(271 days)
Somryst is a prescription-only digital therapeutic intended to provide a neurobehavioral intervention (Cognitive Behavioral Therapy for Insomnia - CBT-I) in patients 22 years of age and older with chromic insomnia. Somryst treats chronic insomnia by improving a patient's insomnia symptoms.
Somryst is a 9-week prescription digital therapeutic (computerized behavioral therapy) used in the treatment of chronic insomnia. Somryst is based on principles of Cognitive Behavioral Therapy (CBT) for Insomnia, Sleep Restriction, and other proven psychosocial treatment elements, which are delivered in a sequence of "cores" of patient education, training and skill building. The therapy is delivered via a mobile application intended to be used on a patient's mobile device and consists of text, video, animation and graphics. Clinicians, as part of a patient's general treatment program, have access to a clinician dashboard that shows patient utilization and engagement with the application.
Here's an analysis of the acceptance criteria and the studies that prove Somryst meets these criteria, based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The FDA clearance document for Somryst does not explicitly list "acceptance criteria" in a typical quantitative pass/fail format with predefined thresholds for performance metrics. Instead, it demonstrates the device's efficacy by comparing its performance to a control group in several clinical studies. The implicit acceptance criterion is that Somryst should significantly improve insomnia symptoms compared to usual care or a control.
Below is a summary of the reported device performance from the two principal clinical studies, showing the statistically significant improvements.
| Performance Metric | Acceptance Criteria (Implied) | Somryst Performance (UC+SHUTi) - ANU Study (N=574) | Somryst Performance (UC+SHUTi) - UVA Study (N=151) |
|---|---|---|---|
| Insomnia Severity Index (ISI) Score Reduction | Significant reduction in ISI compared to control group. | Week 9: LS Mean change of -8.63 vs. -2.85 for control (LS Mean Difference: -5.78; p<0.0001) Month 6: LS Mean change of -8.17 vs. -3.86 for control (LS Mean Difference: -4.31; p<0.0001) Month 12: LS Mean change of -8.21 vs. -4.63 for control (LS Mean Difference: -3.59; p<0.0001) | Week 9: LS Mean change of -7.83 vs. -2.94 for control (LS Mean Difference: -4.89; p<0.0001) Month 6: LS Mean change of -8.52 vs. -5.36 for control (LS Mean Difference: -3.16; p<0.0001) Month 12: LS Mean change of -9.57 vs. -6.04 for control (LS Mean Difference: -3.52; p<0.0001) |
| Proportion of ISI Responders (>=7-point reduction) | Significantly higher proportion of responders than control. | Week 9: 62.8% vs. 14.0% for control (p<0.0001) Month 6: 56.2% vs. 18.9% for control (p<0.0001) Month 12: 59.3% vs. 25.2% for control (p<0.0001) | Week 9: 52.6% vs. 16.9% for control (p<0.0001) Month 6: 59.6% vs. 35.7% for control (p=0.0002) Month 12: 69.7% vs. 43.0% for control (p<0.0001) |
| Proportion of ISI Remitters (ISI score < 8) | Significantly higher proportion of remitters than control. | Week 9: 61.6% vs. 14.9% for control (p<0.0001) Month 6: 63.7% vs. 20.4% for control (p<0.0001) Month 12: 63.0% vs. 25.7% for control (p<0.0001) | Week 9: 40.6% vs. 11.3% for control (p<0.0001) Month 6: 49.1% vs. 24.0% for control (p<0.0001) Month 12: 56.6% vs. 27.3% for control (p<0.0001) |
| Sleep Onset Latency (SOL) Reduction | Significant reduction in SOL compared to control group. | Week 9: LS Mean change of -22.7 minutes vs. -0.46 minutes for control (LS Mean Difference: -22.4; p<0.0001) Month 6: LS Mean change of -22.6 minutes vs. -7.88 minutes for control (LS Mean Difference: -15.1; p<0.0001) Month 12: LS Mean change of -27.6 minutes vs. -10.8 minutes for control (LS Mean Difference: -17.2; p<0.0001) | Week 9: LS Mean change of -21.5 minutes vs. -8.84 minutes for control (LS Mean Difference: -12.6; p<0.0001) Month 6: LS Mean change of -21.1 minutes vs. -13.9 minutes for control (LS Mean Difference: -7.25; p=0.0323) Month 12: LS Mean change of -23.7 minutes vs. -16.3 minutes for control (LS Mean Difference: -7.32; p=0.0255) |
| Wake After Sleep Onset (WASO) Reduction | Significant reduction in WASO compared to control group. | Week 9: LS Mean change of -28.8 minutes vs. -11.0 minutes for control (LS Mean Difference: -18.8; p<0.0001) Month 6: LS Mean change of -27.6 minutes vs. -12.5 minutes for control (LS Mean Difference: -15.6; p<0.0001) Month 12: LS Mean change of -25.1 minutes vs. -9.36 minutes for control (LS Mean Difference: -16.5; p<0.0001) | Week 9: LS Mean change of -24.9 minutes vs. -8.46 minutes for control (LS Mean Difference: -17.2; p<0.0001) Month 6: LS Mean change of -23.9 minutes vs. -12.9 minutes for control (LS Mean Difference: -12.1; p=0.0006) Month 12: LS Mean change of -28.4 minutes vs. -16.8 minutes for control (LS Mean Difference: -12.7; p<0.0001) |
2. Sample Size for Test Set and Data Provenance
The "test set" in this context refers to the participants in the two clinical trials where the effectiveness of Somryst (referred to as SHUTi in the studies) was evaluated.
