Trial design

The study is a prospective randomized controlled multicenter trial that compares the care of patients with suspected OSA who receive telemedicine-assisted standard care (telemedicine group) to those who receive standard care only (control group) in accordance with existing guidelines. Eligible patients with OSA will be randomly assigned (1:1) to either the telemedicine or the control group and will be followed up for 12 months.

Participants, interventions, and outcomes

The target group comprises patients with a high risk of having existing OSA. Patients over 18 years of age and with a score ≥ 3 in the STOP-Bang questionnaire (snoring, tiredness, observed apnea, blood pressure, body mass index, age, neck size, gender) indicating suspected OSA fulfill the criteria for study participation (Table 1). Exclusion criteria are known OSA with a history of PAP intolerance in the past and acute or untreated internal, neurological, or psychiatric diseases, as impacts on sleep quality requiring other therapies can be assumed. The study explicitly includes patients with pre-existing risk factors such as chronic cardiovascular diseases.

Table 1 STOP-Bang questionnaire

Patient recruitment will take place in participating medical centers in the outpatient sector in the German federal state of North Rhine-Westphalia. Outpatient doctors with one of the following specialties can participate in the project: general medicine, internal medicine, pneumology, cardiology, neurology, and otorhinolaryngology. After provision of information and inclusion in the study, central randomization is carried out digitally by the project software (Theracase, Smart‑Q Softwaresysteme GmbH, Bochum). Allocation to the control or telemedicine group follows a 1:1 random principle. The randomization process is not influenced by any of the project partners and cannot be altered. Participants in the control group will continue to receive standard care. For patients in the telemedicine group, polygraphy data are assessed by a sleep specialist of the collaborative telemedicine board. The member of the telemedicine board contacts either the participant or their physician to inform them of further diagnostic steps. Depending on the decision, the participant will be referred to an out- or inpatient sleep laboratory or receive immediate treatment initiation (managed by members of the telemedicine board). Once a treatment indication has been determined, the telemedicine board will also be responsible for structured PAP therapy follow-up using telemedically transmitted data in addition to standard follow-up. After 12 months of study, the telemedicine board’s responsibility will end.

Trial participants and care providers are not blinded after assignment. The evaluating institutions IMIBE and MedMan act as independent consortium partners and are blinded. For process evaluation, EsFoMed GmbH conducts partly standardized expert interviews with patients, care providers, members of the telemedicine board, and medical device providers recruited by the consortium.

All data collected during the study are transmitted to the project platform: clinical data, data on quality of life and treatment satisfaction, therapeutic device data, sociodemographic data, and comorbidities. The members of the collaborative virtual telemedicine board have insight into the collected patient data.

The study was approved by the Ethics Committee of the University Duisburg-Essen (ethical vote number: 22-10538-KOBO).

Interventions

The additional telemedical interventions in the telemedicine group build up on existing structures of standard care but incorporate innovative telemedical approaches at each diagnostic step as well as PAP therapy follow-up. The hypothesis is that a telemedicine-supported patient pathway leads to timely diagnosis, needs-based treatment initiation, and improved adherence to PAP therapy, which in turn results in a higher quality of life. Patients of the control group are treated according to the established standard patient pathway without additional telemedicine support. The existing care structures are initially a common denominator that is modified in the intervention group with the help of telemedical solutions (Fig. 2).

Fig. 2

Study design for obstructive sleep apnea patients: randomized study to evaluate novel additive telemedicine concepts (green fields) based on the existing care structures of standard care (yellow fields). PAP positive airway pressure. (Own figure)

Telemedical support during the diagnostic process

Following the established step-by-step diagnostic process, patients with suspicion of OSA receive cardiorespiratory six-channel polygraphy conducted by a specialist with an additional certification according to the MVV-RL. The examination results, including a medical report as a PDF file and a recommendation for action, are entered on the web-based project platform. For patients in the telemedicine group, sleep specialists of the telemedicine board also evaluate polygraphy findings and recommend the further procedure. They decide whether a patient has an indication for further PSG in a sleep laboratory (inpatient or outpatient) and, if so, whether

If a PSG appointment is required, this appointment is made for the patients in the telemedicine group. All sleep laboratories participating in the project have access to their patients’ data, which are collected on the project platform in the further process. Within the SLEEP WELL study, participating medical caregivers at each level of the diagnostic process (Fig. 2) have the opportunity to contact a sleep specialist of the telemedicine board in a teleconsultation to receive support in the case of questionable findings.

