(338 days)
Rejoyn is a prescription digital therapeutic for the treatment of Major Depressive Disorder (MDD) symptoms as an adjunct to clinician-managed outpatient care for adult patients with MDD aged 22 years and older who are on antidepressant medication. It is intended to reduce MDD symptoms.
Rejoyn (also known as CT-152) is a digital therapeutic smartphone application (app) for the treatment of Major Depressive Disorder (MDD) symptoms. Rejoyn is a prescription smartphone app-based digital therapeutic administered to a user via the user's smartphone device (running Apple iPhone operating system [iOS®] or Android™ operating system [OS]), which delivers a proprietary interactive cognitiveemotional and behavioral therapeutic intervention. The core components of Rejoyn are the Emotional Faces Memory Task (EFMT) exercises, brief cognitive behavioral therapy (CBT)-based lessons to learn and apply key therapeutic skills, and short message service (SMS) text messaging to reinforce CBT-based lesson content and to encourage engagement with the app. It is intended for the treatment of MDD symptoms as an adjunct to clinician-managed outpatient care for adult patients with MDD aged 22 years and older. It is intended to reduce MDD symptoms.
Rejoyn is designed for use as an adjunct to clinician-managed outpatient care over a period of 6 weeks for the treatment of MDD symptoms, followed by a 4-week extension period where CBT-based lesson content will be accessible but no new therapeutic content or EFMT exercises will be available. Rejoyn is not intended to be used as a stand-alone therapy or as a substitution for the patient's clinician prescribed medications.
Here's a summary of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Device Name: Rejoyn™
Regulation Number: 21 CFR 882.5801
Regulation Name: Computerized Behavioral Therapy Device For Psychiatric Disorders
Regulatory Class: Class II
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for Rejoyn are defined by the "Special Controls" for computerized behavioral therapy devices for psychiatric disorders. These special controls mandate clinical data and detailed software documentation. The device's performance is demonstrated through the Mirai trial.
| Acceptance Criteria Category | Specific Acceptance Criteria (from Special Controls) | Reported Device Performance (from Mirai Trial) |
|---|---|---|
| Software Documentation | Software described in detail in SRS and SDS. Software verification, validation, and hazard analysis performed. Software documentation demonstrates effective implementation of behavioral therapy model. | Software documentation provided in 510(k) consistent with FDA guidance. Software verification and validation testing completed. Documentation demonstrates effective implementation of the behavioral therapy model. |
| Clinical Data | (i) Describe a validated model of behavioral therapy for the psychiatric disorder. (ii) Validate the model of behavioral therapy as implemented by the device. | (i) Validated Behavioral Therapy Model: Rejoyn's core components are the Emotional Faces Memory Task (EFMT) exercises and brief cognitive behavioral therapy (CBT)-based lessons, which are described as a "proprietary interactive cognitive-emotional and behavioral therapeutic intervention" that extends findings from earlier EFMT studies demonstrating a reduction in depression symptoms in MDD patients (References 6, 7). |
| (ii) Validation of Implemented Model: The Mirai trial (a pivotal, multicenter, remote, double-blinded, randomized, controlled trial) demonstrated the effectiveness of Rejoyn in reducing depressive symptoms. | ||
| Clinical Efficacy (Primary Endpoint) | Significant reduction in depressive symptoms compared to control at Week 6. | ITT Population: Mean change from baseline to Week 6 in MADRS total score: -8.78 (Rejoyn) vs. -6.66 (Sham). Group difference: -2.12 (p = 0.0211, 95% CI [-3.93, -0.32]). (Met significance level 0.049) |
| Clinical Efficacy (Key Secondary Endpoints - Durability, Patient-Reported, Clinician-Rated) | Durability of effect, improvement in patient-reported outcomes, and clinician-rated severity. | Durability (Exploratory): In mITT, MADRS change to Week 10: -10.96 (Rejoyn) vs. -9.93 (Sham), difference -1.03 (not clinically significant at Week 10 for overall mITT). In the MADRS Anxious Subgroup, change to Week 10: -11.48 (Rejoyn) vs. -9.31 (Sham), difference -2.18. |
| Patient-Reported (PHQ-9 at Week 6): ITT: -6.93 (Rejoyn) vs. -5.15 (Sham), difference -1.78 (p = 0.0012). mITT: -6.68 (Rejoyn) vs. -5.10 (Sham), difference -1.58 (p = 0.0029). Both represent a clinically meaningful improvement. | ||
| Clinician-Rated (CGI-S at Week 6): ITT: -1.03 (Rejoyn) vs. -0.74 (Sham), difference -0.29 (p = 0.0037). mITT: -1.06 (Rejoyn) vs. -0.8 (Sham), difference -0.26 (p = 0.0098). Both represent a clinically meaningful improvement. | ||
| Safety | Acceptable safety profile with low frequency of adverse events, unrelated to the device, and not appreciably different from control group. | No Treatment Emergent Adverse Events (TEAE) assessed as related to Rejoyn. No discontinuations due to TEAEs. No serious TEAEs during treatment period. Most common TEAEs were non-serious and not related to Rejoyn. Low rates of worsening depressive symptoms and suicidality, comparable to or lower than the Sham group. |
| Patient/HCP Satisfaction | Favorable impression of treatment experience and convenience of software. | 85% of Rejoyn participants rated experience as "extremely satisfied" (37.1%), "satisfied" (38.9%), or "somewhat satisfied" (9%). 82.4% of investigators rated convenience as "extremely convenient" (18.7%), "convenient" (49.7%) or "somewhat convenient" (14.0%). |
2. Sample Size Used for the Test Set and Data Provenance
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Sample Size (Test Set):
- Intent-To-Treat (ITT) population: 386 participants (194 Rejoyn, 192 Sham)
- Modified Intent-To-Treat (mITT) population: 354 participants (177 Rejoyn, 177 Sham) (This was the primary population for the primary efficacy endpoint analysis).