-
"The GoodNight Study" (ANU Study):
- Sample Size (Test Set):
- UC+SHUTi group: N=574
- UC+Control group: N=575
- Total participants mentioned in some tables (e.g., ISI, Week 9): UC+SHUTi (250), UC+Control (342). These are "available patient data," possibly reflecting those who completed the assessments at that specific timepoint.
- Data Provenance: Australia (Australian National University, Black Dog Institute, University of Sydney). Prospective randomized controlled trial.
- Sample Size (Test Set):
-
Pivotal Trial (UVA Study - NCT01438697):
- Sample Size (Test Set): Total N=303 adults with chronic insomnia.
- UC+SHUTi group: N=151
- UC+Control group: N=152
- Total participants mentioned in some tables (e.g., ISI, Week 9): UC+SHUTi (133), UC+Control (142).
- Data Provenance: United States (University of Virginia). Prospective randomized controlled trial.
- Sample Size (Test Set): Total N=303 adults with chronic insomnia.
3. Number of Experts and Qualifications for Ground Truth
The document does not describe the use of experts to establish a "ground truth" for the test set in the traditional sense of image annotation or diagnostic consensus. Instead, the ground truth for measuring insomnia severity and outcomes was based on:
- Patient-reported outcomes: Insomnia Severity Index (ISI) questionnaires. The ISI is a validated scale.
- Patient-reported sleep diaries: These were administered online and collected for 10 days within a 2-week window at each assessment time point. These diaries were used to calculate objective-like sleep parameters such as Sleep Onset Latency (SOL) and Wake After Sleep Onset (WASO).
The ISI itself incorporates a defined scoring system for severity and remission, which acts as a standardized "ground truth" established by clinical consensus (as referenced by published psychometric studies of the ISI).
4. Adjudication Method for the Test Set
No explicit adjudication method is mentioned. The primary outcome measures (ISI scores, sleep diary data for SOL and WASO) are quantitative and collected directly from patients. Clinical intervention studies like these typically rely on these validated instruments rather than expert adjudication of individual case outcomes after the trial.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, an MRMC comparative effectiveness study was not done. Somryst is a computerized behavioral therapy device designed to be used by patients, not an AI diagnostic tool that assists human readers in interpreting medical images or data. Therefore, the concept of assessing how much human readers improve with AI assistance is not applicable to this device.
6. Standalone Performance
Yes, a standalone performance study was done. The entire evaluation of Somryst (SHUTi in the studies) was based on its standalone performance in improving insomnia symptoms in patients directly. The comparator was either "Usual Care" plus an attention-matched digital control or an un-tailored digital education program, allowing for the isolation of Somryst's therapeutic effect. The device (SHUTi) itself delivered the intervention without human-in-the-loop assistance for the core therapy delivery. Clinicians had access to a dashboard, but this was for monitoring and management, not direct therapeutic intervention via the device.
7. Type of Ground Truth Used
The ground truth used was primarily patient-reported outcomes and validated psychometric scales:
- Insomnia Severity Index (ISI): A validated questionnaire for assessing insomnia severity. The definitions of "responder" (>=7-point ISI reduction) and "remitter" (ISI score < 8) are based on established clinical criteria derived from psychometric studies of the ISI.
- Sleep diaries: Patient-reported logs of sleep parameters like sleep onset latency (SOL) and wake after sleep onset (WASO). These provide quantitative, if subjective, measures of sleep behavior.
8. Sample Size for the Training Set
The document does not provide a specific "training set" for the Somryst algorithm in the context of machine learning. Somryst is described as a digital therapeutic based on "principles of Cognitive Behavioral Therapy (CBT) for Insomnia, Sleep Restriction, and other proven psychosocial treatment elements." This implies that the therapy logic and content are based on established medical and psychological knowledge (CBT-I protocols) rather than being developed through a data-driven machine learning training process.
