Table 1.
Studies reporting the impacts of ePROs on patient outcomes, utilisation of resources and in chronic disease care.
| Study | Setting, country | Design | Patient group | ePROM intervention, sample size (n) | Usual care (control), sample size (n) | Outcome(s) of interest | Clinical interventions to ePROM data | Result(s) |
|---|---|---|---|---|---|---|---|---|
| Absolom et al.33 | Outpatient, tertiary care providing chemotherapy | Prospective, randomised two-arm parallel group study | Patients initiating systemic treatment (chemotherapy with or without targeted therapies) for colorectal, breast, or gynaecological cancers. | eRAPID was added to usual care. Participants completed online symptom questions from home over 18 weeks (at least weekly plus when having symptoms). Reminders were sent weekly via text or e-mail. (n = 256) | Patients were regularly assessed by oncologists or nurses in clinics or by telephone for toxicity and to prescribe next treatment. Patients contacted the hospital via a 24/7 emergency hotline. (n = 252) | (a) Symptom control at 6, 12, and 18 weeks after baseline.(b) Impacts on hospital services (process of care measures) | Participants received immediate advice on symptom management or a prompt to contact the hospital. The symptom reports were displayed in real time in EPR. Nurses monitored email alerts for severe symptoms. | • Based on FACT-PWB scores, positive effects of eRAPID were observed at 6 (p = 0.028) and 12 weeks (p = 0.039), but there was no significant difference at the primary end point of 18 weeks (p = 0.69) • No between-arm differences were found for chemotherapy delivery, hospital admissions, acute oncology assessments, or emergency hotline calls |
| Basch et al.28 | Outpatient providing tertiary care and chemotherapy, US | Single-centre, non-blinded RCT | Advanced solid tumours - metastatic breast, genitourinary, gynaecologic, or lung cancers | STAR system for symptom monitoring. Includes patient adapted questions from NCI-CTCAE. Email reminders were sent. Computer-experienced (n = 286), computer-inexperienced (n = 155) | Symptoms discussed during clinic. Patients encouraged to telephone between visits for concerning symptoms. Computer-experienced (n = 253), computer-inexperienced (n = 72) | (i) Survival(ii) Quality-adjusted survival(iii) ED visits(iv) HospitalisationAt 1 year for the entire study group and subgroups. | Nursing response to alerts: (i) Telephone for symptom management counselling(ii) Medication initiation/change(iii) Referrals(iv) Chemotherapy dose modification(v) Imaging/test orders | • Survival: STAR versus usual care (75% versus 69%; p = 0.05) • Survival: computer-inexperienced STAR versus usual care (74% versus 60%; p = 0.05) • ED visits: STAR versus usual care (34% versus 41%; p = 0.02) • Quality-adjusted survival, STAR versus usual care (mean: 8.7 months versus 8.0 months; p = 0.004) • ED visits: computer inexperienced subgroups, STAR versus usual care (34% versus 56%; p = 0.02) • Hospitalisation: STAR versus usual care (45% versus 49%; p = 0.08) • Hospitalisation: computer-inexperienced subgroup, STAR versus usual care (44% versus 63%; p = 0.003) |
| Basch et al.29 | Outpatient, US | Single centre, non-blinded RCT; follow-up analysis | Advanced solid tumours - metastatic breast, genitourinary, gynaecologic, or lung cancers | STAR system. | Symptoms discussed during clinic. Patients encouraged to telephone between visits for concerning symptoms. | OS at median follow up of 7 years | Nursing response to alerts: (i) Telephone for symptom management counselling(ii) Medication initiation/change(iii) Referrals(iv) Chemotherapy dose modification(v) Imaging/test orders | Median OS: STAR (31.2 months; 95% CI, 24.5–39.6) versus usual care (26.0 months; 95% CI, 22.1–30.9) (difference, 5 months; p = 0.03) |
| Denis et al.34 | Outpatient, France | Single centre, phase II trial | Patients with surgical excision, complete response, or detectable but non-progressive lung carcinoma | Sentinel PRO system. Weekly reports on 11 symptoms. (n = 49) | Clinic visit and imaging every 2–6 months according to tumour stage and treatment type. | Survival | Phone call to confirm symptoms. Follow-up visits and imaging subsequently organised. | • Median survival: Sentinel (22.4 months) versus usual care (16.7 months), (p = 0.0014). • One-year survival: Sentinel (86.6%) versus usual care (59.1%) |
