CHRODIS criteria applied to the MASK (MACVIA-ARIA Sentinel NetworK) Good Practice in allergic rhinitis: a SUNFRAIL report

A Good Practice is a practice that works well, produces good results, and is recommended as a model. MACVIA-ARIA Sentinel Network (MASK), the new Allergic Rhinitis and its Impact on Asthma (ARIA) initiative, is an example of a Good Practice focusing on the implementation of multi-sectoral care pathways using emerging technologies with real life data in rhinitis and asthma multi-morbidity. The European Union Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS) has developed a checklist of 28 items for the evaluation of Good Practices. SUNFRAIL (Reference Sites Network for Prevention and Care of Frailty and Chronic Conditions in community dwelling persons of EU Countries), a European Union project, assessed whether MASK is in line with the 28 items of JA-CHRODIS. A short summary was proposed for each item and 18 experts, all members of ARIA and SUNFRAIL from 12 countries, assessed the 28 items using a Survey Monkey-based questionnaire. A visual analogue scale (VAS) from 0 (strongly disagree) to 100 (strongly agree) was used. Agreement equal or over 75% was observed for 14 items (50%). MASK is following the JA-CHRODIS recommendations for the evaluation of Good Practices.


Background
European Innovation Partnerships (EIPs) aim to enhance European Union (EU) competitiveness and tackle societal challenges through research and innovation. To tackle the potential of ageing in the EU, the European Commission-within its Innovation Union policy-launched the European Innovation Partnership on Active and Healthy Ageing, Directorate General for Health and Food Safety, Directorate General for Communications Networks, Content & Technology (EIP on AHA, DG Santé and DG CONNECT) [1]. The B3 Action Plan promotes integrated care models for chronic diseases, including the use of remote monitoring.
The initiative AIRWAYS ICPs (EIP on AHA) is the model of chronic diseases of the B3 Action Plan [2,3]. It is a GARD (Global Alliance against Chronic Respiratory Diseases, WHO) Research Demonstration Project [4]. AIRWAYS ICPs was initiated in 2013 by the EIP on AHA Reference Site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon, France) [5]. The aim of AIRWAYS ICPs was to launch a collaboration to develop practical multi-sectoral care pathways (ICPs) in order to: (1) reduce chronic respiratory disease burden, mortality and multi-morbidity; (2) improve education of all stakeholders; (3) improve work productivity; (4) promote AHA; and (5) reduce inequities in all populations globally [3].
An App (Android and iOS) [16] has been developed and is associated with an inter-operable tablet for physicians and other healthcare professionals (HCPs) [17]. An elegant and simple common language, the Visual Analogue Scale (VAS), is used to assess and manage AR [18,19]. It is currently being combined with allergen and pollution exposure using various methods including Google Trends [20,21]. MASK also includes EQ-5D [22,23] and CARAT.
The European Commission is co-funding a large collaborative project named JA-CHRODIS (Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle) in the context of the 2nd EU Health Programme 2008-2013 [24]. JA-CHRODIS has developed a check-list of 28 items for the evaluation of Good Practices (GP) (http://chrodis.eu/our-work/04-knowledgeplatform/). According to the JA-CHRODIS "A GP is not only a practice that is good, but a practice that has been proven to work well and produce good results, and is therefore recommended as a model. It is a successful experience, which has been tested and validated, in the broad sense, which has been repeated and deserves to be shared so that a greater number of people can adopt it. " (http://www.fao.org/docrep/017/ap784e/ap784e.pdf; http://eurohealthnet.eu/sites/eurohealthnet.eu/files/ CHRODIS_Promotion%20Material%20WP5-08.pdf ).