The clinical studies described (ANU and UVA studies) are effectiveness studies, essentially serving as a "test set" to validate the established therapeutic approach delivered by the device.
9. How Ground Truth for the Training Set Was Established
As noted above, there isn't a traditional "training set" with ground truth in the machine learning sense. The "ground truth" for the content and principles of Cognitive Behavioral Therapy for Insomnia (CBT-I) and other psychosocial treatment elements, which form the basis of Somryst, would have been established over decades of clinical research, expert consensus, and efficacy studies in the field of sleep medicine and psychology. It represents established medical knowledge and best practices for treating insomnia.
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September 15, 2023
Pear Therapeutics, Inc. Yuri Maricich, MD, MBA Chief Medical Officer and Head of Development 201 Mission St. #1450 San Francisco, CA 94105
Re: K191716
Trade/Device Name: Somryst Regulation Number: 21 CFR 882.5801 Regulation Name: Computerized behavioral therapy device for psychiatric disorders Regulatory Class: Class II Product Code: QVO
Dear Dr. Maricich:
The Food and Drug Administration (FDA) is sending this letter to notify you of an administrative change related to your previous substantial equivalence (SE) determination letter dated March 23, 2020. Specifically, FDA is updating this SE Letter because FDA has created a new product code to better categorize your device technology.
Please note that the 510(k) submission was not re-reviewed. For questions regarding this letter please contact Pamela Scott, OHT5: Office of Neurological and Physical Medicine Devices, 301-796-5433, PamelaD.Scott@fda.hhs.gov.
Sincerely,
Vivek J. Pinto -S
Vivek Pinto, PhD Director DHT5B: Division of Neuromodulation and Physical Medicine Devices OHT5: Office of Neurological and Physical Medicine Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health
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March 23, 2020
Pear Therapeutics, Inc. Yuri Maricich, MD, MBA Chief Medical Officer and Head of Development 201 Mission St. #1450 San Francisco, California 94105
Re: K191716
Trade/Device Name: Somryst Regulation Number: 21 CFR 882.5801 Regulation Name: Computerized Behavioral Therapy Device For Psychiatric Disorders Regulatory Class: Class II Product Code: PWE Dated: February 26, 2020 Received: February 27, 2020
Dear Dr. Maricich:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration. listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's
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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Vivek J. Pinto -S
Vivek Pinto, PhD Director DHT5B: Division of Neuromodulation and Physical Medicine Devices OHT5: Office of Neurological and Physical Medicine Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K191716
Device Name Somryst
Indications for Use (Describe)
Somryst is a prescription-only digital therapeutic intended to provide a neurobehavioral intervention (Cognitive Behavioral Therapy for Insomnia - CBT-I) in patients 22 years of age and older with chromic insomnia. Somryst treats chronic insomnia by improving a patient's insomnia symptoms.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| ⊠ Prescription Use (Part 21 CFR 801 Subpart D) | ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
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510(k) SUMMARY K191716
In accordance with 21 CFR 807.87(h) and (21 CFR 807.92) the 510(k) Summary for Somryst is provided below.
1. SUBMITTER
| Applicant | Pear Therapeutics, Inc.201 Mission St. #1450San Francisco, CA 94105Tel: 617-932-7108Fax: N/A |
|---|---|
| Contact | Yuri Maricich, MD, MBAChief Medical Officer and Head of DevelopmentPh: 206-369-9784E-mail: yuri.maricich@peartherapeutics.com |
| SubmissionContact | Stephen ShermanVice President Regulatory AffairsPh: 617-456-7682E-mail: Stephen. Sherman@peartherapeutics.com |
| Date Prepared | 25 February 2020 |
2. DEVICE
| Device TradeName | Somryst™ |
|---|---|
| Device CommonName | Prescription digital therapeutic for chronic insomnia |
| ClassificationName | 21 CFR 882.5801 Computerized behavioral therapy device for psychiatric disorders |
| Regulatory Class | II |
| Product Code | QVO |
3. PREDICATE DEVICE
| Sponsor | Pear Therapeutics, Inc. |
|---|---|
| Product | reSET® |
| Regulatory Filing | DEN160018 |
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Pear Therapeutics. Inc. Somryst Traditional 510(k) Premarket Notification Submission
4. DEVICE DESCRIPTION
Somryst is a 9-week prescription digital therapeutic (computerized behavioral therapy) used in the treatment of chronic insomnia. Somryst is based on principles of Cognitive Behavioral Therapy (CBT) for Insomnia, Sleep Restriction, and other proven psychosocial treatment elements, which are delivered in a sequence of "cores" of patient education, training and skill building. The therapy is delivered via a mobile application intended to be used on a patient's mobile device and consists of text, video, animation and graphics. Clinicians, as part of a patient's general treatment program, have access to a clinician dashboard that shows patient utilization and engagement with the application.
