Managing an Ongoing Non-Treatment Research Project

Study documentation, research oversight, and reporting

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

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

Regulatory file
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.
Keep in mind that some documents listed are specific to FDA-regulated drug or device research (e.g. Form FDA 1572, investigational product information) and may not apply to your research.
Delegation of Authority Documentation requirement
In accordance with RCO-203 requirements, a delegation of authority log must be maintained for human subject research protocols. Typically, Banking, Tissue Collection, and IRB-determined minimal risk studies are exempted from this requirement.
If your study requires you to maintain a DOA log:
Use DF/HCC templates, and 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.
Documenting informed consent
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.
- Keep in mind that the consent process may be waived or altered for certain types of research. Review the New Submissions Page for additional guidance.
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)
Source documentation
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:
Subject Registration Requirements
Subject registration in the OnCore Clinical Trial Management System (CTMS) is required for all cancer-related, hypothesis-driven research studies. This includes Observational, Ancillary, Correlative, and Interventional research.
Registration information is used to ensure proper reporting to the IRB, the NCI, and other regulatory agencies.
- For interventional research, registration must occur before any protocol intervention begins. Otherwise, registration must occur within 30 days of obtaining informed consent per 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
Summary Accrual Reporting
For certain non-interventional protocols, registration in OnCore may be performed through submission of summary accrual data. This method must have prior approval from the Office of Data Quality (ODQ) Director.
- Review Summary Accrual Reporting requirements in REGIST-101 and the procedures for using summary accrual in REGIST-OP-1.
- Summary accrual is typically used when accruals require reporting, however not all of the required elements for subject registration are collected, e.g. initials, date of birth, etc.
- Contact ODQ@dfci.harvard.edu with questions or to request use of summary accrual.
SAFETY AND EVENT REPORTING
Defining adverse events in non-treatment research may be particularly challenging. Adverse events are not exclusive to physical harm but may also include psychological, social, economic, or legal harm. Most often this is caused by breaches of confidentiality in research. 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.
- Submit an Event - Adverse Event Violation Reportable New Information or Event - Prospective Exception/Deviation Request form directly in iRIS.
- For additional guidance please review the iRIS WIKI Instructions for Post-NPA Submissions
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 (DFCI IRB) or Progress Report (protocols under an external IRB) form directly in iRIS.
- For additional guidance please review the iRIS WIKI Instructions for Post-NPA Submissions

use of data and specimens

Research information and materials, including previously collected research data and specimens, are considered confidential. Their use and release controlled and governed by DF/HCC policies, IRB requirements, regulations, and contract terms.

Furthermore, any time data or specimens will be shared outside of a DF/HCC institution for research purposes, specific steps must be taken to ensure the subject and the institution is protected.

Secondary Use Research
Secondary Use research is human subjects research where data or specimens were collected under another protocol, for a biobank, or for non-research purposes, and will be used in a new project.
When is a Secondary Use Application required?
A secondary use application must be submitted and approved any time data will be used for a research goal or object that was not specifically stated in the original protocol for which the data was collected.
Submission in iRIS - If you are submitting a Secondary Use project in iRIS, you do not need to include a protocol document. You are only required to complete the Secondary Use Application within iRIS.
Additional Guidance
- Review this e-Learning on Secondary Use and Not Human Subject Research at DF/HCC for guidance on determining whether your research is Secondary Use and additional requirements.
- Secondary Use research at DF/HCC is governed by policy RCO-103: Confidentiality and Secondary Use of Research Information
- Find more resources on the OHRS page for Research with Biological Materials and Data
Data Transfers
PIs who wish to transfer data or samples outside of the institution must contact their home institution's technology transfer department (e.g., BODFI, Innovations) to determine if a material transfer agreement (MTA) or data use agreement (DUA) is required.
- Find additional resources and contacts on the OHRS page for Research with Biological Materials and Data
Ensure your original protocol and consent allow for the new data use
- DF/HCC research involving the future use and sharing of data and specimens must be described in the protocol and the consent form signed by each participant in order for data and/or specimens to be used for future research and/or shared with another institution.
- Without participant consent, data and specimens cannot be used without the IRB's approval of a waiver of informed consent and a waiver of HIPAA authorization.
- If the studies from which the data and/or specimens were collected did not specifically allow for the use of the data as proposed in both the Protocol Document and signed Consent Forms, you must submit a Secondary Use Application.
Note - if additional data/samples will then be collected here at DF/HCC to supplement previously collected data, a New Project Application must be submitted
Institutional Certificates for genomic data sharing
The NIH, as well as many other journals and sponsors, require that genetic data be deposited into the NIH's database for Genotypes and Phenotypes (dbGaP). All data submissions must be accompanied by Institutional Certification.
For additional requirements, and guidance on how to request and obtain Institutional Certification, please review the OHRS Guidance: Institutional Certification Process for Genomic Data Sharing.
HIPAA and PHI
Protected Health Information (PHI) is private information that is subject to protection under the HIPAA Privacy Regulations. HIPAA only applies to Protected HealthInformation - therefore it may or may not apply to social-behavioral research.
- Review the HIPAA Info Sheet - Privacy Rule Overview for specific guidance.
- Reach out to OHRS@dfci.harvard.edu with questions specific to HIPAA and PHI
Case Study - Does HIPAA apply to my research?
Example 1: Research studying how social interactions between colleagues at work affect productivity would not ordinarily involve the use or disclosure of health information and would, therefore, not be governed by the HIPAA Privacy Rule.
Example 2: However, if the research also studies how an individual’s history for treatment of emotional disorders or blood glucose levels affects productivity, the research would involve health information and, therefore, would require compliance with the HIPAA Research Privacy provisions. In this case, one of the following six mechanisms for using or disclosing Protected Health Information must be invoked.

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.

How to change your approved research project
Certain types of studies will require an amendment for any proposed changes. See below for guidance.
Certain types of research typically cannot be altered by an amendment, including Secondary Use, Not Human Subject Research, and Exempt research.
- Rather, if you are adding a new research objective/aim, or altering the objective originally approved by the IRB, then you would need to submit a new research application in iRIS
- Rationale: When it comes to previously collected data being used in a new research project the IRB needs to review each new objective separately, especially with regards to HIPAA, informed consent, and other applicable regulations
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)
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
Changing Principal Investigator (PI)
Changes to any DF/HCC site PI, or the PI of any external site that is relying on the DFCI IRB, 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:
  - - Each site is responsible for making their staff updates in the system and should only include staff from their institution under their Key Study Personnel.
    - Review the iRIS WIKI: Quick Reference Guide
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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 or closing individual arms or cohorts of a study)
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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
If you are expanding your investigator-sponsored research project to external collaborators, you may be subject to the requirements in DF/HCC policy MULTI-100: Investigator-Sponsored Multi-Center Research if the external sites/collaborators are involved in either:
- The recruitment of, or administration of an intervention to, human subjects; OR
- Collection and/or review of data that is identifiable or may be made identifiable by the investigator at that site.
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). This approval is obtained from the 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.
Note - Not Human Subject Research (NHSR) and IRB Exempt studies are not required to submit a study completion form to the IRB.
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
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)
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 (when applicable to your research) 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
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

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.