Aim of the present paper
MASK is one of the GPs of SUNFRAIL (Reference Sites Network for Prevention and Care of Frailty and Chronic Conditions in community dwelling persons of EU Countries, www.sunfrail.eu), an EU project which evaluates GPs on chronic diseases. The aim of the present paper is to report the results of evaluation performed by using the JA-CHRODIS check-list on MASK. The paper has been devised and written by an expert group including MASK and SUNFRAIL experts.
CHRODIS check list 1 Moreover, MASK proposes a common framework of integrated care pathways (ICPs) to facilitate comparability and trans-national initiatives targeted to all populations according to culture, health systems and income [27].

(b) Implementation
AIRWAYS ICPs has developed a strategy for lowresource settings based on existing WHO initiatives such as the WHO Package of Essential Non-communicable disease (PEN [28]) or validated primary management strategies in low-and middle-income countries (LMICs) [29]. The first ARIA workshop report (1999) already had a specific goal to reach patients in LMICs [6]. The expertise of GARD for the deployment of GPs in LMICs is used to address the equity dimensions of MASK. Gender is also considered in ARIA.

Practice (a) Comprehensiveness of the intervention
Pharmacist Specialist (asthma Health promotion is an essential component of GARD and MASK. It is extremely important in AR, particularly for the avoidance of allergen, indoor and outdoor air pollution. Google Trends results will be included next year to inform users of the pollen season. A research project using the App has been initiated to determine the impact of air pollution in AR (POLLAR). Patient empowerment is an essential component of MASK and follows the conclusions of the EU Council of the Polish Presidency [30,31]. Social determinants are considered in the Twinning [26]. WHO defines a setting as "the place or social context in which people engage in daily activities in which environmental, organizational, and personal factors interact to affect health and wellbeing" [32]. The goal of the settings approach is to create supportive environments for optimal health [33]. The model's key principles include flexibility, community participation, partnership, empowerment and equity [32]. One aspect of the current settings approaches of MASK is to improve work and school productivity [34]. Schools have long been used as a setting to provide health services and, in the future, improvement of school performance and exams may be achievable.
The practice implements (1) multi-sectoral care pathways (2) using emerging technologies (3) with real world data (4) for individualized and predictive medicine (5) in rhinitis and asthma multimorbidity, (6) by a multi-disciplinary group or by patients themselves (self-care) using the AIRWAYS ICPs algorithm (7) across the life cycle [16,47].
MASK was initiated by the WHO Collaborating Centre for Asthma and Rhinitis in 2011 and the pilot phase has been completed [8,12,13,17,36,55]. MASK proposes to study the symptoms (rhinitis, conjunctivitis and asthma) and work productivity of patients suffering from allergic symptoms, in particular during the pollen season. Geolocalized users assess their daily symptom control using the touchscreen functionality on their smart phone to click on 5 consecutive VAS measures (VAS-global, VAS-nasal, VAS-ocular, VAS-asthma and VAS-work) and type(s) of treatment used.
A clinical decision support system has been finalized based on an ARIA consensus report [47] and digitalized on tablets for HCPs [17]. A care pathway from the patient to the health care professional has been built. It is currently being combined with Google Trends to assess pollen seasons [20,21], pollen levels and pollution data.
The application is freely available in 17 languages from the Apple App store (iOS) and Google Play Store (Android) in 22 countries (translated and back-translated, culturally adapted and legally compliant). Due to the simplicity of the tool, it can be used in developed and many developing countries (if a smart phone is available).
A pilot study in 5000 users across 20 countries has been analysed. A simple questionnaire administered by cell phones has enabled the identification of phenotypic differences between a priori defined rhinitis groups. The results of the study suggested novel concepts and research questions in AR that cannot be identified using classical methods [56]. A cross-sectional study evaluated the impact of uncontrolled rhinitis assessed by VAS on work productivity using cell phone data collection. It also compared the impact of asthma, rhinitis and conjunctivitis on work [34]. In users with uncontrolled rhinitis, approximately 90% had some work impairment and over 50% had severe work impairment. This pilot study provided not only proof-of-concept for data on the work impairment collected with the app but also data on the app itself, especially the distribution of responses for the VAS. This supports the interpretation that persons with rhinitis report both the presence and the absence Box 4: An effective partnership is in place (e.g. multidisciplinary, intersector, multi-/and alliances) MASK activities are being implemented by a group of 450 members in 70 countries. All stakeholders needed for the implementation of an action plan at the national and local levels actively participate. ARIA has a specific module for pharmacists [35]. Members also include those of previous initiatives such as ARIA [36] and GARD [4,37]. The majority of members have been working together since 1999. The GA 2 LEN (Global Allergy and Asthma European Network, FP6) network of excellence centres of allergy and asthma [38], EUFOREA (European Forum for Research and Education in Allergy and Airway Diseases) [39,40] and members of EIP on AHA commitments for action are also involved. Scientific societies participate in the project as well.

