⚠️ This is a developmental version of the guide and is under active development. Content may change at any time without notice. No official release has been made. The final base canonical URL and hosting location have not yet been determined. This guide should not be used for production implementations.

1. Clinical Trial Matching using USCDI+ 0.1.0

1.1. Introduction

The United States Core Data for Interoperability Plus (USCDI+) Cancer Clinical Trials Matching (CTM) data element list aims to enhance the efficiency, accuracy, and timeliness of screening and matching patients for cancer clinical trials across healthcare systems in the United States. Building on the USCDI foundation, this data element list addresses the unique challenges of determining clinical trial eligibility by establishing standardized, interoperable data elements that support patient-trial screening and matching across institutional boundaries.

1.2. Background

Clinical trial screening and matching face persistent structural barriers that limit the speed and scale of patient enrollment. Eligibility criteria are typically documented in narrative, free-text formats that clinical systems cannot automatically interpret, requiring manual review that is time-intensive and difficult to standardize across institutions. Patient data relevant to trial eligibility including diagnoses, biomarkers, prior treatments, and comorbidities is fragmented across disconnected EHR systems with inconsistent coding and documentation practices. These conditions make it difficult to evaluate patients against multiple trial protocols simultaneously, leading to missed enrollment opportunities and inequitable access to emerging therapies.

Representing eligibility criteria in structured, machine-readable formats, and exchanging the relevant patient data through standardized interfaces, enables automated evaluation of patient data against trial protocols, reducing reliance on manual review and improving matching speed and accuracy, and expanding access to trials across institutions and patient populations. This IG provides the technical framework for achieving that goal.

1.3. Scope, Usage, and Audience

The USCDI+ Cancer CTM IG is designed to serve stakeholders across the clinical trial ecosystem. This guide provides tailored guidance for each audience:

• Healthcare Providers and Care Teams: Access standardized patient data to identify and screen eligible patients for relevant trials within existing clinical workflows.
• Research Institutions and Trial Sponsors: Use structured, interoperable data to design computable eligibility criteria, streamline recruitment, and reduce screening burden across sites.
• Clinical Trial Management Systems: Ingest and evaluate standardized patient data against trial protocols, enabling automated and scalable matching across institutions.
• EHR Vendors and Health IT Developers: Apply data capture and exchange standards that support trial matching without requiring custom integration for each.
• Regulatory Agencies: Access consistent, structured trial and patient data to support oversight and alignment with federal clinical research requirements.
• Patients and Advocates: This guide is a technical specification and not intended for direct patient use. Organizations implementing this IG are encouraged to develop plain-language materials explaining how standardized trial matching may improve access to clinical trials.

1.4. Overview of Implementation Guide

The IG is built on the following foundational components, which together define how clinical data must be represented and exchanged to support the matching workflows described above.

• USCDI+ Cancer Clinical Trials Matching Data Element List: Defines the clinical data elements required for eligibility determination and matching, including diagnoses, biomarkers, prior treatments, comorbidities, and relevant demographic and social determinants of health data.
• HL7 FHIR R4: Provides the base specification for representing and exchanging patient and trial data in structured, machine-readable formats used throughout this guide.
• US Core 6.1.0: Establishes US realm baseline conformance expectations. All profiles in this IG are derived from or aligned with US Core 6.1.0.
• mCODE 4.0.0 (hl7.fhir.us.mcode): Provides foundational oncology FHIR profiles for cancer diagnoses, staging, biomarkers, and treatment history. CTM profiles are derived from or aligned with mCODE where applicable. See the Dependencies section for version and derivation details.

Together, these components provide the technical foundation for consistent, scalable trial matching across institutional boundaries.

1.5. How to Read This Implementation Guide

This Implementation Guide contains multiple sections to support a wide range of stakeholders.

The table below lists the major sections of the IG, a brief description of each, and the audiences most likely to find each section relevant.

Section	Description	Primary Audience
Introduction	Provides context and objectives for cancer clinical trial matching and the role of interoperable data exchange in improving patient access to trials.	All
Background	Describes the structural barriers that limit clinical trial screening and matching, and establishes the case for standardized, interoperable data exchange.	All
Scope, Usage, and Audience	Defines the scope of this guide and identifies the stakeholders it is designed to serve.	All
Overview of the Implementation Guide	Describes the foundational standards and technical components on which this IG is built.	All
Limitations and Challenges	Highlights implementation barriers and constraints that apply to the current version of this guide.	All
Privacy and Security Considerations	Outlines the privacy, security, and compliance obligations that apply to data exchange workflows implemented under this guide.	Healthcare Providers, EHR Vendors and Health IT Developers, Clinical Trial Management Systems
Dependencies on Other IGs	Lists the implementation guides on which this IG depends, including version and dependency type.	EHR Vendors and Health IT Developers, Clinical Trial Management Systems
USCDI+ CTM Data Elements	Defines the clinical data elements required for eligibility determination and matching, with data class descriptions and mapping rationale.	Healthcare Providers, Research Institutions and Trial Sponsors, EHR Vendors and Health IT Developers
FHIR Artifacts (forthcoming)	Provides the complete index of FHIR profiles, extensions, value sets, and code systems defined in this guide.	EHR Vendors and Health IT Developers, Clinical Trial Management Systems
Downloads (forthcoming)	Provides downloadable versions of this guide and associated artifacts.	EHR Vendors and Health IT Developers, Clinical Trial Management Systems

Readers who wish to contribute to the development of this guide or submit comments and suggestions are encouraged to participate in HL7 connectathons where this IG is present, and submit feedback through the project's GitHub repository.

