1. CTRP User Call January 8, 2014 Gene Kraus CTRP Program Director

2. Agenda Welcome CTRP Topics -Trial Categories – Interventional/Non-Interventional -Status -Phase -Trial Data Verification Highlights of Latest CTRP release - 3.10 Wrap-up

3. Clinical Trial Categories

4. Interventional Trials -Clinical Research Category in which individuals are assigned by an investigator based on a protocol to receive specific interventions. -The participants may receive diagnostic, therapeutic, behavioral or other types of interventions. -The assignment of the intervention may or may not be random. -The participants are followed and biomedical and/or health outcomes are assessed. (Source: http://prsinfo.clinicaltrials.gov/definitions.html and http://cancercenters.cancer.gov/documents/CCSGDataGuide508C.pdf )http://prsinfo.clinicaltrials.gov/definitions.html http://cancercenters.cancer.gov/documents/CCSGDataGuide508C.pdf ALL other trials are considered Non-Interventional

5. Clinical Trial Categories Non-Interventional Trials - Observational -Clinical Research Category in which the studies focus on cancer patients and healthy populations that involve no intervention or alteration in the status of the participants. -Biomedical and/or health outcome(s) are assessed in pre- defined groups of participants. -The participants in the study may receive diagnostic, therapeutic, or other interventions but the investigator of the observational study is not responsible for assigning specific interventions to the participants of the study.

6. Clinical Trial Categories Non-Interventional Trials - Ancillary / Correlative - Ancillary: studies are stimulated by, but are not a required part of, a main clinical trial/study, and utilize patient or other resources of the main trial/study to generate information relevant to it. -Ancillary studies must be linked to an active clinical research study and should include only patients accrued to that clinical research study. -Only studies that can be linked to individual patient or participant data should be reported.

7. Clinical Trial Categories Non-Interventional Trials - Ancillary / Correlative - Correlative: laboratory based studies using specimens to assess: cancer risk, clinical outcomes, response to therapies, etc. -Only studies that can be linked to individual patient or participant data should be reported

8. Trial Status

9. Trial Status (CTRP) In Review. Trial is currently under IRB review Withdrawn. Trial has been withdrawn from development and review prior to enrollment of the first participant. Approved. Trial has been approved, but is not yet recruiting or enrolling participants. Active. Trial is open for accrual and enrollment. Enrolling by Invitation. Participants are being (or will be) selected from a predetermined population. Temporarily Closed to Accrual. Participant recruitment or enrollment has been halted prematurely but may resume. Participants already on trial continue to receive intervention. Temporarily Closed to Accrual and Intervention. Participant recruitment or enrollment has been halted prematurely but may resume. Participants already on trial do not receive intervention. Closed to Accrual. Trial has been closed to participant accrual, but trial is ongoing (i.e., participants continue to receive treatment and/or examination). Closed to Accrual and Intervention. Trial has been closed to participant accrual. Participants already on trial do not receive treatment, but continue to be monitored for endpoints such as long-term survival. Administratively Complete. Participant recruitment or enrollment has been halted prematurely (for example, due to poor accrual, insufficient drug supply, IND closure, etc.), and will not resume. Participants already on the trial do not receive further treatment or examination. Complete. Trial has been closed to accrual and follow-up. Participant treatment/intervention has been completed and participants are no longer monitored for trial endpoints (i.e., last patient's visit has occurred). The trial has met its objectives.

10. Trial Status (ClinicalTrials.gov) recruitment status Not yet recruiting. The study has not started recruiting participants. Recruiting. The study is currently recruiting participants. Active, not recruiting. The study is ongoing (that is, participants are receiving an intervention or being examined), but potential participants are not currently being recruited or enrolled. Completed. The study has ended normally, and participants are no longer being examined or treated (that is, the "last subject, last visit" has occurred). Terminated. The study has stopped recruiting or enrolling participants early and will not start again. Participants are no longer being examined or treated. Suspended. The study has stopped recruiting or enrolling participants early, but may start again. Withdrawn. The study stopped early, before enrolling its first participant. Enrolling by invitation. A study that selects its participants from a population, or group of people, decided on in advance by the researchers. These studies are not open to everyone who meets the eligibility criteria, but only to people in that particular population, who are specifically invited to participate. Unknown. A study in ClinicalTrials.gov with a status of Recruiting; Not yet recruiting; or Active, not recruiting and whose status has not been verified within the past 2 years. Studies with an Unknown recruitment status are considered open studies or closed studies, depending on their last known recruitment status Source: http://clinicaltrials.gov/ct2/about-studies/glossary#recruitment-statushttp://clinicaltrials.gov/ct2/about-studies/glossary#recruitment-status