Box 5: The intervention is aligned with a policy plan at local, national, institutional and international levels
The intervention is linked with WHO (GARD research demonstration project), the EU (DG Research [41][42][43], DG CONNECT and DG Santé [44]), National Plans (e.g. Finnish Allergy Plan) [45,46] and EIP on AHA Reference Sites. ARIA is used by the European Medicines Agency (EMA) and the Australian Medical Agency for the labelling of AR interventions.
(b) Description of the practice of symptoms (submitted). The results of the treatments reported by users may represent a breakthrough in the management of CRDs (in preparation).
Aiding risk stratification in chronic disease patients with a common strategy, AIRWAYS ICPs has developed a simple stratification algorithm for asthma control and severity (following a 2009 WHO meeting) which can be extended to all chronic diseases unifying the classification of the diseases for clinical, research and public health use [49,57,58].
The potential for inequities arising from the use of MASK has been considered. MASK might raise legal and ethical questions in employment (work productivity) or access to private insurance. However, users are anonymized. The freely-available App increases accessibility for vulnerable groups, although concerns on the digital divide should be addressed [59]. The application requires a smart phone, which limits its universal access at the moment. Notwithstanding, the authors consider that the information obtained from the current smart phone users will benefit future users, in a progressively higher number.
Box 7: The design describes the practice in terms of purpose, SMART objectives, methods (e.g. recruitment, location of intervention, concrete activities), and timeframe (sequence, frequency and duration) The MASK approach is following SMART objectives: • Specific-Target a specific area for improvement (AR and multi-morbid asthma, addressing symptoms, medication and quality of life). The methods are clearly stated and published [16].
• Recruitment: The Allergy Diary was used by people who downloaded it from the Apple App store, Google Play store, and other Internet sources. A few users were clinic patients that were asked by their physicians to access the app. Due to anonymization (i.e. no name or address) of data, no personal identifiers were gathered. None of the users were enrolled in a clinical study as we aimed to have a real life assessment. There was no specific advertisement or other recruitment campaign. • The Allergy Diary collects information on allergic symptoms.

Ethical considerations
Box 8: The intervention is implemented equitably, i.e. proportional to needs Box 9: Potential burdens, including harm, of the intervention for the target population are addressed ICT can improve health outcomes, quality of life and efficiency of health care processes but may also contain disruptive consequences. Moreover, the implementation of 'e-health applications' is rather complicated. E-health applications do not (often) provide direct benefit that can be easily measured [60]. Incentivising further technological development without putting enough emphasis on and properly supporting, even financially, its adoption is likely to widen the serious 'technology consumption gap' that we all witness [61]. Nevertheless, mobile phones are widely used among populations with poor access to health care and limited education. They provide the opportunity to disseminate relevant information and empower individuals for guided self management of diseases. MASK is currently investigating these aspects. The Terms of Use [56] have been translated into all relevant languages and customized according to the legislation of each country in order to allow the use of the results for research purposes.
The data were anonymized except for geolocalized data to the area-level [56]. The European Commission's Article 29 Working Party states that geolocation information is personal data (http://ec.europa.eu/newsroom/just/ item-detail.cfm?item_id=50083) and that information can be collected, shared, or stored only with the express consent of the individual. This is the case for MASK because users agree to geolocation in the terms of use of the App. Moreover, geolocation is optional and each user can allow it or not on his/her cell phone. Geolocation, if active, can be disallowed at any time. Finally, geolocation is not used in the data mining process and the phone IP is not retained.
Formal Institutional Review Board (IRB) approval was not required for the first two studies. An IRB approval has been requested for the Twinning. Although registered as CE1, the App is considered as a non-medical device by the MHRA (Medicines and Healthcare products Regulatory Agency, UK Government, www.gov.uk/ government/organisations/medicines-and-healthcareproducts-regulatory-agency) and by the Ethics Committee of Cologne University.

Evaluation
However, a sufficient amount of data is needed and results are expected in 2018.
Box 11: There is a defined and appropriate evaluation framework assessing structure, process and outcomes. The use of validated tools and/or the results of evaluation are linked to actions to reshape the implementation accordingly and/or the intervention is assessed for efficiency (cost vs. outcome) MASK data are available using a real-time database and results are regularly published. Some 2016 data are already in press [34,56].
The results of 2016 have induced a change in some of the questions of the App and in the re-analysis of data using a novel approach, which suits observational studies better. In randomized controlled trials (RCTs), each subject is randomly assigned to a treated or control group, whereas observational studies examine the possible effect of a treatment on subjects where the investigator has no control over the experiment and cannot randomize the allocation of subjects [62]. This can create bias, may mask cause and effect relationships or, alternatively, suggest incorrect correlations. However, observational studies reflect "real world" use and practice more closely than RCTs in terms of the heterogeneous patient populations included and the variety of medical interventions [63]. They can provide clinically-relevant information, not necessarily provided by RCTs. Given the limitations of an observational study approach, it is important to optimize their study design to maximize their validity. In particular, known causes of bias and confounding should be measured [63].
The Twinning questionnaire in the 24 Reference Sites has been updated based on 2016 data [26].
One of the major goals of MASK is to improve loss of work productivity due to AR. Costs range from 30 to 60 B€ a year in Europe [64]. The pilot study allowed us to show that MASK can accurately assess work productivity [34]. In the Twinning, work productivity will be assessed in several settings including the Northern Ireland NHS, North of England and Valencienne, France hospitals.
EQ-5D is one of the MASK tools and will make it possible to assess the cost-effectiveness of interventions.

Box 12: Evaluation results achieve the stated goals and objectives
The results of ARIA are clear, but the results of MASK can only be assessed and its impact understood when a sufficient number of users will have been monitored. Interim data from pilot studies are encouraging [26,34,56]. They show in 11,300 users (June 17) that the phenotype of AR can be assessed and some features such as work productivity can be appraised.
Box 13: Evaluation Information/monitoring systems are in place to regularly deliver data aligned with evaluation and reporting needs A real-time database is available and the statistical analysis of the data is in place, allowing for a few preliminary reports to be published or in preparation already.

Box 14: The intervention is assessed for outcomes, intended or unintended
Outcomes measured by MASK include not only multiple symptoms but also EQ-5D and work productivity assessment.

