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MobIle health-Care system for monitoring toxicity and symptoms in cAncer patients Receiving diseasE-oriented therapy

Periodic Reporting for period 1 - iCARE (MobIle health-Care system for monitoring toxicity and symptoms in cAncer patients ReceivingdiseasE-oriented therapy)

Période du rapport: 2016-06-01 au 2017-11-30

The European Project iCARE “MobIle health-Care system for monitoring toxicity and symptoms in cAncer patients Receiving diseasE-oriented therapy” (ERC-2015-PoC- 693680) started on June 1, 2016 and ended on November 30, 2017 with the aim of designing, prototyping and testing in a clinical asset a mobile health-care system to monitor toxicity and symptoms in cancer patients under disease-oriented therapy.
Lately, targeted therapy against metastatic cancer is spreading, bringing many advantages with respect to the traditional approaches to cancer therapies. Indeed, new generation drugs have been designed to hit therapeutic targets, as tumor cells, in a less traumatic and toxic way than traditional chemotherapy and allow to individualize the treatment according to the tumor’s biological characteristics. Such drugs are preferred by most physicians and patients because they bring many benefits in terms of therapy’s effectiveness and survival rate, while improving patients’ quality of life by enabling home treatments.
Such drugs, however, are still under study, and symptoms and duration of side effects are highly varying and not fully predictable yet. The management of these side effects and symptoms related to both the treatment and the disease in at-home settings may affect patient’s adherence to therapy. It is therefore mandatory to implement protocols to monitor compliance, side effects and treatment or disease related symptoms.
Nowadays, adherence to therapy is checked through refill histories and pill count; compliance is promoted by counselling patients, asking patients to keep a diary of doses and side effects, and following up with patients at clinic visits or through telephone contacts; side effects of treatments and symptoms are evaluated at hospital in an ambulatory basis, and their monitoring is carried out by periodically submitting questionnaires to patients.
A major drawback of this approach is that the evaluation is not timely and reliable in several cases, based on data periodically reported by the patients and/or caregivers, typically once per month. Today’s ICT technologies offer methods to timely evaluate patients treated at home, with more objective and validated instruments. In particular, they can widely support both patients to keep compliant to therapies, and physicians to monitor their patients more closely by receiving frequent feedbacks about their symptoms and side effects. The collection of patients’ data will provide reliable statistics about treatments with experimental drugs.

THE iCARE SYSTEM
iCARE is a mobile health-care system to monitor toxicity and symptoms in cancer patients under disease-oriented therapy. It is an integrated platform, interfaced to the patient’s smartphone, that enables the constant monitoring of the compliance to the therapy and periodically sends relevant reports to the medical unit. A novel smartphone’s app collects patients’ feedbacks about side effects through questionnaires collected three times per week, in full compliance with current cancer medical protocols (i.e. digital versions of E.S.A.S. and C.T.C.A.E. questionnaires). The physician is provided with both a mobile app and a clinical management system.
The PATIENTS’ MOBILE APP for smartphone or tablet allows them to login and automatically download data about the therapy they have to follow, i.e. the prescriptions, which are remotely filled in directly by the reference physician. They can also consult the list of scheduled appointments and fill in the E.S.A.S./C.T.C.A.E. questionnaires about symptoms and side effects of drugs; the questionnaires are then sent to the physician. Patients receive (video/audio) reminders every time it occurs that: 1) an appointment is scheduled for the next day, 2) it is time to take some medicines, 3) it is time to fill in the questionnaires for monitoring symptoms, toxicity and side effects.
The PHYSICIANS’ MOBILE APP allows them to consult the list of their next appointments and to receive automatic alarms if either the therapy is not correctly followed by patients, some values from their questionnaires are worrying, or feedback from patients is not constantly received.
The CLINICAL MANAGEMENT SYSTEM allows physicians to manage patients and their data, such as appointments, prescriptions, drugs and received questionnaires and alarms.
iCARE is built with particular attention to usability and privacy of data. Its architecture involves a remote server which collects all data and which the mobile apps and the clinical management system connect to. Furthermore, the prototype of a SMART BLISTER DEVICE was created and experimented, in order to automatize (and simplify) the monitoring of the adherence to therapy.

