Managing an Ongoing Clinical Research Project

Maintaining Study Documentation

Research teams are required to prepare and maintain regulatory documentation demonstrating appropriate study conduct, and comprehensive case histories on each research subject

Please review the sections below for more information. Additional documentation requirements related to events or information that requires reporting to the DF/HCC, IRB, regulatory agencies, or other oversight bodies can be found in the Oversight and Reporting tab on this page.

Essential regulatory documents must be maintained for all research conducted at DF/HCC to ensure compliance with federal, IRB, and DF/HCC policy requirements. Specific requirements can be found in DF/HCC policy RCO-203: Regulatory Documentation.
Use the DF/HCC Regulatory File - Required Document List to ensure all required documentation is on file.
Below are some additional documents and resources that may be helpful in meeting these requirements:
- RCO-OP-2: Completion of Form FDA 1572 (DF/HCC Operation)
- Regulatory File Checklist for NCTN Trials
In accordance with RCO-203 requirements, a delegation of authority log must be maintained for all applicable studies. When using the DF/HCC templates, follow the process outlined in RCO-OP-1: Documenting Delegation of Authority.
To summarize, this means the following:
- All delegated study team members must have a Policy and Signature Record on file to verify their signature and initials - these should be maintained centrally.
- TheDF/HCC DOA Log Template must be used to document delegated study staff for each individual study, including what role/tasks they are approved to perform by the PI.
- Use the DF/HCC Key: Delegation of Tasks for Clinical Research to appropriately assign staff with the correct role on the DOA Log.
Researchers must obtain and document the informed consent of research participants in accordance with DF/HCC Policy CON-100: Informed Consent Process and any specific requirements from the IRB of record.
Below are some additional documents and resources that may be helpful in meeting these requirements:
- Use of Informed Consent Documents Posted to OncPro (DFCI IRB Operation)
- Guidance on Documenting Informed Consent
- Informed Consent Documentation Template
- Electronic Consent (DFCI IRB Guidance)
- CON-101 Obtaining Informed Consent from Non-English Speakers (DF/HCC Policy)
- DFCI IRB Translated Short Forms
- Consenting Blind or Illiterate Subjects (DFCI IRB Policy)
- Consent for Continued Participation upon reaching Age 18 (DFCI IRB Policy)
- CON-OP-1: Reconsent/Patient Notification Guide (DF/HCC Operation)
Researchers are required under DF/HCC policy DOC-100: Research Subject Documentation to prepare and maintain adequate and accurate case histories that record all observations and other data pertinent to the investigation on each research subject.
Below are some additional documents and resources that may be helpful in meeting these requirements:
Please refer to DF/HCC policy INV-100: Research Pharmacy Standard Policy and INV-OP-1: Mandatory Research Pharmacy Procedures for general pharmacy operations and documentation practices. If you have any questions, we recommend reaching out to the research pharmacy at your institution.
Below are some additional documents and resources that may be helpful in meeting these requirements:
- INV-101: Transfer of Investigational Drug(DF/HCC Policy)
- INV-103: Protocol Mandated Drug Taken at Home (DF/HCC Policy)

Research Oversight and Required Regulatory Reporting

The Principal Investigator has the ultimate responsibility to oversee research conduct at their site and ensure required information is reported to the IRB, FDA, and other regulatory bodies when applicable.

DF/HCC research is also subject to internal oversight via monitoring, internal audits, and ongoing review by applicable oversight committees such as the SRC, DSMC and DSMB.

