Table 1 Study and population characteristics of included studies (ordered by DiGA category, then alphabetically by DiGA name)

Kalmeda

Ears

Other diseases of the ear, not elsewhere classified (H93.1)

Stover¹⁸

Parallel two-arm RCT

Self-guided, app-based intervention; based on cognitive behavioral therapy (CBT); exercises focusing on mindfulness, acceptance, self-efficacy, and relaxation; no individual customization; no reminder

9

Care as usual (CAU); access to DiGA after 3 months (waitlist)

N = 187 (IG: 94, CG: 93)

Sex female IG: 52.1% (N = 49), CG: 44.1% (N = 41); mean age: IG: 48.1 (SD 12.8), CG: 48.4 (SD 12.2)

Kalmeda

Ears

Other diseases of the ear, not elsewhere classified (H93.1)

Walter et al.¹⁹

Parallel two-arm RCT

Self-guided, app-based intervention; based on CBT, focusing on mindfulness, acceptance, self-efficacy and relaxation; no individual customization; no reminder

9

Care as usual (CAU); access to DiGA after 3 months (waitlist)

N = 187 (IG: 94; CG: 93)

Sex female: IG: 52.1% (N = 49), CG: 44,1% (N = 41); mean age: IG 48.1 (SD 12.8), CG 48.4 (SD 12.2)

Kranus Edera

Genitals, Kidneys, and Urinary Tract

Other diseases of the penis (N48.4)

Wiemer et al.⁴⁵

Parallel two-arm RCT

Self-guided, app-based intervention; multidisclipinary program with daily and weekly exercises, including cardiovascular training, pelvic floor exercises, and psychoeducation modules (texts, videos); training tailored based on initial assessment; no reminder

3

Care as usual (CAU); access to DiGA after 3 months (waitlist)

N = 241 (IG: 122; CG: 119)

Sex female IG: 0% (N = 0), CG: 0% (N = 0); mean age IG: 53.76 (SD 13.62) CG: 49.74 (SD 12.73)

HelloBetter Diabetes

Hormones and Metabolism

Diabetes mellitus, type 1 (E10), Diabetes mellitus, type 2 (E11)

Balzus et al.⁴⁶

Parallel two-arm RCT

Self-guided, web-based intervention; based on CBT techniques, including interactive modules (videos, audios, texts, exercises) and online diary; tailored based on individual progress; no reminder.

2

Access to DiGA after 12 months (waitlist)

N = 254 (IG: 128, CG: 126)

Sex female IG 63.3% (N = 81), CG 62.7% (N = 79); mean age: IG: 50.2 (SD 11.6), CG: 51.3 (SD 11.9)

Oviva Direkt für Adipositas

Hormones and Metabolism

Obesity (E66.00, E66.01)

Gemesi et al.⁴⁷

Parallel two-arm RCT

Self-guided, app-based intervention; multi-modal weight loss program including modules for diet, physical activity, and behavioral change strategies; tailored based on individual weight loss goals and progress; automated progress feedback and reminder to enter data

3

Care as usual (CAU); access to DiGA after 3 months (waitlist)

N = 168 (IG: 84; CG: 84)

Sex female: IG 67.9% (N = 57), CG 60.7% (N = 51); mean age: IG 47.4 (SD 11.5), CG 46.3 (SD 10.6)

zanadio

Hormones and Metabolism

Obesity (E66.00, E66.01)

Roth et al.⁴⁸

Parallel two-arm RCT

Self-guided, app-based intervention; multimodal weight loss approach combining nutrition, exercise, and behavioral therapy; tailored based on individual weight loss goals and progress; no reminder

12

Continuity of life routines, self-initiated weight loss activities allowed; access to DiGA after 3 months (waitlist)

N = 150 (IG: 76; CG: 73)

Sex female IG 90.7% (N = 69); CG: 91.8% (N = 67); mean age: IG 43.8 (SD 10.6), CG 42.9 (SD 11.1)

Kaia Rückenschmerzen

Muscles, Bones, and Joints

Back pain (M54)

Priebe et al.³⁴

Cluster RCT

Self-guided, web-based intervention; multidisciplinary approach with educational content, physiotherapy, and mindfulness exercises, teleconsultation for patients at high risk of chronic back pain; no tailoring of content; no reminder

6

Standard treatment (according to national guidelines)

N = 1245 (IG: 933; CG: 312)

Sex female IG: 65% (N = 606); CG- 64% (N = 200); mean age: IG: 42 (SD 12.4); CG: 37 (SD 12.6)