1.6. Limitations and Challenges

This Implementation Guide establishes a framework for interoperable clinical trial matching, but several limitations apply to the current version:

1. Eligibility Criteria Coverage: Complex or highly protocol-specific criteria -- including certain biomarker combinations, investigator assessments, or rare disease parameters -- may not yet be fully representable within the current profiles.
2. EHR Data Variability: Screening accuracy depends on the completeness and consistency of source data. Where records are incomplete or inconsistently coded, automated screening results may require human review before being used to identify potential trial opportunities.
3. Adoption and Conformance: The utility of this IG scales with adoption. Institutions implementing only partial conformance may experience limited interoperability with more fully conformant systems.
4. Scope of Equity Data: The IG supports capture of demographic and social determinants of health data but does not prescribe how that data should factor into matching logic or trial prioritization. Guidance on equity-informed matching is outside the current scope.
5. Regulatory Alignment: This IG does not constitute regulatory guidance. Sponsors and institutions remain responsible for ensuring that trial matching workflows comply with applicable FDA regulations, IRB requirements, and informed consent obligations.
6. Resource Constraints: The technical staff, infrastructure, and operational capacity required to implement this IG may not be uniformly available across organizations. Smaller institutions, safety-net hospitals, and community oncology practices may face disproportionate barriers, limiting the reach of interoperable trial matching in precisely the settings where expanded trial access is most needed. Implementers are encouraged to pursue phased conformance approaches and engage available HL7 implementation support resources.

1.7. Privacy and Security Considerations

Implementers are responsible for ensuring all data exchange workflows comply with applicable federal and state requirements, including HIPAA, the Common Rule (45 CFR Part 46), and institution-specific data governance policies.

Implementers SHOULD be familiar with and adhere to the following HL7 FHIR security and privacy guidelines:

• Security & Privacy module
• Security Principles
• Implementer's Checklist

Additional considerations specific to this IG include:

1. Consent and Authorization: Patient data exchanged for trial matching must be handled in accordance with applicable informed consent requirements and institutional data use agreements. Implementing organizations are responsible for establishing consent processes that satisfy IRB requirements prior to deployment.
2. Minimum Necessary Standard: Data exchange should be limited to the elements needed for the specific clinical trial screening or eligibility evaluation use case.
3. Cross-Institutional Data Exchange: When patient data crosses institutional boundaries, appropriate data use agreements, business associate agreements, and access controls must be in place before exchange occurs.
4. De-identification: Where full patient-level data is not required, implementers should consider whether de-identified or pseudonymized data can satisfy the use case, consistent with HIPAA Safe Harbor or Expert Determination standards.

Issues or concerns regarding privacy, security, or safety should be submitted through the Health IT Feedback and Inquiry Portal or the relevant project repository.

1.8. Dependencies on Other IGs

Implementation Guide	Version	Dependency
HL7 FHIR R4	R4	Base specification for all profiles in this IG. US Core and mCODE are both derived from R4.
US Core	6.1.0	Establishes US realm baseline conformance expectations. All profiles in this IG are derived from or aligned with US Core 6.1.0.
mCODE (minimal Common Oncology Data Elements)	4.0.0	CTM profiles for cancer diagnoses, staging, biomarkers, and treatment history are derived from or aligned with mCODE 4.0.0 where applicable. mCODE 4.0.0 is derived from US Core 6.1.0, which is itself derived from FHIR R4.

1.9. Acknowledgements

This Implementation Guide was developed as part of the USCDI+ Cancer initiative with funding from the National Cancer Institute (NCI) and the Office of the National Coordinator for Health Information Technology (ONC), through sustained collaboration across the clinical, research, regulatory, and health IT communities.

Special thanks to:

• HL7 International: For providing the FHIR standards and implementation guide framework on which this work is built.
• Clinical Research and Industry Partners: For contributing expertise in trial design, eligibility criteria development, and patient recruitment.
• Regulatory Agencies: For guidance on aligning trial matching workflows with applicable federal requirements and NIH policies governing clinical research.
• Healthcare Organizations: For sharing implementation insights, use cases, and clinical workflows that informed the data elements and exchange specifications in this guide.
• Technical and Clinical Experts: For their contributions to the development, review, and refinement of the profiles, conformance requirements, and eligibility criteria representations in this guide.

Health Level Seven, HL7, CDA, CCD, and FHIR are registered trademarks of Health Level Seven International in the US Trademark Office.

This guide includes SNOMED CT content, copyright © 2002+ SNOMED International, and distributed by agreement between SNOMED International and HL7. This agreement does not cover the implementer's use of SNOMED CT.

This guide contains content from LOINC. LOINC is copyright © 1995-2024, Regenstrief Institute, Inc., and the Logical Observation Identifiers Names and Codes (LOINC) Committee. It is available at no cost under the license at https://loinc.org/kb/license. LOINC® is a registered United States trademark of Regenstrief Institute, Inc.

mCODE® is a trademark owned by the American Society of Clinical Oncology (ASCO) and is used with permission herein.

This guide contains content from RxNorm, produced by the U.S. National Library of Medicine (NLM), National Institutes of Health, Department of Health and Human Services; NLM is not responsible for this guide and does not endorse or recommend it. The use of RxNorm in this guide is pursuant to HL7's status as an NLM UMLS licensee; that license does not convey the right to use RxNorm to implementers, who must obtain their own license.