Office of Patient-Centered Outcomes Research (OPCORe)

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

The mission of CCR is to improve the lives of all cancer patients by solving important, challenging and neglected problems in cancer research and patient care through a world-leading basic, translational and clinical research and patient care program. Integral to this is the development and evaluation of novel therapeutic approaches evaluated in early-phase trials. Importantly, in these early phase clinical trials, toxicity and tolerability are the primary questions being addressed. Standard toxicity assessments provide only limited or inadequate information, whereas patient-focused approaches using clinical outcomes assessments (COAs), in which information is gathered on the impact of treatment on the person and not only on tumor response, would markedly enhance the understanding of the patient experience in these trials. Patients are uniquely positioned to inform understanding of the therapeutic context for drug development and evaluation of these outcomes. The FDA has noted the need for more systematic ways of gathering patient perspective on their condition and patient experience related to novel therapies on how they feel and function through the use of COAs. COAs can broadly be classified into four distinct groups based on how data is collected, including information taken directly from the patient (Patient-reported outcomes or PROs), information gleaned from clinical observation (ClinROs); other observer reported outcomes (ObsROs), and data from performance on a task or test (PerfOs) (http//www.fda.gov/media/104969/download ). In cancer-related clinical trials, PROs are increasingly encouraged by regulatory agencies and advocacy groups alike to describe the clinical benefit of a therapeutic regimen. This includes information on disease-associated symptom or functions as a component of determining treatment efficacy and in understanding treatment-associated symptomatic toxicities. These measures, which collect information directly from the patient, without interpretation by somebody else, provides further understanding of the patient perspective about the impact of treatment. The incorporation of PROs in early phase clinical trials is increasingly important as there has be a shift in the clinical trial landscape towards early-phase studies, where data from well-designed and pivotal phase I/II trials is leading to accelerated drug approval. Therefore, having PROs incorporated in these early phase trials can inform the primary trial objective and provide critical information that can be used to support labeling claims in the future. There are many examples where the value of outcomes measures has been instrumental in assessing treatment efficacy in both Phase II and III trials. Additionally, these measures also provide valuable insights about the impact of the disease and its treatment that are critical in improving patient care even when the treatment does not prove to have sufficient activity against the cancer. A recent study of 248 patients participating in Phase I trials at M.D. Anderson Cancer Center revealed that 67% of the patients had seven or more concurrent symptoms and more than half of the patients reported that at least 3 of these symptoms were rated as moderate-to-severe. Surprisingly, this was more frequent in the younger patients compared to those over 65 years of age, highlighting the need for systematic evaluation (starting before treatment) in order to get an accurate assessment of the impact and tolerability of treatment on patients. https://pubmed.ncbi.nlm.nih.gov/31761957/ . The NCI has a long-standing commitment to patient-centered research. This has included development of tools to measure outcomes such as the development of a PRO version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), with demonstrated validity in early phase trials https://pubmed.ncbi.nlm.nih.gov/33392443/, in addition to supporting development of other PRO questionnaires funded through R Grant and other mechanisms. Inclusion of these outcomes has been encouraged and is considered standard in NCI sponsored cooperative group trials and in CTEP-sponsored Phase III trials. The clinical research program of CCR is uniquely poised to lead efforts in systematic integration of these measures in early phase clinical trials and to align with guidance from the NCI and FDA on the importance of these efforts. The proposed program would systematically integrate COAs into the clinical trials conducted at the CCR, provided valuable insight into the patient experience and provide opportunity for evaluation of innovative approaches to data collection and analysis. A centralized CCR program will be created through formation of the Section of Patient Centered Outcomes within the program of the NCI Clnical Director within CCR. As outlined below, the program would be instituted in several phases, starting first with Core Module development for inclusion in all trials, engagement of key stakeholders and agencies and infrastructure development. The use of a core set of symptoms common across cancers in addition to treatment-specific symptomatic toxicities will be foundational for Phase II and III, in which novel integration of measures, use of technology, and integration of care can be incorporated. The proposed plan and timeline is as follows: PHASE I (YEAR 1) Establish Stakeholder Advisory Board, set up infrastructure for electronic data capture and reporting, develop core construct set of outcomes measures Develop template for incorporation into ongoing and future clinical trial protocols for selected clinical branches and cancers, pilot and evaluate system with established metrics of feasibility and success. PHASE II (YEAR 2-3) Expand core construct use throughout CCR clinical research, develop process for enhanced core concepts based on population or target, launch enhanced core concept development as part of scientific review. PHASE III (YEAR 3-5) Develop enhanced technology platform to enable incorporation of these devices (smart wearables, virtual reality as examples) into assessment plan Integrate symptom management into assessment core, align CCR Outcomes initiative with early phase protocols (ie integrated palliative care) or across stand-alone studies.