Dec. 11, 2015:

What are the responsibilities of BTCRC regulatory managers?

BTCRC regulatory managers assist with all aspects of regulatory issues related to BTCRC research, including interactions with consortium members, institutional review boards, and regulatory agencies. Regulatory services include:

  • Essential document collection and tracking
  • Initial IND (FDA) submission and maintenance of the IND
  • Distribution of updated study documents to site staff
  • Review and approval of site documents
  • Ensuring all IRB approvals are obtained by sites
  • Central IRB submissions of study materials, when applicable
  • Trial master file maintenance

What information should I send to the regulatory manager?

The most common documents the regulatory manager will request from your sites are:

  • Study-Specific Documents
    • FDA Form 1572
    • Financial Disclosure Form from the principal investigator and each sub-investigator(s) listed on the 1572
    • Delegation of Authority log
    • Protocol Signature Page
    • Institutional Review Board (IRB) approval for the protocol, informed consent document(s), investigator’s brochure (as applicable), and any patient materials (e.g., drug diaries, brochures, advertisements)
    • IRB membership roster and/or statement of compliance
  • Site-Specific Documents
    • Current curriculum vitae (CV) for all investigators/sub-investigators listed on the 1572 (signed/dated within 2 years)
    • Clinical licenses for the principal investigator and each sub-investigator, if licensed
    • Educational completion certificates of human subject protection training and good clinical practice (for all staff members on 1572)
    • Clinical lab certificates/reference ranges
      • Current normal-range values for each laboratory listed on the 1572
      • Clinical Laboratory Improvement Amendments (CLIA) for each laboratory
      • College of American Pathologists (CAP) for each laboratory (as applicable)

The regulatory should be notified of any change in staff, study performance sites, and IRB approvals. Although monitors will regularly visit your site for audit, it is preferred that you contact the regulatory manager with all regulatory communications.

What are common errors?

The most common errors include missing and expired documents, inconsistency in documentation, and failure to secure approval from the regulatory manager.

Missing and expired documents: BTCRC Administrative Headquarters will request new versions of all site-specific regulatory documents every 2 years. However, we understand that institutions may have varying policies for the timeframe of renewal. If the site can provide an institutional SOP or a Note to File signed by the PI or site administrator explaining the renewal period, we will extend the requirement from 2 years to up to 5 years.

In addition, sites often neglect to update us with new information. Any time information submitted on the study-specific documents changes, such as staff, performance sites, or labs, including name or address changes, all relevant documents should be updated accordingly and documents provided to BTCRC Administrative Headquarters.

Inconsistency: Ideally, the names or addresses of staff, clinics, and labs would be noted in the same way across all regulatory documents. Care should be taken when preparing the 1572 form to ensure all information is accurate and matches the supporting regulatory documents. However, sometimes this is not the case, through either typographical error or other causes. For instance, an investigator may go by her middle name, but her CV only lists her first and last name. The name of a laboratory may be abbreviated in order to fit on the CLIA certificate. In cases where there is a discrepancy that the site’s regulatory staff cannot remedy, a Note to File (signed & dated by the site PI) should be supplied to BTCRC Administrative Headquarters explaining the inconsistency.

The delegation of authority log is another document where we see inconsistency. Please have all staff who are assigned essential study tasks sign this document. If an investigator or other site staff member is listed on the 1572, requests access to the study database, or attends the site start-up meeting, BTCRC Administrative Headquarters will cross-reference this information with the delegation of authority log.

Failure to secure approval: BTCRC Administrative Headquarters requires sites to submit their draft 1572 forms to the regulatory manager prior to having the PI sign. This elps to ensure the accuracy of the contents and that trial information and central labs are listed correctly, allows Administrative Headquarters to start tracking the site and personnel documents we may need against what we currently have on file.

If a BTCRC trial requires an IND, who is the holder of the IND?

If a trial requires an Investigational New Drug (IND) application, BTCRC Administrative Headquarters can do the initial IND submission, as well as maintain the IND throughout the lifecycle of the trial. In this case, Administrative Headquarters is not the IND holder; the lead investigator holds the IND as the Sponsor-Investigator. Any or all of the responsibilities of the Sponsor-Investigator of an IND may be delegated to Administrative Headquarters, including the submission to the FDA of protocol amendments and annual reports on the progress of the investigation, and ensuring that FDA and all participating investigators are promptly informed of significant new adverse effects or risks with respect to the investigational drug.

To what regulatory authorities should I report my SAE and who does the reporting?

  • Central reporting: Participating sites will submit all serious adverse events (SAEs) to Hoosier Cancer Research Network (HCRN). As administrative headquarters for the Big Ten Cancer Research Consortium (BTCRC), HCRN will submit qualified SAEs (based on the guidelines for reporting SAEs listed in the protocol) to the study drug provider. Per FDA guidelines, HCRN will report all possibly related and unexpected SAEs to the FDA/regulatory authorities via a MedWatch report, as well as distribute the report to each participating site.
  • Local reporting: Each participating site should follow their standard operating procedures for reporting SAEs to their local IRB and other oversight committees.

Can I email my SAE report to Administrative Headquarters?

Yes, you may email your SAE to safety@hoosiercancer.org.

When should I report the SAE?

SAEs should be reported within 24 hours of becoming aware of event. If limited information is available, provide as much information as possible at the time of the initial report.

What date should be used for onset date — the date when symptoms started or the date the patient was admitted to the hospital?

The onset date is the date the event became serious. For example, if the SAE criteria being met is “hospitalization,” the onset date is the date of admission.

About the Big Ten Cancer Research Consortium: The Big Ten Cancer Research Consortium creates a unique team-research culture to drive science rapidly from ideas to treatment-changing paradigms. Within this innovative environment, today’s research leaders collaborate with and mentor the research leaders of tomorrow with the unified goal of improving the lives of all patients with cancer.

About the Big Ten Conference: The Big Ten Conference is an association of world-class universities whose member institutions share a common mission of research, graduate, professional and undergraduate teaching and public service. Founded in 1896, the Big Ten has sustained a comprehensive set of shared practices and policies that enforce the priority of academics in the lives of students competing in intercollegiate athletics and emphasize the values of integrity, fairness and competitiveness. The broad-based programs of the 14 Big Ten institutions will provide over $200 million in direct financial support to almost 9,500 students for more than 11,000 participation opportunities on 350 teams in 42 different sports. The Big Ten sponsors 28 official conference sports, 14 for men and 14 for women, including the addition of men’s ice hockey and men’s and women’s lacrosse since 2013. For more information, visit www.bigten.org.