Of the patients randomized to the telemedicine group, N = 371 will be chosen for the so-called innovative pathway by members of the telemedicine board: patients with a high pre-test probability, clear OSA findings in polygraphy, and low comorbidity burden. The selection is made via randomization in the project platform. These patients receive their PAP initiation directly in the home environment without undergoing PSG in the sleep laboratory but with polygraphic control (see below).

PAP-based telemonitoring system

After confirmation of the OSA diagnosis, PAP therapy initiation will be carried out according to guidelines except for in patients randomized to the innovative pathway. In the telemedicine group, patients are supplied with telemedicine-capable PAP devices. The devices transmit treatment data to the manufacturer’s data cloud (AirView, ResMed; prisma CLOUD, Löwenstein Medical) via integrated wireless technology. After initiation of PAP therapy, all patients in the telemedicine group will receive up to 12 months of telemedicine follow-up provided by the telemedicine board in addition to the standard treatment follow-up. Members of the telemedicine board have access to the following data, which they check regularly according to pre-specified intervention descriptions:

device sends data, but usage < 4 days/week;

device sends data but not used for 4 days in a row;

device does not send data for 4 days in a row;

device sends data but usage < 4 h/day for 7 days in a row;

AHI under therapy > 10.0/h;

relevant leakage;

treatment problem on the part of the patient;

problems with the manufacturer’s therapy-accompanying app; and

other.

Standardized interventions carried out by the telemedicine board were developed following framework recommendations of the TIDieR checklist (TIDieR: Template for Intervention Description and Replication; [10]; Fig. 3).

Fig. 3

Telemedically supported PAP-therapy follow up in telemedicine group and in innovative pathway. (Own figure)

Thus, in case of problems with PAP therapy, the members of the telemedicine board can intervene at an early stage to optimize the treatment, e.g., by providing advice on mask fitting, pressure adjustment, mask change, or a change of the treatment mode. The patients are contacted and supported in order to achieve optimal use of the PAP therapy devices, to reduce the PAP termination rate, and to optimize quality of life. In case of persistent problems with PAP therapy despite adjustments, the telemedicine board can also judge PAP therapy to be non-successful and switch to oral appliances as second-line therapy according to existing guidelines. This ensures timely and guideline-compliant treatment of patients in the telemedicine group. PAP-derived treatment data as well as actions of the telemedicine board are logged in the project platform.

Patients of the innovative pathway also receive telemedicine-capable devices and will be monitored daily by the members of telemedicine board within the first 3 months after home-based PAP initiation. After the first 3 months, patients of the innovative pathway will receive telemedically supported PAP follow-up for the remaining 9 months. In the case of problems with therapy, members of the telemedicine board will evaluate whether additional PSG is necessary to solve the problems.

Outcomes

The central goals are to provide timely needs-based care for OSA patients with an improvement in the quality and efficiency of care and to eliminate the existing care deficit. Furthermore, PAP therapy compliance and thus quality of life should be improved. To achieve these outcomes, telemedical care concepts will be used in addition to standard care in the telemedicine group. The primary endpoint is a clinically relevant improvement in disease-specific quality of life (FOSQ). Secondary endpoints are as follows:

daytime sleepiness (measured by ESS);

general health-related quality of life (measured by EQ5D);

PAP therapy adherence (discontinuation rate, daily usage from of device-internal use statistics);

objective therapy quality (mask fit, residual sleep-disordered breathing);

number of guideline-compliant treatments;

time from initial diagnosis to PAP therapy initiation;

patient-reported satisfaction and acceptance;

satisfaction and acceptance reported by health care providers;

resource use and resulting intervention costs (e.g., staff time, costs of IT infrastructure);

total costs based on claims data, including, e.g., medication, specialist contacts, hospital stays, and cost utility and cost effectiveness;

noninferiority of home-based telemedically supported PAP therapy initiation compared to initiation in a sleep laboratory with regard to therapeutic effect, adherence, and quality of life in the innovative pathway;

hurdles and facilitators for acceptance by patients and health care providers; and

relevant targets for implementation of the new procedures into standard medical care in the case of a positive project evaluation.