11. CTRP Status – Definition -ClinicalTrials.gov Status – Definition In Review - Trial is currently under IRB review. -Not yet recruiting - Participants are not yet being recruited Withdrawn - Trial has been withdrawn from development and review prior to enrollment of the first participant. -Withdrawn - Study halted prematurely, prior to enrollment of first participant Approved - Trial has been approved, but is not yet recruiting or enrolling participants. -Not yet recruiting - Participants are not yet being recruited Active - Trial is open for accrual and enrollment. -Recruiting - Participants are currently being recruited Enrolling by Invitation - Participants are being (or will be) selected from a predetermined population. -Enrolling by Invitation - Participants are being (or will be) selected from a predetermined population Temporarily Closed to Accrual - Participant recruitment or enrollment has been halted prematurely but may resume. Participants already on trial continue to receive intervention. -Suspended - Recruiting or enrolling participants has halted prematurely but potentially will resume. Temporarily Closed to Accrual and Intervention - Participant recruitment or enrollment has been halted prematurely but may resume. Participants already on trial do not receive intervention. -Suspended - Recruiting or enrolling participants has halted prematurely but potentially will resume Closed to Accrual - Trial has been closed to participant accrual, but trial is ongoing (i.e., participants continue to receive treatment and/or examination). -Active, not recruiting - Study is ongoing (i.e., patients are being treated or examined), but participants are not currently being examined or treated (i.e., last patient’s last visit has occurred) Trials Status Matching Chart

12. CTRP Status – Definition -ClinicalTrials.gov Status – Definition Closed to Accrual and Intervention - Trial has been closed to participant accrual. Participants already on trial do not receive treatment, but continue to be monitored for endpoints such as long term survival. -Active, not recruiting - Study is ongoing (i.e., patients are being treated or examined), but participants are not currently being examined or treated (i.e., last patient’s last visit has occurred) Administratively Complete - Participant recruitment or enrollment has been halted prematurely (for example, due to poor accrual, insufficient drug supply, IND closure, etc.), and will not resume. Participants already on the trial do not receive further treatment or examination -Terminated - Recruiting or enrolling participants has halted prematurely and will not resume; participants are no longer being examined or treated. Complete - Trial has been closed to accrual and follow-up. Participant treatment/intervention has been completed and participants are no longer monitored for trial endpoints (i.e., last patient's visit has occurred). The trial has met its objectives -Completed - The study has concluded normally; participants are no longer being examined or treated (i.e., the last patient’s last visit has occurred) Trials Status Matching Chart

13. CTRP – Current Trial Status Date CTRP - Current Trial Status Date is the date that the trial entered that status, e.g., -Trial became open to patient accrual (active) on 8/8/13 -The trial remains open and is registered in CTRP on 12/10/13 -Then the date of the current trial status, active, is 8/8/13

14. Trial Phase

15. Clinical Trial Phase It is important for the entire portfolio of interventional trials registered in CTRP to have an accurate Phase listed. When Registering, Amending or Updating a trial please be sure to have the current, accurate phase listed. Please make sure you list phase in Registration

16. CTRP - Definitions of Trial Phases 0 - Exploratory trials, involving very limited human exposure, with no therapeutic or diagnostic intent (e.g., screening studies, micro dose studies). See FDA guidance on exploratory IND studies for more information. I - Includes initial studies to determine the metabolism and pharmacologic actions of a medical approach in humans, the side effects associated with increasing doses or exposure, and to gain early evidence of effectiveness; may include healthy participants and/or patients. I/II - Includes trials that are a combination of phases I and II. II - Includes controlled clinical studies conducted to evaluate the effectiveness of the medical approach for a particular indication or indications in patients with the disease or condition under study and to determine the common short-term side effects and risks. II/III - Trials that are a combination of phases II and III. III - Includes expanded controlled and uncontrolled trials after preliminary evidence suggesting effectiveness of the medical approach has been obtained, and are intended to gather additional information to evaluate the overall benefit-risk relationship of the drug and provide an adequate basis for physician labeling. IV - Studies of FDA-approved drugs, interventions, tests or diagnostic procedures to delineate additional information including the medical approach risks, benefits, and optimal use. NA (Not applicable) - For trials without phases (most likely non-interventional trials).

17. CTRP – Definitions of Trial Phases - Pilot Pilot Trials -The initial study examining a new method or treatment. -If the trial is a Pilot trial, please indicate as a separate choice at time of registration.

18. CTRP Registration

19. CTRP Registration (Phase)

20. CTRP Registration (Pilot option)

21. Trial Data Verification

22. Trials must now be reviewed for accuracy twice each year. -The Date is calculated by last verification date Automated E-mail reminders will now be sent to trial owners, submitters and site administrators -First email sent 30 day prior to due date -Second email sent 15 days prior to due date Verification ability will be available to trial owners or submitters.

23. Trial Data Verification Emails Who will receive the 30 day and 15 day notices to verify data -The system sends emails to: trial submitters trial owners administrators Will they receive a single mail with all trials needing verification or a separate email for each trial. -The system is designed so that the email reminders are grouped by person, when possible. That is, typically, a recipient should receive a single email reminder for all his/her trials that are nearing their Verification Due Date, as opposed to a separate email for each trial.

