CFAs: Improving Methods for Conducting Patient-Centered Comparative Clinical Effectiveness Research (US)

For the 2024 Methods PFA, PCORI has identified the following areas as programmatic priorities that address important methodological gaps and lead to improvements in the strength and quality of evidence generated by CER studies:

• Methods to Improve the Use of Artificial Intelligence (AI) and Machine Learning (ML) in Clinical Research
• Methods to Improve Study Design
• Methods to Support Data Research Networks
• Methods Related to Ethical and Human Subjects Protections Issues in patient-centered CER.

Priorities

• Methods Related to Ethical and Human Subjects Protections (HSP) Issues in Patient-Centered CER: PCORI is interested in funding projects to address important ethical and HSP issues related to the conduct of patient-centered comparative clinical effectiveness research. The following topics are priorities for this area:
  • Measures Recruitment and informed consent processes for participation in clinical research in the context of randomized controlled trials (RCTs), cluster RCTs, pragmatic trials, adaptive or platform trials, decentralized clinical trials, observational studies (including those conducted in learning health care system settings), and natural experiments. Applications examining alterations of consent are welcome.
  • Assessing the concept of minimal risk in clinical research (including clinical trials)
  • Review and monitoring activities, including protocol adherence and adjudication of study outcomes
• Methods to Improve Study Design: PCORI is interested in funding projects that foster improvements in clinical research study designs to address patient-centered CER questions. The following topics are priorities:
  • Methods to improve the design and conduct of Sequential Multiple Assignment Randomized Trials (SMART)
  • Methods to improve the design and conduct of decentralized clinical trials (DCTs)
  • Methods to manage adaptation of treatment strategies while minimizing threats to internal validity in studies of complex interventions
  • Methods to improve the design and conduct of patient-centered CER studies in circumstances limiting the use of RCTs
  • Methods to improve the design and conduct of patient-centered CER studies in the identification, recruitment, and retention of study participants
• Methods to Support Data Research Networks: PCORI is interested in funding projects that offer generalizable and scalable insights into multisite patient-centered CER using data research networks. Applications that address Data Research Networks must address one or more of the following priorities for this area:
  • Methods to improve distributed analyses in data research networks
  • Methods to improve data quality in data research networks
  • Methods to promote interoperability of data science methods and data across data research networks
• Methods to Improve Use of Artificial Intelligence and Machine Learning in Clinical Research: PCORI is interested in funding methodological research that seeks to improve how massive amounts of data from a variety of electronic health data sources1 can be appropriately analyzed and integrated into clinical care and health care delivery systems. The following topics are priorities:
  • Approaches to integrate heterogeneous data sources (e.g., with differing noise properties, quality, and measurement frequencies), approaches to extracting informative representations from unstructured data (e.g., continuous temporal measurements, images, or text), and approaches to modeling longitudinal EHD
  • Approaches to improve integration and analysis of rare event or outcome data
  • Methods for causal inference machine learning to estimate heterogeneous treatment effects
  • Methods to assess dimensions of data quality (e.g., methods to assess data validity and reproducibility of model training data sets)
  • Approaches to data collection and provenance that minimize bias and unfairness
  • Approaches to developing new LLMs, calibrating existing LLMs to new data, developing approaches to improve multi-modal data streams (e.g., extracting and incorporating information from images, audio/video, patient reported/generated data from sensor/wearable/personal devices); and developing experimental methods, tests, or other approaches to assess LLMs’ validity and/or safety
  • Approaches to assessing robustness and resilience of algorithms to withstand changes in patient demographics, data sources, and clinical contexts
  • Approaches to improving transparency of algorithms outputs to users to promote engagement and use of methods
  • Approaches that support innovations in the identification, recruitment, and retention of study participants

Topic & Themes

• The purpose of identifying these Topic Themes is to encourage submissions to these areas, not to limit submissions to only these themes. The Methods PFA welcomes all investigator-initiated research that meets the requirements of this PFA. The Topic Themes, clustered into three groups, are as follows:
  • Populations:
    • Improving outcomes for people with intellectual and developmental disabilities (IDDs)
    • Promoting health for older adults
    • Promoting healthy children and youth
  • Health Behaviors:
    • Addressing substance use
    • Addressing violence and trauma
  • Health Conditions:
    • Addressing COVID-19
    • Addressing rare diseases
    • Improving cardiovascular health
    • Improving mental and behavioral health
    • Managing pain
    • Preventing maternal morbidity and mortality (MMM)
    • Promoting sleep health

Funding Information

• Funds Available: Up to $12 million
• Total Direct Costs: Up to $750,000
• Maximum Project Period: Up to Three years

Eligibility Criteria

• In general, applications for the conduct of research and management of funding may be submitted by appropriate academic research, private sector research, or study-conducting entities. This may include, among others, agencies and instrumentalities of the federal government, nonprofit and forprofit research organizations, and colleges and universities.

For more information, visit PCORI.