- Safety Sample: 373 participants (187 Rejoyn, 186 Sham)
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Data Provenance: The Mirai trial (NCT04770285) was a pivotal, multicenter, remote, double-blinded (patients also blinded to hypothesis), randomized, controlled trial. The study was conducted virtually, with participants across multiple centers, implying a prospective and multi-site data collection. No specific country of origin is mentioned, but "multicenter" typically implies multiple sites within a region (e.g., US).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
The ground truth for the clinical effectiveness was established through commonly used and validated psychiatric assessment scales:
- Montgomery-Asberg Depression Rating Scale (MADRS): This is a clinician-rated scale. The study states the benefit was "consistently rated by independent assessors via the MADRS," indicating multiple clinicians likely contributed to these assessments. Specific number and qualifications are not detailed, but it is implied they are qualified clinicians for psychiatric assessment.
- Clinical Global Impression-Severity Scale (CGI-S): This is also a clinician-rated scale, where benefit was "rated by study investigators via the CGI-S." Again, specific numbers and qualifications of these "study investigators" are not explicitly stated, but they would be medical professionals involved in the clinical trial.
4. Adjudication Method for the Test Set
The text indicates that the trial was "double-blinded (patients also blinded to hypothesis)" and assessments were made by "independent assessors" (for MADRS) and "study investigators" (for CGI-S). There is no explicit mention of an adjudication method like 2+1 or 3+1 for resolving discrepancies in assessments. However, the use of "independent assessors" for the primary outcome measure (MADRS) suggests a measure to reduce bias.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, an MRMC comparative effectiveness study was not done in the context of radiologists or similar image interpretation professions. This device is a digital therapeutic for psychiatric disorders, not an imaging diagnostic tool requiring multiple readers to interpret cases. The effectiveness study compared the device (Rejoyn) to a Sham control group, not human readers with and without AI assistance.
6. Standalone Performance
Yes, a standalone (algorithm only without human-in-the-loop performance) study was effectively done. Rejoyn is a "prescription digital therapeutic" that provides "proprietary interactive cognitive-emotional and behavioral therapeutic intervention" directly to the user via a smartphone app. The trial design assessed the effectiveness of this app-based intervention (Rejoyn) against a Sham app, with both groups continuing "clinician-managed outpatient care" and "antidepressant medication." The primary efficacy endpoint measured the change in MADRS total score directly attributable to the Rejoyn app's use as an adjunct, demonstrating its standalone contribution to reducing MDD symptoms beyond standard care.
7. Type of Ground Truth Used
The ground truth was based on expert clinical assessments and patient-reported outcomes using validated scales:
- Clinician-rated scales: Montgomery-Asberg Depression Rating Scale (MADRS) and Clinical Global Impression-Severity Scale (CGI-S).
- Patient-reported outcomes (PROs): Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7).
These are standard, widely accepted measures for assessing depressive and anxiety symptoms in clinical trials.
8. Sample Size for the Training Set
The provided document describes a pivotal clinical trial (Mirai Trial) used for validation. It does not provide details about a training set for the development of the Rejoyn algorithm itself. Digital therapeutics often undergo iterative development and testing, but the specifics of a "training set" in the machine learning sense are not included in this regulatory summary, which focuses on the clinical validation of the final product.
9. How the Ground Truth for the Training Set Was Established
As mentioned above, the document does not include information about a "training set" for the algorithm itself. The focus is on the clinical validation of the device's effectiveness using the Mirai trial. If Rejoyn's "proprietary interactive cognitive-emotional and behavioral therapeutic intervention" involves machine learning components that were "trained," the methods and ground truth for that training are not detailed in this 510(k) summary. The summary highlights that the software documentation demonstrates Rejoyn "effectively implements the behavioral therapy model," suggesting the model itself is based on established therapeutic principles (EFMT and CBT).
§ 882.5801 Computerized behavioral therapy device for psychiatric disorders.
(a)
Identification. A computerized behavioral therapy device for psychiatric disorders is a prescription only device intended to provide a computerized version of condition-specific behavioral therapy as an adjunct to clinician supervised outpatient treatment to patients with psychiatric conditions. The digital therapy is intended to provide patients access to therapy tools used during treatment sessions to improve recognized treatment outcomes.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Clinical data must be provided to fulfill the following:
(i) Describe a validated model of behavioral therapy for the psychiatric disorder; and
(ii) Validate the model of behavioral therapy as implemented by the device.
(2) Software must be described in detail in the software requirements specification (SRS) and software design specification (SDS). Software verification, validation, and hazard analysis must be performed. Software documentation must demonstrate that the device effectively implements the behavioral therapy model.
(3) The following labeling must be provided:
(i) Patient and physician labeling must include instructions for use, including images that demonstrate how to interact with the device.
(ii) Patient and physician labeling must list compatible devices.
(iii) Patient and physician labeling must include a warning that the device is not intended for use as a standalone therapy.
(iv) Patient and physician labeling must include a warning that the device does not represent a substitution for the patient's medication.
(v) Physician labeling must include a summary of the clinical testing with the device.