| Submitted By: Mike Hamidi
/ Vulcan
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| Data Element Information |
| Use Case Description(s) |
| Use Case Description |
Development of Data Element:
- Event: When a clinical trial is initiated, the protocol is created to define the objectives, study design, and methodology. This typically occurs during the protocol authoring phase, involving teams of clinical researchers, regulatory personnel, and sponsors.
- Specific Setting: The creation of the clinical trial protocol typically happens within clinical research systems or protocol authoring tools, and is finalized before any participant recruitment or trial execution begins. It must be submitted to regulatory bodies (e.g., U.S. FDA) for approval.
- Frequency: This data element is collected once per clinical trial during the trial design and setup phase. However, it can be updated if amendments to the protocol are required throughout the trial's lifecycle.
Use of Data Element:
- Event: The clinical trial protocol is used during various stages of the trial for execution, monitoring, and reporting. For example, it guides clinicians and researchers in determining participant eligibility based on inclusion/exclusion criteria, scheduling procedures, and specifying treatment assignments or randomization plans.
- Specific Setting: Throughout the trial, the protocol is referenced by clinical sites during patient visits, to conduct assessments, administer treatments, or collect relevant data as specified. It is also referenced by other clinical research documents (e.g., the statistical analysis plan, clinical study report).
- Frequency: The protocol is used continuously throughout the duration of the trial for procedural guidance and adherence to pre-defined activities.
Exchange of Data Element:
- Event: The protocol is exchanged between the trial sponsor and various stakeholders, including regulatory bodies (e.g., FDA, EMA), institutional review boards (IRBs), clinical research sites, and possibly contract research organizations (CROs) to ensure compliance, consistency, and transparency.
- Specific Setting: For instance, before trial initiation, the protocol is submitted to regulatory authorities for approval. During the trial, any protocol amendments are exchanged to update relevant stakeholders. Protocols are also shared with clinical trial sites to guide operational activities and procedures.
- Frequency: Protocol data exchange happens at least once (during initial submission), but can occur multiple times for amendments, interim reports, or final submission of the trial data.
Optionality or Frequency of Use:
- Collection: Required once, during trial design, but updates may happen with amendments.
- Use: Continuously referenced throughout the trial for guiding operations.
- Exchange: Initially required during trial submission, with potential updates during protocol amendments.
The considerations above illustrate both clearly defined events for collecting and using the protocol, as well as scenarios where it is exchanged across stakeholders, demonstrating its necessity for trial consistency, regulatory approval, compliance, and interoperability. |
| Estimate the breadth of applicability of the use case(s) for this data element
|
The breadth of applicability for the use case of a clinical trial protocol is extensive, spanning across the entire clinical research landscape and involving multiple stakeholders. Below are key aspects to consider:
1. Global Regulatory Requirements:
- Clinical trial protocols are universally required by regulatory authorities (e.g., U.S., FDA, EMA, MHRA, NMPA) for any clinical study involving human subjects, making this use case relevant for clinical trials conducted in any country.
- Protocols are essential for drug development (pharmaceutical companies), medical device trials, biotechnology research, and academic research, impacting research efforts across a wide variety of healthcare domains.
2. Types of Clinical Trials:
- Protocols are used in all phases of clinical trials (Phase I-IV), from early-stage human safety studies (Phase I) to large-scale efficacy trials (Phase III) and post-marketing surveillance (Phase IV).
- They are also essential for decentralized clinical trials (DCTs), which involve telemedicine, remote monitoring, and patient-collected data, as well as traditional site-based trials.
3. Interdisciplinary Use:
- Clinical trial protocols are utilized by diverse stakeholders, including clinical researchers, physicians, regulatory professionals, data managers, and biostatisticians, making the data element highly applicable across multiple disciplines.
- Within healthcare settings, it is used by hospitals, clinical research organizations (CROs), biopharmaceutical companies, and academic medical centers.