24. Trial Data Verification is Important Because… Verifying the record will ensure that the content and status of the clinical trial abstract is accurate, and reflects all changes that may have occurred since its last review by the trial owner or submitter. ClinicalTrials.gov requires that each record be updated twice each year. Those using CTRP generated XML will have an updated file for ClinicalTrials.gov.

25. Trial Data Verification For the trial to be verified, the trial must be in an “abstraction verified” state Trial status can NOT be: -Withdrawn -Administratively Complete -Complete Email reminders will be turned on: January 13, 2014

26. Trial Data Verification

29. CTRP 3.10 New Features

30. CTRP 3.10 – What’s New Registration - Trial Data Verification Now trial submitters are required to review their trial data semi- annually. The system now tracks users' semi-annual reviews and updates to their trials. The system now is able to send email reminders to open trial record owners, submitters, and site administrators to verify their trial data in the CTRP database. - Other (Consortia) Trials. CTRP now accepts submission of Other (Consortia) Trials. −An example might be an NHLBI trial

31. CTRP 3.10 – What’s New Registration - Multiple Data Table 4 Funding Sponsors Users can now add more than one Data Table 4 Funding Sponsor to a trial. Users can add Data Table 4 Funding Sponsors as part of an original submission or as part of an Amendment, but not an Update. - Industrial Trials Users can now register Industrial trials in the CTRP by specifying the ClinicalTrials.gov NCT Identifiers associated with the trials and importing them directly from ClinicalTrials.gov. Industrial trials in CTRP will no longer be associated with trial owners. −Previous owners of Industrial trials in the CTRP are now no longer associated with those trial records in CTRP if they have ClinicalTrials.gov NCT Identifiers. −Previous owners of Industrial trials in the CTRP will remain associated with those trial records in the CTRP if they have not been assigned ClinicalTrials.gov NCT Identifiers.

32. Importing an Industrial Trial from ClinicalTrials.gov

34. CTRP 3.10 – What’s New Registration - Sponsor/Responsible Party The data CTRP collects for Sponsor/Responsible Party now better aligns with the Sponsor and Responsible Party data that ClinicalTrials.gov records. Users can now specify Sponsor-Investigator as the Responsible Party. - Primary Completion Date. Users can now enter a Primary Completion date that is earlier than the Current Trial Status Date. - Amendments. Users can now submit amendments to trials in CTRP with the Trial Status "In Review".

35. CTRP 3.10 – What’s New Registration - Grants When registering a trial, users are now prompted to enter all NCI grant information. The system now includes a look-up feature that assists users when entering NCI grant numbers. - CTRP System-Generated Emails The CTRP system now sends emails to users that have been formatted to improve readability and clarity. Improved emails now contain additional data elements that provide additional useful information regarding the referenced trials.

36. CTRP 3.10 – What’s New Subject Accrual - Non-Interventional Trials. Support has been added for submission of accrual data for non- interventional trials. Support covers both Abbreviated (summary level accrual submissions) and Complete (Subject level accrual submissions) for non-interventional trials A new feature now lets users switch between Summary and Subject level accruals for non-interventional trials (as long as no accrual data has been submitted yet). - Prior Submissions. The Prior Submissions page has been redesigned and enhanced. Removed the previous redirect so that users can once again access the Prior Submissions page from the Accrual application

37. Prior Submissions Page

38. CTRP 3.10 – What’s New Subject Accrual - Batch Submissions The system now supports UTF-8 formatted.txt files. Improved handling of Zip files −The system now is able to better handle unexpected errors in Zip files. −The system now sends the submitter an email notification even if the uploaded Zip file has unexpected formatting or data errors and cannot be processed. −The system now is able to partially process Zip files. If a Zip file contains some valid files and some invalid files, the system will process any of valid files that it can.

39. CTRP 3.10 – User Guides CTRP User Guides https://wiki.nci.nih.gov/display/CTRPdoc/NCI+Clinical+Trials+Reporting+Program+%28CTRP%29+User%27s+Guid es CTRP Registration Site User Guide https://wiki.nci.nih.gov/display/CTRPdoc/Contents+-+CTRP+Registration+Site+User%27s+Guide+v3.10 CTRP Subject Accrual User Guide https://wiki.nci.nih.gov/display/CTRPdoc/Contents+-+CTRP+Subject+Accrual+User%27s+Guide+v3.10

40. Reminder Just a final reminder that accrual reporting started last October. If any centers are still having troubles with completing their Accrual Reporting, Please reach out to us and we will be glad to work with you

41. In Conclusion CTRP Topics covered today: -Trial Categories – Interventional/Non- Interventional -Status -Phase -Trial Data Verification Highlights of Latest CTRP release - 3.10

42. Send questions / topics for future calls

43. Thank You