Translating Scientific Evidence Into Practice Using Digital Medicine and Electronic Patient Reported Outcomes

Delivery of healthcare has been traditionally limited to in-person office visits or hospitalizations, while patients spent the majority of their time at home or work. Digital Medicine (e.g. apps, remote monitoring, telemedicine, patient reported outcomes ePRO has the potential to bridge this gap, but it is unclear how to implement in a mainstream clinical practice that can lead to high-level patient and provider adoption. Through the creation of a Digital Transformation Network (DTN) for Inflammatory Bowel Disease (IBD), the study team plans to reduce digital disparities and scientifically address the evidence gap of digital health interventions across populations and communities.

AIM I. Unify existing digital assets (mobile app, ePROs, assessment for digital disparities and behavioral health, referral to IBD home and health education) into an IBD Digital Therapeutics Toolkit and integrate with EHRs at 3 CTSA hubs. Hypothesis: Integration with EHRs will lead to higher adoption by providers and limit disruption of workflow.

AIM II: Establish baseline levels of digital connectivity, disease control, quality of life and care metrics in cohorts at the three IBD centers. Hypothesis: A multipronged approach of assessment through text, phone, an app, and in-person will yield higher adoption.

AIM III. Implement and evaluate precision-matched interventions (digital skills, social determinants, behavioral health, monitoring through apps, and referral to interdisciplinary care) among 1500 patients with IBD using a stepped-wedge, cluster- randomized trial. Hypothesis: Medical homes supported by a unified platform will translate to sustainable improvement in population health outcomes. Analyze the Impact of DTN interventions. The primary outcome will be the improvement of the percentage of patients in DTN in disease control and decrease in urgent care utilization (emergency department visits and hospitalization days) across the three CTSA sites.

AIM IV. Support sustainability and dissemination across CTSA sites. Hypothesis: The patient- centric DTN will be sustainable through alignment with value-based healthcare.

Anticipated Impact: About 2 million Americans suffer from IBD and many more with chronic inflammatory diseases. The study team hopes that this study will help the study team build an evidence-based approach to determine whether digital medicine can engage a diverse group of patients and improve outcomes; and if yes, how it can be reproduced and replicated across different settings to address theT3 and T4 translational gaps.

• Digital Transformation Network (DTN) Program (Behavioral): Patients will be screened based on ePRO and online assessment tool results to be identified to be eligible for enrollment into the DTN program. The results of ePROs and online assessments will be used to precision match patients to in-person care at the IBD home or to IBDTx care pathways. RxUniverse platform allows the creation of adaptive pathways based on feedback loops that provide relevant on-demand resources based on patient care touch-points. For example, a patient with mild depression or anxiety, maybe offered an online DTx and if not useful, link to telepsychiatry or in-person psychiatry consultation. Patients will transition into the intervention DTN arm at set intervals by site.

Primary outcomes

• Proportion of Participants in Disease Control [End of Control Period (Week 0) and End of Intervention Period (Week 52)]: Proportion of participants in disease control at assessments at end of control period (week 0) and at end of intervention period (week 52). Disease control is defined by normalization of inflammatory markers and ePROs (PRO2<8 and PRO3<13). PRO2 measures stool frequency and bleeding while PRO3 measures the number of liquid or soft stools, abdominal pain and general well-being. Inflammatory markers including Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP) and Fecal Calprotectin will be dichotomized using cut-offs of <30mm/hr, <5mg/L and <250 μg/g respectively for normal values.
• Change in Number of Unplanned Acute Care [12 months before intervention and 12 months after intervention]: Change in number of unplanned acute care. Unplanned acute care is defined as the number of ED visits and hospitalizations days 12 months before the intervention and the last 12 months of DTN intervention.