INTENDED USE/ INDICATIONS FOR USE ડ.
Somryst is a prescription-only digital therapeutic intended to provide a neurobehavioral intervention (Cognitive Behavioral Therapy for Insomnia - CBT-1) in patients 22 years of age and older with chronic insomnia. Somryst treats chronic insomnia by improving a patient's insomnia symptoms.
6. SUBSTANTIAL EQUIVALENCE
Somryst is a prescription digital therapeutic that is considered a computerized behavioral therapy device for a psychiatric disorder (chronic insomnia) per 21 CFR 882.5801, like reSET®, the proposed predicate from Pear Therapeutics. Somryst shares the same Intended Use, and differs in Indications for Use, as it is used in patients with chronic insomnia instead of Substance Use Disorder (SUD) like the predicate. However, the differences in indications do not represent a new Intended Use, as they are related only to the different psychiatric disorder being treated and the different standard of care in each patient population as compared to the predicate.
Somryst and reSET have similar technological characteristics. They are both comprised of a patient-facing mobile medical application to deliver a form of Cognitive Behavioral Therapy and a clinician dashboard to facilitate patient management, tracking, and clinical decision-making, have substantially similar software architecture and features, utilize the same therapeutic delivery components (text, audio, visuals, video), and are both prescription digital therapeutic devices. Somryst has the same Intended Use as reSET, and minor differences in technological characteristics. The software and clinical validation data demonstrate that Somryst doesn't raise different types of questions of safety or effectiveness. Thus, considering available performance testing, Somryst is considered substantially equivalent to reSET.
6.1. Intended Use Analysis
Both the subject device (Somryst) and the predicate device (reSET) are computerized behavioral therapy devices for psychiatric disorders. The products deliver digitized CBT, are deployed through mobile applications for smart devices, have a sequence of content modules with similar behavioral treatment techniques, software architecture, and are both prescription devices. The indications are for different psychiatric disorders; however, this does not constitute a new intended use and thus, reSET can be used as the predicate for Somryst.
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Pear Therapeutics, Inc. Somryst Traditional 510(k) Premarket Notification Submission
| Characteristic | reSET (Predicate) | Somryst (Candidate) |
|---|---|---|
| Regulatory Classification | 21 CFR 882.5801 Computerized behavioraltherapy device for psychiatric disorders. | 21 CFR 882.5801 Computerized behavioraltherapy device for psychiatric disorders. |
| Indications for Use | Increase abstinence and retention in patientswith Substance Use Disorder (SUD) | Treat patients with chronic insomnia. |
| Intended User Population | Patients, Licensed healthcare providers(physicians, practitioners, psychologists,and registered nurses) | Patients, Licensed healthcare providers(physicians, practitioners, psychologists, andregistered nurses) |
| Medical Device Type | Software as a Medical Device (SaMD) | Software as a Medical Device (SaMD) |
| Prescription | Yes | Yes |
| Software Architecture | Patient facing mobile application, clinicianfacing dashboard, backend services | Patient facing mobile application, clinicianfacing dashboard, backend services |
| Mechanism of Action | Cognitive Behavioral Therapy (for SUD) | Cognitive Behavioral Therapy (for Insomnia) |
| Software Content | Text, video and audio content | Text, video and audio content |
| Therapy Duration | 12-weeks (90 days) | 9-weeks (63 days) |
| User Interface | Software application that requires users tolog in, go through modules of therapeuticcontent (text, video, audio), interact withdevice (through quizzes, contingencymanagement, reporting cravings, etc.), andreceive prompts/ feedback. | Software application that requires users to login, go through modules of therapeutic content(text, video, audio), interact with device(through sleep diary and interactive activities,etc.), and receive prompts/ feedback. |
| Mobile Platform | Smartphones, tablets (iOS and Android) | Smartphones, tablets (iOS and Android) |
6.2. Technological Characteristics Comparison
The minor differences in technological characteristics reflect the different clinical needs for the user populations (chronic insomnia vs. substance use disorder) and the disease-specific CBT for each. These differences do not raise different types of questions of safety and effectiveness.
7. PERFORMANCE DATA
7.1. Non-clinical Testing
Software verification and validation testing was completed and documentation was provided as recommended by Guidance for Industry and FDA Staff: Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices (2005) for a Moderate Level of Concern device.
