Exercise and Nutrition to Improve Cancer Treatment Outcomes (ENICTO): A Place for Implementation Science in Efficacy Trials?

We have been increasingly interested in considering how initiatives supporting behavioral intervention efficacy trials can involve the implementation science (IS) investigative community. The ENICTO consortium is using its cooperative agreement structure to include an opportunity to take an IS lens to efficacy trials that, in turn, may inform and hasten pragmatic work and translation. This opportunity is due in part to the focused and clinically relevant question in all ENICTO trials (i.e., will exercise/nutrition intervention improve completion of cancer therapy?), the ability to clearly distinguish research from key non-research activities that would occur if the intervention were broadly implemented, and the capacity to document the critical functions of exercise/nutrition interventions in ENICTO. The Implementation Science and Cost Working Group (ISCWG) within ENICTO was formed to examine and pursue opportunity for IS, and its activities will be further described in a later section. For more information on the ENICTO projects and coordinating center, please visit the consortium website.

As first step, some background may be useful. Substantial evidence supports the efficacy of exercise and dietary intervention to generally improve physical health, emotional wellbeing, and quality of life among cancer survivors, and recommendations for cancer survivors’ physical activity and diet have been put forth by leading organizations such as the American Cancer Society, American College of Sports Medicine, and the American Society of Clinical Oncology. However, these documents largely focus on the post cancer-treatment period. The purpose of NCI’s ENICTO is to fill a key research gap concerning the efficacy of specific exercise and/or medical nutrition interventions to improve the completion of cancer therapy, to determine intervention effects on related factors (e.g., chemotoxicities, adverse events, and health care utilization), and to generate information that may inform clinical care of cancer survivors. ENICTO involves four clinical trials (U01 projects) across 11 research sites and a coordinating center (U24). Each awardee also receives dedicated funding for collaborative studies and activities, a unique feature of the initiative. The ENICTO steering committee, comprising one principal investigator from the coordinating center and each U01 project along with an NCI representative, serves as the initiative’s main governing board to determine internal policies and procedures, form working groups and committees, and identify cross-consortium research questions and opportunities for novel data collection. Participants in the consortium includes investigators, research fellows and students from U01 project sites and the coordinating center, and NCI collaborators. Within this structure, the PI team of each U01 project pursues their distinct research aims, but also cooperates with the coordinating center in collecting and sharing protocol intervention delivery information and de-identified common data elements. Common elements include participant demographic factors, body composition, diet, general physical activity and exercise prescription information, physical fitness as well as chemotherapy relative dose-intensity data and patient-reported outcomes. In collaboration, the consortium can pursue research questions collectively that are not possible by individual projects and generate new data. A further ENICTO objective is to provide resources and information to the wider investigator community, such as creating a common elements database (to be available in a controlled-access data repository maintained by the NIH at the conclusion of ENICTO, estimated in the fall 2027) and launching the Exercise Oncology/Oncology Nutrition (EON) Network to engage with the broader clinician and researcher communities outside of the consortium.

The ISCWG was formed with the recognition that while exquisitely designed clinical exercise/nutrition trials can provide an explanation for how interventions affect cancer treatment completion, fuller understanding and elucidation of their approach complexity may facilitate further pragmatic research and translation to clinical care. It is important to appreciate that exercise-oncology/nutrition interventions are by nature complex, especially when offered in conjunction with cancer treatment. They require specialized staff training, interactions among staff to schedule and deliver exercise to patients, and coordination with clinical staff often involving adaptations at patient, staff, and organizational levels. Yet, while there is an impressive body of evidence supporting the efficacy of exercise/nutrition interventions for cancer survivors, implementation research in this area is nascent, especially during cancer treatment. The ISCWG leverages the ENICTO structure and includes goals around analytic approaches for how interventions are implemented within studies with an eye toward identifying research tasks from those related to direct clinical care. In addition, the working group is considering cost analyses and how to assess participant satisfaction and other factors that may relate to future translational research.

The first ISCWG project is underway to examine, from the outset, by whom and how complex exercise/nutrition interventions are delivered and adapted, considering similarities and differences across projects. At this point, team members are coalescing information contained in project protocols, staff training, and operating procedure documents to list core intervention component functions and forms that can be tracked over time. These data will ideally contribute to further activity such as possibly generating intervention cost estimates and inform future working group activity and ideally provide pilot data for new research applications. The workgroup is led by Drs. Karen Basen-Engquist and Borsika Rabin, a consultant to the coordinating center, and involves Dr. Wynne Norton from NCI, and participation from ISCWG members from each U01 project and the other coordinating center members. ENICTO looks forward to sharing updates of future implementation science related activities.