All cancer-relevant clinical trials conducted at DF/HCC are required to register subjects in the OnCore Clinical Trial Management System (CTMS). Registration information is used to ensure proper reporting to the IRB, the NCI, and other regulatory agencies.
- Registration must occur before any protocol treatment/intervention begins. Exceptions are outlined in policy REGIST-101: Subject Registration.
- For most studies, the de-centralized registration process is followed (study staff perform the registration procedures in OnCore themselves).
- For detailed guidance on registration procedures, updating subject status, etc. please review REGIST-OP-1: Subject Registration Procedures
Safety and Event Reporting
The IRB must be notified of all adverse events, along with all protocol deviations, violations, identified conflicts of interest, and other events. Please see below for guidance on these reporting requirements.
- DF/HCC policy RCO-204: Safety and Event Reporting (applies to all DF/HCC research, regardless of IRB of record)
Additional resources for studies reviewed under the DFCI IRB:
- Adverse Event Reporting Policy (DFCI IRB Policy)
- Deviation / Violation / Exception and Other Event Reporting Policy (DFCI IRB Policy)
- Minor Violation Log Template(DFCI IRB Template)
Note - Additional policies and requirements may apply for studies reviewed by an external single IRB of record.
IND / IDE SAFETY REPORTS
There are additional requirements for Principal Investigators conducting research under an IND or IDE. Please review the following for additional guidance on the review and receipt of these safety reports:
Continuing Review / Progress Report
The IRB is required to conduct continuing reviews of research, typically once a year for clinical trials.
- Submit your Continuing Review / Progress Report form directly in iRIS
- For additional guidance please review the iRIS WIKI Instructions for Post-NPA Submissions
Accrual Monitoring
The SRC along with DF/HCC leadership has established specific criteria to assess whether trials are deemed slow or rapidly accruing and when trials trigger closure or additional follow-up assessment due to accrual progress.
Review COM-OP-2 for detailed guidance on accrual criteria and what triggers a warning or closure, the appeal process, and more.
Annual Scientific Progress Review
Annually, each cancer-relevant DF/HCC trial will be reviewed by the SRC. The review includes, but is not limited to, accrual performance, scientific merit, trial completion and publication.
Internal Audits by ODQ
All DF/HCC research is subject to internal audits by the Office of Data Quality (ODQ) per DF/HCC policy AUD-100: Audits and Inspections. The PI and research team will be notified if a study is selected for audit.
- AUD-OP-1: Internal Auditing Procedures (DF/HCC operation)
- Guidance on Responding to Audit Findings(DF/HCC guidance)
- For additional guidance and FAQs, please visit the ODQ Audit page and select the "Internal Audits" tab.
FDA INSPECTIONS/AUDITS
- If you have been notified of an external audit or inspection, please contact your institutional clinical trials office immediately.
- With the assistance of the institutional clinical trials office, send formal DF/HCC notification to applicable parties on the External Audit Contact List by following the procedures outlined in AUD-OP-2: FDA and Other Regulatory Inspections.

Additional resources for sponsor investigators

DF/HCC investigators who sponsor their own research projects have additional responsibilities to ensure appropriate oversight and compliance with reporting requirements.

Registration
DF/HCC investigator-sponsored clinical trials must be registered and updated/maintained on ClinicalTrials.gov. The requirements for which studies must register are outlined in DF/HCC policy REGIST-200: Registration of Clinical Trials on ClinicalTrials.gov.
- The Office of Data Quality (ODQ) will assist the Sponsor-Investigator (aka the "Responsible Party") in creating the initial registration.
- The Sponsor-Investigator is then responsible for reviewing and releasing the registration, and for updating the registration at least every 6 months until completion, or as required.
- Please find additional guidance and contacts on the ODQ ClinicalTrials.gov page
Results Reporting
For applicable trials, results must be reported to ClinicalTrials.gov within 1 year of the primary completion date.
- Find detailed guidance on when and how to report results in the DF/HCC ClinicalTrials.gov Results Reporting Training and Guidance
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OBtaining and Maintaining an ind/ide
DF/HCC Sponsor-Investigators who hold an IND or IDE should ensure review the following for guidance on maintenance:
- RCO-OP-4: Obtaining and Maintaining an IND (DF/HCC Operation)
- RCO-OP-5: Obtaining and Maintaining an IDE (DF/HCC Operation)
COntacting the FDa and reporting safety events
- View contact information for reporting emergencies or problems with FDA-regulated products: Contact the FDA
- MedWatch Online Reporting Form
SAFETY Reporting
DF/HCC sponsor-investigators must conduct a prompt review of all new information relevant to the safety of the research in order to determine the significance of the information in light of previous, similar reports or any other relevant information. As the sponsor, the sponsor-investigator must determine whether any changes are needed to the protocol or consent form as a result of new information.
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DATA AND SAFETY MONITORING COMMITTEE (DSMC)
- The DF/HCC DSMC is charged with monitoring high-risk Pilot, Phase I and Phase II clinical trials initiated and conducted by DF/HCC investigators.
- If your study is under review by the DSMC, please review DF/HCC operation COM-OP-5 for detailed guidance on review procedures, data submission compliance criteria and more.
DATA AND SAFETY MONITORING BOARD (DSMB)
- The DF/HCC DSMB reviews safety, efficacy and study progress for randomized DF/HCC investigator-sponsored protocols that otherwise do not have an independent DSMB assigned. Typically this includes, but is not limited to phase II and phase III randomized protocols.
- The study biostatistician and sponsor-investigator (or designee) are responsible for preparing and providing ODQ with a Data and Safety Monitoring Report prior to each meeting.
- Review DF/HCC operation COM-OP-6 for detailed guidance on review procedures, criteria and more.
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Changes to Approved Research

There are many types of changes that can occur during an ongoing research project. Many of these changes require approval by the IRB of record.