Vivira

Muscles, Bones, and Joints

Osteochondrosis of the spine (M42.0, M42.1, M42.9), other diseases of the spine and back, not elsewhere classified (M53.2, M53.8, M53.9), back pain (M54.4, M54.5, M54.6, M54.8, M54.9), biomechanical dysfunctions, not elsewhere classified, Segmental and somatic dysfunctions (M99.02, M99.03, M99.04), Other biomechanical dysfunctions (M99.82, M99.83, M99.84)

Weise et al.⁴⁹

Parallel two-arm RCT

Self-guided, app-based intervention; based on movement therapy and functional regional interdependence; multimodal approach (video, audio, text) with daily movement exercises; adaptation of exercise selection based on user feedback; no reminder

3

Standard physiotherapy treatment according to guidelines; access to DiGA after 3 months (waitlist)

N = 215 (IG: 108; CG: 107)

Sex female IG 47.2% (N = 51), CG: 59.1% (N = 62); mean age: IG: 57.4 (SD 13.8), CG: 57.3 (SD 13.5)

elevida

Nervous System

Multiple sclerosis [Encephalomyelitis disseminata] (G35)

Pöttgen et al.⁵⁰

Parallel two-arm RCT

Self-guided, web-based intervention; based on CBT; simulated dialogs and exercises to manage fatigue; content dynamically adjusted based on user responses; no reminder

3

Care as usual (CAU); access to DiGA after 6 months (waitlist)

N = 275 (IG: 139, CG: 136)

Sex female IG: 82% (N = 114); CG: 79% (N = 108); mean age: IG: 40.8 (SD 11.1); CG: 41.9 (SD 9.4)

HelloBetter Stress and Burnout

other

Problems related to difficulties in coping with life (Z73)

Heber et al.⁵¹

Parallel two-arm RCT

Self-guided, web-based intervention; based on Lazarus´ transactional model of stress, applying problem solving and emotional regulation strategies; exercises with interactive elements (audio, video, downloads); tailored based on individual progress; non-therapeutic feedback after session completion and optional mobile reminders

1.75

Care as usual (CAU); access to DiGA after 1.75 months (waitlist)

N = 264 (IG: 132, CG: 132)

Sex female IG 73,5% (N = 97), CG 72.7% (N = 96); mean age: IG: 42.4 (SD 10.7), CG: 44.2 (SD 9.6)

deprexis

Psychology

Depressive episode (F32.0, F32.1, F32.2), recurrent depressive disorder (F33.0, F33.1, F33.2)

Klein et al.¹⁶

Parallel two-arm RCT

Self-guided, web-based intervention; based on CBT technique including cognitive restructuring, mindfulness, acceptance, and behavioral activation; engaging users in interactive exercises, daily symptom tracking, and feedback; tailored based on feedback; daily messages via SMS or e-mail, and reminder after no use for 2 weeks

3

Care as usual (CAU); access to DiGA after 6 months (waitlist)

N = 1.013 (IG: 509, CG: 504)

Sex female: IG 68,8% (N = 350), CG 68.5% (N = 345); mean age: IG 42.8 (SD: 11); CG 42.9 (SD 11)

deprexis

Psychology

Depressive episode (F32.0, F32.1, F32.2), recurrent depressive disorder (F33.0, F33.1, F33.2)

Meyer et al.¹⁷

Parallel two-arm RCT

Self-guided, web-based intervention consistent with CBT; offering simulated dialog including cognitive restructuring, behavioral activation, mindfulness, problem solving, positive psychology; engaging users in exercises with worksheets, summary sheets, audio-recordings, photos, illustrations, and symptom tracking; content tailored following feedback; optional daily reminder per sms or e-mail

3

Care as usual (CAU); access to DiGA after 6 months (waitlist)

N = 163 (IG: 78; CG: 85)

Sex female: IG: 74.4% (N = 58), CG: 75.3% (N = 64); mean age: IG: 44 (SD 11.02); CG: 40 (SD 11.48)

HelloBetter Panik

Psychology

Phobic disorders (F40.01), other anxiety disorders (F41.0)

Ebenfeld et al.³⁷

Parallel two-arm RCT

Guided, web- and app-based intervention; offering CBT training, including psychoeducation, cognitive restructuring, relaxation, and exposure exercises; no tailored content; written feedback by coach after every session to increase adherence and motivation; reminder sent by coaches if no login for 1 week

2

Access to DiGA after 6 months (waitlist)

N = 92 (IG: 45, CG: 47)

Sex female IG 60% (N = 27); CG: 51% (N = 24); mean age IG 39.33 (SD 10.83), CG 37.43 (SD 10.03)

HelloBetter Vaginismus Plus

Psychology

Sexual dysfunction not caused by an organic disorder or disease (F52.5, F52.6)