Sample size

The clinical significance limit for the primary endpoint FOSQ is 1 point. To calculate the number of cases, two scenarios were assumed: a difference of 1 or 2 points, with an effect size of d = 0.3, α‑error of 0.05, power of 80%, PAP therapy indication rate of 72%, PAP therapy discontinuation rate of 11%, and a general dropout rate of 15%. This results in patient numbers of n = 2425 and n = 4448. A clinically significant difference can thus already be expected among all patients included in the first 18 months. Among all included patients n = 4448 (after 33 months), a clinically significant difference in the FOSQ can already be detected after a shorter follow-up duration (3 months). Based on the existing literature and clinical experience, it was estimated to be necessary to include n = 371 suitable patients in the innovative pathway, which is clearly sufficient for proving noninferiority compared to standard PAP initiation in a sleep laboratory assuming an effect size of d = 0.3, an α‑error of 0.05, a power of 80%, and a dropout rate of 20% (Fig. 4).

Fig. 4

Distribution of the number of patients in the study groups. (Own figure)

Recruitment

A long study inclusion period (Q2/2022 to Q4/2024) enables recruitment of a total number of 4448 patients. The collected data of all included patients will be analyzed during clinical evaluation. The follow-up period will be 12 months, whereby patients recruited towards the end of the recruitment period will have a shorter follow-up period as follow-up examinations will take place only until the end of Q1/2025 to ensure a sufficient analysis period. Figure 5 shows the recruitment timeline.

Fig. 5

Timeline of recruitment with follow-up timepoints. (Own figure)

Data collection and statistical analysis methods

The following data are collected during primary data collection: clinical data, data on quality of life and treatment satisfaction (can be entered by patients using electronic questionnaires), therapeutic device data (usage times, relevant leakages, residual sleep-disordered breathing), sociodemographic data (age, gender, living situation, etc.), and comorbidities. Patients are reminded by e‑mails or by study nurses to submit the questionnaires during follow-up electronically, by post, or by telephone. For patients in the telemedicine group, telemedically transmitted PAP device data are used for regular PAP follow-ups according to established intervention descriptions by members of the collaborative telemedicine board. Every additional contact with the patient as well as the reason for and duration of the contact and any resulting measures are documented on the project platform. This is not possible for patients in the control group; PAP therapy discontinuation or termination is therefore only detected at the regular PAP therapy follow-up after 6 months according to standard care or after 12 months at the final telephone-based study follow-up. The reason for discontinuation will be documented appropriately. For patients included from Q2/2024, the follow-up phase is shortened accordingly to a minimum of 3 months until the end of data collection in 03/2025. All clinical data entered on the project platform will be analyzed using descriptive statistical methods (calculation of mean values and standard deviations). The health economic evaluation of SLEEP WELL contains a cost-effectiveness and cost-utility analysis. To estimate the intervention costs, the resource use due to the new form of care will be collected using questionnaires and usage data on the project platform. Based on claims data of the involved statutory health insurances, costs will be summarized to calculate the overall costs. Outcomes will be taken from the primary data of the project. The incremental cost effectiveness will be calculated according to the difference-in-difference method. Due to the follow-up period of up to 12 months and the time lag to acquiring final claims data, only patients included up to Q2/2023 (n = 2425) can be considered in the health economic analysis. The expert interviews conducted during the process evaluation are recorded, transcribed, and analyzed using qualitative content analysis based on Mayring with the MAXQDA software (VERBI Software GmbH, Berlin, Germany).