Please review the sections below for more information on different types of changes and what is required.

PRE AND POST AMENDMENT SUBMISSION
Certain tasks must be completed outside of iRIS prior to and immediately after submitting and amendment to ensure appropriate coordination and communication within DF/HCC.
- DF/HCC Pre and Post Submission Checklist
HOW TO SUBMIT AN AMENDMENT
Amendments are submitted directly in iRIS.
- To ensure that your amendment is routed for the appropriate review and approval, be sure to correctly select the type of change, as well as any and all components of the research that are affected (e.g. therapy, participating sites, etc.)
- Review the iRIS WIKI - Post NPA Submissions for detailed guidance on the submission process
Types of changes requiring an amendment
Amendments must be submitted for any proposed changes to the research that require review and approval by the IRB. This includes, but may not be limited to:
- Any changes to the approved Protocol / Consent Form
- Status changes (re-opening, suspending)
- Changes to participant facing information, including documents, systems, and verbal scripts.
- Changes to recruitment methods / materials / advertisements / reimbursement / participant payments
- Adding or removing a DF/HCC participating site
- Changes to a Principal Investigator at a DF/HCC site
- Changes that impact participant privacy, data collection, data storage, data use (including use of a new database, device, or other technology)
Changing Principal Investigator (PI)
Changes to any site PI requires an amendment (see above). Research teams must not manually update or change the PI in OnCore or iRIS.
Review the following for guidance:
- PI Transfer Checklist - Managing PI transfers into/out of DF/HCC
- iRIS WIKI Guidance: Process for Adding or Changing Investigators - Add Site or Change in PI
Change to Research Staff
Non-PI staff changes do not require an amendment.
- Ensure new staff have fulfilled all DF/HCC, institutional and protocol-specific training requirements - Go to the New Staff Onboarding and Training page for guidance and resources
- Updating research staff in OnCore:
  - - Each site is responsible for updating and maintaining their protocol-specific study team lists in OnCore.
    - Review the OnCore WIKI: Quick Guide for Updating the Staff Tab in OnCore
- Updating research staff in iRIS:
  - Additional Guidance: e-Learning: Protocol Staff Changes (15 minutes)
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CHANGES THAT DON'T REQUIRE AN AMENDMENT
Some operational changes can be made without a formal amendment. These types of changes are outlined in the following guidance:
- iRIS WIKI: Post NPA Submissions
Examples of of Other types of changes:
- Administrative Modifications (e.g., IB update, lab manuals and operational documents, pharmacy manual, etc.)
- Dose/Cohort Open/Closure Form (opening a newly declared dose for an existing cohort within the approved protocol, or opening/closing an existing dose/cohort)
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Additional Resources for sponsor-investigators

Guidance for adding external sites to an investigator-sponsored study.

Amendments on Multi-Center Trials
The sponsor-investigator, or a designee, must communicate all protocol and informed consent updates to participating external sites and ensure the changes are implemented in a timely manner. The sponsor-investigator should wait until the changes are IRB approved before sending the final revised documents to other sites. When applicable, external sites can then submit the revisions to their own local IRB for review.
Requirements for Investigator-Sponsored Multi-Center Trials
Prior to expanding a trial to any external (non-DF/HCC) sites, the sponsor-investigator must fulfill several requirements as outlined in DF/HCC policy MULTI-100: Investigator-Sponsored Multi-Center Research and operation MULTI-OP-1: Review and Approval Process for Investigator-Sponsored Multi-Center Trials.
To summarize, these requirements include:
- Complete a one-time Multi-Center Sponsor Training, provided by the Office of Data Quality:
  - - Click hereto complete the 25 minute eLearning
- Obtain a signed Institutional Multi-Center Approval Form from assigned institutional reviewer:
  - - Institutional Contacts for Multi-Center Review
- Submit an Amendment to:
  - Indicate "Investigator-Sponsored Multi-Center" in the NPA
  - Update the protocol to:
    - Include applicable language (e.g. subject registration procedures, drug distribution, etc.) for external, non-DF/HCC sites
      Include a protocol-specific Multi-Center Data and Safety Monitoring Plan (DSMP) to the protocol (required for all interventional trials) - Use the DF/HCC Multi-Center DSMP Template to ensure required components are present
Adding/removing External Sites to a Multi-center trial
For approved multi-center trials, a request to add, remove or close external sites must be submitted in iRIS using the Sponsor-Investigator Add/Open/Complete External Site form.
The following documents can be attached to the form:
- Signed Institutional Multi-Center Approval Form from allowing the addition of the site (required to add sites)
  - See Institutional Contacts for Multi-Center Review
- IRB approval from the IRB of record for the site (required to add or complete sites)

