T16 Phase I studies – Phase I units and you, a Phase I unit’s expectation – A Day in the Life of a Phase I Study Coordinator Jeffery Wong, Clinical Research Coordinator, Nucleus Network Ltd

A Day in The Life of A Study Coordinator Main objectives: –To create awareness and a better understanding of a Phase I clinical research co-ordinator’s (CRC) role –To provide an understanding of the intensity of Phase I clinical trials –To highlight some of the differences between Phase I trials and later phase trials

A Day in The Life of A Study Coordinator Clinical Research Co-ordinator Principal Investigator Ethics Committee Technical/ Study Logistics Recruitment/ Screening Clinical Trials Pharmacy Data Management Subjects/ Participants Commercial Sponsor

A Day in The Life of A Study Coordinator Principal Investigator Report and discuss any adverse events as well as any subject safety concerns. - Daily updates if conducting MAD study Provide PI with periodic update on study progress. Ethics Committee Prepare ethics submission package in conjunction with Project Manager Provide safety updates, submit amendments and obtain approvals. i.e. fortnightly safety reports. Provide annual progress reports.

A Day in The Life of A Study Coordinator Commercial Sponsor Provide updates to Sponsor/CRA pertaining to recruitment and progress of study. Clarify specific protocol requirements i.e. inclusion/exclusion criteria, study procedures. Confirm timeline for DSMB and the data required for evaluation. DSMB meetings could be fortnightly. Provide daily AE and safety lab updates via . SAE reporting.

A Day in The Life of A Study Coordinator Recruitment/Screening Ensure adequate subjects are recruited for each study including availability of alternate subjects. Up to 4 – 6 volunteers being screened daily Average screening window is 28 days Ensure exclusion/inclusion criteria are clear to minimise ratio of screen failures. Patient/Subject Ensure subjects’ compliance and their understanding of each study’s requirements. Ensure subjects’ safety and comfort whilst participating in a study i.e. laundry, catering, entertainment etc.

A Day in The Life of A Study Coordinator Technical/Study Logistics Ensure study related samples i.e. PK, PD and PGx are appropriately processed and shipped to specified destination as indicated in study protocol. Shipment could occur on the same day after last sample is collected. Liaise with technical lead to ensure study laboratory requirements are adequate. Liaise with other contracted laboratories i.e. Melbourne Path, Alfred Path etc. Short turnaround time for results.

A Day in The Life of A Study Coordinator Clinical Trials Pharmacy Provide prescriptions to Clinical Trials Pharmacy for dispensing of IP –Dispensing of IP could take place on the morning of dosing. Ensure proper destruction/return of IP post dosing – IP accountability. Data Management Ensure completeness of source documentation. Ensure CRF transcription is performed in a timely manner in accordance with pre-defined timelines. Ensure open queries are resolved.

A Day in The Life of A Study Coordinator Scenario Study 1: Dosing Day Very intense with all activities running by the clock. –Triplicate ECGs, Supine/Seated/Standing vitals, multiple blood sampling time points Every team member needs to know their role and be on stand by to provide assistance. Every change in circumstances result in a chain reaction i.e. delay in dosing. Food effect trials have additional concerns i.e. meal times & type of food. Sponsors may witness dosing or require verbal updates on day of dosing.

A Day in The Life of A Study Coordinator Day BREAKFAST7:007:207:408:008:208:40 Chest Auscultation7:107:307:508:108:308:50 IOP Assessment7:157:357:558:158:358:55 Subject Supine/Remove water7:207:408:008:208:409:00 Predose Vitals/Oximetry7:237:438:038:238:439:03 Predose ECG7:267:468:068:268:469:06 LFT Assessment7:307:508:108:308:509:10 End of Predose PK urine7:357:558:158:358:559:15 Predose PK/ Safety7:508:108:308:509:109:30 End of Dose 18:208:409:009:209:4010:00 (IPD) PK BloodIPD (IPD) OximetryIPD 5min PK Bood8:258:459:059:259:4510:05 10min PK Blood8:308:509:109:309:5010:10 15min Chest Auscultation/AE Check8:328:529:129:329:5210:12 15min Oximetry8:338:539:139:339:5310:13 15min PK Blood8:358:559:159:359:5510:15 Subject Supine8:378:579:179:379:5710:17 30min ECG8:409:009:209:4010:0010:20 30min LFT Assessment8:459:059:259:4510:0510:25 30min PK Blood8:509:109:309:5010:1010:30 1hr Chest Auscultation9:109:309:5010:1010:3010:50 Subject Supine9:129:329:5210:1210:3210:52 1hr Vitals Signs/AE Check9:159:359:5510:1510:3510:55 1hr ECG9:179:379:5710:1710:3710:57 1.0hr PK Blood9:209:4010:0010:2010:4011:00 1.0hr LFT Assessment9:259:4510:0510:2510:4511:05 1.5hr PK Blood9:5010:1010:3010:5011:1011:30 Subject Supine10:1410:3410:5411:1411:3411:54 2.0hr ECG10:1710:3710:5711:1711:3711:57 2.0hr PK Blood/AE Check10:2010:4511:0511:2511:4512:05 2.5hr PK Blood10:5011:1011:3011:5012:1012:30 Subject Supine11:1411:3411:5412:1412:3412:54 3.0hr ECG11:1711:3711:5712:1712:3712:57 3.0hr PK Blood11:2011:4012:0012:2012:4013:00 3.5hr PK Blood11:5012:1012:3012:5013:1013:30 Subject Supine12:1112:3112:5113:1113:3113:51 4.0hr Vital Signs/AE Check12:1412:3412:5413:1413:3413:54 4.0hr ECG12:1712:3712:5713:1713:3713:57 4.0hr PK /Safety Blood12:2012:4013:0013:2013:4014:00 IOP Assessment12:2512:4513:0513:2513:4514:05 LUNCH12:3012:5013:1013:3013:5014:10 Fig 1. Study Task Pad

