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Submitting a Protocol

UPCC Numbers

A protocol cannot be submitted to the CTSRMC without a UPCC number which is the number the ACC uses to track protocols. The UPCC# is a coded number that allows us to track protocols by disease and year.

For Cooperative Group protocols, you do not need to request a UPCC number but you still have to submit your study documents to the CTSRMC. These studies will be tracked by the Cooperative Group number. Please make sure all documents submitted to the CTSRMC include the UPCC number.

Request a UPCC number

Protocol Registration for Cooperative Group Protocols

Cooperative Group protocols must be evaluated for competitiveness and prioritization to ensure they are not overlapping other protocols. These protocols are audited and used in NCI reports (e.g. Summary 4) therefore all Cooperative Group protocols must be registered in the Protocol Tracking database, the CTSRMC uses Velos.

The following qualify as Cooperative Groups:

Please note, consortiums and networks are not considered NCI designated Cooperative Groups. These protocols must be submitted to the CTSRMC for full committee review unless the protocol is funded via a federal peer-review mechanism.

Types of Protocols Reviewed by the CTSRMC 

NCI requires the CTSRMC to review and track all the following categories and types of protocols:

Clinical Research Category:
  • Involving an agent or device with therapeutic intent
  • Involving other types of interventions (i.e. behavioral modification, nutritional protocols, exercise, counseling, etc.);
  • Involving no intervention
Trial or Study Type
  • Therapeutic: therapeutic intent using drugs, radiation, surgery, other biological agents, or behavioral or other interventions.
  • Prevention: for the modulation of cancer risk and inhibition of cancer progression using chemoprevention drugs, nutritional, dietary, behavioral, or other interventions.
  • Supportive Care: intended to improve the comfort and quality of life for the patient using drugs, nutritional, dietary, behavioral or other interventions.
  • Screening, Early Detection, or Diagnostic: directly testing the efficacy of devices, techniques, procedures; or tests for earlier or more accurate detection or diagnosis of disease.
  • Epidemiologic, Observational, or Outcome: among cancer patients and healthy populations that involve no intervention or alteration in the status of the participants, e.g., surveillance, risk assessment, outcome, environmental, and behavioral studies.
  • Ancillary: studies that are stimulated by, but are not a required part of, a main clinical trial/study, and that utilize patient or other resources of the main trial/study to generate information relevant to it. Ancillary studies included must be linked to an active trial or epidemiologic or other study and should include only patients accrued to that trial or study. Only studies that can be linked to individual patient or participant data should be reported.
  • Correlative: Laboratory based studies using specimens to assess cancer risk, clinical outcomes, response to therapies, etc. Only studies that can be linked to individual patient or participant data should be reported.

Submission Process and Required Documents

Protocols submitted to the CTSRMC via the Human Subjects Electronic Research Application (HS-ERA) may encounter delays in review related to HSERA workflows outside the control of CTSRMC staff. For the most timely response and processing, investigators are encouraged to submit a complete protocol packet to the CTSRMC via the CTSRMC listserve CTSRMC_SUBMISSIONS@LISTS.UPENN.EDU.

Protocols must be submitted to the CTSRMC prior to, or at the same time as the IRB to avoid delays related to stipulations and related edits. 

 

If you prefer to submit to the CTSRMC via the IRB’s HSERA, when completing your submission, you must check the box for CTSRMC review required. The CTSRMC will be alerted that your protocol is waiting for review. If you do not check the CTSRMC box, we will not know about your protocol and review will be delayed.

Your submission must minimally include an:

  • HSERA application
  • Full study protocol
  • A grant application or HSERA application will not be accepted in lieu of the full study protocol.
  • Study informed consent form(s) and HIPAA consent (if not included in the study consent)
  • ACC template Monitoring Plan
  • Justification and Prioritization form (for full-committee review only)
  • Disease Team/Focused Group review form (for full-committee review only)

The following must be included if applicable:

  • IND/IDE documentation (where applicable)
  • Investigator's Brochure or Manufacturing Specifications (where applicable)
  • Multi-site Justification Form
  • Multi-site Manual of Procedures
  • Multi-site DOCM Monitoring Plan

Submission Deadlines

A complete protocol packet must be submitted to CTSRMC_SUBMISSIONS@LISTS.UPENN.EDU no later than noon on the last Wednesday of the month preceding the meeting.

Issues identified by CTSRMC staff, related to protocol submissions packets must be resolved by the study team prior to the submission deadline to prevent the submission from being deferred to a later meeting date.

Two-Stage CTSRMC Review

Early in the development of their protocols, investigators may request a two-stage CTSRMC review. We have found that the availability of this review process option improves the quality of protocols submitted to both the CTSRMC and IRB, streamlines the process of gaining final approval and reduces staff development efforts. It is especially valuable for our more junior investigators. In this process the Committee will review the protocol in the standard manner but will not make a formal determination of approval or assign a priority score. This process allows the investigator to work out significant kinks in the protocol design prior to final submission to the CTSRMC for scientific review and the IRB for ethical review.

