Usual Care Inside a Trial

Part of ICH E6(R3) Annex 2 for Site Staff: Pragmatic Elements and Real-World Data.

About 5 minutes. Free, in your language, no account needed.

Expert review pending. CRLN wrote this lesson against the ICH E6(R3) Annex 2 text adopted on 3 June 2026. It has not yet been reviewed by a subject matter expert. Always follow your protocol, your sponsor and your regulator.

Why this matters

Pragmatic trials try to answer questions in the setting where care really happens. That makes them useful, and it changes daily work at a site: some data come from routine visits, some tasks are done by clinicians who never joined the study team, and the line between "care" and "trial" needs to be drawn on purpose.

What a pragmatic element is

The Annex 2 introduction describes pragmatic elements as parts of usual clinical practice brought into the design and conduct of a trial. Usual clinical practice means the established, day-to-day processes healthcare professionals use when caring for patients. Pragmatic elements can include:

• eligibility criteria and trial processes that reflect usual practice for that patient population;
• care given in normal settings, such as hospitals, healthcare centers, primary physicians and local healthcare providers;
• streamlined data collection, for example capturing only the minimum necessary data, or capturing data only when routine care produces it.

The Annex notes that DHTs and automated exports from EHRs can help streamline data collection.

What the protocol has to say

Section 3.2.1 asks that the design elements, data sources and operational approaches be described in the protocol, with a brief explanation of why they are appropriate, fit for purpose and feasible. Section 3.2.2 adds that when a trial includes activities that are part of usual practice, the sponsor should check that this is fit for purpose and complies with regulations, and the protocol should clearly describe how, by whom and under what circumstances those activities are done.

For site staff, this is the document to read when you are unsure whether a task is "ours" or "routine". If the protocol does not make it clear, ask before the first participant is enrolled.

Who needs training and delegation

Section 2.4.1 draws the line you will use most:

• A usual care task that does not need knowledge of the protocol or trial documents does not require protocol training. Instead, arrangements must make the records available to the investigator, covering data sharing, record keeping such as certified copies, privacy and data integrity.
• A task that does need protocol knowledge must be done by delegated, appropriately trained healthcare professionals.

Two errors are common. One is putting every clinician in the building on the delegation log and requiring protocol training for routine care. That adds work without adding protection, and it is not what Annex 2 asks. The other is treating a trial-specific assessment as routine because it happens during a routine visit. A scale that exists only in the protocol is a trial task wherever it is done.

Data that vary by setting

Section 3.2.3 notes that data from different sources and practice settings can vary, for example because measurements are taken at different times. The impact should be considered in the design and discussed in the protocol or related documents such as the statistical analysis plan. At a site, this shows up as values that do not line up neatly with visit windows. Record what happened; do not adjust dates or values to fit the schedule.

Engaging the people who do the care

Section 3.1.2 says early engagement of healthcare professionals and investigators is critical when a trial uses these methods. It can help with infrastructure, with protocols that fit usual practice and with spotting where training or support is needed. If you work at a site asked for feasibility on a pragmatic trial, your knowledge of how care actually runs there is exactly what this section is asking for.

Safety in a pragmatic trial

Section 3.9.2 asks that the approach to safety management and reporting be described in the protocol or related documents, taking the methods into account. It also says that where appropriate, consideration should be given to ICH E19, which covers a selective approach to safety data collection in certain late-stage or post-approval trials. A pragmatic design may collect less routine safety data, by design. That never means a serious event someone tells you about can be ignored. Follow the protocol's safety plan.

In practice

• For each task in a pragmatic study, decide: usual care with a records arrangement, or a trial task needing delegation and training.
• Check that routine results really reach the investigator, and in what form.
• Record values and dates as they happened, even when they fall outside a visit window.
• Know what the protocol's safety plan asks you to collect and report.

Key takeaways

• Pragmatic elements bring usual clinical practice into a trial, including streamlined data collection (Annex 2, Introduction).
• The protocol should state how, by whom and when usual care activities are done (section 3.2.2).
• Usual care tasks need records arrangements; protocol-dependent tasks need delegation and training (section 2.4.1).
• Data from different settings vary, and the plan should account for it (section 3.2.3).