Clinical Study Schedule of Activities, published by HL7 International / Biomedical Research and Regulation. This guide is not an authorized publication; it is the continuous build for version 2.0.0-snapshot built by the FHIR (HL7® FHIR® Standard) CI Build. This version is based on the current content of https://github.com/HL7/Vulcan-schedule-ig/ and changes regularly. See the Directory of published versions

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Official URL: http://hl7.org/fhir/uv/vulcan-schedule/ImplementationGuide/hl7.fhir.uv.vulcan-schedule				Version: 2.0.0-snapshot	Highlight text changes?
IG Standards status: Trial-use				Maturity Level: 4	Computable Name: StudyScheduleOfActivities
Other Identifiers: OID:2.16.840.1.113883.4.642.40.64

This is a snapshot of v2.0.0 of the Schedule of Activities FHIR Specification. It has been developed against FHIR R6 ballot 5. As such time that FHIR R6 becomes an offical HL7 specification, this snapshot will be converted to depend on the official FHIR R6 and this snapshot will no longer be available.

Background

Vulcan Schedule of Activities (SoA) Project

The core of this project is to define a usable pattern for a Clinical Trial Schedule of Activities structure using FHIR Resources and Processes, such that:

• it can be shared
• it can be interpreted, and
• it can be implemented in healthcare systems, such as electronic health record (EHR)/personal health record (PHR) systems and/or clinical research systems

The conduct of Clinical Trials are guided by the International Conference on Harmonization (ICH) guidelines for Good Clinical Practice (GCP) E6 (R2).¹ Core to this is the writing of a Clinical Trial Protocol, a document intended to describe the objectives, design, methodology, statistical considerations and aspects related to the organization of the clinical trial.

Trial protocols provide the background and rationale for conducting a study, highlighting specific research questions that are addressed, and taking into consideration ethical issues. Trial protocols must meet a standard that adheres to the principles of Good Clinical Practice, and are used to obtain ethics approval by local Ethics Committees or Institutional Review Boards.

The Clinical Trial Protocol incorporates all the aspects of what is needed to define how the study is to be conducted and reviewed; for the purposes of this first iteration of the Implementation Guide we are constraining the scope to focus just on the elements incorporated in the Schedule of Activities.

What is the Schedule of Activities?

The NCI Controlled Vocabulary definition of the Schedule of Activities is: ²

A standardized representation of planned clinical trial activities including interventions (e.g., administering drug, surgery) and study administrative activities (e.g., obtaining informed consent, distributing clinical trial material and diaries, randomization) as well as assessments. See also schedule of assessments. Compare to study design schematic.

It is a focused section of the Protocol Document that lays out what activities are expected, and structurally when they are expected to occur. It is a design that is interpreted by the stakeholders to drive how the study is defined, planned and performed.

One of the factors influencing the move towards more complex study designs is the escalating cost of conducting clinical research. As drug development becomes more expensive, sponsors are increasingly motivated to maximize the scientific and commercial value from each study. This has led to a shift away from traditional, linear study designs towards more intricate protocols that can answer multiple questions simultaneously, evaluate several treatments, or study various patient populations within a single trial framework.

This drive for efficiency has given rise to adaptive designs and master protocols, such as platform, basket, and umbrella trials. These modern approaches often incorporate conditional logic, where the study path for a participant can change based on interim results, biomarker status, or other criteria. Consequently, the schedule of activities is no longer a static table but a dynamic plan with branching pathways and conditional events. While these designs can accelerate drug development and reduce overall costs, they introduce significant complexity in defining, implementing, and managing the schedule of activities across different systems. Additionally, under the guise of Adaptive Trial Design the implementation of the study can change significantly for patients as the trial progresses.

