Clinical Trials Reporting Program (CTRP) and

Clinicaltrials.gov (CT.gov)

Helpful tips and guidance

Objectives

NCI’s Clinical Trials Reporting Program (CTRP) Overview

CTRP – What is it? • CTRP is an NCI mandated comprehensive protocol

registration database of regularly updated information on all “NCI-supported” clinical trials.

• The database was created due to the initiative of the Clinical Trials Working Group (CTWG) Report

• It was created to help identify gaps and duplicative studies in clinical research and to facilitate prioritization of clinical trials for the NCI

• Any NCI-supported interventional trials opened to accrual as of or after January 1, 2009 requires registration

• Cancer Centers were able to apply for supplemental funding to help fund a CTRP Coordinator position

CTRP – What is it? • “NCI-supported” means “all trials sponsored or

otherwise financially supported by the NCI.” This means that all interventional clinical trials conducted at NCI-designated Cancer Centers must be registered no matter who the sponsor is including Investigator- Initiated and industry sponsored trials

• Exceptions to this rule are studies that are reviewed and monitored by NCI CTEP, DCP PIOs, and NCI CCR. These trials are not required to be registered via the CTRP registration site by the designated Cancer Centers

What does this mean for the UWCCC?

• For our purposes, all interventional trials (therapeutic, supportive care, and prevention) as well as Screening, Detection, and Early Diagnostic studies that are considered IITs will be required to be registered via CTRP

• Who is responsible for the registration? Your UWCCC CTRP Coordinator!

What does the CTRP Coordinator do? • The CTRP Coordinator performs the initial

registration of required trials into the CTRP Registration database

• The coordinator is also responsible for all updates to trials once registered including submission of major amendments, status updates, participating site information, and accrual

What information is required for registration into CTRP?

• Minimum information required for registration: – Protocol Number – Protocol Title – Trial Type – Phase – Current Trial Status and Date – this includes anticipated completion dates – Lead Organization – PI – NIH Grant information if applicable – Responsible Party – Regulatory Information

• See CT.GOV/CTRP tab in the Main Tab of the PC Console in OnCore – Trial Related Documents

• Protocol • Participating Site List • IRB Approval Document OR Memo of Pending IRB Approval when registration

occurs pre-approval

What happens when a study is

registered? • Once a study has been registered, the NCI

CTRO staff extracts the information from the protocol and registration page and plugs it into a Trial Summary Report (TSR)

• The TSR is sent to the CTRP Coordinator for review to ensure accuracy

• Once reviewed, the coordinator accepts the TSR (or submits revisions) and the study is considered registered in CTRP

What exactly is a Trial Summary Report (TSR)?

• A summary of the information found in the protocol

• This summary is equivalent to the information that has to be uploaded into ClinicalTrials.gov (CT.gov) – As we’ll discuss later, the TSR is what allows the CTRP

coordinator to upload the CT.gov submissions at the click of a button. A few minor tweaks are done to the record in CT.gov to ensure that the sponsor and organization information are listed correctly.

– This is why it is important that the groups fill in the required information in the CT.gov/CTRP tab and the Study Completion Dates in OnCore – which will also be discussed later in the presentation

National Institutes of Health (NIH) ClinicalTrials.gov (CT.gov) Overview

CT.gov – What is it? • CT.gov, originally developed in 2000, is a

mandated public access protocol registration database originally developed by the NIH in collaboration with the Food and Drug Administration (FDA)

• The FDA Amendment Act (FDAAA) added additional requirements for CT.gov including results reporting in September 2007

CT.gov – What is it? • The Food and Drug Administration (FDA)

requires study registration (along with results and adverse event reporting) for Phase II - IV interventional drug, biologic or device trials ("applicable clinical trials")

What is an “applicable clinical trial”? • Trials of drugs and biologics that are subject to FDA

regulation • Trials of devices which provide health outcomes

subject to FDA regulation and which require pediatric postmarket surveillance

• This generally includes interventional studies of FDA regulated drugs, biologics, or devices that meet one of the following: – Trial has one or more sites in US – Trial is conducted under an FDA IND or IDE – Trial involves a drug, biologic, or device manufactured in

the US and is exported for research

What types of trials are excluded? • Per FDAAA 801 the following are excluded:

– Phase I* drug trials – Trials where the primary outcome measures feasibility

and not health outcomes – Trials not including drugs, biologics, or devices – Non-interventional trials such as cohort or case-

control studies – Trials ongoing as of 9/27/2007 but reached

completion before 12/26/2007 *Please note – it is best practice, regardless of phase to register all interventional trials per the ICMJE requirements which will be discussed

Who requires registration? • FDA - within 20 days of first patient accrued • ICMJE - before 1st patient accrued • Center for Medicare & Medicaid Services

(CMS) requires the registration of most studies billing third parties for study related services- UW Health Research Billing Compliance Program requires an NCT # (CT.gov registration number) before trial can be approved

International Committee of Medical Journal Editors (ICMJE)

• ICMJE recommends that all medical journal editors require registration of clinical trials in a public registry

• Trials must be registered at or before the time of the first patient enrollment for consideration of publication

• ICMJE defines a clinical trial as any research project that prospectively assigns people/groups of people to an intervention to study the relationship between a health intervention and health outcome

• Much bigger scope than CT.gov for registration

What does ICMJE have to do with UWCCC?

