How to Register Your Trial ClinicalTrials.gov How to Register Your Trial Adapted from the work of the Clinical and Translational Science Awards (CTSA) program’s Clinical Trials Registration Workgroup of the Regulatory Knowledge Key Function Committee 2013 http://catalyst.harvard.edu

ClinicalTrials.gov Database operated by the National Library of Medicine (NLM) What you’ll find at ClinicalTrials.gov: Registration Results (including Adverse Events) *This presentation focuses solely on registration.*

ClinicalTrials.gov – Registration Information Description of study Study type, phase, design, outcome measures Recruitment information Eligibility criteria, locations, recruitment status Administrative and other information Key dates and contact information Helpful links to add MEDLINE publications, consumer health information, FDA information

ClinicalTrials.gov – Account Information Each institution has a umbrella ClinicalTrials.gov account. Each institution has a “PRS Administrator” assigned. The PRS Administrator can create individual accounts for investigators and study staff at the institution within the institutional account. The Responsible Party (RP) is responsible for registering the study. Each study receives only one record, regardless of number of sites.

ClinicalTrials.gov – Obtaining your log-in and user account Provide the following information to your PRS Administrator: Desired user name Full name (e.g., John J Smith, MD) Email address Phone number PRS Administrator sends request to ClinicalTrials.gov ClinicalTrials.gov emails user notifying of account creation and provides temporary password (within two days) You may now log into the ClinicalTrials.gov Protocol Registration System: https://register.clinicaltrials.gov/

ClinicalTrials.gov Login Page Organization Name = Your Institution

Responsible Party vs. Record Owner The Responsible Party (RP) is responsible for registering their study record on ClinicalTrials.gov, ensuring accuracy, and making sure that the content is up to date. The RP is the only one that can “approve” and “release” the record to ClinicalTrials.gov. Record Owner (RO) can be anyone with an account; the record is stored in RO’s account. TIPS: If the RP is the Principle Investigator (PI), it may be easiest if the PI is also the RO. The RO can use the “access list” to grant additional users access to the specific record for editing purposes (e.g. if the PI is the RO, he/she can provide access to the study coordinator by selecting the study coordinator from the access list.)

Responsible Party Refresher ICMJE: Anyone can register, but generally it’s the PI. FDAAA: The Responsible Party (RP) defined as IND / IDE holder OR If no IND/IDE: The RP is the industry, cooperative group, consortium or other external sponsor that initiated the study OR If initiated by a principal investigator, the RP is the grantee institution (e.g. your institution) OR, if no external funding, the PI 8

Responsible Party Refresher (cont’d) Under FDAAA, RP can be designated to another party that: Is responsible for conducting the study Has access to and control over the data Has the right to publish the trial results, AND Has the ability to meet the requirements Example of RP designation PI initiated study at institution X funded by NHLBI Institution X is the RP Institution can designate the PI as the RP 9

ClinicalTrials.gov Menu Get prepared for registration! Read these documents before you try to register your study: Quick Start Guide FAQs User’s Guide Protocol Data Element Definitions After log in: Blue Menu box is what everyone sees. (PRS Administrators see both blue and yellow menu boxes) Check out the “Help” section To create a new protocol record, click “Create”

Registration in Create/Modify View * = Required fields Click on any underlined words in the left column for the official definition and number of characters allowed for this field. FDAAA = this information is required to comply with US Public Law 110-85, Section 801 – FDAAA (FDAAA) = this information may be required to comply with FDAAA.

Enter IRB information here Review Board Approval Enter IRB information here Pfizer Pfizer Pfizer Pfizer Pfizer See the list of oversight authorities for a comprehensive list of all such organizations world-wide. E.g. IRB, FDA etc. Pfizer

Responsible Party Designation Each institution may handle names and titles of the responsible party differently. Make sure you understand your institution’s policies. Note: the investigator must be registered with ClinicalTrials.gov to appear on the list. The list is organized by the first letter of the username, for example, Thomas Adams (tadams) would appear with the “T”s.