| Denis et al.35 | Outpatient, France | Multicentre phase III randomised trial | Advanced stage IIA (TXN1) to IV, non-progressive small cell or non–small cell lung cancer. Post treatment or on maintenance chemotherapy. | Sentinel PRO system. Weekly reports on 12 symptoms. (n = 60) | Routine follow up with CT scans scheduled every 3–6 months according to disease stage. Patients were encouraged to call between visits if they had new or progressive symptoms. (n = 61) | (i) OS(ii) PFSMedian follow up 9 months. | Alerts prompted by the Sentinel PRO system were confirmed by a phone call from the oncologist and led to an unscheduled visit. | • Median OS: Sentinel, 19.0 months (95% confidence interval [CI] = 12.5 to non-calculable) versus usual care, • 12.0 months (95% CI = 8.6–16.4), (one-sided p = 0.001). • HR = 0.32 [95% CI = 0.15–0.67]; one-sided p = 0.002). • PFS was not statistically significantly different between the two arms (p = 0.13). • Rate of imaging reduced 49% per patient per year in Sentinel versus usual care. |
| Denis et al.36 | Outpatient, France | Multicentre phase III randomised trial.Final overall analysis; 10 patients who received usual care had not relapsed and crossed over to ePRO intervention. | Advanced stage IIA (TXN1) to IV, non-progressive small cell or non–small cell lung cancer. Post treatment or on maintenance chemotherapy. | Sentinel PRO system. Weekly reports on 13 symptoms. | Routine follow-up with CT scans scheduled every 3–6 months according to disease stage. Patients were encouraged to call between visits if they had new or progressive symptoms. | OS after 2 years of follow up | Alerts prompted by the Sentinel PRO system were confirmed by a phone call from the oncologist and led to an unscheduled visit. | • Median OS without censoring for crossover: Sentinel (22.5 months) versus usual care (14.9 months) HR = 0.59 [95%CI, 0.37–0.96]; p = 0.03) • Median OS with censoring for crossover: Sentinel (22.5 months) versus usual care (13.5 months) HR = 0.50 [95% CI, 0.31–0.81]; p = 0.005) • Death: 29 (47.5%) in Sentinel and 40 (66.7%) in usual care |
| de Thurah et al.31 | Outpatient, Denmark | Pragmatic noninferiority RCT at two centres. | Rheumatoid arthritis | AmbuFlex ePRO system used as a decision aid in deciding whether patients required an outpatient appointment. The 11-item Flare-RA was used.Arm 1: Follow up by a rheumatologist (PRO-TR) (n = 93)Arm 2: Follow up by a nurse (PRO-TN) (n = 88) | Physicians saw patients in the outpatient clinic every 3–4 months. (n = 94) | Change in DAS28 after week 52. | Patients in the AmbuFlex groups were seen in outpatient clinic if their Flare-RA score was ⩾2.5 and/or their C-reactive protein (CRP) level was ⩾10 mg/litre. | • Noninferiority was established for the DAS28 in both AmbuFlex groups when compared with usual care. In the ITT analysis: • Mean differences in the DAS28 score between PRO-TR versus usual care = −0.10 ([90% CI]:−0.30, 0.13) • Between PRO-TN versus usual care = -0.19 (90% CI: -0.41, 0.02). • Including 1 yearly visit to the outpatient clinic patients in: • PRO-TN: 1.72 ± 1.03 visits/year • PRO-TR: 1.75 ± 1.03 visits/year • Usual care: 4.15 ± 1.0 visits/year. |
| Fjell et al.37 | Outpatient, Sweden | non-blinded RCT at two centres | Patients with breast cancer undergoing neoadjuvant chemotherapy. | The Interactive ‘Interaktor’ ePRO application for symptom reporting, self-care advice and symptom management during neoadjuvant chemotherapy. Utilised 14 questions. Email reminders were sent. (n = 74) | (i) Outpatient visits before each chemotherapy treatment(ii) A visit where the treatment, related symptoms and how to manage them were discussed.(iii) Contact number for a nurse for treatment related concerns (n = 75) | Symptom burden two weeks after completing chemotherapy | Patients had continuous access to evidence-based self-care advice and relevant websites. An alert triggered a notification suggesting to the patient related self-care advice. An alert also initiates a phone call from a nurse. | Using the MSAS questionnaire, Interaktor group had: • Lower prevalence of nausea (p = 0.041), vomiting (p = 0.037), and feelings of sadness (p = 0.003) • Less overall symptom distress (p = 0.004), and physical symptom distress (p = 0.031). • Lower scores in the total MSAS (p = 0.033). Effect size = 0.26– 0.34.Using the EORTC QLQ-C30, Interaktor group had: Higher emotional functioning (p = 0.008) |
