Table 1.

Randomized controlled trials comparing digital health technologies vs. traditional clinical encounters in monitoring and managing patients with IBD

Study ID	Author, year	Study, location, patient population, centers	Number of groups, number of study participants, and attrition rates	Outcomes and measurement tools	Intervention, control, and face-to-face clinic visits
1	Cross R, 2019	RCT, United States, adults, multicenter	3 groups: 1. TELE-IBD weekly (W) 2. TELE IBD every other week (EOW) 3. Control 348 enrolled: 117 control, 115 EoW, and 116 W Attrition rates: 8.5% control, 13.9% EoW, and 19% W	Disease activity: HBI for CD and SCCAI for UC/indeterminate patients QoL: IBQ questionnaire Utilization of health care resources: reviewed EMR for healthcare utilization (hospitalizations, surgery, emergency department and office visits, procedures, intravenous therapeutics, and telephone and electronic encounters)	Intervention: web- and mobile-based (secure messaging to patients from web-portal) – TELE-IBD system. Bidirectional communication between patients and healthcare providers via text messages only. Patients would receive individualized alerts and action plans based on responses. Control: standard of care following evidence-based guidelines Both the intervention and control groups underwent study visits at baseline, 6 and 12 months in addition to their routine clinic visits.
2	Cross R, 2012	RCT, United States, adults, multicenter	2 groups: 1. UCHAT – comprised of a home unit, decision support server, and a web-based clinician portal 2. Best available care (BAC) 167 eligible → 113 refused to participate BAC 22, UCHAT 25 Attrition rates: 15% BAC, 32% UCHAT	Disease activity: Seo index QoL: IBDQ questionnaire Treatment Adherence: Morisky Medication Adherence Score	Intervention: web-based (decision support server and a clinician portal) and home unit (netbook computer and electronic scale). Patients answered questions about their symptoms, treatment side effects or adherence, and received IBD-related education using the home unit, which occurred weekly. Control: standard of care following evidence-based guidelines All patients underwent clinic visits every 4 months.
3	De Jong, 2017	RCT, Netherlands, adults, multicenter	2 groups: 1. Web-based (myIBDcoach) 2. Control 3000 patients asked to participate → 2091 excluded (41% did not return invitation letter and 12% declined participation) Telemedicine 465, Control 444 Did not report attrition rate.	Disease activity/outcomes: number of flares as measured by Monitor IBD at Home (MIAH) questionnaire QoL: SIBDQ questionnaire Treatment adherence: Morisky Medication Adherence Scale Healthcare utilization: IBD-related hospitalizations, emergency room visits, surgeries, and/or corticosteroid use Others: self-efficacy, diagnosis and treatment related knowledge, smoking behaviors, and number of outpatient visits	Intervention: Web-based system (myIBDcoach) that monitors and registers questions for disease activity, treatment use, treatment adherence, treatment satisfaction, side effects. questions on factors affecting disease, patient reported outcomes (PRO) on quality of life and work productivity. At least one routine outpatient clinic visit per year with as-needed visits based on alarm symptoms identified through myIBDcoach. Control: standard of care following local protocol. Patients received routine clinic visits.
4	Elkjaer M, 2010	RCT, Denmark and Ireland, adults, multicenter	2 groups: 1. Web (Constant-Care) (W) 2. Control (C) Denmark: Web 105, Control 106 485 pts with UC invited→ 50% no response and 2% denied → 233 pts randomized (117 web + 116 control) → 105 web + 106 control at baseline → 89 web + 97 control at 12-month follow-up Web: 10 never attended baseline; 4 refused participation after baseline; others no longer qualified Control: 8 never attended baseline; 3 refused to participate after baseline; others no longer qualified Ireland: Web 51, Control 41 100 pts randomized (52 web + 48 control) → 5 excluded (age limit) → 51 web + 41 control at baseline → 40 web + 38 control at 12 months follow-up	Disease activity: SCCAI QoL: SIBDQ Others: Compliance questionnaire (CQ); Satisfaction questionnaire (SQ); knowledge base regarding IBD, medication, diet, and complications; anxiety and depression; and generic health survey with SF-36 for Denmark and SF-12 for Ireland	Intervention: web-group received disease specific education and self-treatment via http://www.constant-care.dk. All web-patients and their relatives were educated on IBD-related topics (recognizing a flare, disease course, surgeries, etc.) as part of their enrollment. If patients had a relapse, they were asked to log on weekly for a total of 4 weeks (otherwise once a month if they were in remission) and could be treated acutely for 4 weeks with 4 grams daily of 5-aminosalicylic acid (ASA). Additional treatment with topical 5-ASA and/or prednisolone was individualized. Control: standard of care with routine appointments. All patients had visits at baseline, 6 months and at 12 months.
