Cancer Institute Clinical Trials Office
Our office is centralized providing support for Cancer Institute clinical investigators in the development, implementation and completion of clinical trials. We are the hub for clinical trials support activity and is a vital component of the clinical research infrastructure in the Cancer Institute. Our team of clinical trials professionals are led by Director, Cindy Naret, with the support and leadership of Chandra Belani, M.D., Interim Medical Director and Deputy Director, Associate Director for Clinical Research for the Cancer Institute. We serve as a shared resource to provide assistance to clinical investigators in all aspects of clinical trial development, processing, coordination and management. The team is composed of clinical research coordinators, regulatory specialists, data management staff, a financial analyst, a data base network administrator, and a support associate. Trials presently coordinated by the CTO include pilot and Phase I-III treatment trials as well as trials for cancer prevention. General functions and support provided by the CTO are listed below.
CTO Support for the PSHCI Scientific Review Committee (SRC) Process
CTO support for SRC submission includes assisting the investigator in the completion of the SRC checklist for new protocol submission; identifying the CTO, Penn State Hershey Cancer Institute and Penn State Milton S. Hershey Medical Center resources to be utilized in the conduct of the study; assisting the investigator in responding to the feedback from the SRC, including assembly of responses from the investigator or facilitating commentary with an industry sponsor where appropriate; and in tracking all aspects of SRC review and approval to ensure prompt submission to the IRB once SRC approval is secured.
CTO Support Specifically Related to Investigator-Initiated or Peer-Reviewed Trials
The CTO is committed to the Institutional prioritization of investigator-initiated and peer-reviewed trials. The CTO facilitates the following efforts for such trials:
- Assisting investigators with all aspects of NCI/CTEP filing for investigator-initiated trials authored by our site. This begins with preparation and submission of a Letter of Intent (LOI) and progresses through protocol iterations hopefully resulting in an approved protocol for implementation.
- CTO review and input focusing on the trial’s logistics (e.g., clarity of inclusion/exclusion criteria, study calendar, patient flow, instructions for dose modification), regulatory reporting requirements (e.g., adverse event reporting), and the development of consent forms without the aid of a model consent form from an outside source.
- Facilitating version control and protocol documentation as a point of contact for studies led by our partners at other sites.
- Preparing and submitting all serious adverse event reports (SAEs) to the appropriate internal and external entities for events occurring at our site.
- Developing customized case report forms and reports utilizing OnCore® clinical trials management application.
- Tracking and disseminating IRB review and approval so that it is available to the lead site on trials with our consortium partners, ensuring the appropriate distribution of notification of our activation to NCI/CTEP and Theradex.
- Assisting investigators in the preparation of IND applications for investigator-initiated protocols for which our Cancer Institute investigators will hold the IND. This includes full IND applications as well as applications for exempt IND status. CTO staff will also facilitate all aspects of tracking the IND submission, annual reports, and submission of any serious adverse event (SAE) reports.
- CTO staff participate in weekly U01/phase I teleconferences with clinicians and research staff from the Cancer Institute and U0P, as noted above, to discuss overall conduct of phase I trials (e.g., trial status, enrollment, toxicity, dose level assignment, protocol compliance).
- CTO staff participate in monthly N01/phase II teleconferences with clinicians and research staff from sites involved in the CCC-P efforts, as noted above, to discuss the overall conduct of phase II trials (e.g., trial status, enrollment, salient toxicities).
- Facilitating the registration of clinical trials information on ClinicalTrials.gov.
CTO Support for the Institutional Review Board (IRB) Process
CTO facilitates IRB review of clinical trials by providing the following support to the principal investigator:
- Developing required forms and documents for IRB submission (i.e., application, protocol abstract, local consent form[s], recruitment materials); assembling other required documentation for IRB submission (e.g., full protocol, investigator’s brochure).
- Providing timely submission and tracking of all IRB activities for new protocols, including initial submission, and deliberations back and forth in answering IRB questions, ensuring the best possible timeline for approval of new studies.
- Providing timely submission and tracking of modification requests to the IRB. This includes an awareness of staying within required timelines for IRB approval of amendments on NCI/CTEP and cooperative group trials.
- Providing timely submission and tracking of IRB renewals. This includes assembly of required documentation for the renewal packet involving input from the clinical research coordinator, data manager and regulatory specialist.
- Providing up-to-date status information and approved documents to the study team throughout the regulatory processing of documents, with manual and electronic checks in place to ensure the use of correct versions of protocols, consent forms, eligibility checklists and other documents.
- Submitting all serious adverse event (SAE) reports to the IRB as per their guidelines. Any resultant modifications to the consent forms based on new risks identified or changes in the frequency of risks are also accomplished by CTO staff.
- Preparing internal documentation and submitting (where appropriate per local guidelines) all outside safety reports received on trials.
- Submitting all data safety monitoring information received from sponsors on multi-center trials and from our Cancer Institute DSMB to the IRB.
- Submitting ongoing communications regarding the status of the study (i.e., study suspension, study closure) to the IRB and all team members.
- Facilitating ongoing communication between IRB staff and CTO staff, as well as leadership of the IRB and CTO where appropriate, to ensure prompt and effective resolution of any issues that may arise.
CTO Support for Industry-Sponsored Trials, Regulatory Processes
Investigator-initiated and peer-reviewed trials remain the highest priority in our Cancer Institute. However, the CTO is also committed to supporting industry trials that would provide additional treatment options for cancer patients. The following services are provided:
- Providing sponsors and CROs (contract research organizations, for industry sponsors) with required documentation at the outset of each trial, i.e., Form FDA 1572; curriculum vitae and medical licensure of principal investigators and sub-investigators; laboratory licensure and certification; protocol signature page(s); financial disclosures for principal investigator and sub-investigators; delegation of authority log(s) for investigators and all members of the research team; and other study-specific forms as required by sponsor/CRO.
