ICH GCP E6 (R3): When Digital Health Became Everyone’s Responsibility

For a long time, Digital Health Technologies lived in a comfortable grey zone.

Sponsors relied on them.
Vendors built and operated them.
And GCP mostly looked the other way—as long as things seemed to work.

ICH GCP E6 (R3)* quietly closes that grey zone.

It does so not by adding pages of technical requirements, but by aligning GCP with how clinical trials actually run today: digital, decentralized, and dependent on technology that directly affects patients and data.

A new kind of realism

Earlier versions of GCP were designed for a world where data appeared during site visits and lived in binders. Oversight happened after the fact.

Today, data streams continuously from patients’ homes. Devices update themselves. Algorithms translate signals into endpoints. Decisions happen in near real time.

E6(R3) accepts this reality—and then asks a harder question: Who is actually in control of the systems that matter most?

Its Principles

	Ethical Conduct	Clinical trials must be conducted ethically, with due regard to the rights, safety, and well-being of trial participants.
2	Scientific Validity	Trials should be scientifically sound and described in a clear, detailed protocol to ensure the validity of results.
3	Informed Consent	Participants must provide voluntary, informed consent before participating in a trial, with full understanding of risks and benefits.
4	Data Integrity	Accurate and reliable data collection, recording, and reporting are crucial to ensure the validity of trial outcomes.
5	Investigator & Sponsor Oversight	Sponsors and investigators must ensure adequate oversight, monitoring, and documentation throughout the trial.
6	Quality Management	A quality management system must be implemented, emphasising risk-based approaches to maintain data integrity and patient safety.
7	Proportional Risk	The level of risk to trial participants should be proportionate to the potential benefits, with a focus on minimising risks related to participant rights, safety, and data reliability.
8	Protocol Compliance	All trial activities must strictly follow the approved protocol and regulatory requirements, ensuring consistency and compliance.
9	Investigator Qualifications	Investigators must possess adequate education, training, and experience to perform their role competently.
10	Roles and Responsibilities	Clearly define roles and responsibilities within the trial, especially when tasks are dele-gated, while maintaining ultimate accountability with the sponsor or investigator.
11	Record Keeping and Reporting	Comprehensive documentation and reporting are essential for transparency, reproducibility, and compliance with regulatory requirements.

Where sponsors now stand

For sponsors, E6(R3) draws a clear line in the sand.

Technology can be outsourced. Accountability cannot.

If a digital tool influences safety, efficacy, or trial decisions, regulators now expect sponsors to:

• understand how that technology works,

• know its limitations and risks,

• and remain in control when something changes mid-study.

Saying “the vendor manages that” is no longer a sufficient answer. Oversight is no longer about trusting contracts—it’s about being able to explain and defend how digital systems support the trial.

In practice, this means sponsors must engage earlier, ask deeper questions, and treat digital health with the same seriousness as any other trial-critical system.

Where vendors now stand

For vendors, E6(R3) changes the tone of the relationship.

Digital health providers are no longer just service suppliers. They are now part of the GCP ecosystem—whether or not they carry that label contractually.

This brings new expectations:

• transparency around validation and limitations,

• discipline around updates, changes, and version control,

• and readiness to support inspections, audits, and regulatory questions.

The vendors who thrive under E6(R3) won’t be the ones who promise speed alone, but the ones who can clearly show how their technology holds up under regulatory scrutiny.

Decentralized trials make this unavoidable

The rise of decentralized and hybrid trials makes this shift impossible to ignore.

When devices sit in patients’ homes rather than at sites, the line between “technology issue” and “trial issue” disappears. Training, usability, connectivity, logistics, and support all become part of trial quality.

E6(R3) doesn’t treat decentralization as an exception anymore. It treats it as normal—and expects both sponsors and vendors to behave accordingly.

The real change

The biggest change in E6(R3) isn’t technical.

It’s cultural.

Digital health is no longer something happening around the trial. It is happening inside it. And GCP now reflects that.

For sponsors, that means ownership.
For vendors, that means maturity.
For both, it means fewer assumptions—and far fewer grey areas.

* Note: ICH GCP E6(R3) refers to the latest version of the International Council for Harmonisation's (ICH) guideline for Good Clinical Practice (GCP), which sets global ethical and scientific quality standards for designing, conducting, recording, and reporting clinical trials involving human participants, with the recent update (R3) focusing on flexibility for new technologies, diverse trial types, and incorporating a risk-based Quality by Design (QbD) approach for data integrity and patient safety.