Evidence generation and approval of digital health applications in Germany

Digital transformation of Germany’s healthcare system—
The Digital Healthcare Act

Digitalization and innovative healthcare structures offer major opportunities for improving healthcare in Germany. But when it comes to implementing digital solutions, the German healthcare system was not considered as adaptive, resulting in a need for more innovative healthcare and a corresponding legal framework. As a response, the Act to Improve Healthcare Provision through Digitalization and Innovation (Digital Healthcare Act, DVG) came into force in December 2019. The law contains several measures to accelerate the implementation of digital solutions in the German Statutory Health Insurance (SHI). Among others, it enables digital health applications (DiGA) to be prescribed by healthcare providers and to be reimbursed by the SHI. DiGA are defined as CE-marked medical devices with their main function depending on digital technologies, such as smartphone apps or browser-based web applications. To be reimbursed, DiGA are required to pass an assessment of the Federal Office for Drugs and Medical Devices (BfArM). A successful assessment leads to a listing in the directory of reimbursable DiGA, enabling each healthcare provider to prescribe the DiGA and therefore making it easily accessible and free of charge for millions of individuals covered by the SHI system. Details of the assessment procedure are described below.

Road to reimbursable DiGA—The fast-track process

The BfArM assessment procedure is referred to as the fast-track process as manufacturers receive notification of the result within 3 months after submitting an application. The assessment determines whether the DiGA fulfills all requirements regarding necessary product qualities (eg, data protection specifications) and whether the use of the DiGA results in a positive healthcare effect. Positive healthcare effects can either be a medical benefit (eg, an improved health status or a shorter disease duration) or a patient-relevant improvement of healthcare structures and processes (eg, facilitated access to care, improved patient autonomy, or disease coping strategies). To prove a DiGA’s positive healthcare effect, manufacturers must provide quantitative results of a comparative study conducted in Germany as part of their application. This study needs to demonstrate the superiority of using the DiGA over not using it in terms of at least one claimed positive healthcare effect. If the manufacturer can present a study meeting all requirements recorded by law, an application for a final listing in the DiGA directory is suggested. If the manufacturer is not yet able to present a study sufficient to prove a positive healthcare effect, the DVG enables an application for a provisional listing in the DiGA directory. Nevertheless, the application for provisional listing needs to show the DiGA’s product quality as well as include systematically evaluated data generated within a study using the DiGA and demonstrating a likely positive healthcare effect. The DiGA will become visible in the directory as soon as the BfArM approves the preliminary listing, marking the beginning of the 1-year test phase during which the study results for final listing can be submitted. In case of a negative decision by the BfArM at the end of the 1-year test phase, the DiGA will be removed from the directory. An overview of the fast-track process can be found in Figure 1.

Figure 1: Overview of the fast-track process

_{Source: BfArM, 2020.}

Status quo—Overview of reimbursable DiGA

Since the fast-track process launched in May 2020, the BfArM has received 99 applications in total (last update on October 27, 2021). Whereas the majority of manufacturers applied for a provisional listing in the DiGA directory (n=73 applications), fewer manufacturers have applied directly for a final listing (n=26 applications). As depicted in Figure 2, considering all applications received to date, about half (n=49 applications) were withdrawn by the manufacturers. Reasons for withdrawals are not publicly available but may include incompleteness of the application or failure to meet study requirements, highlighting the importance of understanding the process and planning accordingly. As of October 2021, the BfArM has issued 24 positive and 5 negative decisions, while 21 applications are currently still under review.

Figure 2: Results of the BfArM assessment procedure¹

_{¹Last updated on October 27, 2021.}

Of the 24 reimbursable DiGA, 18 are provisionally listed and 6 are finally listed, 13 are smartphone apps, and 11 are browser-based web applications. Nearly half (n=11) of listed DiGA target psychologic disorders are depression, anxiety, tobacco addiction, or alcohol dependency. Other DiGA are designed to help patients with multiple sclerosis, diabetes, tinnitus, or migraine. All but one listed DiGA (n=23) claim a positive healthcare effect in terms of a medical benefit, with most of these (n=22) defining the medical benefit as at least an improvement in the patients’ health status. Some manufacturers also claim an improvement in quality of life or a shortened disease duration. Looking at the type of evidence submitted or planned to prove these positive healthcare effects, there is a consistent trend towards randomized controlled trials. Overall, 23 DiGA manufacturers have either already conducted such a study or are planning to do so during the test phase.

How to provide evidence—Typical study phases

Studies to demonstrate positive healthcare effects and thus support of final listing in the DiGA directory are usually designed as prospective studies. However, the specific study design and evaluation methods strongly depend on the type of DiGA and the intended positive healthcare effect. Local guidelines may provide useful orientation for study planning. The conduct of prospective studies can be divided into three phases, which are summarized in Figure 3: study set-up, study execution, as well as study analysis, reporting and close-out.

Figure 3: Typical phases of a prospective evaluation study

_{EC – Ethics Committee; eCRF – electronic case report form; EDC – electronic data capture.}

The first phase encompasses all planning-relevant steps for the study, starting with the development of the study protocol, the selection of the relevant study sites and the development of the electronic system to support data collection as well as the statistical analysis plan. Most studies require an informed consent of the patient as well as an approval of the respective ethics committee in Germany, including a data protection review of the study. After the official registration of the study, the site training can be carried out. The second phase refers to the initiation of the site and the recruitment of patients while site and data management and monitoring as well as study documentation (including the electronic trial master file) are ongoing in the background. After the database is locked, the data can be analyzed and presented in the final study report. Furthermore, the results can be published in scientific journals. Additionally, it is mandatory to publish complete study results in a public register such as the German Register of Clinical Studies (DRKS) one year after study completion at the latest. 

As a successful completion of these phases is fundamental for a final listing in the DiGA directory and reimbursement by the SHI, it is recommended to start study planning as early as possible. This way, it is more likely to have an adequately conducted study as well as a well-prepared application. However, the large proportion of application withdrawals by manufacturers that is currently observed suggests that awareness about required evidence is lacking as the assessment procedure and related demands are new. Thus, especially for DiGA in early phases of development which cannot present existing usage data, it is essential to start planning early as systematically evaluated study data are necessary, even for a provisional listing in the DiGA directory.

The article should be referenced as follows: 

Röhrkaste J, König C, Krinke K, Braun S. Evidence generation and approval of digital health applications in Germany. HTA Quarterly. Winter 2021. https://www.xcenda.com/insights/htaq-winter-2021-evidence-generation-approval-dtx-germany/

Sources

• BfArM. (2020). The Fast-Track Process for Digital Health Applications (DiGA) according to Section 139e SGB V. A Guide for Manufacturers, Service Providers and Users. 
• BfArM. (2021). DiGA-Verzeichnis. Retrieved from https://diga.bfarm.de/de/verzeichnis
• German Federal Government. (2019). Entwurf eines Gesetzes für eine bessere Versorgung durch Digitalisierung und Innovation (Digitale-Versorgung-Gesetz – DVG). Retrieved from https://www.bundesgesundheitsministerium.de/fileadmin/Dateien/3_Downloads/Gesetze_und_Verordnungen/GuV/D/Digitale-Versorgung-Gesetz_DVG_Kabinett.pdf
• German Federal Ministry of Health. (2020). Ärzte sollen Apps verschreiben können. Retrieved from https://www.bundesgesundheitsministerium.de/digitale-versorgung-gesetz.html
• German Federal Ministry of Health. (2021). DiGA Digital Health Applications. Retrieved from https://www.bfarm.de/EN/Medical-devices/Tasks/Digital-Health-Applications/_node.html