Zarski et al.³⁵

Parallel two-arm RCT

Self-guided, web-based intervention; based on CBT for GPPPD; including cognitive restructuring, psychoeducation, mindfulness, relaxation, strengthening dyadic coping; tailored content based on user feedback; motivational text messages and practice reminders by eCoach if module was not completed in 7 days, semi-structured personalized written feedback on session by eCoach

8 sessions

Care as usual (CAU); access to DiGA after 6 months (waitlist)

N = 200 (IG: 100, CG: 100)

Sex female: IG 100% (N = 100), CG 1005 (N = 100); mean age: IG 29.46 (SD 9.82); CG: 28.04 (SD 7.84)

Invirto-die Therapie gegen Angst: agoraphobia

Psychology

Phobic disorders (F40.00, F40.01)

Zurowski et al.³⁸

Parallel two-arm RCT

Guided, app-based, virtual reality intervention; based on CBT for anxiety disorder, including exposure exercises; 2 video-telephone contacts with therapists; content disorder-specific but not tailored; daily reminders via SMS and e-mail

Self-paced, ~2 months; optional 4 additional months

Active control with supportive contacts every 4 weeks; care as usual (CAU); access to DiGA after 6 months (waitlist)

Agoraphobia: N = 103 (IG: 72, CG: 31)

Sex female: IG:62.5% (N = 45), CG: 80.7% (N = 2); mean age: IG: 35.8 (SD 9.4), CG: 36.3 (SD 10.5)

Invirto-die Therapie gegen Angst: panic disorder

Psychology

Other anxiety disorders (F41.0)

Zurowski et al.³⁸

Parallel two-arm RCT

Guided, app-based, virtual reality intervention; based on CBT for anxiety disorder, including exposure exercises; 2 video-telephone contacts with therapists; content disorder-specific but not tailored; daily reminders via SMS and e-mail

Self-paced, ~2 months; optional 4 additional months

Active control with supportive contacts every 4 weeks; care as usual (CAU); access to DiGA after 6 months (waitlist)

Panic disorder N = 84 (IG: 58, CG: 26)

Sex female: IG:62,1% (N = 36), CG: 69.2% (N = 18); mean age: IG: 37 (SD 12), CG: 36.5 (SD 12.3)

Invirto-die Therapie gegen Angst: social phobia

Psychology

Phobic disorders (F40.1)

Zurowski et al.³⁸

Parallel two-arm RCT

Guided, app-based, virtual reality intervention; based on CBT for anxiety disorder, including exposure exercises; 2 video-telephone contacts with therapists; content disorder-specific but not tailored; daily reminders via SMS and e-mail

Self-paced, ~2 months; optional 4 additional months

Active control with supportive contacts every 4 weeks; care as usual (CAU); access to DiGA after 6 months (waitlist)

Social phobia N = 110 (IG: 67, CG: 43)

Sex female: IG: 52.2% (N = 35), CG: 58.1% (N = 25); mean age: IG:32,36 (SD 9.91), CG: 32.9 (SD 9,6)

Mindable: Panik und Agoraphobie

Psychology

Phobic disorders (F40.0), Other anxiety disorders (F41.0)

Helbig-Lang et al.³⁹

Parallel two-arm RCT

Self-guided, app-based intervention; based on exposure therapy; including psychoeducation, symptom monitoring (diary), and exposure exercises; exercises adjusted according to patients´ anxiety levels and feedback in app, users can create and modify their own exposure exercises; weekly check-ups based on DSM-5 to increase engagement

2

Standard self-help recommendations during the waiting period, permission to seek external help such as psychotherapy; not reported whether access to DiGA was granted after waiting period

N = 107 (IG: 57; CG: 50)

Sex female IG 71,9% (N = 41), CG: 82% (N = 41); mean age: IG: 36.35 (SD 14.4), CG:35.82 (SD 14.17)

NichtraucherHelden-App

Psychology

Mental and behavioral disorders caused by tobacco (F17.2)

Rupp et al.⁴⁰

Parallel two-arm RCT

Self-guided, app-based intervention; based on smoking cessation strategies, offering behavioral support and structured modules including progress tracking; personalized support and guidance based on user´s progress and needs; no reminder

Duration of intervention not clear: no start date set; 9 core units plus optional 76-day follow-up care

Brief advice yet no treatment, patients asked to use no other app or support; access to DiGA after end of study (waitlist)

N = 661 (IG: 336; CG: 325)

Sex female: IG: 61.2% (N = 205); CG: 61.8% (N = 197), mean age: IG 46 (SD 12), CG 46 (SD 12)

