Relying exclusively on presenting clinical manifestations (e.g., using clinical disease activity indices) for treatment strategies is rarely successful in modifying the course of IBD, and telemonitoring can therefore not rely on the monitoring of symptoms alone . Clinical disease activity indices are nonspecific and do not correlate well with endoscopic activity [9]. Conventional blood tests (including hemoglobin, C-reactive protein, and erythrocyte sedimentation) are used frequently in the diagnostics and disease assessment of IBD. However, the sensitivity of these tests is insufficient to detect intestinal inflammation [10], limiting their use in telemonitoring .

Currently, FC is the most suitable biomarker for intestinal inflammation to be used for telemonitoring. FC is a noninvasive biomarker found in stool that can detect histological inflammation despite endoscopic remission [11–13]. Calprotectin levels in patients with sustained deep remission during treatment with infliximab remained very low (median < 40 mg/kg at all time points). Patients who flared had significantly higher FC levels (median > 300 mg/kg) 3 months before the flare. Two consecutive FC measurements of > 300 mg/kg within a 1-month interval were identified as the best predictor of flare (61.5 % sensitivity and 100 % specificity) [14]. FC constitutes about 60 % of the total protein in the cytosol of neutrophil granulocytes and levels correlate with the influx of neutrophils into the intestine [15]. Importantly, FC is stable in feces for up to 7 days at room temperature and can be accurately measured in small stool samples by several commercially available enzyme-linked immunosorbent assays (ELISAs) [16–19]. Recently, smart phone tests for FC have been developed, thus offering the possibility for home analysis of FC by patients [5, 20]. Home-testing of FC takes 18 min to carry out (Fig. 7.2) and has surprisingly high sensitivity and specificity. Coefficient of variation was between 4 and 12, with less than 10 being considered a useful and fair laboratory test [5] .

Of particular interest for the telemonitoring IBD patients is the ability of FC to differentiate IBD from irritable bowel syndrome (IBS) [21–23], assess IBD activity, and predict a relapse [14, 24, 25]. IBD patients often report symptoms referable to the gastrointestinal (GI) tract, without objective evidence of ongoing disease activity and 25–50 % of the IBD patients in clinical remission have symptoms compatible with a diagnosis of IBS [26]. A meta-analysis of the diagnostic precision of FC in distinguishing between IBD and non-IBD found that using a cutoff level of 50 μg/g gave a pooled sensitivity of 89 % and pooled specificity of 81 %. Even higher diagnostic precision was reported for a cutoff value of 100 μg/g [27]. FC can therefore be used to prevent excessive treatment of IBS-like symptoms and reduce the need for endoscopy [28] .

Furthermore, FC is able to differentiate well between active and inactive IBD. FC correlates significantly with endoscopic disease activity [10; 12, 29] and normalization of FC levels is a surrogate marker for mucosal healing [30, 31]. In UC, FC correlates with disease extent and disease severity [12]. FC is also able to differentiate endoscopically inactive disease from mild, moderate, and severely active disease [11]. In CD , FC also correlates with endoscopic disease activity [29, 30]. In a study of 126 patients with IBD (87 patients with CD and 39 patients with UC), FC >  250 μg/g gave a sensitivity of 71 % and a specificity of 100 % (PPV 100 %, NPV 47 %) for active mucosal disease activity in UC. The same study also found that in CD, FC ≤ 250 μg/g predicted endoscopic remission with 94 % sensitivity and 62 % specificity (PPV 49 %, NPV 97 %) [12]. A recent meta-analysis combined the results of 13 studies on the diagnostic accuracy of FC in differentiating between patients with active IBD and those in remission; it found that a cutoff of 250 μg/g in IBD resulted in a pooled sensitivity of 80 % and a specificity of 82 % [32] .

Finally, increasing levels of FC can predict clinical relapse in CD and UC patients, especially for colonic and ileocolonic CD . A meta-analysis used data from six prospective studies investigating the predictive ability of FC and found a pooled sensitivity and specificity of FC to predict relapse of quiescent IBD of 78 and 73 %, respectively [33]. FC cutoff values ranged from 150 to 250 μg/g.

Thus, FC is a reliable biomarker for intestinal inflammation. Periodic testing of FC for guidance of IBD treatment and disease monitoring—especially with FC testing being compatible with eHealth solutions that can be used in the patient’s home [5]—is a promising alternative to current standard care [34] .

PROs capture the patient’s illness experience in a structured format and may help the physicians to better understand symptoms from the patient’s perspective [35] . PROs measure any aspect of health directly reported by the patient (e.g., physical, emotional, or social symptoms) and may help to direct care and improve clinical outcomes [36]. Currently, the US Food and Drug Administration (FDA) is moving away from using disease activity indices as clinical trial endpoints and towards PROs when assessing the patient’s experience of symptoms and objective measures of disease [37].

The ultimate PRO is improvement in HRQoL. HRQoL is a subjective measure of a person’s physical and psychological well-being and represents a patient’s assessment of how a particular disease or intervention has affected their life. Patients with IBD experience an impaired HRQoL when compared with a healthy background population [38–40]. Disease course and activity [41, 42], perceived quality of care delivered, and the individual’s psychological status and social support [43, 44], are important factors affecting HRQoL .