Registration Tips: Brief title and summary should be in lay language. Caution: abbreviations must be identified the first time they are used in the protocol section, for example in the brief summary or detailed description. Overall Recruiting Status and Recruiting Status in the locations must match Dates are needed for Study Start Date, and Primary and Study Completion Dates Change the Verification Date to the current month and year (this updates the record) Keep the primary completion date current. This is an important date for ClinicalTrials.gov – your study may end up on the “problem list” if the date is not current.

Entering the Study Type

Entering the Study Type: DEFINITIONS Observational: Studies in human beings in which biomedical and/or health outcomes are assessed in pre-defined groups of individuals. Subjects in the study may receive diagnostic, therapeutic, or other interventions, but the investigator does not assign specific interventions to the subjects of the study. Interventional: Studies in human beings in which individuals are assigned based on a protocol to receive specific interventions. Subjects may receive diagnostic, therapeutic, or other types of interventions. The assignment of the intervention may or may not be random. The individuals are then followed and biomedical and/or health outcomes are assessed. Expanded Access: Records describing the procedure for obtaining an experimental drug or device for patients who are not adequately treated by existing therapy, who do not meet the eligibility criteria for enrollment, or who are otherwise unable to participate in a controlled clinical study. Expanded access records are used to register all types of non-protocol access to experimental treatments, including protocol exception, single-patient IND, treatment IND, compassionate use, emergency use, continued access, and parallel track. Definitions from: https://register.clinicaltrials.gov/prs/html/definitions.html

How to Enter Outcome Measures easur Outcome measure information: Please be as specific as possible. Title: include the name of the specific measure. Avoid using verbs, that is, do not put “To determine…” Time Frame: must have a time point at which the outcome is assessed for the specific metric used (hours, days, weeks, years) Hint: specify which study day it is measured - do not use “until the end of study or death.” For guidance see page 3 of: http://prsinfo.clinicaltrials.gov/ProtocolD etailedReviewItems.pdf. Description: describes what will be measured, not why it is measured. If the outcome measure is a questionnaire or scale, provide the range and what low or high scores mean. Safety Issue: Is this outcome measure assessing a safety issue?

Example of Problematic Primary Outcome Measure This outcome measure is a problem because the title and time frame are not specific enough. How will the study measure nausea? When will it be measured, specifically? If these fields are not clear, the study registration will get comments from the QA reviewers, and could be delayed.

Example of Corrected Primary Outcome Measure* This outcome measure is now much more specific and provides a specific time when it will be measured. Notice that additional information is provided about the nausea scale: the range, what the beginning and end of the scale mean, and the definition of “improved.” * Note: Secondary Outcome Measure fields require same information

How to Enter Arms/Interventions Information If the same intervention (e.g., drug) is used in multiple arms, enter information about the intervention only once, even if the dosage is different. Use the Cross-Reference section to specify which arm the intervention is associated with.

Central Contact/Location Info Please list the person providing centralized coordinated recruitment information. Locations: Please list all sites if the study is multi center. Recruitment Status should match the Overall Recruiting Status above. Note: Please fill this section in completely. This information will give participants the correct information on whom to contact.

See http://prsinfo.clinicaltrials.gov/ProtocolDetailedReviewItems.pdf. Completed all fields and Ready to Release your study on ClinicalTrials.gov Please ensure you have thoroughly reviewed your study record… All fields should be completely filled out and in lay language (where possible) All red errors must be corrected Any misspelled words should be corrected Acronyms and abbreviations should be spelled out Be sure your study record complies with the ClinicalTrials.gov standards. See http://prsinfo.clinicaltrials.gov/ProtocolDetailedReviewItems.pdf.

Next Action: Complete: The person updating the record will click on “Complete” to indicate that the study is ready for the “Approve” and “Release” actions. Approve and Release: The Responsible Party of the study needs to click on “Approve” and “Release” for the record to be sent to ClinicalTrials.gov’s Quality Assurance (QA) group for review and to be published on the ClinicalTrials.gov website.

