Objectives Patient recruitment is a critical factor for successful completion of a clinical trial. Decentralized trial recruitment allows potential subjects to be identified via the electronic health record (EHR) and approached through digital channels. We sought to understand the real-world effectiveness of decentralized trial recruitment leveraging electronic patient reported outcomes (ePROs) in patients with inflammatory bowel disease (IBD).

Methods As part of a National Institutes of Health (NIH) funded multi-site clinical trial, we designed an EHR-integrated decentralized trial recruitment process to contact eligible patients at three tertiary IBD centers. We leveraged the Commure Engage/Rx.health (Mountain View, California) digital health formulary and automation engine integrated with Epic Systems (Epic Systems, Verona, WI) to digitally approach patients in an automated manner (with human-in-the loop) to complete the online enrollment process and monitor adherence with ePROs.

Results Using digital outreach complemented by in-person engagement, we approached 6,687 eligible patients over 12 months and successfully enrolled 543 patients (mean age 40.7 ± 15.7 years, 63.3% females, 39.4% ulcerative colitis, 60.6% Crohn’s disease). 81.2% were recruited from bulk outreach methods. Gender (P<0.01), and race (P<0.01) were significantly associated with digital clinical trial enrollment. Patients were continually monitored with ePROs throughout the duration of the study.

Conclusions This is one of the first studies to show the feasibility and successful recruitment of patients with IBD using automated digital outreach. We found a combination of outreach methods with human in the loop an effective strategy for clinical trial accrual. These findings suggest that ePROs can be successfully used in IBD centers to support treat-to-target strategy.

Study Highlights

What is Known:

The most common reason for clinical trial failure is lack of accrual.

Clinical trial recruitment strategies have remained largely unchanged despite technological advances.

There is limited real world data around the use of electronic patient reported outcomes on a digital platform for patients with inflammatory bowel disease

What is New Here

ne of the first studies to employ a prospective decentralized recruitment approach for a multicenter clinical trial in inflammatory bowel disease.

feasibility of an automated digital outreach for enrollment and continued monitoring using electronic patient reported outcomes

Potential Competing Interest: -Dr. Atreja holds a patent for the RxUniverse (Prescription Universe) software platform that is licensed from Icahn School of Medicine at Mount Sinai to Rx.Health, Inc. (New York, NY) and acquired by Commure Inc. (MountainView, CA). Ashish Atreja owns stock in Commure, Inc and has recused himself from data analysis. - Sarthak Kakkar, Sravya Kurra, Garauv Narang, and Priya Patel are employees of Commure Inc. (Mountain View, CA) and own stock. They have recused themselves from data analysis.

NCT04345393

Financial Support: The study is funded by NIH (5U01TR00299704U01, Principal Investigators Dr. Sands, Dr. Atreja, and Dr. Rizk) Translating Scientific Evidence into Practice using Digital Medicine and Electronic Patient Reported Outcomes

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

We performed a NIH-funded multi-site trial focused on patients with IBD to first enroll patients via a decentralized recruitment process and then to establish baseline levels of disease control while implementing precision-matched interventions to improve outcomes using ePRO assessments at three tertiary IBD referral centers across the United States: Mount Sinai, University of California, Davis (UC Davis Health), and Cleveland Clinic. We utilized a centralized institutional review board (IRB) at all sites via a SMART IRB framework. A single centralized IRB protocol was created using Advarra services. Each site then reviewed the centralized IRB for approval at their institution which included ethical aspects of implementing and studying the intervention. A common protocol was submitted to Advarra Central IRB which addressed any potential conflicts of interest.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

↵** Co-Senior Authors

Guarantor of the article: Maged Rizk, MD and Ashish Atreja, MD, MPH

Financial Support The study is funded by NIH (5U01TR00299704U01, Principal Investigators Dr. Sands, Dr. Atreja, and Dr. Rizk) Translating Scientific Evidence into Practice using Digital Medicine and Electronic Patient Reported Outcomes

Potential Competing Interest:

-Dr. Atreja holds a patent for the RxUniverse (Prescription Universe) software platform that is licensed from Icahn School of Medicine at Mount Sinai to Rx.Health, Inc. (New York, NY) and acquired by Commure Inc. (MountainView, CA). Ashish Atreja owns stock in Commure, Inc and has recused himself from data analysis.

- Sarthak Kakkar, Sravya Kurra, Garauv Narang, and Priya Patel are employees of Commure Inc. (Mountain View, CA) and own stock. They have recused themselves from data analysis.

All data produced in the present study are available upon reasonable request to the authors