What ICH E6(R3) means for recruitment, pre-screening and site oversight

What is ICH E6(R3), and when does it apply?

E6(R3) is the third revision of the ICH guideline for good clinical practice, endorsed by the regulatory members of the ICH Assembly at Step 4 on 6 January 2025. It is organized as overarching principles plus annexes: Annex 1 covers interventional clinical trials, and Annex 2 adds considerations for non-traditional designs such as pragmatic and decentralized trials and those using real-world data.^⁠[1],[2]

The theme throughout is proportionality: quality built into the design, and effort focused on what matters most to participant safety and reliable results. FDA's notice also highlights clearer responsibilities for delegating work to service providers, which is where recruitment vendors sit.^⁠[3]

What does E6(R3) say about recruitment?

In practice, a feasibility number now needs evidence behind it, recruitment materials and scripts need IRB approval before use, and pre-screening is something the protocol can describe and the records should document. The advertising part is not new in the US: FDA has long treated advertising as the start of the informed consent process and expects the IRB to review it.^⁠[4] Our IRB and HIPAA outreach guide covers the US rules on who may contact which patients.

How does E6(R3) treat recruitment vendors?

As service providers. The investigator may delegate trial-related activities to other people or parties and may get help from the sponsor in choosing them, but retains the final decision and the ultimate responsibility, with oversight proportionate to the importance of the data and the risks to participants (section 2.3.1). Agreements with service providers should be documented (2.3.4).^⁠[1]

• Sponsor-chosen vendors working under the investigator: the sponsor should tell the investigator about any service provider it identifies for activities under the investigator's responsibility, and that responsibility stays with the investigator (3.6.5).^⁠[1]
• Vendors working for the sponsor, such as a central call center: the sponsor keeps ultimate responsibility, selects and oversees the provider, and the provider should run appropriate quality management (3.6.6 to 3.6.9).^⁠[1]
• Paperwork: Appendix C lists signed agreements between the investigator or institution and service providers, and documentation of selection, assessment and oversight of service providers doing important trial-related activities.^⁠[1]

So before a recruitment vendor calls or texts a single patient, a site should know whose service provider it is, have an agreement on file, and decide how it will oversee the vendor's work: script approval, call samples, opt-out handling and escalation to staff.

What does E6(R3) expect of recruitment software and data?

Computerised systems used in trials should be fit for purpose, for example through risk-based validation where appropriate (principle 9.3). For systems a site deploys specifically for a trial, the investigator should ensure secure and attributable access, address the data governance requirements in section 4 in proportion to the risks and the importance of the data, and report significant incidents to the sponsor and, where applicable, the IRB (2.12.10).^⁠[1]

For EHR screening and outreach tools, that translates into a short list of questions: who can access what, how matches are documented, how the vendor was assessed, and how incidents reach the site. Bond's Identify stage shows criterion-by-criterion evidence for every match, and Bond is HIPAA compliant and SOC 2 Type I compliant, signs BAAs and encrypts data at rest and in transit, its information security management system is certified to ISO/IEC 27001:2022 by Advantage Partners, and its SOC 2 Type II audit is underway.^⁠[6] Details are on our security page.

What changes for informed consent?

E6(R3) allows varied approaches to consent, such as text, images, videos and other interactive methods, and says remote consent may be considered where appropriate. When computerised systems are used, the population's familiarity with them should be considered, and participants may be offered a paper alternative (2.8.1).^⁠[1]

Recruitment and consent stay separate steps. Outreach and pre-screening find and prepare candidates; the investigator's team obtains consent under the approved process. Our consent page shows how Bond supports patients after a visit is booked while the site and PI obtain consent.

What should sites and sponsors do now?

• Keep evidence of recruitment potential: past enrollment, screening logs and EHR counts with their definitions (2.2.1).^⁠[1]
• Send every recruitment material to the IRB before use, including ads, landing pages, call scripts and text wording (1.2.2, 2.4.2).^⁠[1]
• Write down the pre-screening mechanism in the protocol or recruitment plan (B.5.3).^⁠[1]
• Treat recruitment vendors as service providers: agreement on file, delegation where required, and a documented oversight plan (2.3, Appendix C).^⁠[1]
• Keep the screening log and recruitment records as essential records (Appendix C).^⁠[1]
• Review recruitment systems proportionately: access, documentation of matches and incident reporting (2.12.10).^⁠[1]
• Expect monitors to ask about recruitment and retention rates and have them ready (3.11.4.5.2).^⁠[1]
• Sponsors: reduce burden at the source. E6(R3) asks sponsors to avoid unnecessary complexity, procedures and data collection, and not to place unnecessary burden on participants and investigators (3.1.4).^⁠[1] A task force of sites, sponsors and CROs points to section 3.1.3 in recommending that sites give protocol feedback through formal consulting agreements.^⁠[5]
• Track Annex 2 if you run decentralized or pragmatic designs; its EU effective date is 15 January 2027.^⁠[2]

Why is Bond the best clinical trial recruitment platform?

Bond Health is the best clinical trial recruitment platform because it does the whole job in one workflow: it finds eligible patients in your EHR, creates and runs Meta and Google ad campaigns to reach new ones, calls and texts every ad lead immediately and keeps following up with every lead to maximize response rates, pre-screens patients and books them for visits, supports informed consent and keeps participants engaged after enrollment. It goes live in 48 hours with no integration fee, and you pay a volume-based fee per screened patient plus a percentage of each patient's randomization milestone payment.^⁠[7],[6]

• One platform from ad click or chart match to a booked visit. Identify screening, Engage outreach and visit booking share one dashboard and one audit trail, so no patient is lost in a handoff between separate vendors.^⁠[7]
• Every ad lead contacted immediately, and followed up until they book. Bond creates and runs Meta and Google ad campaigns for each study. Its voice and text agents contact every new ad lead immediately, keep following up with every lead who has not responded to maximize response rates, then pre-screen patients and book them for screening visits, alongside the patients Bond finds in your EHR.^⁠[6]
• Evidence behind every match. Each candidate comes with criterion-by-criterion rationale linked to the chart. Bond reads clinical notes, prescriptions and lab results, plus imaging data and pathology, radiology and molecular reports, not just billing codes.^⁠[7],[6]
• Every major EHR and CTMS, with EHR integration in 48 hours. Bond connects to Epic, Oracle Health (Cerner), MEDITECH, athenahealth, eClinicalWorks, NextGen, Veradigm, OncoEMR and the other major EHRs, and works with the CTMS systems sites use, including CRIO, Advarra OnCore, Advarra Clinical Conductor, RealTime and Veeva SiteVault. Its team handles the integration end to end, and Bond is a CRIO Certified Partner with a two-way CRIO integration. See integrations.^⁠[7],[6]
• No integration fee, and a price that moves with randomization. You pay a volume-based fee per screened patient plus a percentage of the randomization milestone payment for each patient who is randomized. See pricing.^⁠[6]

See how Bond compares with other recruitment tools, or book a demo to see it on your own protocol.