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7.2. Clinical Testing
A responsive browser-based equivalent to Somryst ("SHUTi") was evaluated in "The GoodNight Study: Prevention of Depression Through Internet-based Insomnia Treatment', a large-scale, randomized controlled trial (ACTRN12611000121965) sponsored by the National Health and Medical Research Council (NHMRC).[1], [2], [3] This trial was performed by the Australian National University in collaboration with investigators at the Black Dog Institute, University of Sydney, and University of Virginia. The main objective of the study was to evaluate the efficacy of a web-based insomnia intervention, Sleep Healthy Using the Internet (SHUTi) for treatment of patients with chronic insomnia against a control arm of Usual Care (UC) and an attention-matched control (HealthWatch). [1], [2]
All study participants received usual care (UC) consisting of behavioral treatment, pharmacotherapy and/or self-treatment (e.g. visit to a general practitioner for sleep and/or mood problems, pharmacotherapy (e.g. for sleep and/or mood problems), over-the-counter sleep aids, visit to a sleep specialist, visit to a mental health provider).
Participants were randomized 1:1 to 9 weeks of treatment with the following:
- UC+SHUTi: Usual Care + SHUTi (now known as SomrystTM) ●
- UC+Control: Usual Care + Attention-matched, Digital Control
The Digital Control intervention (HealthWatch) was an interactive health and lifestyle web program that contained information about a range of health content (e.g., environmental health, nutrition, activity, medication) but had no specific mental health or sleep-related content. HealthWatch also administered weekly surveys on these topics to match for interaction required in the treatment group.
Participants in the UC+SHUTi group (n=574) were asked to complete all six Cores within the 9week treatment period. Participants randomized to UC+Control (n=575) were asked to complete nine internet-delivered modules within the 9-week treatment program, thus matching the attention components of SHUTi. Insomnia symptoms were evaluated for all participants at baseline, the end of the 9-week treatment period and the 6-month, and 18-month follow-up via the Insomnia Severity Index (ISI) and sleep diaries. Sleep diaries were administered online and collected for a period of 10 days (within a 2-week window), at each assessment time point. Sleep diaries were used to calculate diary-derived composite variables, including sleep onset latency (SOL, minutes to fall asleep) and wake after sleep onset (WASO, minutes awake during the night).
Insomnia Severity Index (ISI)
Insomnia severity was reduced at both week 9 (p<0.0001) and month 6 (p<0.0001) among participants who received UC+SHUTi as compared to UC+Control. The average reduction in ISI score was greater at week 9 and month 6 for the UC+SHUTi arm (mean -8.61 and -8.16 respectively) than the UC+Control arm (mean -2.87 and -3.90). The difference between the groups was significant at each timepoint (p<0.0001).
An analysis of the proportion of study participants deemed treatment responders and remitters was performed using the ISI data. Responders were defined by demonstration of an ISI score reduction of > 7 points clinically. A reduction of 7 or more points is considered optimal to detect treatment responders as it represents a threshold change in insomnia severity category.[4] Remitters were defined as participants achieving an ISI score of < 8, a validated cutoff score for insomnia remission.[4] As defined by the ISI, a score ranging between 0 - 7 indicates 'no clinically Somryst 510(k)
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significant insomnia', a score 8 - 12 indicates 'subthreshold insomnia', a score 15 -21 indicates 'clinical insomnia (moderate severity)' and a score 22-28 indicates "clinical insomnia (severe)'.[4][5]
The proportion of participants in each treatment group deemed treatment responders at week 9, month 6, and month 12 were compared using a chi-square test. Likewise, the proportion of participants in each treatment group deemed treatment remitters at week 9, month 6, and month 12 were compared using a chi-square test.
The proportion of treatment responders identified in each treatment group and their comparison at each timepoint is shown in Table 1. Using criteria of insomnia treatment response (reduction of > 7 points on the ISI from baseline), 62.8% of the UC+SHUTi group were deemed treatment responders from baseline to week 9 compared with 14.0% of the UC+Control group. At the 6 months follow-up, 56.2% of the UC+SHUTi group and 18.9% of the UC+Control group were considered responders. At month 12 follow-up, 59.3% of the UC+SHUTi group and 25.2% of the UC+Control were deemed treatment responders. The difference between treatment groups was significant at all timepoints evaluated (p<0.0001).
Table 1. Comparison of proportion of ISI responders (reduction in ISI score > 7 points from baseline) by timepoint.
| Time of Assessment | UC+SHUTi Proportion | UC+Control Proportion | P value |
|---|---|---|---|
| End of Treatment Period(Week 9) | 157 (62.8%) | 48 (14.0%) | <0.0001 |
| Month 6 Follow-up | 127 (56.2%) | 53 (18.9%) | <0.0001 |
| Month 12 Follow-up | 96 (59.3%) | 58 (25.2%) | <0.0001 |
Note: p values are not adjusted for multiplicity and analyses are based on available patient data.
