347:61:000000000-A9B8J:1:1101:15578:1705 1:N:0:1 CTCGACGTCGGCAAGGGTCAGGTCGTGGTGGTGCTCGGCCCCTCGGGCTCGGGCAAATCGACGTTGTGCCGCACGATCAATCGCCTCGAG + 1>11>ADDA?1000000BFFFFHF0E?/AFEECGHH//AEEEGGEC?GGH?/@@GGFHHE0EEEFHGGHHGGGEGGHHGHFHGGGGGG/CHGG @M00347:61:000000000-A9B8J:1:1101:13636:1714 1:N:0:1 CGATTCGACGGCCTGTTCATCGCCGACGTGCTCGGTACCTACGACGTGTACGGCGGCAGCGACGAGGCCGCGATCCGTCACGCCGCGCAG + 111>AFABA1@AAEFGGGFGFFCFA?E/EFHGHGGGHGHHHHE?FGGGHHHHGGGGGEEECEGGGG?CGGGGGGGGHGHGGCFGCCGGG @M00347:61:000000000-A9B8J:1:1101:15489:1729 1:N:0:1 TATCGGAAGAGCACACGTCTGAACTCCAGTCACACAGTGATCTCGTATGCCGTCTTCTGCTTGAAAAAAAAAAAACAAACCAATAAACAA CPTR-RDST Data Platform 2014 Workshop Slides 16
RDST Data: SNP report example SNP reports CPTR-RDST Data Platform 2014 Workshop Slides 17
RDST Data: phenotypic data example resistance test data https://tbdr.org/cgi/tbdr CPTR-RDST Data Platform 2014 Workshop Slides 18
RDST Data: clinical data example (hypothetical data) STUDYID DOMAIN USUBJID AGE SEX RACE ARM 19 DM 10001 27 F WHITE Ethambutol 5 Times Per Week 19 DM 10002 63 M WHITE Moxifloxacin 3 Times Per Week 19 DM 10003 42 M BLACK OR AFRICAN AMERICAN Moxifloxacin 5 Times Per Week 19 DM 10004 30 F ASIAN Moxifloxacin 5 Times Per Week 19 DM 10005 29 M BLACK OR AFRICAN AMERICAN Moxifloxacin 3 Times Per Week 19 DM 10006 35 M BLACK OR AFRICAN AMERICAN Ethambutol 3 Times Per Week STUDYID DOMAIN USUBJID MBTESTCD MBTEST MBORRES MBSPEC VISIT 19 DM 10007 46 F UNKNOWN Ethambutol 3 Times Per Week 13 MB 10001 AFB Acid Fast Bacilli NEGATIVE SPONT SPUTUM WEEK 8 19 DM 10008 34 F BLACK OR AFRICAN AMERICAN Moxifloxacin 5 Times Per Week 19 DM 10009 55 M BLACK OR AFRICAN AMERICAN Ethambutol 3 Times Per Week 13 MB 10001 ORGANISM Organism Present NEGATIVE FOR TUBERCULOSIS SPONT SPUTUM WEEK 4 19 DM 10010 42 M ASIAN Moxifloxacin 5 Times Per Week 13 MB 10001 MTBINH M.tuberculosis INH Resistant POSITIVE NON-OVERNIGHT SP SCREENING 19 DM 10011 23 F BLACK OR AFRICAN AMERICAN Ethambutol 3 Times Per Week clinical trial data 19 DM 10012 47 F WHITE Ethambutol 3 Times Per Week 15 MB 10001 ORGANISM Organism Present NEGATIVE FOR TUBERCULOSIS SPONT SPUTUM WEEK 4 19 DM 10013 25 F BLACK OR AFRICAN AMERICAN Moxifloxacin 5 Times Per Week 13 MB 10002 AFB Acid Fast Bacilli NEGATIVE SPONT SPUTUM WEEK 8 19 DM 10014 21 M WHITE Ethambutol 3 Times Per Week 19 DM 10015 79 M WHITE Moxifloxacin 3 Times Per Week 13 MB 10002 ORGANISM Organism Present POSITIVE FOR M. TUBERCULOSIS COMPLEX SPONT SPUTUM SCREENING 19 DM 10016 27 F ASIAN Moxifloxacin 3 Times Per Week STUDYID DOMAIN USUBJID MOTESTCD MOTEST MOORRES MOSTRESC MOLOC VISIT MODY 19 DM 10017 37 M BLACK OR AFRICAN AMERICAN Ethambutol 3 Times Per Week 15 MB 10002 ORGANISM Organism Present POSITIVE FOR M. TUBERCULOSIS COMPLEX SPONT SPUTUM SCREENING 17 MO 10001 CAVIT Cavitation Y Y LUNG, LEFT SCREENING -4 19 DM 10018 28 M BLACK OR AFRICAN AMERICAN Moxifloxacin 3 Times Per Week 13 MB 10003 ORGANISM Organism Present NEGATIVE FOR TUBERCULOSIS INDUCED SPUTUM WEEK 4 17 MO 10002 CAVIT Cavitation Y Y LUNG, LEFT SCREENING -5 15 MB 10004 ORGANISM Organism Present NEGATIVE FOR TUBERCULOSIS SPONT SPUTUM WEEK 4 17 MO 10002 PLEURALDPleural Disease N N LUNG, LEFT SCREENING 1 17 MO 10004 PLEURALDPleural Disease N N LUNG, LEFT SCREENING -8 17 MO 10005 CAVIT Cavitation N N LUNG, LEFT SCREENING -9 17 MO 10005 CAVIT Cavitation N N LUNG, LEFT SCREENING -15 17 MO 10006 CAVIT Cavitation Y Y LUNG, LEFT SCREENING 1 17 MO 10006 PLEURALDPleural Disease N N LUNG, LEFT SCREENING -7 CPTR-RDST Data Platform 2014 Workshop Slides 19
Recommend
More recommend