| Handa et al.38 | Outpatient, Japan | Single centre RCT | Patients undergoing breast cancer chemotherapy. | The BPSS smartphone/PC application. A support tool for supportive management for adverse drug reactions.Patients’ symptoms were recorded using the CTCAE v4.0. (n = 47) | (i) Patients received explanatory materials compiled by drug manufacturer(ii) Medical staff recommended patients record their progress using their own notes. (n = 48) | Change in HADS score baseline and after completion of 4 chemotherapy courses | None reported | For the BPSS app group there were no significant differences in HADS: Anxiety: 1.66 (95% CI, 0.92–2.40)Depression: 0.09 (95% CI, −0.70–0.87). |
| Kricke et al.39 | Outpatient, US | Single centre, observational study | Patients with suspected or confirmed SARS-CoV-2 infection | A daily electronic symptom and coping questionnaire. n = 6006 completed at least a questionnaire. | Not applicable | (i) Track illness(ii) Offer support(iii) Identify worsening patients | The programme used text message reminders, and telephone-based care. Members of the medical team evaluated symptom severity, provided information, and referred patients with severe symptoms to the ED. | • Of those who filled out a questionnaire, on any given day, about 20% reported concerning symptoms. • An average of 9 patients per day went to the ED (SD: 5; range: 1–21) |
| Kroenke et al.40 | Outpatient, US | Multicentre, RCT | Patients screened positive for at least one SPADE (sleep, pain, anxiety, depression, and low energy/fatigue) symptom (their underlying chronic conditions were unspecified) | Participants electronically completed the PROMIS profile-29. Feedback of their symptom scores were provided to clinicians. (n = 150) | Participants also electronically completed the PROMIS profile-29. No feedback was provided to clinicians (n = 150) | (i) 3-month change in composite SPADE score | Clinicians received symptom scores for patients in the feedback group | • Non-significant trend favouring the feedback compared with control group (between-group difference in composite T-score improvement, 1.1; p = 0.17). |
| Mooney et al.41 | Outpatient, US | Multicentre, RCT | Patients starting chemotherapy (underlying diagnosis unspecified). | Patients in the Symptom Care at Home (SCH) arm called the automate system daily to report symptom severity. They received self-management coaching. Alerts of poorly controlled symptoms were sent to nurses who intervened following a decision support guidance. (n = 180) | Patients also called the automate system daily to report symptom severity daily but did not receive any further interventions (n = 178) | • Symptom severity across all symptoms • Number of severe, moderate symptom days • Individual symptom severity |
Patients in the SCH arm received self-management coaching. Alerts of poorly controlled symptoms were sent to nurses who intervened following a decision support guidance. | • Symptom severity across all symptoms was significantly less among SCH participants (p < 0.001). • Average reduction of symptom severity for SCH arm was 3.59 points (p < 0.001), roughly 43% of usual care. • SCH arm had significant reductions in severe (67% less) and moderate (39% less) symptom days compared with usual care (both p < 0.001). • All individual symptoms, (except diarrhoea), were significantly lower in the SCH arm (p < 0.05). |
| Nipp et al.32 | Inpatient setting, US | Single centre, non-blinded, pilot RCT | Patients with advanced cancers who have unplanned hospital admissions | The IMPROVED monitoring system was used by participants to report daily symptoms. (n = 75) | Participants also reported their symptoms each day using tablet computers. Clinicians did not receive their symptom reports. (n = 75) | Preliminary efficacy of IMPROVED for: (i) Improving symptom burden(ii) Health care utilisation among hospitalised patients with advanced cancer. | The oncology team received the symptom reports for patients on IMPROVED and discussed these during morning rounds. Responses to the ePRO data were based on clinical judgement. | • Patients assigned to IMPROVED had a greater proportion of days with lower psychological distress: 0.12 (95% CI, 0.03– 0.21; p = 0.008). • Patients assigned to IMPROVED experienced improvements in their average symptom scores for drowsiness (B = −0.54, 95% CI: −1.04 to −0.05; p = 0.033) and shortness of breath (B = −0.43, 95% CI: −0.75 to −0.11; p = 0.009), but not for other individual physical symptoms. • No significant intervention effects on patients’ hospital length of stay. |