iCARE CLINICAL OBSERVATIONAL PILOT STUDY
After the lab testing, iCARE has been trialed through a proof of concept pilot study developed and conducted by the medical staff of the Hospital of L’Aquila, connected to the University of L’Aquila, assisted by a technical researcher of SMARTLY s.r.l. The pilot study took into account the needs of patients during oral cancer treatments, the promising potential of iCARE emerging technology, and evidences associated with the use of mobile applications in other chronic diseases.
During the first phase the oncologist has investigated discourse of cancer patients and created multimedia materials on evaluation and management of chemotherapy-related and cancer-related symptoms. The test sessions were led by a member of the iCARE research team with experience in usability tests. The oncologists were allowed to interact with the mobile phone version. While browsing through the screens, all oncologists were asked to speak about their expectations regarding the interaction with the buttons and drop-down menus, the navigation and the clarity of the information presented in each of the components. Supplier testers were also asked to comment on how patients could integrate with their care delivery strategies. All suggestions have been addressed and improvements were implemented.
Feedbacks from patients allowed the readily bugs fixing. Most patients found the app easy to use and appreciated the fact that prescriptions and appointments data get automatically updated from server, without requiring any action from them. The possibility to fill the questionnaires for toxicity and side effects whenever necessary was perceived as a comforting feature.
Recruitment of participants succeeded in the involvement of 11 cancer patients, who agreed to trial the preliminary version of the system on Android smartphones, checking the easiness to use of the App with minimal training from written or spoken instructions. Then, according to the approved ethical protocol, participants agreed to use iCARE for the evaluation and management of chemotherapy-related and cancer-related symptoms, while continuing to receive medical care from their oncologist, primary care physicians and other care teams as usual. During the study, patients received notifications on their phones to assess their symptoms control over the past 24 hours three times per week throughout the study period. Participants were followed up for three months, all patients completed the study. Out of a total of 449 alarms, 3% were for moderate or severe symptoms or side effects, 56% for not filling in the questionnaires, and 41% for not taking the pharmacological therapy. Patients learned how to use the application sufficiently quickly, practiced tasks easily and liked to work with the application. Oncologists had to get acquainted to a new way of working.

iCARE ETHICAL COMPLIANCE TO EUROPEAN STANDARDS
iCARE provides an integrated digital platform to obtain accurate chemotherapy toxicity reflection, provides a better means of monitoring related chemotherapy toxicity and has the potential to reduce chemotherapy-related morbidity. It collects and allows to query SENSIBLE DATA about patients and their health. Hence, it involves several ethical aspects that have been monitored and appropriately managed, in compliance with the European Regulation, and under the continuous supervision of an external ethical advisor appointed on purpose, who certified that the main ethical aspect concerns the Protection of Individuals with regard to the PROCESSING OF PERSONAL DATA, in compliance with EU Regulation 2016/679 of the European Parliament and Council of 27 April 2016. The development of iCARE system involved activities aimed to meet the relevant ethical requirements, ranging from data encryption and user authentication to remote mechanisms that allows physicians to remove data stored locally on the smartphones in case of loss. In conclusion, the iCARE Digital Collaboration Platform is primarily a software that does not interfere in any way with the treatment of a clinician in normal clinical practice, and any changes to this treatment will not be affected by participation in the study, as there is no change in the normal way to act as an oncologist with regard to monitoring the evolution of the symptoms and the side effects of therapy, while having an ICT monitoring system. It is not configured as a medical device, therefore it is not subject to EU Regulation 2017/745 of April 5, 2017. Finally, it guarantees the processing of data in compliance with EU regulations on clinical trials, including EU Regulation no. 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials for medicinal products for human use and Regulation 2016/679.