4. Applicability in Data Standards and Interoperability:
- The protocol's design, including its use in structured data collection, enhances interoperability between systems (e.g., EHRs, CTMS, ePRO) and facilitates the exchange of clinical trial data between sponsors, regulatory authorities, and clinical research sites.
- Protocols are critical for ensuring compliance with data standards like CDISC and HL7 FHIR, which are used across clinical trials to harmonize data exchange and streamline regulatory submissions.
5. Applicability in Trial Design and Operational Execution:
- Protocols serve as the blueprint for trial execution, impacting the scheduling of activities, participant eligibility, and data collection. This makes the use case applicable to all clinical trial sites, principal investigators, and research teams involved in implementing the trial procedures.
6. Breadth of Healthcare Conditions:
- Protocols are used across the full spectrum of diseases and conditions, from common conditions like cardiovascular disease, diabetes, and oncology, to rare diseases and specialized fields like gene therapy and precision medicine.
7. Use in Both Public and Private Sectors:
- The use case is applicable to government-sponsored trials, including NIH or WHO trials, as well as those initiated by private companies and academic institutions.
8. Frequency of Use:
- As clinical trials are conducted globally for new treatments, therapies, and medical devices, the use case for a clinical trial protocol is frequent and ongoing. Thousands of clinical trials are initiated annually worldwide, each requiring a protocol.
Conclusion:
The use case for the clinical trial protocol is highly broad in its applicability, relevant to all stakeholders involved in clinical research, and critical to the global regulatory framework governing clinical trials. Its importance spans various types of trials, healthcare conditions, industries, and countries, ensuring its frequent and essential use across the clinical research lifecycle.
The Utilizing of the Digital Protocol (UDP) encompasses the overall use case(s) which are done in collaboration with the Vulcan, TransCelerate, ICH M11/M2, CDISC, and FDA (see https://confluence.hl7.org/display/VA/Utilizing+the+Digital+Protocol+-+UDP)
Additional Supporting FHIR IGs:
Adverse Event Clinical Research 1.0.1 - STU1 (see https://hl7.org/fhir/uv/ae-research-ig/STU1/index.html)
Adverse Event Clinical Research R4 Backport 1.0.1 - STU1 (see https://hl7.org/fhir/uv/ae-research-backport-ig/)
Clinical Study Schedule of Activities 1.0.0 - trial-use (see https://hl7.org/fhir/uv/vulcan-schedule/STU1/) |
| Link to use case project page |
https://confluence.hl7.org/display/VA/Utilizing+the+Digital+Protocol+-+UDP |
| ONC Priority |
- Mitigate health and health care inequities and disparities
- Address public health interoperability needs of reporting, investigation, and emergency response
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| Maturity of Use and Technical Specifications for Data Element |
| Applicable Standard(s) |
For a clinical trial protocol, the following terminology code systems are commonly used or may be used for greater interoperability:
1. SNOMED CT: Standardizes clinical concepts like medical conditions, procedures, and outcomes (e.g., inclusion/exclusion criteria).
2. LOINC: Standardizes lab tests, clinical measurements, and observations collected during the trial.
3. RxNorm: Used for medication coding, especially when the protocol involves drug interventions or dosing regimens.
4. ICD-10/ICD-11: Defines diagnoses and health conditions for eligibility or adverse event reporting.
5. MedDRA: Used to code adverse events, ensuring consistent reporting across trial sites.
6. CDISC Terminology: Supports standardization of clinical trial data elements (e.g., protocol design, trial outcomes) in regulatory submissions. Accessible via NCI terminology services.
7. WHODrug: Standardizes coding for medications in clinical trials, especially for drug safety and efficacy reporting in global trials.
8. NDC: Used to identify medications in the U.S. for protocol interventions or treatments.
9. CPT: Standardizes medical procedures and services for protocol-specified interventions, such as diagnostic tests or treatments.