• Some trials that are considered “interventional” IITs by our standards may not necessarily be required per FDAAA guidelines to be registered to CT.gov – however – for publishing purposes – they must be registered

• This means it is best to err on the side of caution and register the trial – as stated on the ICMJE website – “Those who are uncertain whether their trial meets the expanded ICMJE definition should err on the side of registration if they wish to seek publication in an ICMJE journal”

Why comply with Registration?

• Failing to register or report results for "applicable clinical trials" in a timely manner can result in significant monetary penalties imposed by the FDA

• Failure to register ( before the first patient accrued) may result in a rejection of a publication by ICMJE

CT.gov – Results Reporting

What about Results Reporting?

• Per the FDAAA 801 requirements, the Responsible Parties must submit scientific and administrative information about trial results into CT.gov within a year of study completion

• Submitting results is similar to preparing a manuscript for publication

• Individuals familiar with the study design and data

analysis (such and the PI or statistician) must be involved in order to accurately summarize the information

Results Reporting: Brief Overview

• Scientific information is submitted as four separate modules: – Participant Flow – Baseline Characteristics – Outcome Measures & Statistical Analyses – Adverse Events

• These modules display information in a series of data tables

Results Reporting – Participant Flow

• “A table...,including the number of patients who dropped out of the clinical trial and the number of patients excluded from the analysis, if any.”

• The module should account for all enrolled participants, and should inform the interpretation of study outcomes by interpretation of study outcomes by illustrating which participants were analyzed

Results Reporting – Baseline Characteristics

• “A table of the demographic and baseline data collected overall and for each arm of the clinical trial…” – Number of participants – Age – Gender – Race – Ethnicity – Region of enrollment

Entered for each Arm

Results Reporting – Outcome Measures & Statistical Analyses

• “…a table of values for each of the primary and secondary outcome measures for each arm of the clinical trial…including the results of scientifically appropriate tests of the statistical significance of such outcome measures.”

Results Reporting – Adverse Events • “A table of anticipated and unanticipated

serious adverse events grouped by organ system, with number and frequency of such event in each arm of the clinical trial.”

Results Reporting: Miscellaneous • Many helpful templates for results reporting

can be found at http://clinicaltrials.gov/ct2/manage-recs/how-report

• Results reporting MUST be done by the research staff who have worked closely with the protocol – the investigator and the statistician MUST be involved in the process – it is the investigator’s responsibility

Bringing it all together

What happens after registration to

CT.gov? • Once the study has been accepted, the CTRP

coordinator enters the NCT number into OnCore and tells the DOWG the trial has been registered.

• Trial ownership is transferred back to the DOWG in order to allow the group to be able to make the timely updates and amendments as required

• Why back to the DOWG? – Amendment information, status changes, etc. must be entered manually, therefore someone who has intimate knowledge of the protocol requiring updates must be the one responsible to ensure key points are updated appropriately

Why tie CTRP and CT.gov together?

• Both databases require registration of interventional trials and utilize similar information

• CTRP “talks” to CT.gov – this is how we are able to centralize protocol registration for the Cancer Center into CT.gov

• By utilizing the CTRP registration process, the steps for registering trials to CT.gov became much less complicated and can be handled by a central person instead of each DOWG having to manually register trials

What does this mean for the UWCCC?

• Centralizing CT.gov registration frees up time for the DOWGs and PIs

• It falls into the workflow that coincides with CTRP registration

• Central registration helps to meet the new Center for Medicare & Medicaid (CMS) requirements having the NCT number in OnCore before IRB Approval

How will this impact workflows? • DOWGs may need to change workflows to enter the

following fields in OnCore by PRMC Approval for studies requiring CT.gov registration: – Enter the “Completion Dates” in PC Console → Main →

Details Tab under “Completion Dates”. Follow the OnCore DFDs for instructions.

– Fill out the CT.Gov/CTRP Tab in PC Console → Main → CT.GOV/CTRP. Follow the OnCore DFDs for instructions.

• DOWGs must also contact the CTRP Coordinator via email once a qualifying trial has been PRMC approved and attach the protocol to the email. This is a back-up verification to ensure that no qualifying protocols would miss a deadline for registration

How are trials registered in CT.gov via CTRP?

• The CTRP Coordinator registers trials with CTRP at PRMC approval – pending IRB approval.

• NCI CTRO Staff extract information from the protocol to provide the TSR

• The coordinator reviews the TSR and either approves the TSR or submits changes

• Once the TSR has been approved the trial can be automatically uploaded to CT.gov via CTRP

CTRP and CT.gov - What does the future hold?

• Although it may seem like the work can be duplicative – both registries were created for different reasons and are managed by separate entities

• CTRP is working towards working with cancer centers to simplify Summary 4 reporting

QUESTIONS?