Clinical trial referrals: how physicians can refer patients without doing the eligibility work

Clinical trial referrals represent one of the highest-leverage decisions a treating physician can make. A single conversation, a shared link, or a secure handoff can connect a patient with a research option that would otherwise stay out of view. For many physicians, however, the word "referral" has historically carried an expectation of protocol review, eligibility screening, and follow-up coordination that sits well outside routine clinical practice. That expectation is out of step with how modern referral pathways are structured. Under current U.S. Food and Drug Administration (FDA) guidance and international Good Clinical Practice standards, a physician can refer a patient to a clinical trial without performing eligibility work, signing investigator paperwork, or taking on any protocol-level obligation.

Why physician referrals matter in clinical trials

Most U.S. patients receive care in community and specialty practice settings rather than at academic research centers. In oncology alone, the American Cancer Society Cancer Action Network reports that more than 85 percent of patients receive care in community settings, where trial visibility is naturally lower. The referral from a treating physician is often the moment a patient first learns that a research option exists.

Patient willingness is not the barrier. Analysis of pooled trial data by Unger and colleagues, published in the Journal of the National Cancer Institute, found that when eligible patients are actually offered participation, more than half enroll, and this pattern holds across racial and ethnic groups. Survey data from the Tufts Center for the Study of Drug Development indicates that roughly 90 percent of physicians feel comfortable discussing trials with patients. The volume of referrals does not reflect that comfort level, and the reason is structural rather than attitudinal.

For a foundational overview of how the treating physician sits within the broader research ecosystem, see The Clinician’s Role in Expanding Trial Access for Patients.

What counts as a clinical trial referral

A referral in the modern sense is a defined, bounded action. It has three parts: identifying a patient who may be a fit for a study, sharing accurate information about the study or the referral pathway, and directing the patient or their information to the group that will take the process forward. That is the complete referral.

Everything downstream sits with other parties. Pre-screening, defined as the initial review of a patient’s history and condition against a study’s inclusion and exclusion criteria (the medical and demographic requirements that determine who can join), is not part of the referral itself. Neither is the final eligibility determination, informed consent, or enrollment. Each of those functions has a designated owner in the study workflow, and none of them require action from the referring physician.

The conversational side of the referral, including how to introduce the topic during a routine visit, is covered in Bridging the Gap: How HCPs Can Talk to Patients About Research Opportunities.

Referring physician vs study investigator

The regulatory distinction between a referring physician and a study investigator is well established, and recent guidance from 2024 and 2025 has clarified the point in ways that directly benefit community and specialty clinicians.

A study investigator, whether principal investigator or sub-investigator (a physician formally listed on the study team who conducts protocol activities under the principal investigator’s oversight), is documented on Form FDA 1572 for studies conducted under an Investigational New Drug application. Signing that form commits the investigator to conduct the study in accordance with the protocol, Good Clinical Practice, and applicable regulations. It is a binding regulatory role.

A referring physician signs none of this. FDA guidance on Form 1572 states that clinical staff who provide ancillary or intermittent care but who do not make a direct and significant contribution to the clinical data are not required to be listed. The FDA’s final guidance on Conducting Clinical Trials With Decentralized Elements, issued in September 2024, extends that logic explicitly to local healthcare professionals who perform activities within their normal clinical practice. Such clinicians are not classified as trial personnel. The International Council for Harmonisation’s revised Good Clinical Practice guideline, ICH E6(R3), finalized in January 2025, removed the requirement to list on the delegation log individuals whose activities fall within their standard clinical practice.

The practical result is that a treating physician can refer a patient to a study, continue seeing that patient for routine care, and retain their existing clinical role without becoming a regulated member of the research team.

For a deeper look at the professional boundaries at play, see Ethical Responsibilities of HCPs in Clinical Research.

Who handles eligibility, consent, and enrollment

The functions that historically discouraged referral, including protocol review, inclusion and exclusion checking, informed consent, and enrollment, are handled by parties other than the referring physician in a modern pathway.

Initial pre-screening is typically conducted by trained clinical staff at a matching platform or research site. This is a structured review of the patient’s condition, medical history, and basic eligibility factors against the study’s criteria. It is not a diagnostic assessment and it does not alter the patient’s care plan.

Final eligibility determination is the responsibility of the research site team. Site staff review the patient’s records, coordinate any protocol-specified tests, and confirm whether the patient meets every criterion the study requires.

Informed consent is, by regulatory design, reserved for the research site. The FDA has stated that obtaining informed consent is not an appropriate activity for a local healthcare professional to perform, because it requires detailed knowledge of the protocol, the study’s risks and benefits, and the participant’s rights. Enrollment and the study walk-through, including the participant’s first visit and orientation to the study procedures, are also handled by the site team.

For a site-side view of how pre-screening is being structured to reduce friction across the workflow, see Pre-Screening Smarter: How Technology Reduces Screen Failures at Sites.

How simple referral pathways expand trial access

Evidence from published health services research shows that when the referral action is simplified, referral volume rises substantially. In a study by Embi and colleagues, published in the Archives of Internal Medicine, an electronic health record alert that allowed physicians to refer a patient to a trial with a single action, with all downstream screening handled by the study coordinator, produced roughly a tenfold increase in physician referrals compared with the pre-alert baseline. Enrollment approximately doubled over the same period. Physicians who had never previously referred patients accounted for the majority of new referrals after the alert was activated.

The mechanism is straightforward. When the burden of screening, protocol interpretation, and follow-up coordination sits with the referring physician, the referral competes with every other task in a clinical day and usually loses. When the burden is separated from the referral, the referral action becomes small enough to fit into normal practice.

The access implications extend beyond raw volume. Because most patients are treated in community settings, referral-friendly pathways help patients who would otherwise never encounter a research option.

This dynamic is especially relevant to community-based practice. See How Community Physicians Can Expand Clinical Trial Participant Pools for a related discussion.

How AI matching and nurse pre-screening support the referral

DecenTrialz is built around the principle that the referring physician should not have to perform eligibility work to refer a patient. The platform combines AI-assisted participant matching with registered nurse-led pre-screening, and coordinates the handoff to the research site team.

A physician’s role in this workflow is limited to what already fits inside routine practice. The physician identifies a patient who may be a candidate, shares information about the referral pathway or submits a secure referral, and continues the existing care relationship with the patient. AI-assisted matching narrows the field of potentially relevant studies against the patient’s clinical profile. A registered nurse then conducts pre-screening, walks the patient through what participation would involve, and confirms basic eligibility factors before any research site contact is made. The research site team takes over from that point for final eligibility determination, informed consent, walk-through, and enrollment.

To see how this pathway fits with an ongoing patient relationship, visit decentrialz.com.

Referring patients as part of good clinical practice

The American Medical Association’s Code of Medical Ethics frames the treating physician’s core responsibility as presenting patients with accurate information about their medical options. When a clinical trial is a potentially appropriate option, informing the patient of that possibility is consistent with that duty. The AMA Journal of Ethics has noted that when a physician is not part of a trial’s investigator team, the referral itself is the appropriate action, and detailed protocol information is provided by the study investigator at the time of enrollment.

The referral role, as it exists today, was designed to preserve exactly that professional boundary. A treating physician can inform, refer, and continue caring for the patient. The research site team carries the regulatory weight of the study. The matching platform and pre-screening nurse handle the interface work between them. Under this structure, physician referrals become a routine extension of good clinical practice rather than a specialized undertaking.

To learn more about how DecenTrialz supports physicians in referring patients without adding to clinical workload, visit decentrialz.com.