Protocol Review and Monitoring System

The Protocol Review & Monitoring System (PRMS) continues to provide oversight of the scientific aspects of all clinical research conducted at the UNM Comprehensive Cancer Center (UNMCCC) and its statewide clinical trials network, The New Mexico Cancer Care Alliance (NMCCA). This includes review, prioritization, and monitoring of clinical trials to ensure that a selective, innovative, and balanced portfolio is maintained that is responsive to the needs of our population. Since the last review, the PRMS has instituted changes related to trial prioritization and monitoring of the trial menus.

Teresa Rutledge, MD, (left) and Ursa Brown-Glaberman, MD

Trial Prioritization and Process Changes

The Protocol Review and Monitoring System (PRMS) oversees and provides independent, peer review of the scientific merit, priority, and progress of all cancer studies involving human subjects conducted at the University of New Mexico Comprehensive Cancer Center.  The PRMS is the cornerstone of UNMCCC to implement science-driven clinical trials discovered and conceptualized in concert with the three research programs and consortium members. It is also a unique structure to implement, via the same process, clinical research studies for the State of New Mexico through the Cancer Care Alliance (NMCCA). NMCCA is the UNMCC’s statewide cancer clinical trials network, a collaborative 501c3 university-community consortium which includes 12 additional community-based hospitals and health centers and over 100 community-based physicians.

PRMS functions are accomplished by rigorous review in a two-stage process conducted by: 1) Disease-specific Clinical Working Groups (CWGs), where initial assessment of value, fit, and prioritization within the existing portfolio of studies is performed including an assessment of each study’s accrual feasibility; and 2) the Protocol Review and Monitoring Committee (PRMC), which is the definitive independent authority for determining which studies proceed to activation based on scientific merit.  An additional element for in-depth study feasibility review was implemented in May 2019 via a newly formed Feasibility Committee (FC) whose members evaluate human and other resource, finance and operational needs and make recommendations to the CWGs and PRMC. The PRMS, comprised of the CWG and PRMC review processes, do not duplicate or overlap with the responsibilities of the IRB or the activities of other data and safety monitoring entities. As a member of ORIEN, the UNMCCC PRMS will participate in the ORIEN Scientific Review Committee for multi-site studies activated through ORIEN to support this CCSG change.

There are 8 active CWGs, the majority tumor site specific: 1) Breast, 2) Gyn, 3) GI, 4) Lung, 5) Genitourinary, 6) Heme, 7) Head and Neck and a multi-site Phase 1 CWG. In 2019, two additional CWGs were added: Peds and Population Science. The CWG leaders meet monthly with the AD of clinical Research (Muller) to review strategy, performance, barriers to enrollment and operational issues The Clinical Working Groups are charged with creating a comprehensive clinical trials menu that meet the needs of the New Mexico catchment area prioritizing NCTN/NCORP and investigational initiated trials that are derived from the center’s science.  CWGs provide rigorous trial evaluation and either decline competing or irrelevant trials for their respective patient population or approve a trial which is then evaluated in the feasibility committee and then sent for scientific review to the PRMC. The PRMC has final and independent authority with regards to determining which studies will be activated based on scientific merit and which underperforming studies will be closed.

In 2018, the UNMCCC Clinical Working Groups vetted in aggregate 57 studies and forwarded 53 of these studies to PRMC for review. Once received by the PRMC, 23 of these studies received an initial expedited review by the PRMC Chair as they had already received an appropriate external scientific peer-review, and 30 of these studies, primarily representing UNMCCC’s investigator-initiated and industry-sponsored trials, were forwarded for full PRMC review. 20.75 percent (11/53) of the studies reviewed by the PRMC required modifications prior to being approved, and 4 studies were disapproved and not allowed to proceed through the activation process. In addition, the PRMC also conducted scientific and accrual progress reviews for all actively accruing UNMCCC studies for which 5 underperforming studies were closed in 2018.

Monitoring

Accrual for all interventional studies is monitored quarterly.  If a study has not met at least 50% of the annual target accrual during the first six months after activation, the PRMC will send a communication to the PI requesting information about the low accrual and a revised recruitment plan. At nine months, if the study is still not meeting 50% of annual target accrual, the PRMC will notify the PI that the study has been placed on the list for closure at 12 months unless the PI can provide appropriate 1) justification for low accrual (e.g., study placed on hold by sponsor for safety reasons); 2) planned revisions, amendments to the study to facilitate accrual; 3) revised recruitment strategy (e.g., opening the studies at other institutions). At the annual accrual monitoring review, if the study has still not met 50% of annual target accrual and there is no evidence that actions taken by the PI has or will enhance accrual, the PRMC will close the study to enrollment.  Studies will be continued to be monitored in subsequent years every six months.  However, year two expectations are 75% of annual targeted accrual.

Future Plans

The PRMC under its contemporized SOP will continue to streamline processes to support efficient trial activation.  The PRMC has revised membership to ensure the availability of seasoned reviewers for new studies.  The PRMS will be evaluating a plan to increase the scientific rigor of the review process inclusive of continued scientific relevance of ongoing trials and will close studies based on the better defined SOP put in place in 2019.