Vulcan SoA Implementation Guide (IG)

This IG is intended to provide a roadmap for adopters looking to use FHIR resources in order to support the planning and implementing Clinical Research designs. The Schedule of Activities is defined ​in a clinical trial as a standardised representation of planned activities, including interventions (e.g., administering drug, surgery), study administrative activities (e.g., obtaining informed consent, distributing clinical trial material and diaries, randomization) and assessments.​

​The purpose of the Schedule of Activities is to communicate the scheduling of the planned activities required to support the research objectives of the study to enable operational implementation.​

Within the Vulcan SoA project we have considered the following study types:

• Prospective – e.g., randomized clinical trials (RCT), concurrent cohort studies, observational studies, epidemiology, real world evidence (RWE) studies, pragmatic clinical trials
• Retrospective – e.g., cohort studies, case-control studies, real world evidence (RWE)
• Hybrid - combining both prospective + retrospective components

Examples of positive outcomes for this project include:

• Participant identification – feasibility , inclusion/exclusion criteria (prospective/retrospective)​
• Participant management – appointment scheduling (prospective)​
• Real world evidence – research data selection (retrospective)​
• Audit/Inspection – regulatory oversight period identification ​
• Resource planning (prospective)​
• Logistics planning (prospective)​
• Protocol adherence – streamlined deployment of protocol updates
• Portfolio management – reporting consistency across sites
• Site operational efficiency – task automation (e.g. order entry, reminders, etc) based on SoA
• Digital SoA can "serve as single source of truth" and be re-purposed downstream
  • Automate creation of EDC specification
  • Automate creation of SDTM datasets (especially trial design domains)
• Help/automate sites set up a study leading a reduced site burden
• Help sites run a study (scheduling, procedures to be performed)
• Help ensure compliance with a protocol
• Ensure SoA/protocol is implemented uniformly across sites

This iteration of the IG is designed to provide directional guidance and not be a prescriptive instruction of how to exactly implement SoA across all systems. As we learn more about how the different systems work and can be interfaced, we will continue to improve the IG to accommodate more use cases; iteratively working towards a solution that will be both functional and scalable.

The ICH Clinical Electronic Structured Harmonised Protocol³ (M11) has provided a standardised structure for Clinical Trial Protocols. The HL7 Vulcan Utilising the Digital Protocol (UDP) IG is providing a framework for representing a Digital Protocol using FHIR resources. The Vulcan Schedule of Activities project can be used to represent the Schedule of Activities from the digital protocol as part of the UDP IG. The projects are aligned and are intended to be reviewed together; however the Schedule of Activities IG can be reviewed and used independently of the UDP IG.

Future elements for the Implementation Guide

There are different levels of complexity of SoA, which may not be fully represented in the current iteration of this IG. For example, how the design of an SoA may be implemented concerning different protocol types (e.g., adaptive, master, umbrella, basket, etc.). Furthermore, the type of research can vary across SoA designs, such as randomized vs. observational clinical trials, including the different data modalities to collect data (e.g., electronic data capture vs. direct data capture). The scope for the IG has been constrained to deliver a minimal viable solution for representation of a SoA. The following topics will be or have been evaluated for incorporation in the IG:

• Management of protocol compliance (deviations, violations, etc.)
• Complex protocols (e.g., adaptive, umbrella, basket)
• Non-trial integrations (e.g., use of RWD such as a vital statistic registry that determines a patients death via f/up period)
• How adjudications are managed
• Patient site transfers (i.e., relocations)
• Patients re-enrolling multiples times
• Inclusion/Exclusion criteria
  • Computable and Evaluable criteria that can be defined and processed by electronic systems
  • Complex inclusion/exclusion criterions
• Enhanced SoA headers (e.g., that include visit type such as home health, satellite site, virtual)
• How to better describe more complex activities (multi-omics, digital therapeutics, etc.)
• Tracking of primary, secondary, tertiary, and exploratory endpoints
• Instructional guidance in other protocol sections/footers that provide additional detail
• Managing multiple sub-study consents that can occur throughout the trial (some voluntary and others conditional-based)

Note that many of these expand the existing scope of the SoA project and will work best in a collaboration with other research-aware IGs such as the Vulcan Retrieval of Real World Data for Clinical Research IG and Vulcan Utilising the Digital Protocol. We have a rigorous process for evaluating and incorporating use cases into the development process.

References