Closing a study and sharing data

There are specific requirements when preparing to share and/or publish data or complete a research project. In addition to DF/HCC requirements, there may be study-specific stipulations (e.g., in the protocol or contract) that must be followed.

Preparing to Complete a Research Project
A research project can only be completed with the IRB after:
- enrollment has ceased;
- all subjects have completed the protocol, including any follow-up activities;
- all data collection is complete
Please review below for additional steps and requirements:
- RCL-100: Preparation for Site Close Out(DF/HCC Policy)
- RCL-OP-1: Procedures for Study Completion(DF/HCC Operation)
Once all study completion steps are finished, the Core Site PI must submit the appropriate study completion documentation to the IRB via iRIS. See the "IRB Completion" section for more information.
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Completing a STudy with the IRB
- For studies that register subjects in OnCore, ODQ must confirm the study is ready to be completed prior to the IRB submission. Click here to submit a request to ODQ.
- Once all research close out activities are complete, the Core Site will submit the a study completion request in iRIS.
- The IRB will send an approval of study completion that must be filed with essential regulatory documents.
For additional guidance, please review:
- RCL-OP-1: Procedures for Study Completion
FDA-regulated research
When applicable, the sponsor-investigator may also need to provide a final study report to the FDA.
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Record Retention
Once a study is IRB completed, there are specific requirements for the long-term archival of applicable study documents and files.
Study teams must comply with any sponsor requirements, institutional policies, and the requirements outlined in the below resources:
- RCL-101: Record Retention for Completed Research (DF/HCC Policy)
- RCL-OP-1: Procedures for Study Completion (DF/HCC Operation)
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Investigator-Sponsored research

There are additional requirements for sharing and publishing data as well as responsibilities for completing research at all participating sites for a DF/HCC investigator-sponsored study.

release of research data
- Ensure all release and use of research information complies with the requirements outlined in DF/HCC policy RCO-103: Confidentiality and Secondary Use of Research Information as well as the protocol, contract, grant, etc.
- In Summary:
  - - The release of research information (including data) to entities outside of and within the DF/HCC is controlled, and must meet specific processes and requirements.
    - Additionally, research information may not be used for secondary research projects (not specified in the original protocol) without permission of the Sponsor and approval of the IRB of record.
Data requests
- The DF/HCC sponsor-investigator (or designee) must submit a formal data request to the Office of Data Quality (ODQ) to request the release of research data.
- This must occur prior to any formal analysis, publication, sharing, presentation, or transfer of any research data.
- To submit a Data Request to ODQ, click here

Complete Research at All sites

The sponsor-investigator is responsible for ensuring research has been closed and completed for each participating site.

Ensure the following steps have been completed at each DF/HCC site and at every external collaborating site:

Data Management	Ensure all CRF data entry is complete and all queries are resolved Ensure all subjects are up to date in OnCore and have an Off Study status Confirm that all data analysis is complete
Investigational Product	All IP has been returned or destroyed in accordance with INV-100 Copies of Accountability Logs have been collected
Regulatory Documents	Ensure all required regulatory documents for the Trial Master File have been collected from each site. Refer to the DF/HCC Required Document List
Miscellaneous	Ensure that any equipment on loan has been returned (EKG machines, electronic diaries, etc.) Verify final payments to the sites Ensure all stored specimens have been shipped
FDA Communication (if applicable)	A final study report has been submitted to the IND Submit one of the following: Annual Report (if other protocols under the IND remain active) An amendment to withdraw the IND (if all protocols under the IND have been completed with the IRB)

Once the above have been verified for each site, the sponsor-investigator should notify each site that they may complete with the IRB. IRB approval of study completion for each site should be filed in the Trial Master File. The Core Site may then submit the appropriate study completion documentation to the IRB via iRIS. See the "IRB Completion" section for more information.