10. UCUM: Standardizes units of measurement (e.g., mg, mL) used in clinical observations or lab results.
11. HCPCS: Complements CPT by coding medical products, services, and equipment used in U.S. trials.
These code systems ensure global semantic interoperability, consistency, compliance, and accuracy in clinical trial data collection and exchange.
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| Additional Specifications |
The Utilizing of the Digital Protocol (UDP) encompasses the overall use case(s) which are done in collaboration with the Vulcan, TransCelerate, ICH M11/M2, CDISC, and FDA (see https://confluence.hl7.org/display/VA/Utilizing+the+Digital+Protocol+-+UDP). This set of FHIR IGs are yet to be published. However, there are existing published FHIR IGs below that reflect different aspects of the clinical trial protocol.
Supporting FHIR IGs:
Adverse Event Clinical Research 1.0.1 - STU1 (see https://hl7.org/fhir/uv/ae-research-ig/STU1/index.html)
Adverse Event Clinical Research R4 Backport 1.0.1 - STU1 (see https://hl7.org/fhir/uv/ae-research-backport-ig/)
Clinical Study Schedule of Activities 1.0.0 - trial-use (see https://hl7.org/fhir/uv/vulcan-schedule/STU1/) |
| Current Use |
(Level 0) Captured, stored, or accessed in limited settings such as a pilot or proof of concept demonstration |
| Extent of exchange
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(Level 0) Limited environments, such as connectathons or pilots |
| Supporting Artifacts |
There are several artifacts that have demonstrated electronic exchange. A few examples include, but not limited to, clinical trial adverse events, schedule of activities, definitional planning, among others. There are additional details not mentioned in the supporting FHIR IGs, which include the following resources:
https://confluence.hl7.org/display/VA/Vulcan+Schedule+of+Activities
https://confluence.hl7.org/display/VA/Project+Documentation
https://confluence.hl7.org/display/VA/Utilizing+the+Digital+Protocol+-+UDP
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| Potential Challenges |
| Restrictions on Standardization (e.g. proprietary code) |
Here's are key terminology systems listed that may be used in clinical trial protocols, which are proprietary or generally free to use:
Proprietary Terminologies:
1. CPT: Requires a licensing agreement for commercial use.
2. MedDRA: Requires a subscription fee for access and use.
3. WHODrug: Requires a subscription for access.
4. RxNorm: While generally available for use, it is maintained by the U.S. National Library of Medicine, and some integrations may have licensing restrictions.
5. CDISC Terminology: Typically requires membership or subscription for full access. However, the terminology is also freely available via NCI terminology services.
Free or Publicly Available Terminologies (with some conditions):
1. SNOMED CT: Generally free for specific uses, but may have licensing fees for broader applications.
2. LOINC: Available for free use, but commercial applications may have licensing requirements.
3. ICD-10/ICD-11: Generally available for use; however, specific uses may be subject to licensing conditions depending on the organization.
4.NDC: Publicly available in the U.S., but access to specific databases may involve fees.
5. UCUM: Free to use for standardization purposes.
6. HCPCS: Generally free to use, but specific codes may have licensing implications.
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| Restrictions on Use (e.g. licensing, user fees) |
Yes, there may be restrictions on the use of clinical trial terminology and data systems, including licensing and user fees. However, the restrictions may vary from design and development of the clinical trial protocol versus implementation, use, and sharing.
1. Data Access and Sharing:
- Clinical trial data is often subject to confidentiality agreements and data sharing restrictions to protect participant privacy and proprietary information.
- Some organizations may impose restrictions on how clinical trial data can be shared, particularly with external parties or for secondary research purposes.
2. Regulatory Compliance:
- Clinical trials must comply with regulations from bodies like the FDA or EMA, which include guidelines on the use of protocols, data reporting, and documentation.
- Researchers must adhere to good clinical practice (GCP) guidelines, which impose additional requirements on the conduct of clinical trials.