A similar pattern was observed for insomnia remitters (Table 2). Using an ISI score of <8 as a cutoff point, 61.6% of the UC+SHUTi group at week 9, 63.7% at month 6, and 63.0% at month 12 were considered insomnia remitters compared with 14.9% of the UC+Control group at week 9, 20.4% at month 6, 25.7% at month 12. The difference between treatment groups (using criteria of either <10 or <8) was significant at every assessment timepoint analyzed (p<0.0001).
Table 2. Comparison of proportion of ISI remitters (ISI score of < 8) by timepoint.
| Time of Assessment | UC+SHUTi Proportion | UC+Control Proportion | P value |
|---|---|---|---|
| End of Treatment Period(Week 9) | 154 (61.6%) | 51 (14.9%) | <0.0001 |
| Month 6 Follow-up | 144 (63.7%) | 57 (20.4%) | <0.0001 |
| Month 12 Follow-up | 102 (63.0%) | 59 (25.7%) | <0.0001 |
Note: p values are not adjusted for multiplicity and analyses are based on available patient data.
The percentage of participants that achieved a clinically meaningful insomnia treatment response or remission was higher among participants using UC+SHUTi, demonstrating efficacy of UC+SHUTi, compared to UC+Control.
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Effectiveness Outcomes Summary
A summary of the effect of therapy on change from baseline for chronic insomnia outcomes in the ANU study is provided in Table 3 below.
Table 3. Summary of ANU Study effect of therapy on change from baseline at the treatment period (week 9) and followups (6 & 12 months).
| Assessment | Timepoint | UC+SHUTi | UC+Control | LS MeanDifferences | P value | ||
|---|---|---|---|---|---|---|---|
| Number ofSubjects | LS Mean | Number ofSubjects | LS Mean | (95% CI) | |||
| ISI | End ofTreatmentPeriod (Week 9) | 250 | -8.63 | 342 | -2.85 | -5.78(-6.50, -5.06) | <0.0001 |
| Month 6 Follow-up | 226 | -8.17 | 280 | -3.86 | -4.31(-5.09, -3.53) | <0.0001 | |
| Month 12Follow-up | 162 | -8.21 | 230 | -4.63 | -3.59(-4.46, -2.71) | <0.0001 | |
| SOL | End ofTreatmentPeriod (Week 9) | 124 | -22.7 | 131 | -0.46 | -22.4(-29.7, -15.1) | <0.0001 |
| Month 6 Follow-up | 161 | -22.6 | 201 | -7.88 | -15.1(-21.2, -9.09) | <0.0001 | |
| Month 12Follow-up | 130 | -27.6 | 191 | -10.8 | -17.2(-23.0, -11.3) | <0.0001 | |
| WASO | End ofTreatmentPeriod (Week 9) | 124 | -28.8 | 131 | -11.0 | -18.8(-24.7, -13.0) | <0.0001 |
| Month 6 Follow-up | 161 | -27.6 | 201 | -12.5 | -15.6(-21.1, -10.1) | <0.0001 | |
| Month 12Follow-up | 130 | -25.1 | 191 | -9.36 | -16.5(-23.1, -9.91) | <0.0001 |
Note: p values are not adjusted for multiplicity and analyses are based on available patient data.
Data from the Pivotal Trial – UVA also supports to the proposed indications of use. This additional pivotal trial, NCT01438697, is an investigator-initiated study, funded by the National Institute of Mental Health (NIMH) and titled "An Internet Intervention for Insomnia: Efficacy and Dissemination."[6] The randomized controlled trial of 303 adults with chronic insomnia was led by investigators at the University of Virginia (UVA Study).[6]
Study participants (n=303) were between the ages of 21-65, with sleep-onset insomnia and/or sleep maintenance insomnia (>30 minutes for at least 3 nights/week), insomnia symptoms lasting at least 6 months, an average total sleep time ≤ 6.5 hours per night, and reported significant distress or impairment in social, occupational, or other areas of functioning caused by sleep disturbances (or associated daytime fatigue).
All study participants received Usual Care (UC) consisting of behavioral treatment, pharmacotherapy and/or self-treatment (e.g., visit to a general practitioner for sleep and/or mood (e.g. pharmacotherapy (e.g., for sleep and/or mood problems), over-the-counter sleep aids, visit to a sleep specialist, visit to a mental health provider. The Digital Control program provided access to nontailored and fixed digital material about insomnia symptoms; the effect, prevalence, and causes of insomnia; when to see a physician; and basic lifestyle, environmental, and behavioral strategies to improve sleep.