ClinicalTrials.gov QA ClinicalTrials.gov does a manual review If there are QA issues, the record owner and RP will receive an email notification from ClinicalTrials.gov with comments. The study will be reset to “In Progress”. QA Comments must be addressed and the RP must re-release the record to ClinicalTrials.gov. Once a record passes ClinicalTrials.gov’s QA review, the study is assigned an NCT number and published on the “public” side of the database. Journal editors often request the NCT number as proof of compliance with ICMJE requirements; The NCT number is often published in journal articles. ClinicalTrials.gov review of registrations takes about 5-7 business days. You may receive some QA comments if the record is lacking required information, or if the information is not clear. The study registration will not receive an NCT number until these QA comments are resolved. Your record is not officially registered until an NCT# is assigned.

Published Registration The searchable, public view of the database is at: www.clinicaltrials.gov

Summary of Registration Process Fill out Registration (“Create” a record) Actions: In progress: Fields to be completed Completed: Ready for Approval and Release Approved/Released: RP is sole party that can “Approve & Release” ClinicalTrials.gov conducts QA review of record Once it passes review, an NCT number is assigned and the registration is posted on the public ClinicalTrials.gov webpage

Maintaining a ClinicalTrials.gov record Records must be updated every 6 months – unless Overall Recruitment Status changes, then you should update the record within 30 days. Records must be updated within 30 days after the completion date. Failure to update information on ClinicalTrials.gov can result in penalties NOTE: ClinicalTrials.gov uses the “Record Verification Date” as the trigger for determining the next 6 month update.

Updating Your Record Log into ClinicalTrials.gov Click on “Modify” Click on “Edit” to open the study. Make appropriate changes by clicking on “Edit” along the side in the study record. If no changes have occurred in the last 6 months, update the Record Verification Date by clicking the “Edit” button next to the field. Be sure click on “Complete” when finished updating. Study is ready for “Approval” and “Release” Know who is responsible for “Approval” and “Release” – The RP is responsible for Approval and Release.

General Tips on Updating Your Record Complete all fields Use spelling tool for spelling errors (on the main protocol page, the third tab to the right of “Main Menu”) Spell out acronyms and abbreviations Use language that is easily understood by the general public for the Brief Title and Brief Description. Use the EDIT links to make changes or “Edit All” link at top Check for errors and warnings Check for notes (optional to address) 29

Can a study record be deleted off of ClinicalTrials.gov? Only if the study record has never been released to ClinicalTrials.gov Otherwise, no. ClinicalTrials.gov serves as a long-term public registry. Once a study record is published, it remains in the system even after a trial has closed. If you find a duplicate, contact ClinicalTrials.gov at register@clinicaltrials.gov. 30

Checking your Problem Records PRS System identifies current ‘Problem Records’: Records that have not been marked as completed Active studies that have not been updated in the past 6 months Records missing one or more data elements required by FDAAA, such as: Responsible Party, Study Start Date, Primary Completion Date and Primary Outcome Measure Records that appear to be overdue for registration of results per FDAAA

ClinicalTrials.gov – Help & User Guide

Additional Resources ClinicalTrials.gov: How to Submit Studies: http://clinicaltrials.gov/ct2/manage-recs FDAAA related information: http://clinicaltrials.gov/ct2/manage-recs/fdaaa For specific questions or comments: register@clinicaltrials.gov. Office of Extramural Research (OER): http://grants.nih.gov/Clinicaltrials_fdaaa/ Frequently Asked Questions for NIH Grantees: http://grants.nih.gov/Clinicaltrials_fdaaa/faq.htm ICMJE FAQs: http://www.icmje.org/faq_clinical.html Instructions for Authors sections of ICMJE journals all have information regarding clinical trial registration Contact your institution’s Clinical Trials Registration Administrator via the Harvard Catalyst Regulatory Atlas:http://connects.catalyst.harvard.edu/regulatoryatlas/?mode=c&id=50

This slide set was made possible by a collaboration of CTSA organizations (Mayo Clinic, Partners HealthCare, University of Michigan Medical School, University of Rochester) and the National Library of Medicine.    The Clinical and Translational Science Awards Program (CTSA) is part of the Roadmap Initiative, Re-Engineering the Clinical Research Enterprise and is funded by the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH).