APP-based Medical Device for Education and Training of Inhalation Technique

Worldwide COPD and asthma are prevalent diseases causing death, health problems, impaired quality of life and high costs for individuals and society. Pharmacological therapies for respiratory diseases are commonly delivered by inhalers allowing for lung deposition of the medication. Guidelines for chronic obstructive pulmonary diseases (COPD) and asthma address that patients should receive regular education and correction of inhalation technique. Acceptable inhalation technique is an effective prevention of uncontrolled symptoms and exacerbations for both asthma and COPD. Therefore, education of inhalation technique is a prerequisite to ensure good treatment response. The education of inhalation technique is usually given by nurses, pharmacists or medical doctors and includes training and demonstration of inhaler use and correction of errors at clinical appointment, by observing if patient correctly can manage critical steps of getting the inhaler ready for inhalation by shaking the inhaler, remove the cap, execute the dose correctly and hold breath after inhalation.

Different inhaler devices have different properties of inspiratory resistance and flow to ensure drug deposition in the lungs. Patient's ability to breath in and the internal resistance of the inhaler affects if drug particles will reach the inflammatory of lungs. Particularly, children, and patients with reduced lung function, e.g. during acute exacerbation, risk not being able to inhale properly. Furthermore elderly, irrespectively of COPD could also have compromised ability to generate a sufficient inspiratory flow. Therefore, when prescribing a new inhaler for treatment it is important to evaluate the most appropriate inhaler device for the patient. Overall, there are two major groups of inhalers, dry powder inhaler (DPI) or metered dose inhaler (MDI), with different properties regarding inhalation technique. MDI requires the patient to breath in the drug slowly, and DPI require a more forceful inhalation. A critical challenge is therefore to assess if the inspiratory flow agrees with specific requirement of particular inhaler in use. Although different types of DPI exist (eg. Turbuhaler, Diskus, Novolizer, Breezhaler), generally an airflow is generated through the DPI during inhalation if the breath in flow is sufficiently strong the medication powder leaves the inhaler and enters the mouth and airway. When inhaling, the resistance of the DPI generates a pressure drop and the drug particles are released. The inspiratory outcomes determining optimized lung deposition are the peak inspiratory flow (PIF), the inhalation time, as well as the time to PIF. Late PIF and low volume increases the risk that limited amount of drug particles reaches the lungs, instead, are deposited in the mouth, which can explain poor treatment response.

In view of available literature, clinicians are confronted to control that patient handle their inhalator and generate sufficient high inspiratory flow rate for optimal lung deposition before prescribing DPIs. Inspiratory flow rate can be assessed with the mechanical devices. This is a hand-held manual meter that enables assessment of PIF through adjustable resistance selected for a relevant inhalator (DPI or MDI). Additionally, app-based digital devices could provide even more extensive and detailed characterization of patient's ability to perform acceptable inspiratory flows regarding pre-specified outcomes of PIF, time to PIF, and flow over time, to ensure optimal lung deposition of the inhaled drug and for evaluation of treatment response. App-based digital device may offer patient's a simpler support for education and training of inhalation technique. Therefore, an app-based medical device for improving inhalation techniques was developed. The concept of the device consists of app-based materials for education and a CE-marked wireless spirometer (in this study, MIR AsthmaTuner) and CE-marked Airflow Trainer (MIR) to simulate the internal resistance of the common inhalers in use (DPI or MDI). To determine if patient can fulfill acceptable inspiratory flows of milliliters (mL) per second (s), PIF (flow/min), time to PIF (s), inhalation time (s), but others such as area under the curve, and inhalation flow acceleration may be added in the future.

The investigational device is a separate module, inhalation app-module, embedded in the Cloud-based CE-marked system called AsthmaTuner. The study hypothesis is that regular education and training with the medical device measurement will improve patients' ability to correctly use their inhalers over time. Thus, the aim of this study is to assess the effect of app-based medical device for education and training on inhalation techniques at 6-12 weeks follow-up visit in subjects with asthma and COPD. Secondary aim is to evaluate if the medical device is feasible to use in clinical practice. The study endpoints are peak inspiratory flow (PIF), time to PIF, flow (litre per min), inhalation time (seconds) and breath hold (seconds) divided by DPI and MDI, together with assessment of how the patient handles their inhaler according to a set of critical criteria. Patients treated for COPD or asthma in primary or secondary care will be invited to participate in a two-armed stratified randomised controlled blinded study (RCT) over 6-12 weeks.

The patient will download AsthmaTuner to their smartphone that connects to a Bluetooth spirometer (in this study, MIR AsthmaTuner). Inhalation test through Airflow Trainer, an adjustable resistance mounted on the home spirometer (Airflow Trainer), determines if the inhalation flow agrees with the endpoints for the inhaler used by study subject. The expected results of this trial will allow us to determine if app-based inhalation device improves inhalation technique compared with standard care. The goal of this project is to provide sufficient information for a CE-marked product of the inhalation app-module. The study will be performed by Karolinska Institutet (KI), B. Nordlund research group, also being the sponsor, but supported technically and intellectual expertise from Astra Zeneca and MediTuner AB (the owner of AsthmaTuner).