3. Intellectual Property Rights:
- Any inventions or findings resulting from clinical trials may be subject to intellectual property laws, which can restrict the use or sharing of certain data or methodologies.
4. Licensing for Software Tools:
- Many clinical trial management systems (CTMS) and electronic data capture (EDC) systems are proprietary and require licenses or fees for use, impacting the overall budget and resources for conducting clinical trials.
These restrictions are designed to ensure compliance, protect participant rights, and maintain the integrity of clinical research. |
| Privacy and Security Concerns |
Privacy and security concerns with the use and exchange of clinical trial may include different factors. However, those factors will vary from design and development of the clinical trial protocol versus implementation, use, and sharing.
1. Data Breaches: Unauthorized access to sensitive participant information can lead to identity theft and exploitation.
2. Informed Consent: Ensuring participants understand how their data will be used and shared is critical to maintain trust.
3. Data Anonymization: Inadequate anonymization can risk re-identification of participants, violating privacy.
4. Compliance with Regulations: Failure to adhere to regulations like HIPAA or GDPR can result in legal penalties and reputational damage.
5. Data Sharing Risks: Sharing data with multiple stakeholders increases the risk of exposure, necessitating robust data governance policies. |
| Estimate of Overall Burden |
The overall burden to implement a fully digital (e.g., using FHIR) represented clinical trial protocol includes:
1. Training and Education: Significant effort required to train healthcare professionals and researchers on FHIR standards.
2. System Integration: Upgrading or replacing existing systems to ensure compatibility with FHIR interoperability.
3. Data Migration: Transitioning existing data to the FHIR format, which may require substantial resources.
4. Regulatory Compliance: Ensuring adherence to data privacy and security regulations, necessitating additional processes.
5. Ongoing Maintenance: Continuous updates and maintenance of FHIR implementations to keep systems compliant and functional.
Total Estimated Burden:
The total burden for implementation across the broader healthcare community encompasses substantial resource allocation and effort across these areas, impacting both clinical trial operations and the broader healthcare ecosystem. However, although there are challenges the benefits highly outweigh them. |
| Other Implementation Challenges |
Implementing a fully digitized (e.g., using FHIR) clinical trial protocol presents several challenges, including the need for standardization across diverse systems and stakeholders, which can hinder interoperability. Ensuring data quality and consistency during migration can also be problematic, as can training staff to effectively use new technologies. Additionally, regulatory compliance poses ongoing challenges, especially in navigating privacy concerns and maintaining data security.
Despite these challenges, the benefits of implementation are significant. It enhances data accessibility and exchange between systems, improving collaboration among researchers and healthcare providers. FHIR also facilitates real-time data sharing, enabling quicker decision-making and potentially leading to improved patient outcomes. Ultimately, while implementation requires effort and resources, the long-term efficiencies and advancements in clinical research can outweigh the initial hurdles. |
ONC Evaluation Details
Each submitted Data Element has been evaluated based on the following criteria. The overall Level classification is a composite of the maturity based on these individual criteria. This information can be used to identify areas that require additional work to raise the overall classification level and consideration for inclusion in future versions of USCDI
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Criterion #1
Maturity - Current Standards |
Level 0
- Data element is not represented by a terminology standard or SDO-balloted technical specification or implementation guide.
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Criterion #2
Maturity - Current Use
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Level 1
- Data element is captured, stored, or accessed in at least one production EHR or HIT module.
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Criterion #3
Maturity - Current Exchange |
Level 0
- Data element is electronically exchanged in limited environments, such as connectathons or pilots.
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Criterion #4
Use Case(s) - Breadth of Applicability |
Level 1
- Use cases apply to several care settings or specialties.
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| Evaluation Comment |
Narrow use case of a Problem or Health Concern |
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Official Website of the Assistant Secretary for Technology Policy/Office of the National Coordinator for Health IT
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