iCARE’S SOCIO-ECONOMIC IMPACT
iCARE system will enable a WIDE SPREAD OF HOME TREATMENT OF CANCER patients, preserving their comfortable lifestyle, and allowing significant resource savings. Usability is one of the key points of such system, which everyone should be able to use. Particular attention has been kept for privacy of data, by adopting strong security measures. The key features offered by iCARE system bring advantages to both patients and physicians. iCARE is a self-contained system which could bring great advantages in terms of time and money.
In fact, using iCARE reduces the costs of the healthcare system, boosts the home therapy approach, avoiding long waiting lists for visits; collects useful statistics and data about both drugs and their effectiveness, about illnesses and patients’ responses to therapies, more quickly and with improved accuracy than traditional approaches to data collection.
The natural evolution of the iCARE system is its incorporation into the production processes of big PHARMACEUTICAL COMPANIES. The possibility to offer to the home therapy a level of control of the critical therapies, comparable to that obtainable in the hospital structures, allows to create a new approach to the illness which has organizational and economic implications of great importance.
Since a long time, the NATIONAL HEALTH SERVICE has taken the path of home care for patients with chronic diseases in order to reduce the number of hospitalizations by obtaining substantial reductions in spending. For this reason, the National Health Service has both the economic resources and strong motivations to invest in technologies that broaden the possibility of home care. This strategy induces the pharmaceutical industry to adapt with products and medicines in line with the needs of home therapies.
Another direction of iCARE evolution is a system that can easily manage complex therapies at home, at hospitals and at elderly nursing homes. The new system can be obtained simply adopting part of the iCARE system, that is the one relative to therapy management. Several sources of information state that the European population is aging more and more as life expectancy has now exceeded 80 years of life, with regions showing peak of more than 85 years, in average. European States need to take care of this situation in order to improve elderly wellbeing and to easy their health care management. The complex therapy management system would help European populations since, when an elder gets sick, his life and the life of his/her relatives can drastically change. This smart system aims at: 1) Facilitating the management of (even complex) medical treatments by reminding the time and posology to be taken for each drug. This will reduce drugs’ intake errors, the stress of patients and their caregivers in following complex therapies, by increasing their quality of life; 2) Timely communicating to whom it may concern (e.g. patients and caregivers) that a drug is over and it should be prescribed again by the physician, also remembering the opening hours of the medical studio or Hospital pharmacy department; 3) Timely communicating to whom it may concern (e.g. patients and/or caregivers) that (life-saving) medicines have been correctly or incorrectly taken with respect to the medical prescription (that is, considering both posology and time of drug intake, when applicable); 4) Reducing errors in medication intakes, especially for patients with important pathologies and co-morbidities; as a positive consequence, this would also reduce assistance and hospitalization costs; 5) Increasing the compliance of the patients to specific medical treatments. This system will mitigate several problems, such as e.g. the health care of elderly people. The economic value must be evaluated not on the cost of the apparatus but on the economic savings that are generated.
SMARTLY s.r.l. has already started to present iCARE in medical and technical environments, especially to multinational pharmaceutical industries, raising particular interest for oncologic and psychiatric therapies and for prevention and wellness preservation of aging population.
In particular, iCARE has been presented in:
1. D. Cassioli, “i-CARE: Sistema di assistenza sanitaria mobile per monitorare la tossicita’ e i sintomi nei pazienti affetti da tumore in terapia orientata alla malattia,” FESTIVAL DELL’INNOVAZIONE IN SANITA’ PUBBLICA - Special Session on “e-Health per la prevenzione e riabilitazione,” - Pisa ITALY, 26-28 October 2017
2. D. Cassioli and F. Aielli, “i-CARE: Sistema di assistenza sanitaria mobile per monitorare la tossicita’ e i sintomi nei pazienti affetti da tumore in terapia orientata alla malattia,” 17° CONGRESSO NAZIONALE DELL’ASSOCIAZIONE ITALIANA DI TELEMEDICINA ED INFORMATICA MEDICA @iTIM 2017 - ICT nell'emergenza sanitaria, ambientale e naturale, Sistemi di telecontrollo e telesoccorso, Big Data per prevenzione, simulazione e analisi statistica - L’Aquila, ITALY, 2-4 November 2017
3. A. Di Marco, “Tecnologia ICT per il monitoraggio e il supporto della terapia” – Special Session in “Monitoraggio Telematico in Psichiatria: nuove tecnologie,” XXII CONGRESSO NAZIONALE DELLA SOCIETA’ ITALIANA DI PSICOPATOLOGIA - Progetto Promozione Salute Mentale 20.20: Psicopatologia: connessioni, culture, conflitti - Roma ITALY, 21-24 February 2018
4. F. Aielli, D. Cassioli, S. Curini, A. Di Marco, S. Pace, “iCARE: Mobile health-Care system for monitoring toxicity and symptoms in cAncer patients Receiving diseasE oriented therapy,” Poster presentation at the 5th International Conference on Model-Driven Engineering and Software Development (MODELWARD 2017), Porto (PT), 19-21 February, 2017.

A follow-up of iCARE is the APP “Rilevatore di Emicrania Cronica” which is available in the Google Play Store at https://play.google.com/store/apps/details?id=it.smartlysrl.emicrania and in the Apple Store at https://itunes.apple.com/it/app/rilevatore-emicrania-cronica/id1319246161 for detecting and classifying headaches based on questionnaires about symptoms, as established by the medical protocol on this matter.

Coordinator Contact:
SMARTLY: Natives of Smart Living s.r.l.
c/o University of L'Aquila (DISIM)
via Vetoio snc, L'Aquila
67100 ITALY

Email: info@smartlysrl.it
Website: http://www.smartlysrl.it