Empowerment and participation
Box 15: The intervention develops strengths, resources and autonomy in the target population(s) (e.g. assets-based, salotogenic approach) MASK focusses on factors that support human health and well-being, rather than on factors that cause disease. This "salotogenic approach" is concerned with the relationship between health, stress, and coping [65]. AR is particularly suited for the model since AR is not a lethal disease, does not lead to ED visits or hospitalizations but has a major impact on quality-of-life [66,67], school and work [34,[68][69][70][71][72][73][74][75][76][77][78]. The evolutionary nature of the development of the app allows for continual assessment of both recording and intervention. This offers the potential for the technological intervention, always blended with clinician input, to induce behavioural change in patients to improve their outcomes [79]. Furthermore, MASK may provide a model for evaluating feasibility and effectiveness of using mobile technology for empowering individuals for diagnosis, early recognition of worsening of their diseases and guided self management of chronic diseases.
Patients, clinicians and other HCPs are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice and patients are often unsatisfied by their treatment. Severe Chronic Upper Airway Disease (SCUAD) defines uncontrolled AR patients despite optimal pharmacotherapy [80] and accounts for 10-20% of patients receiving treatment for AR [81]. A large number of AR patients appear to be self-managing their condition with few interactions with their doctor regarding their allergy prescription [82]. Many AR patients use over-the-counter (OTC) drugs [35,83,84] and only a fraction have had a medical consultation. The vast majority of patients who visit GPs or specialists have moderate/severe rhinitis [85][86][87]. A large number of OTC or prescribed drugs are available for the patient who can also choose alternative medicine or allergen-specific immunotherapy [88]. The app will also be useful in the early identification of those who are unaware of being affected by allergic rhinitis, and of the fact that symptoms can be controlled. The MASK ICPs consider a multi-disciplinary approach including self-management as proposed by AIRWAYS ICPs [2]. In the Allergy Diary, both OTC and prescribed medications are listed and the list has been customized for each country.
In order to assess the participation of the target population, a qualitative study has been carried out in users in France (MADoPA, http://www.madopa.fr/). The results of the study are under evaluation and we plan to extend the study to the European population to better understand the participation of the target population. The preliminary data of the study indicated that users were willing to show their data to their physician. A new functionality has therefore been added (March 1, 2017) allowing patients to print their data. There is no direct link from the patient's cell phone to the physician's computer (to comply with regulations).

Box 17: The intervention is designed and implemented in consultation with the target population
Quality of life-normal life despite the disease, cure and prevention-represents the patient's goal in AR and asthma [31]. Patient perspective, represented by patients' organizations, arises from the collective experience of patients (as well as their parents and partners) living with allergy. The European Federation of Allergy and Airways Diseases Patients' Associations (EFA, http:// www.efanet) is an alliance of 41 allergy, asthma and chronic obstructive pulmonary disease (COPD) patients' organizations in 25 countries. Patient perspective has been incorporated at all levels of ARIA, GARD and MASK, from the early steps.
The goal and rationale of patient involvement in medical decisions is patient empowerment [31]. Empowered patients know their disease, have the skills and motivation to take good care in their everyday life, adjust treatment, are prepared in new or potentially exacerbating situations, detect side-effects, contact a healthcare professional when needed and adhere to treatment regime. Many tools support empowerment, shared decision making models and patient education. Another key aspect of patient involvement in medical decisions is the involvement of patient representatives in the healthcare policy and organization in practice. The members of EFA have developed tools to help in involvement in medical decisions and empowerment. These tools were acknowledged while developing MASK.  However it should be noted that sustained engagement by individual patients is not necessarily a measure of success. For example, patients with intermittent allergic rhinitis may choose to inform MASK only at specific times of the year.

Sustainability
MACVIA-France Reference Site [89] and to lead the MASK project (see Box 20).

Scalability
Box 21: There is broad support for the intervention amongst those who implement it There are 450 stakeholders in the MASK working groups, from over 70 countries and all continents. They represent all groups from patients to policy makers, practicing health care professionals and key opinion leaders.

Box 22: There is broad support for the intervention amongst the intended target populations
This has not yet been evaluated. It is planned for 2017 by the Twinning [26]. MASK focuses on factors that support human health and well-being, as well as on factors that cause disease ("salutogenic approach" [65]). An important outcome of MASK is work productivity. The same applies for school learning as AR has a detrimental effect on learning and on the results of exams [90]. Quality-of-life is tested using EQ-5D.