The evaluation of safety and effectiveness of SHUTi to improve sleep, perceived health status, and overall quality of life was evaluated. Participants were randomized 1:1 to 9 weeks of treatment with
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one of the following:
- UC+SHUTi: Usual Care + SHUTi
- . UC+Control: Usual Care + digital patient education for insomnia
Participants in the UC+ SHUTi group (n=151) were asked to complete all six Cores within the 9-week treatment period. Participants randomized to UC+Control (n=152) were able to read the patient education material immediately upon completion of the baseline assessments and could log in to review the material as often as they desired throughout the treatment period. Insomnia symptoms were evaluated for all participants at baseline, the end of the 9-week treatment period and the 6- and 12month follow-up via the ISI and sleep diaries were administered online and collected for a period of 10 days (within a 2-week window), at each assessment time point. Diaries were used to calculate diary-derived variables, including SOL and WASO.
The primary outcome measures of the study were insomnia symptoms, SOL, and WASO measured via ISI and daily sleep diary data at the end of the 9-week treatment period and the 6- and 12-month follow-up.
Insomnia severity was reduced at both week 9 (p<0.0001) and month 6 (p<0.0001) among participants who received UC+SHUTi as compared to UC+Control. The average reduction in ISI score was greater at week 9 and month 6 Follow-Up for the UC+SHUTi arm (mean -7.83 and -8.52 respectively) than the UC+Control arm (mean -2.94 and -5.36, respectively). The difference between the groups was significant at each timepoint (p<0.0001).
An analysis of the proportion of study participants deemed treatment responders and remitters was performed using the ISI data. Responders were defined by demonstration of an ISI score reduction of > 7 points clinically. A reduction of 7 or more points is considered optimal to detect treatment responders as it represents a threshold change in insommia severity category.[4] Remitters were defined as participants achieving an ISI score of < 8, a validated cutoff score for insomnia remission.[4] As defined by the ISI, a score ranging between 0 - 7 indicates 'no clinically significant insomnia', a score 8 - 12 indicates 'subthreshold insomnia', a score 15 - 21 indicates 'clinical insomnia (moderate severity)' and a score 22 - 28 indicates "clinical insomnia (severe)'.[4], [5]
The proportion of participants in each treatment group deemed treatment responders at week 9, month 6, and month 12 were compared using a chi-square test. Likewise, the proportion of participants in each treatment group deemed treatment remitters at week 9, month 6, and month 12 were compared using a chi-square test.
The proportion of treatment responders identified in each treatment arm and their comparison at each time point is shown in Table 4. Using criteria of insomnia treatment response (reduction of >7 points on the ISI from baseline), 52.6% of the UC+SHUTi arm were deemed treatment responders at week 9 compared with 16.9% of the UC+Control arm. At month 6 follow-up, 59.6% of the UC+SHUTi arm and 35.7% of the UC+Control arm were considered responders. At month 12 follow-up, 69.7% of the UC+SHUTi arm and 43.0% of the UC+Control arm were deemed treatment responders. The difference between treatment groupswas significant at all timepoints evaluated.
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| Time of Assessment | UC+SHUTi Proportion | UC+Control Proportion | P value |
|---|---|---|---|
| End of Treatment Period(Week 9) | 70 (52.6%) | 24 (16.9%) | <0.0001 |
| Month 6 Follow-up | 68 (59.6%) | 46 (35.7%) | 0.0002 |
| Month 12 Follow-up | 85 (69.7%) | 55 (43.0%) | <0.0001 |
Table 4. Comparison of proportion of ISI responders (reduction in ISI score > 7 points from baseline) by timepoint.
Note: p values are not adjusted for multiplicity and analyses are based on available patient data.
A similar pattern was observed for insommia remittance (Table 5). Using an ISI score of <8 as a cutoff point, 40.6% of the UC+SHUTi arm at week 9, 49.1% at month 6, and 56.6% at month 12 were considered insomnia remitters compared with 11.3% of the UC+Control arm at week 9, 24.0% at month 6, and 27.3% at month 12. The difference between treatment groups (using criteria of either <10 or <8) was significant at every assessment timepoint analyzed.
Table 5. Comparison of proportion of ISI remitters (ISI score of < 8) by timepoint.
| Time of Assessment | UC+SHUTi Proportion | UC+Control Proportion | P value |
|---|---|---|---|
| End of Treatment Period(Week 9) | 54 (40.6%) | 16 (11.3%) | <0.0001 |
| Month 6 Follow-up | 56 (49.1%) | 31 (24.0%) | <0.0001 |
| Month 12 Follow-up | 69 (56.6%) | 35 (27.3%) | <0.0001 |
Note: p values are not adjusted for multiplicity and analyses are based on available patient data.