PLEASE NOTE: Protocols submitted for the two-stage review process must have been vetted for acceptance and prioritization by the disease-specific team and/or cancer center program prior to being submitted so as to not place unnecessary administrative burdens on support staff and the Committee. Documentation of support must be included with your submission.

Scientific Review of Protocols

The CTSRMC and PPRC review protocols by Full-Committee, Expedited or Fast Track mechanisms.

Full- All therapeutic intervention and some other intervention protocols (at the Chair's discretion).

  • These protocols are assigned to a primary, secondary and statistical reviewer. The committee may request additional reviewers at its discretion.
  • The average time from submission to review is six business days and a letter is sent to investigators within three business days following the full convened meetings.

PLEASE NOTE: Protocols submitted for full review must have been vetted for acceptance and prioritization by the disease-specific team and/or cancer center program prior to being submitted so as to not place unnecessary administrative burdens on support staff and the Committee. Documentation of support must be included with your submission. Your protocol will be not be added to the review agenda without this documentation.

Expedited- Some other intervention, some non- intervention protocols (at the Chair's discretion), Compassionate Use and Expanded Access.

  • These protocols are assigned to a primary, statistical and regulatory reviewer. They do not go to the full committee and thus there are no deadlines for submission.
  • The average time from submission to review is ten business days following the day the complete submission (nothing missing, not errors) is received.

Fast-Track- Any protocol that is endorsed by the Cancer Center Director as being of high scientific and clinical priority to receive full CTSRMC review via this time-sensitive mechanism.

  • Protocol must be of high scientific and clinical priority; and (at least one of the following applies)
  • Anticipated demand from patients is self-evident
  • If it is a multi-site study, a Penn faculty member is a bona fide leader of the study
  • Regulatory correspondence indicates a good-faith attempt on the part of the PI to make the regular CTSRMC deadline (e.g. if the protocol was received by the PI six weeks ago there is no reason it should receive an expedited review today)
  • No competing trials (ACC wide)
  • Must be able to enroll subjects shortly after receiving CTSRMC approval

Criteria for Fast Track Ineligibility (some or all apply):

  • Any study with the potential for higher than average perceived or actual risk to subjects (e.g. gene therapy, live virus, adoptive cellular transfer, first-in-man) is not appropriate
  • Phase 3 studies
  • Requests made within five business days of a regular full CTSRMC meeting
  • Studies that are still awaiting an IND/IDE determination from FDA
  • Studies that have been tabled by the IRB
  • In-house studies without funding

Protocols are submitted following the standard process. The average CTRSMC review time from submission is one business day and the average response time from submission to CTSRMC response is four business days.

CTSRMC Review Exempt- Retrospective chart reviews and residual specimen collection/analysis not requiring study or HIPAA consent. These protocols must be sent to the CTRSMC for administrative acknowledgement but are not scientifically peer-reviewed.

Protocol Review Criteria

The review criteria that are used to assess scientific rationale, study design, expected accrual rates, biostatistical input and feasibility for completion within a reasonable time period are detailed below.

Significance

  • Does this study address an important problem?
  • If the aims of the protocol are achieved, how will scientific knowledge or clinical practice be advanced?
  • What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Approach

  • Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project?
  • Does the protocol acknowledge potential problem areas and consider alternative strategies? 

Innovation

  • Is the protocol original and innovative?
  • Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area? 

Feasibility

  • For this study is it feasible to relate endpoints to objectives?
  • Is the study designed in such a way that it can be conducted at this institution?

Competing studies

  • Are there other studies currently open or in development that will directly compete with this study for subjects?
  • If there are competing studies, is there a plan for managing how subjects will be routed to each study?
  • Are there currently studies open that are better options for subjects than this study?
  • If there are competing studies that are better options for subjects, is it likely that this study will meet its accrual goal?

Women, Minorities and Children

  • The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed.

Statistical Design

  • Correct statistical model being used
  • Accrual rate and/or study duration
  • Sample size justified
  • Maximum number of patients justified
  • Appropriate outcome parameters
  • Stopping guidelines
  • Clear specification of primary and secondary hypotheses
  • Adequate proposed testing of primary and secondary hypotheses
  • Primary endpoints for interim and final analysis
  • Plans for data analysis
  • Clear statement of data analysis in relation to objectives
  • Method of randomization and stratification (as applicable)
  • Error levels (alpha and beta) (as applicable)
  • Differences to be detected for comparative studies (as applicable)
  • Size of the confidence intervals to be constructed around the estimated outcomes (as applicable)
  • Hypotheses to be tested in ancillary studies (as applicable)

At the conclusion of the review the Committee votes on whether or not the protocol will be approved, approved with stipulations or disapproved. All protocols that fall into one of the approved categories are assigned a priority score as follows:

1.0-1.9 (outstanding science, high priority, important)

2.0-2.9 (good science, lower priority, worthwhile)

3.0-3.9 (no scientific impact, no priority, not worthwhile)

This score should be used by ACC research programs to prioritize their research portfolios and resource allocation thus ensuring that the most important and impactful research is appropriately supported.