Description of the investigational device:

The investigational device is the inhalation app-module which will be investigated in this clinical study, version number later than 5.4.13.5. In this study, it will be used in combination with the MIR AsthmaTuner spirometer and Airflow Trainer (adjustable resistance). The inhalation module starts with patients selecting their inhaler type (DPI or MDI). This leads to written instructions which show patients how they should inhale their medication. The patient is then forwarded to the training part of the module, which allows a patient to inhale through their spirometer which is fitted with the Airflow Trainer (MIR). The patient will be able to see how their inhalation went and will pass or fail the training. A potential benefit of the app-based investigational device is the education patients receive about the medication they take. Patients cannot reach the status of 'medication mastered' until they have also completed two quizzes. The first quiz teaches foundations of asthma or COPD (or both if patient has both diagnoses) while the second quiz touches on more advanced topics within the diseases and tips for effectively managing them daily. The inhalation flow is measured by the wireless spirometer (MIR AsthmaTuner), using connecter (Airflow Trainer) for creating inspiratory flow resistance that corresponds to resistance of the prescribed inhalator as presented in Appendix 2.

The product description and regulatory classification of AsthmaTuner according to MDR is class 2b.

A.2.B Details concerning the manufacturer of the investigational device Manufacturer MediTuner AB Address Peter Myndes Backe 8 118 46 Stockholm Sweden SRN SE-MF-000028534 PRRC Karlijn van Herpen Email Karlijn@asthmatuner.com Phone +46 72 853 80 46

AsthmaTuner - version number 5.4.13.5 is a CE-marked MDR, class 2b device. SpiroBank Smart or Smart One spirometer - Medical International Research (MIR) is CE-marked.

Airflow Training - Medical International Research (MIR) is CE-marked.

Traceability:

The serial numbers of AsthmaTuner spirometer (SpiroBank Smart/Smart One) are being used, can be traced through the backend of the AsthmaTuner system. The Airflow Trainers from MIR come in batches. Batch number 01 will be used in this clinical study.

Intended purpose of the investigational device:

The intended purpose of the investigational device is to support education, training, and assessment of inhalation technique for patients in clinical practice and in self-management to optimize response and adherence to self-treatment. However, the inhalation tool will be part of the AsthmaTuner system and will not be released as stand-alone device. Therefore, it will eventually be covered by the intended use of AsthmaTuner, which is:

The intended use of AsthmaTuner is to improve asthma control for adults and children over the age of 6. This is mainly done by providing information and treatment recommendations which are generated based on a patient's lung function, symptoms, and physician-prescribed treatment plan. Furthermore, AsthmaTuner facilitates the management of respiratory diseases by processing lung function and user-reported data and by providing information to adults and children over the age of 6. Any form of diagnosis of asthma or other respiratory diseases shall be done by a healthcare professional, so home use is only for indicative purposes

Populations and indications The populations and the indications for which the investigational device is intended is any subject above the age of 6 receiving pharmacological treatment through MDI or DPI devices, commonly for treatment of inflammatory respiratory conditions of asthma and/or COPD.

Necessary training based on risk assessment. According to the risk analysis assessment there are no risks which require necessary training or experience to use the inhalation app-module. Additionally, the device has instructions embedded into the software, which have been deemed safe and effective through usability testing.

Description of the current state of the art in clinical care Inhaled therapy with DPI or MDI is the cornerstone of asthma, COPD, and other respiratory diseases. Therefore, standard educational program should contain training about correct inhalation technique. The recommendations about choice and effective use of inhaler devices for educational program are presented in Table 1 according to Global Initiative for Asthma (GINA).

Table 1: Recommendations of effective use of inhaler devices according to GINA - Global Initiative for Asthma guidelines.

CHOOSE:

* Choose the most appropriate inhaler device for the patient before prescribing treatment. Consider the preferred medication, available devices, patient skills, environmental impact and costs. * Ensure that patient have no physical or functional barriers that limit use of the inhaler. * Avoid use of multiple different inhalers types where possible, to avoid confusion.

CHECK:

* Check inhaler technique at every opportunity * Ask the patient to show how they use their inhaler (don't ask if they know how to use it) * Identify any errors using device specific checklist (Table 2).

CORRECT:

* Show the patient how to use the inhaler correctly with a physical demonstrating, e.g. by using a placebo inhaler. * Check technique again, paying attention to critical steps putting patient at risk not receiving inhaled medication. You may need to repeat this process 2-3 times within the same session for the patient to master the correct techniques \[21\]. * Identify any errors using a device-specific checklist (Table 2). * Consider an alternative device only if patient cannot use the inhaler correctly after several training attempts. * Re-check inhaler technique frequently