Several different instruments exist for the assessment of HRQoL in IBD [45]. Disease-specific questionnaires for HRQoL—derived from and validated in the relevant disease groups—are the most sensitive indicators of change over time or with treatment. Generic instruments, on the other hand, are used to show similarities or differences among groups or populations; however, they may not be sensitive to changes over time or subsequent to treatment in groups of patients with specific diseases [46]. Until recently, most eHealth trials have used the disease-specific Inflammatory Bowel Disease Questionnaire (IBDQ) [47, 48], with or without the generic short form (SF-36 or SF-12) [49] questionnaire. The IBDQ instrument comprises 32 items that measure the following broad domains: physical health, psychological health, social relationships, and environment. The patient’s answers are scored on a seven-point Likert scale, in which “7” corresponds to the highest level of functioning . A cumulative score above 170 points represents good QoL, with scores ranging from 32 to 224. The s-IBDQ is a shorter version of the original instrument (comprised only ten questions, but representing all four domains) that may be more convenient for use in the clinical setting as well as in eHealth applications. The range of scores of the SIBDQ is 10–70 points with a score of 50 comparable to 170 in IBDQ [48, 50].

The SF-36 is a generic HRQoL questionnaire containing 36 items. Thirty-five of the items are grouped into eight multi-item scales: physical function, social function, role limitations due to physical problems, role limitations due to emotional problems, energy/vitality, mental health, bodily pain, and general health perception. It also contains a one-item measure of self-evaluated change in health status (health transition) over the previous year. For each question, the raw score is coded and transformed into a percentage, with 0 indicating the least favorable possible health status and 100 indicating the most favorable. The 12-Item SF-12 is a short form survey derived from the SF-36 instrument and developed to reduce respondent burden while achieving minimum standards of precision for purposes of group comparisons involving multiple health dimensions [49, 51] .

Different approaches to telemonitoring of IBD patients have been tested in clinical trials. While some have used Internet communication for distance consultations between patients and physicians or between physicians [52, 53], the most innovative systems have implemented the regular monitoring of patient-reported symptoms and PROs.

The home telemanagement in UC (UC HAT) [54] system has been developed to aid patients with self-managed care through remote clinical monitoring of symptoms , HRQoL, and adherence to therapy. This system is comprised a patient unit (laptop and electronic weighing scale for weekly self-testing), a decision support server, and a web-based clinician portal. It also includes an integrated disease-specific education curriculum. Besides recording the data, the system is able to send alerts to the clinician portal-based on remarkable responses, thereby enabling each side to act accordingly. The mobile Health PROMISE Platform [55] is a newly developed PRO and decision support platform. Using the application, patients can track their HRQoL (e.g., sIBDQ) and symptoms, and providers can use the visual data in real time, integrated with eHealth records, to provide better care to their entire patient population.

The Constant Care application [2, 56–59], on the other hand, combines web-based disease monitoring with an eHealth algorithm that actively provides treatment advice and is able to aid patients in treatment adherence and individual dosing of medication. It consists of a patient education package (eLearning and educational video clips further illustrating the information contained on the website, medication, and the study conditions) and a web-based disease monitoring package. Using the disease monitoring package, patients are able to record their disease activity as well as their FC levels, the latter being measured using a smart phone application and home testing kit of FC. Based on these results, disease activity is visualized according to a “traffic light” system of green, yellow, or red color, to illustrate inflammatory activity. The Constant Care application then directs individualized treatment for the patient (Fig. 7.1). The administrator part of the web application, which is only accessible to the investigators, allows the treating physician to monitor the patients .

A promising validated mobile Health Index for remote monitoring of IBD disease activity revealed good receiver operating characteristic (ROC) curves and will in future be tested for usability and feasibility in clinical practice [60]. Web applications in eHealth care have to follow the rules of the European Union (EU) and nationally for database constructions, and to protect the patients by anonymous data registration, login, and unique password [61]. Conformité Européenne (CE) marking is mandatory in the EU in accordance with regulation for database [62] .

Many systems systems exists among which Epic offers an integrated suite of health care software and their applications support functions related to patient care, including registration and scheduling; clinical systems for doctors, nurses, emergency personnel, and other care providers; systems for lab technologists, pharmacists, and radiologists; and billing systems for insurers.

Due to the Office of the National Coordinator for Health Information Technology, sharing health data from other software is possible as rules were produced in a 10-year vision and agenda to achieve healthcare interoperability in 2014.

EPIC provides electronic records systems for many academic medical centers in the USA. In Europe, EPIC has been installed in several countries including the UK, the Netherland, and Denmark. In Denmark, installation of EPIC is in progress at a cost of 840,000,000 DKK (Approx. 140,000,000$) [63] in all hospitals in the capital region and whole of the Zealand where the capital Copenhagen is situated covering with its 2.5, 5 million people about 1/2 of the Danish population. A feature in the Epic system is the possibility for telemedicine applications to be integrated into the electronic record system. In Denmark this feature will be included 2016 in accordance with the overall ambition to make telemonitoring available for all patients with chronic diseases.