Novego Depressionen bewältigen

Psychology

Depressive episode (F32.0, F32.1, F32.2), Recurrent depressive disorder (F33.0, F33.1, F33.2), persistent affective disorder (F34.1)

Baumeister and Moritz⁴²

Parallel two-arm RCT

Self-guided, web-based intervention; based on CBT, system therapy, mindfulness therapy; interactive exercises (text, audio, video, illustrations) on psychoeducation, and exercises; modules compiled from pool based on initial questionnaire, but standardized CBT content; e-mail or sms reminder, written support for questions, and crisis hotline

3

Care as usual (CAU); access to DiGA after 6 months (waitlist)

N = 303 (IG: 153; CG: 150)

Sex female: IG: 69.9% (N = 107); CG: 74% (N = 74); mean age: IG: 40.82 (SD 11.91), CG: 40.54 (SD 13.11)

Selfapys Online Kurs bei Depression

Psychology

Depressive episode (F32.0, F32.1), recurrent depressive disorder (F33.0, F33.1)

Krämer et al.³³

three-arm RCT

Unguided or self-guided, web-based intervention; based on CBT, systemic therapy, mindfulness training; engaging users in active exercises, mood trajectory; personalized feedback, individual goals can be set and reviewed; optional reminder e-mails and chat support to clarify questions; in guided group, personal guidance by psychotherapists (weekly telephone calls) to discuss exercises

3

Weekly standardized mindfulness exercises via email, with content comparable to that of a self-help mindfulness guide; permission to seek pharmacological/psychological treatments in waiting time (CAU); access to intervention after 6 months

N = 401 (IG1 N = 151, IG2 N = 150, CG N = 100)

Sex female: IG1: 83.4% (N = 126); IG2: 84% (N = 126); CG: 81% (N = 81); mean age: IG1: 38 (SD 10.7) IG2: 37 (SD 10.8) CG: 36 (SD 11.9)

Selfapys Online-Kurs bei Generalisierter Angststörung

Psychology

Other anxiety disorders (F41.1)

Rubel et al.⁴¹

Parallel two-arm RCT

Self-guided, web-based intervention; based on CBT and mindfulness-based therapy; including interactive mindfulness, exposure, and problem-solving exercises; in-depth modules individually selectable based on users' needs; no reminder

3

Care as usual (CAU); access to DiGA after 3 months (waitlist)

N = 156 (IG: 78; CG: 78)

Sex female: IG: 88.5% (N = 69), CG: 75.6% (N = 59); mean age IG: 33.2 (SD 10.5), CG: 37.2 (SD 12.4)

somnio

Psychology

Non-organic sleep disorders (F51.0), sleep disorders (G47.0)

Lorenz et al.⁴³

Parallel two-arm RCT

Self-guided, web-based intervention; based on CBT for insomnia; including modules for sleep continuity, sleep quality and daytime performance, sleep diary; self-paced with feedback on progress on individual goals; tailored dialog with animated sleep coach based on individual response behavior; e-mail reminder if sleep diary is not filled in, continuing with program conditional on sleep diary completion

1.5

Care as usual (CAU); access to DiGA after 1.5 months (waitlist)

N = 56 (IG: 29; CG: 27)

Sex female IG: 72% (N = 21), CG: 67% (N = 18); mean age: IG: 41.72 (SD 17.31), CG: 44.04 (SD 20.05)

velibra

Psychology

Phobic disorders (F40.01, F40.1), other anxiety disorders (F41.0, F41.1)

Berger et al.⁴⁴

Parallel two-arm RCT

Self-guided, web- and app-based intervention; based on CBT emphasizing transdiagnostic principles; including psychoeducation, cognitive-behavioral and anxiety management exercises, symptom tracking; content tailored based on user responses to symptom tracking questions; daily diary tasks and reminders via SMS or email to support engagement.

2.25

Care as usual (CAU); access to DiGA after 9 weeks (waitlist)

N = 139 (IG: 70; CG : 69)

Sex female IG 69% (N = 48); CG 72% (N = 40); mean age: IG: 42.1 (SD 12.2), CG: 41.8 (SD 12.2)

vorvida

Psychology

Mental and behavioral disorders due to alcohol (F10.1, F10.2)

Zill et al.³⁶

Parallel two-arm RCT

Self-guided, web-based intervention; based on CBT; including psychoeducation, self-monitoring and behavioral strategies, mood checker; program adapts based on user input and behavior (simulated dialog); daily reminder via SMS

6

Care as usual (CAU); access to DiGA after 6 months (waitlist)

N = 608 (IG: 306; CG: 302)

Sex female IG: 56% (N = 170); CG: 49% (N = 149); mean age: IG: 40.4 (SD 11.2); CG: 40.7 (SD: 12.1)