- Maintaining the regulatory binder throughout the course of the study, updating the above documents when necessary.
- Coordinating team attendance required at sponsor-initiated meetings, i.e., pre-study (site evaluation) meeting; Investigator’s meeting (off site); study initiation visit (on site); and ongoing monitoring visits throughout the course of the trial.
- Submitting serious adverse events (SAEs) occurring at our site to areas noted in the sponsor’s protocol, as well as internally as appropriate (i.e., IRB).
- Completing required logs for the sponsor (e.g., screening, enrollment).
- Participating in sponsor/CRO teleconferences on the trial’s progress, where appropriate.
CTO Support for Fiscal and Contractual Processes
The following services are provided by our staff regarding the fiscal and contractual processes for clinical trials:
- Costing out of each new trial in a timely manner to ensure that industry funding will cover the costs of procedures and labor for the trial during the start-up, implementation and maintenance stages. The goal is to recoup all the costs of carrying out the trial from the industry sponsor and to make sure reasonable milestones for the flow of the reimbursement are reached. The CTO financial analyst works with investigators, clinical research coordinators and appropriate clinical staff in order to ensure the appropriate designation of standard of care versus research-related procedures. The CTO also works with ancillary departments to ensure appropriate pricing for research-related procedural costs. Care is also taken to ensure the appropriate capture of costs for labor in regards to trial start-up, maintenance and close-out.
- Ensuring consistency among the trial budget, contract and consent form with regard to financial issues.
- Working with appropriate clinic and utilization review staff to provide consultation for research subjects regarding third party billing and all other aspects of their financial obligations.
- Reconciling, on a monthly basis, the appropriate billing to research subjects.
- Tracking milestones from the patient calendars and following contractual milestones to ensure appropriate and timely billing to sponsors; tracking for the payment of invoices.
- Processing contracts with Penn State University Office of Research Administration. This involves tracking as well as familiarity with key points in the contract in order to ensure the appropriate resolution of contractual terms.
Implementation and Coordination of Clinical Trials
Many of the activities in relation to new trial start-up described above pertain to efforts of CTO regulatory staff and the financial analyst. The clinical research coordinators (CRC) and data managers do have important roles in the start-up activities and those are described where appropriate. However, once a trial is deemed regulatory and contractually ready for implementation, the scope of the work dramatically shifts from the regulatory and business staff to the CRC and the data manager. Likewise, close communication with regulatory and business personnel must remain throughout the trial to ensure upkeep of those areas as the trial proceeds (e.g., for modifications, regulatory renewals, safety reporting and other tasks deemed appropriate). The following services are provided by CTO staff throughout the conduct of the study:
- Coordinating and attending sponsor team meetings (e.g., off-site investigator meetings, on-site study initiation visits).
- Developing and completing necessary protocol tools and worksheets (i.e., source document worksheets, logs, physician orders, laboratory requisitions).
- Screening potentially eligible subjects; including assurance of appropriate HIPAA consent to allow for the review of patients’ protected health information (PHI) for clinical trials.
- CRC participating, with the investigator, in the informed consent process for all potentially eligible trial subjects. The CRC is responsible for the documentation of the informed consent process in the patient chart and research record. Informed consent is an ongoing process, and the CRC continually educates the subjects (and family members, when appropriate) about all aspects of the subject’s participation in the trial.
- Scheduling the collection of screening/baseline information for each potential subject (i.e., laboratory and pathology requirements). This includes following protocol-specific specimen handling and shipping requirements.
- Completing all aspects of screening patients for eligibility; attaching to the eligibility checklist all relevant source documentation evidencing the subject’s eligibility to participate in the trial. If the CRC has questions about a patient’s eligibility for a study, it is discussed with the principal investigator. Should there be opposing views about a patient’s eligibility among the principal investigator, co-investigators and/or the CRC, the CRC will promptly bring them to the attention of the CTO Director, who will immediately involve Dr. Belani, Interim Medical Director, where necessary, so that an accurate and swift determination of eligibility can be made. Once a subject is deemed eligible, the CRC registers them on study according to sponsor and protocol-specific requirements.
- Managing any ongoing radiology and pathology reviews as required per protocol.
- Scheduling the collection of on-study and follow-up assessments for each subject to ensure compliance with protocol and study calendar parameters throughout the course of the trial.
- Identifying, assessing and documenting all adverse events (AEs) and serious adverse events (SAEs) during the trial and required follow-up periods. Reporting the AEs and SAEs on appropriate forms, to appropriate internal and external entities per protocol, and within required timeframes. This includes collection of all required laboratory and follow-up information from medical records and outside sources.
- Capturing data and completing case report forms in a timely and accurate manner. Ongoing communication among members of the study team helps to assure such timely and accurate data collection; CRCs and data managers meet at least weekly.
Centralized Clinical Trials Management System
Our office OnCore® (On-line Clinical Oncology Research Environment) as the primary data management system for clinical trials activity. OnCore® was developed by Forte Research Systems, Inc., and is a highly secure, web-based, cancer-specific, customizable system that provides fully integrated clinical data management and protocol management capabilities. OnCore® houses regulatory tracking information, study management activity and clinical data. Additionally, OnCore® provides NCI-designated cancer centers with the ability to provide the NCI required reports. To date, more than 25 different cancer centers are using OnCore® as customized for their site.