Governance
One major problem of all allergic diseases is compliance with treatment. If appropriately theorized and developed, ICT solutions are expected to improve compliance possibly by inducing behavioural change, and therefore the control of AR and asthma [91]. However, this component has not yet been tested in MASK.
Box 27: There is a specific knowledge transfer strategy in place (evidence into practice) The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing [51]. The overarching goals of the MASK approach are to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.
Scaling-up strategies in Europe and beyond The scaling up strategy has been clearly defined and approved by AIRWAYS ICPs members. It follows the EIP-AHA recommendations on a 5-step framework: [1] what to scale up: (1-1) databases of Good Practices, (1-2) assessment of viability of the scaling up of Good Practices, (1-3) classification of Good Practices for local replication; and [2] how to scale up: (2-1) facilitating partnerships for scaling up, (2-2) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. Scaling-up will take place within and beyond Europe with GARD [25,30,31,45,92].
MASK is implemented in 22 countries (17 languages). We aim to include five more countries in 2017.
Strengthening the WHO NCD Action Plan AIRWAYS ICPs is a GARD demonstration project (WH0). It is in line with the WHO NCD Action Plan since it aims to reduce the preventable and avoidable burden of morbidity, mortality and disability by means of multi-sectoral collaboration and cooperation at national, regional and global levels.
checklist. However, one ear, nose and throat (ENT) expert from Belgium and one Allergy-Public health expert from the UK found that many items were not partly or not in line with the checklist. Overall, from 75 to 94% of items were found to be in line with the CHRO-DIS checklist.
Comments are provided for a percentage of agreement < 75%.
Box 2 At this stage there is no change in MASK incurred by the SurveyMonkey. There will be a revision of the product at the end of 2017 taking the comments into consideration.
Box 8 Since the SurveyMonkey, ethical committee has been granted (Kohln-Bohn Region) and the MHRA and the ethics committee have indicated that the App is not a medical device.
Box 12 More data have been evaluated and there is a strong consistency of results.

Box 13
At this stage there is no change in MASK incurred by the SurveyMonkey. There will be a revision of the product at the end of 2017 taking the comments into consideration.

Box 17
At this stage there is no change in MASK incurred by the SurveyMonkey. There will be a revision of the product at the end of 2017 taking the comments into consideration.

Box 18
At this stage there is no change in MASK incurred by the SurveyMonkey. There will be a revision of the product at the end of 2017 taking the comments into consideration. We use the expertise of WHO GARD to overcome generic barriers that may impact scaling up. Moreover, in each country, a MASK working group is in place to overcome local barriers.

Assessment of the criteria using SurveyMonkey
A SurveyMonkey questionnaire is the easiest way to create surveys and to obtain answers. It allows a survey to be prepared quickly and targeted answers to be obtained from the audience requested. We conducted a Survey-Monkey (www.surveymonkey.com) of expert clinical opinion on the 28 items to assess the robustness of the answers to the boxes. The SurveyMonkey was sent to 34 experts from different fields. For each item, respondents indicated their level of agreement on a VAS ranging from 0 (strongly disagree) to 100 (strongly agree). 18 experts from 12 countries responded (53%). It was decided pre-hoc to stop the survey when a 50% response was achieved. Respondents included allergists, general practitioners, pharmacologists, respiratory physicians or Public Health professionals. Two of the experts did not disclose their affiliation. Five SUNFRAIL experts were included in the survey. We categorized a priori the level of response (in line with the checklist ≥ 80, partly in line with the checklist: 50-79 and not in line with the checklist < 50).
The results are presented in Fig. 2. Most experts agreed that most items were in line with the CHRODIS

Box 19
The transfer of innovation is increasing. It is already implemented in Australia, Brazil, Mexico, and is in process in Argentina, Paraguay and Uruguay. Novel approaches including air pollution and allergen exposure are being considered and should be available by the end of 2018.
Box 20 New private funding has been secured. Moreover, the continuation of the intervention is ensured through institutional ownership.