A Day in The Life of A Study Coordinator Day BREAKFAST7:007:207:408:008:208:40 Chest Auscultation7:107:307:508:108:308:50 IOP Assessment7:157:357:558:158:358:55 Subject Supine/Remove water7:207:408:008:208:409:00 Predose Vitals/Oximetry7:237:438:038:238:439:03 Predose ECG7:267:468:068:268:469:06 LFT Assessment7:307:508:108:308:509:10 End of Predose PK urine7:357:558:158:358:559:15 Predose PK/ Safety7:508:108:308:509:109:30 End of Dose 18:208:409:009:209:4010:00 (IPD) PK BloodIPD (IPD) OximetryIPD 5min PK Bood8:258:459:059:259:4510:05 10min PK Blood8:308:509:109:309:5010:10 15min Chest Auscultation/AE Check8:328:529:129:329:5210:12 15min Oximetry8:338:539:139:339:5310:13 15min PK Blood8:358:559:159:359:5510:15 Subject Supine8:378:579:179:379:5710:17 30min ECG8:409:009:209:4010:0010:20 30min LFT Assessment8:459:059:259:4510:0510:25 30min PK Blood8:509:109:309:5010:1010:30 1hr Chest Auscultation9:109:309:5010:1010:3010:50 Subject Supine9:129:329:5210:1210:3210:52 1hr Vitals Signs/AE Check9:159:359:5510:1510:3510:55 1hr ECG9:179:379:5710:1710:3710:57 1.0hr PK Blood9:209:4010:0010:2010:4011:00 1.0hr LFT Assessment9:259:4510:0510:2510:4511:05 1.5hr PK Blood9:5010:1010:3010:5011:1011:30 Subject Supine10:1410:3410:5411:1411:3411:54 2.0hr ECG10:1710:3710:5711:1711:3711:57 2.0hr PK Blood/AE Check10:2010:4511:0511:2511:4512:05 2.5hr PK Blood10:5011:1011:3011:5012:1012:30 Subject Supine11:1411:3411:5412:1412:3412:54 3.0hr ECG11:1711:3711:5712:1712:3712:57 3.0hr PK Blood11:2011:4012:0012:2012:4013:00 3.5hr PK Blood11:5012:1012:3012:5013:1013:30 Subject Supine12:1112:3112:5113:1113:3113:51 4.0hr Vital Signs/AE Check12:1412:3412:5413:1413:3413:54 4.0hr ECG12:1712:3712:5713:1713:3713:57 4.0hr PK /Safety Blood12:2012:4013:0013:2013:4014:00 IOP Assessment12:2512:4513:0513:2513:4514:05 LUNCH12:3012:5013:1013:3013:5014:10 Fig 1. Study Task Pad

A Day in The Life of A Study Coordinator Scenario Study 2: Source notes documentation Multiple data points due to assessment intensity. –100 – 200 data points from predose to 1 st hr post dose. Documentation involves entry from multiple study personnel (entire study team). Medical history and concomitant medication records are usually brief compared to later phase trials i.e. several volumes.

A Day in The Life of A Study Coordinator Fig 2. Source Notes

A Day in The Life of A Study Coordinator Fig 2. Source Notes

A Day in The Life of A Study Coordinator Scenario Study 3: Data Management QC performed on source documentation prior to being monitored. More and more sponsors are requesting real time data entry. CRA may need to come in and perform SDV whilst data is being entered into the CRFs. Lab results are transferred electronically – dose escalation evaluation. Tight timeline for query resolution before data base lock.

A Day in The Life of A Study Coordinator Conclusion Men can multitask too! Old myth is busted. The success/smooth running of an early phase trial relies heavily on team effort hence clear communication line is imperative. Early phase trials are intense hence study protocol clarity is essential to ensure expectations could be met. Main differences between Phase I trials and later phase trials are the intensity and study timelines.