5	Krier M, 2011	RCT, United States, adults, single center	2 groups: 1. Remote telemedicine encounter (TE) 2. face-to-face standard encounter Remote telemedicine encounter 15, face-to-face standard encounter 19 Did not report attrition rate.	Healthcare utilization: duration of appointment visit, wait time, number of patients seen per clinic day. Others: Measurement of clinical experience and patient’s overall satisfaction on quality of audio and visual presentation in the TE group	Intervention: GI fellow at VA Palo Alto evaluated the patient and could have real-time or off-line consultation with local/remote radiologist, interventional endoscopist, surgeon, and/or pathologist. The GI fellow then returned to the patient-room for a real time Telemedicine Encounter session which included the fellow, patient and remotely located attending. Telemedicine encounter with IBD specialist remotely located. Control: standard encounter with fellow and attending in the clinic
6	Linn AJ, 2018	Cluster RCT, Netherlands, adults, multicenter	2 groups: 1. Intervention – patients received weekly text messages to improve medication adherence and counseling performed by IBD nurses 2. Control group – standard of care 201 patients were asked to participate → 29 patients refused, 12 patients did not meet inclusion criteria and for other reasons → 160 patients were included. Attrition rate: In part 2 of the study, only 28 of 52 patients in the experimental group completed the study, while 22 of 33 patients in the control group completed the study	Treatment adherence: 5-item Medication Adherence Report Scale (MARS) Others: patient satisfaction, beliefs about medication, and self-efficacy	Intervention: received a combination of weekly text messages and counseling by nurses specialized in IBD care who underwent a twelve weeks course on communication with IBD patients. Control: Received standard care – usual education.
7	Akobeng AK, 2015	RCT, United Kingdom, children/ teenagers (age 8 – 16), single center	2 groups: 1. Intervention – telephone consultation 2. Control – face-to-face consultation 246 patients were invited to participate → 86 randomized → 42 in control and 44 in intervention. IMPACT questionnaire returned at 12 months: 37 in control and 30 in intervention. IMPACT questionnaire returned at 24 months: 27 in control and 28 in intervention	Disease activity: number of disease relapses using abbreviated Pediatric Crohn’s Disease Activity Index (aPCDAI) and Pediatric Ulcerative Colitis Activity Index (PUCAI) QoL: Pediatric IBD-specific IMPACT Healthcare utilization: number of hospital admissions, duration of consultations, and costs to the UK National Health Service Others: patient and parent satisfaction	Intervention: Gastroenterology doctor would contact the patient and parents via telephone number that the parents and patient would provide. Control: routine face-to-face care
8	Carlsen K, 2017	Open labeled randomized controlled trial, Denmark, children/adolescents (ages 10–17), single center *Non-biologic cohort	2 groups: 1. eHealth – web-application young.constant-care.com (YCC). Web-based disease monitoring. 2. Control – standard visits every 3 months 99 invited → 53 were randomized (27 web, 26 control). 15 completed two years follow-up in web group while 18 completed two years follow-up in control group.	Disease activity: aPCDAI or PUCAI Medication adherence: MARS QoL: IMPACT III and HRQoL Others: school absence	Intervention: The pediatric adult eHealth program (www.young.constant-care.com) was based on the adult eHealth web program (www.constant-care.com). Individualized action plans based on a combination of fecal calprotectin, symptoms and web-based algorithm. On-demand outpatient visits in addition to 1 planned visit annually. Control: patients were managed according to the national pediatric IBD standard care in Denmark.
9	Carlsen K, 2017	Open labeled intervention study, Denmark, children/adolescents (ages 10–17), single center *Biologic cohort	2 groups: 1. eHealth – web-based program to help individualize infliximab (IFX) treatment based on disease activity assessment on a composite score. Using young.constant-care.com 2. Control – standard of care *Control group was followed for a shorter period than the eHealth group. eHealth – 29 patients; control – 21 patients. Ultimately, 13 patients dropped out of the study and only 16 completed the trial.	Disease activity: aPCDAI or PUCAI QoL: HRQoL and IMPACT III Other: drug safety (blood samples were taken before IFX infusions to measure trough levels and levels of antibodies).	Intervention: patients would enter weekly PUCAI/abbrPCDAI weekly until next IFX treatment. A fecal calprotectin stool sample was also collected. The TIBS score was reflected in a traffic light system where alarm symptoms would prompt the families to consult IBD provider for treatment decisions. Control: patients received IFX infusion every 8 weeks but intervals could be altered as needed to gain control of the disease.