The percentage of participants that achieved a clinically meaningful insomniatreatment response or remission was higher among participants using UC+SHUTi, demonstrating efficacy of UC+SHUTi, compared to UC+Control.
Effectiveness Outcomes Summary
A summary of effect of therapy on change from baseline for chronic insomnia outcomes in the UVA Study is provided in Table 6 below.
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| Assessment | Timepoint | UC+SHUTI | UC+Control | LS MeanDifferences(95% CI) | P value | ||
|---|---|---|---|---|---|---|---|
| Number ofSubjects | LS Mean | Number ofSubjects | LS Mean | ||||
| ISI | End ofTreatmentPeriod (Week9) | 133 | -7.83 | 142 | -2.94 | -4.89(-6.02, -3.75) | <0.0001 |
| Month 6Follow-up | 114 | -8.52 | 129 | -5.36 | -3.16(-4.41, -1.91) | <0.0001 | |
| Month 12Follow-up | 122 | -9.57 | 128 | -6.04 | -3.52(-4.87, -2.18) | <0.0001 | |
| SOL | End ofTreatmentPeriod (Week9) | 128 | -21.5 | 130 | -8.84 | -12.6(-18.3, -6.92) | <0.0001 |
| Month 6Follow-up | 113 | -21.1 | 123 | -13.9 | -7.25(-13.9, -0.62) | 0.0323 | |
| Month 12Follow-up | 121 | -23.7 | 127 | -16.3 | -7.32(-13.7, -0.90) | 0.0255 | |
| WASO | End ofTreatmentPeriod (Week9) | 128 | -24.9 | 130 | -8.46 | -17.2(-24.3, -9.97) | <0.0001 |
| Month 6Follow-up | 113 | -23.9 | 123 | -12.9 | -12.1(-19.2, -5.01) | 0.0006 | |
| Month 12Follow-up | 121 | -28.4 | 127 | -16.8 | -12.7(-18.9, -6.51) | <0.0001 |
Table 6. Summary of UVA Study effect of therapy on change from baseline in chronic insomnia outcomes as assessed at the end of the treatment period (week 9) and follow-ups (6 & 12 months).
Note: p values are not adjusted for multiplicity and analyses are based on available patient data.
No participant-reported Adverse Events (AEs) were reported in either study.
CONCLUSION 8.
Somryst and the predicate reSET have the same Intended Use as computerized behavioral therapy devices for psychiatric disorders. Differences in indications for use are due to differences in clinical needs to the different patient populations but this does not constitute a new intended use. Somryst has similar technological characteristics to reSET, including software architecture, delivery of digitized behavioral therapy through a mobile application, and therapeutic content. Differences in content delivery sequence is due to the unique need for Somryst to collect patient data for sleep diaries, part of CBT-1 (but not for CBT for SUD).
Software testing and pivotal clinical study results validate Somryst towards its proposed Indications for Use. This validation reasonably assures that Somryst is substantially equivalent to the predicate device. Further, Somryst met all of the Special Controls per the requirements of the regulation (21 CFR 882.5801).
Thus, Somryst is substantially equivalent to reSET.
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Pear Therapeutics, Inc. Somryst Traditional 510(k) Premarket Notification Submission
9. REFERENCES
[1] J. A. Gosling et al., "The GoodNight study--online CBT for insomnia for the indicated prevention of depression: study protocol for a randomized controlled trial.," Trials, vol. 15, no. 1, p. 56, Feb. 2014.
[2] H. Christensen et al., "Effectiveness of an online insomnia program (SHUTi) for prevention of depressive episodes (the GoodNight Study): A randomised controlled trial," The Lancet Psychiatry, vol. 3, no. 4, pp. 333-341,2016.
[3] Batterham PJ, Christensen H, Mackinnon AJ, et al. Trajectories of change and long-term outcomes in a randomised controlled trial of internet-based insomnia treatment to prevent depression. BJPsych Open. 2017:3(5):228-235. Published 2017 Sep 25. doi:10.1192/bjpo.bp.117.005231
[4] C. M. Morin, G. Belleville, L. Bélanger, and H. Ivers, "The insomnia severityindex: Psychometric indicators to detect insomnia cases and evaluate treatment response." Sleep, 2011.
[5] C. H. Bastien, A. Vallières, and C. M. Morin, "Validation of the insomnia severity index as an outcome measure for insomnia research," Sleep Med., 2001.
[6] L. M. Ritterband et al., "Effect of a web-based cognitive behavior therapy for insomnia intervention with 1-year follow-up: A randomized clinical trial," JAMA Psychiatry, 2017.
§ 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.