Secondary outcomes

• Northstar Digital Literacy Assessment [week 52]: For participants who screened positive for needing assistance with digital connectivity and skills. Digital skills and connectivity will be assessed using the Northstar digital literacy assessment. A 17-item rating scale, with full score from 0 to 100, with score 85% or above achieve a passing score.
• Digital Disparities Module [1 year after enrollment]: For participants who screened positive for needing assistance with digital connectivity and skills. The digital disparities module is still in development through SBIR. The digital disparities module will assess the impact of digital disparities module in improving digital skills and access to Internet using previously developed digital disparities assessment instrument. The scale for the digital disparities assessment full scale from 0 - 100 where a higher score indicates the patient has a higher level of disparity in digital connectivity, digital skills and digital usage.
• Change in Overall Health Numeric Rating Scale [OHNRS] [End of Control Period (Week 0) and End of Intervention Period (Week 52)]: OHNRS - Full scale from 0 to 10, higher score indicates better health outcomes
• Change in PROMIS Global Scales [End of Control Period (Week 0) and End of Intervention Period (Week 52)]: Change in PROMIS Global scales is a 14-item measure that is part of the PROMIS Social Function. The measure refers to social roles, such as work and family responsibilities, and more discretionary social activities, such as leisure activity and relationships with friends. standardized to the general population, using the "T-Score". The average "T-Score" for the United States population is 50 points, with a standard deviation of 10 points. Higher scores indicate a healthier patient.
• Change in Patient Health Questionnaire (PHQ-4) [End of Control Period (Week 0) and End of Intervention Period (Week 52)]: The Patient Health Questionnaire (PHQ)-4 s a 4 item inventory. Anxiety subscale from 0-6, depression subscale from 0-6, with full scale from 0-12, higher score indicates more symptoms.
• Change in Patient Health Questionnaire (PHQ-8) [End of Control Period (Week 0) and End of Intervention Period (Week 52)]: The Questionnaire Type 9 for Depression (PHQ-8) is a self-administered instrument. Full scale from 0-24, with higher score indicating more severe symptoms. As needed.
• Change in Generalized Anxiety Disorder Scale (GAD-7) [End of Control Period (Week 0) and End of Intervention Period (Week 52)]: The General Anxiety Disorder 7-item questionnaire (GAD-7) is a 7-item questionnaire. Full scale from 0-21, with higher score indicating more symptoms. As needed.
• Improvement in Mucosal Healing [End of Control Period (Week 0) and End of Intervention Period (Week 52)]: Improvement in mucosal healing will be defined as the absence of inflammation on endoscopy (scoring systems) or imaging notes collected from EHR.
• Proportion of Participants With Medication Adherence [End of Control Period (Week 0) and End of Intervention Period (Week 52)]: Proportion of participants with medication adherence will be assessed with the Visual Analog Scale (VAS) using <80% cut-off to designate non-adherence. Full Scale from 0 to 100 with higher score indicating more adherence.
• System Usability Scale (SUS) [End of Intervention Period (Week 52)]: The system usability scale (SUS) is a 10-item Likert scale questionnaire. The range of scores is from 0 - 100 where a SUS score above 68 is considered average.
• Net Promoter Score [End of Intervention Period (Week 52)]: The Net Promoter is a 10 point scale and the full score ranges from -100 to 100 where a higher score translates to higher satisfaction with a product.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Patients with confirmed Inflammatory Bowel Disease (IBD) will be enrolled into DTN in stepped-wedge cluster randomized trial
* Age greater than or equal to 18 years
* Ability to speak or understand English or Spanish Language.

Exclusion Criteria:

\- Condition or disease that, in the opinion of the investigators, may make it exceedingly difficult for the patient to use DTN, including, but not limited to, advanced dementia.

Participant flow

Outcome results

• Proportion of Participants in Disease Control (Primary), Number, proportion of participants: Digital Transformation Network (DTN) Program ; Control Arm 0.43 +/- 0.03
• Change in Number of Unplanned Acute Care (Primary), Mean, events: Digital Transformation Network (DTN) Program ; Control Arm 3.66 +/- 9.50
• Northstar Digital Literacy Assessment (Secondary)
• Digital Disparities Module (Secondary)
• Change in Overall Health Numeric Rating Scale [OHNRS] (Secondary), Mean, score on a scale: Digital Transformation Network (DTN) Program ; Control Arm 6.08 +/- 1.80
• Change in PROMIS Global Scales (Secondary), Mean, T score: Digital Transformation Network (DTN) Program ; Control Arm 45.63 +/- 9.13
• Change in Patient Health Questionnaire (PHQ-4) (Secondary), Mean, score on a scale: Digital Transformation Network (DTN) Program ; Control Arm 3.51 +/- 3.08
• Change in Patient Health Questionnaire (PHQ-8) (Secondary), Mean, score on a scale: Digital Transformation Network (DTN) Program ; Control Arm 13.12 +/- 9.03
• Change in Generalized Anxiety Disorder Scale (GAD-7) (Secondary), Mean, score on a scale: Digital Transformation Network (DTN) Program ; Control Arm 7.01 +/- 5.16
• Improvement in Mucosal Healing (Secondary)
• Proportion of Participants With Medication Adherence (Secondary), Number, proportion of participants: Digital Transformation Network (DTN) Program ; Control Arm 0.91 +/- 0.01
• System Usability Scale (SUS) (Secondary), Mean, score on a scale: Digital Transformation Network (DTN) Program 37.56 +/- 14.51
• Net Promoter Score (Secondary), Mean, score on a scale: Digital Transformation Network (DTN) Program 7.63 +/- 2.56

Adverse events

Time frame: 1 year

• Results publication: Tiles-Sar N, Neuser J, de Sordi D, Baltes A, Preiss JC, Moser G, Timmer A. Psychological interventions for treatment of inflammatory bowel disease. Cochrane Database Syst Rev. 2025 Apr 17;4(4):CD006913. doi: 10.1002/14651858.CD006913.pub3. PMID 40243391

• Study Protocol and Statistical Analysis Plan (PDF, 2023-07-13)
• Informed Consent Form (PDF, 2022-03-04)

• Bruce Sands, MD, Principal investigator, Icahn School of Medicine at Mount Sinai

NIH grants: U01TR002997