10	Del Hoyo, 2019	RCT, Spain, adults, single center	3 groups: 1. Web-based telemedicine - remote monitoring (G_TECCU) 2. Nurse-assisted telephone care (G_NT) 3. Standard care with in-person visits (G_control) 68 patients were invited to participate and ultimately 63 patients were enrolled – 21 patients in each group.	Disease activity: HBI and SCCAI. Partial Mayo score was used for face-to-face visits. Treatment adherence: Morisky-Green index QoL: IBDQ-9 Healthcare utilization: emergency room visits, hospitalizations, IBD-related surgeries, corticosteroid courses Others: work productivity, drug side effects, patient satisfaction	Intervention: web-based telemanagement system (Telemonitoring of Crohn’s Disease and Ulcerative Colitis – TECCU) for remote monitoring of disease activity in patients on corticosteroids, immunosuppressants, and biological agents. Telephone calls or in-persons visits were available to train patients for administration of medications. Control: two groups. Nurse-assisted telephone care or standard face-to-face visits.
11	Heida A, 2017	RCT, Netherlands, adolescents (ages 10 – 19), multicenter	2 groups: 1. Intervention – telemonitoring (web-based) 2. Control – conventional follow-up. 170 teenagers were eligible and randomly assigned to home telemonitoring (n = 84) or standard follow-up (n = 86).	Disease activity: PUCAI and shPCDAI QoL: IMPACT-III Healthcare utilization: cost-effectiveness analysis including direct and indirect medical and non-medical costs	Intervention: Patients received automated email alerts to complete symptom score and send a stool sample for fecal calprotectin assessment. Symptom score and calprotectin stool test was uploaded to an IBD-live website and a color-coded system was used to advise patients the next best course of action. Control: Participants had regular checks and the interval of visits was based on the physician’s discretion.
12	McCombie A, 2020	Noninferiority RCT, New Zealand, adults, multicenter	2 groups: 1. Intervention – 2 smartphone apps for IBD monitoring and management (IBDsmart and IBDoc). 2. Control – usual IBD care from their physician. 107 randomized → 53 allocated to intervention group and 54 allocated to standard care group. 50 patients were ultimately included in each group. Attrition: At baseline, 50 (94%) and 50 (93%) patients completed the questionnaires in the intervention and control groups, respectively. At the end of 12 months of follow-up, 47 (89%) and 49 (91%) patients completed the questionnaire in the intervention and control group, respectively.	Disease activity: HBI and SCCAI Other: usability and acceptability of IBDsmart and IBDoc. Adherence as measured by utilization of applications.	Intervention: 2 smartphone applications for IBD monitoring symptoms and management with IBDsmart and IBDoc. The symptom scores are sent to health care providers. IBDoc calculates fecal calprotectin scores from stool samples provided by IBD patients at home. Patients self-completed HBI/SCCAI through the applications at least quarterly while in person visits were at baseline and 12 months. Control: usual IBD care from their physician.
13	Miloh T, 2017	RCT, United States, children, single center	2 groups: 1. Intervention – 2-way interactive text messaging to encourage medication adherence 2. Control – standard of care 51 children were randomized: 21 in the text-messaging group and 30 in the control group. Attrition rate: 8 (26.7%) and 6 (28.6%) dropped out in the intervention and control group, respectively	Disease Activity: PCDAI and PUCAI Treatment adherence: Morisky questionnaire.	Intervention: 2-way texting messaging (TM) using a centralized website/server. Text messages were sent to the patients and caregiver at set times based on patient preference. Control: standard of care All patients were followed in the pediatric gastroenterology clinic according to their condition and needs for 12 months.
14	Schliep M, 2020	RCT, United States, adults, multicenter	3 groups: 1. TELE-IBD weekly (W) 2. TELE IBD every other week (EOW) 3. Control 348 enrolled: 117 control, 115 EoW, and 116 W Attrition rates: 8.5% control, 13.9% EoW, and 19% W For this subgroup analysis, a total of 217 participants were included in the analysis. 90 in the control, 81 in TELE-IBD W, and 88 in TELE-IBD EOW.	QoL: Short Form 12 Others: Depressive symptoms were assessed with the Mental Health Inventory 5	Intervention: web- and mobile-based (secure messaging to patients from web-portal) – TELE-IBD system. Bidirectional communication between patients and healthcare providers via text messages only. Patients would receive individualized alerts and action plans based on responses. Control: standard of care following evidence-based guidelines Both the intervention and control groups underwent study visits at baseline, 6 and 12 months in addition to their routine clinic visits.

W: Weekly

EOW: Every other week

HBI: Harvey Bradshaw Index

SCCAI: Simple Clinical Colitis Activity Index

CD: Crohn’s disease

UC: Ulcerative colitis

QoL: Quality of Life

HRQoL: Health-related quality of life

IBD: Inflammatory bowel disease

IBDQ: IBD Questionnaire

IBDQ-9: Inflammatory Bowel Disease Questionnaire 9

SIBDQ: Short IBD Questionnaire

EMR: Electronic medical record

MARS: Medication Adherence Report Scale

PCDAI: Pediatric Crohn’s Disease Activity Index

aPCDAI: abbreviated Pediatric Crohn’s Disease Activity Index

shPCDAI: shortened Pediatric Crohn’s Disease Activity Index

PUCAI: Pediatric Ulcerative Colitis Activity Index