Attending the Review of a Protocol

All investigators are invited and encouraged to attend the review of his/her protocol. Attending the review may help expedite the approval process. Once the meeting agenda is finalized, study PIs will receive an e-mail notifying him/her of the location, date and time the CTSRMC will review their protocol.

PIs or his/her designees (should be able to respond clinically/scientifically to members questions) should give the CTSRMC a 5 minute buffer in the start time of their review to allow some flexibility in the timing of the review. The committee makes every effort to stay on time with the agenda, but it should be understood that the complexity of this process may result in delays.

Because this is a closed meeting (confidential) PIs may not sit in the meeting room during the review of other protocols, therefore upon arriving at the meeting location, please stay in the waiting area until the CTSRMC Coordinator calls your name.

Process and Criteria for Prioritizing Protocols

The process for prioritizing clinical protocols lies initially with the disease-specific teams and cancer center research programs. The CTSRMC expects that all protocols that are submitted have been reviewed by the disease programs leaders for appropriateness and prioritization within the program's portfolio prior to being submitted for review. Additionally, the CTSRMC administrative office generates a monthly report on all potentially competing protocols currently open campus-wide. This report is provided to the Chair at the beginning of each meeting. The Chair discusses each protocol on the list of potential competitors as part of the review process with the entire Committee, and asks the PI of the protocol under review to comment on the potential competing protocols. If an overlapping protocol is identified, the PI is asked to provide a formal prioritization management plan as part of his/her stipulation response. This plan must include a statement of support from the disease-specific team leader or the program leader. Protocols will not receive full approval until the Chair is satisfied with the proposed plan.

Although externally peer reviewed and funded protocols are not reviewed for scientific merit, they are administratively reviewed for prioritization and competitiveness with other ongoing or proposed studies at our Center.

Relationship of the CTSRMC and IRB

The CTSRMC is separate and independent of the institutional IRBs. The role of the CTSRMC is complementary to, and does not duplicate or overlap any of the responsibilities of the IRB. The primary focus of the CTSRMC is to ensure that protocols have scientific rationale, merit, feasibility, and appropriate statistical designs, as well as appropriate plans for prioritization. The major focus of the institutional IRB review is subject safety, ethical concerns, equipoise and informed consent procedures. The University of Pennsylvania IRB will not grant final approval for any cancer-related protocol or allow a protocol to open for enrollment until final approval is granted from the CTSRMC. This agreement has been in place at the University of Pennsylvania since 1992.

Monitored Protocols for Progress and Performance

In addition to the initial review of protocols for approval, the CTSRMC/PPRC conducts ongoing review of protocol progress and performance through close accrual monitoring and review of the Continuing Review documentation. The CTSRMC has the authority to close or terminate a protocol for poor accrual and/or scientific progress.

Accrual Monitoring- Every protocol, regardless of sponsor or funding source, is evaluated for accrual progress three months from the date approved by the CTSRMC and every three months thereafter. Studies with aggressive accrual timelines are monitored for accrual commensurate with the protocol defined timeline. Based on the stated accrual goal and protocol duration, an assessment of accrual performance is made. Studies with low or no accrual at the initial three month evaluation are sent a letter requesting an explanation for the current state of accrual and a plan to improve enrollment. The CTSRMC Chair considers the PI's response and decides whether to accept the response, allowing the study to remain open, or closing/terminating the study. The Chair may grant a three to twelve month extension at his/her discretion. At the next review cycle, if the protocol is still underperforming, the PI is asked to provide within ten business days, an explanation for poor enrollment, a plan for improving enrollment, and a justification for continuing the protocol. If the study is allowed to remain open, but has not improved enrollment by the next review window anniversary, the CTSRMC Chair will notify the PI that the Committee has closed/terminated the study. When a study is closed by the CTSRMC, the IRB is notified of the change in study status.

Scientific Progress Monitoring- Every active protocol is reviewed at least annually to assess whether or not the study is making appropriate scientific progress. The Chair and CTSRMC Director review the annual IRB Continuing Review, publications and additional documentation as applicable, for example, IND updates to FDA and DSMB reports. If the Committee believes the study is not making sufficient progress, the research question or therapy is no longer relevant, or the study is no longer meritorious, the CTSRMC will close/terminate the study.

Accrual and Scientific Monitoring for Rare Diseases and Targeted Therapies- Special considerations are given to protocols of rare diseases and molecularly targeted therapies since these protocols generally do not accrue quickly. These protocols are reviewed annually for progress. If the study has made little to no progress at the one-year time point, the PI is asked to explain the status of the study, the patient population at Penn/CHOP and to provide a brief explanation of the plans for progress. The Chair will review the response and make recommendations as deemed necessary.