| Nipp et al.42 | Outpatient, US | Secondary analysis of data from the STAR RCT by Basch et al. | Advanced solid tumours - metastatic breast, genitourinary, gynaecologic, or lung cancers | STAR system. | Symptoms discussed during clinic. Patients encouraged to telephone between visits for concerning symptoms. | To explore the moderating effects of age on the outcomes of the STAR RCT namely: | Nursing response to alerts: (i) telephone for symptom management counselling(ii) medication initiation/change (iii) referrals (iv) chemotherapy dose modification (v) imaging/test orders(i) Survival(ii) ER visits(iii) Hospitalisation |
• Younger patients (median age = 58 years) on STAR experienced lower risk of ER visits (HR = 0.74, P = 0.011) and improved survival (HR = 0.76, P = 0.011) compared with younger patients on usual care. • Older patients (median age = 75 years) did not experience significantly lower risk of ER visits (HR = 0.90, P = 0.613) or improved survival (HR = 1.06, P = 0.753) with the intervention. • There were no moderation effects based on age for HRQOL • and risk of hospitalisation. |
| Rasschaert et al.43 | Outpatient, Belgium | Multi-centre, prospective cohort | Patients with solid tumours (Gastro-intestinal, genito-urinary, breast, ling, head and neck, melanoma, gynae) receiving systemic antineoplastic agent(s) at any stage of their disease. | AMTRA was used for daily symptom reporting. Questions were drawn from PRO-CTCAE. A compliance tool to monitor oral therapies was incorporated in the system. Reminders were sent. (n = 168) | There was no control arm. Usual care included consultation with an oncologist during systemic treatment.Patients were provided information on treatment, toxicities and instructions on contacting the hospital for serious AEs. | Effect on:(i) symptom burden(ii) medication compliance | Staff received detailed training on the system and pathways generated by alerts. For toxicities graded as 1 or 2, self-management information was provided. For severe AE’s, medical staff received emailed alerts, contacted patients to advise or refer to the hospital. | • A reduction of mean grade over time for five toxicities (nausea, constipation, loss of appetite, fatigue, and dyspnea), (p < 0.0001). • Compliance to oral chemotherapy was high using AMTRA, median = 98.7% (95% CI: 93.5–100.0%). |
| Schougaard et al.27 | Outpatient, Denmark | Multi-centre, observational implementation study | Patients with epilepsy, coronary heart disease, narcolepsy, sleep apnoea, prostate cancer, asthma, rheumatoid arthritis, colorectal cancer, and renal failure | AmbuFlex system, where the patients’ ePROs determined the need of an outpatient consultation. Items were ad hoc.Reminders were sent. | Not relevant as system has been implemented for routine use | Impact on utilisation of resources in epilepsy and sleep apnoea clinics | A traffic light alert system was developed.A clinician has to decide whether further contact is needed.Red: Definite need of contact or the patient asks for a consultation. | • Of 8256 telePRO-based contacts from epilepsy outpatients, up to 48% were handled without further contact. • For sleep apnoea up to 57% of the 1424 telePRO-based contacts did not require further contact. • Completion rates were over 90% at baseline and follow up. |
AE, adverse event; AMTRA, ambulatory monitoring of cancer therapy using an interactive application; BPSS, breast cancer patient support system; CI, confidence interval; CT, computerized tomography; CTCAE, common terminology criteria for adverse events; DAS28, disease activity score in 28 joints; ED, emergency department; EORTC QLQ-C30, European organisation for research and treatment of cancer quality of life questionnaire C30; EPR, electronic patient records; ePRO, electronic patient-reported outcome; ER, emergency room; FACT-PWB, functional assessment of cancer therapy scale-general physical well-being subscale; HADS, hospital anxiety and depression scale; HR, hazard ratio; HRQOL, health-related quality of life; IMPROVED, improving management of patient-reported outcomes via electronic data; MSAS, memorial symptom assessment scale; NCI-CTCAE, National Cancer Institute’s common terminology criteria for adverse events; PFS, progression free survival (defined as the duration from randomisation to the first radiologic observation of disease progression or to last follow up when the patient is censored); PRO, patient-reported outcome; PROMIS, patient reported outcome measure information system; RA, rheumatoid arthritis; RCT, randomised controlled trial; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; STAR, symptom tracking and reporting; US, United States.