(269 days)
The Vibrant System is an orally administered Capsule that is indicated for the treatment of adults with chronic idiopathic constipation who have not experienced relief of their bowel symptoms by using laxative therapies at the recommended dosage for at least one month.
The Vibrant System is comprised of two components; a Pod and a single use Capsule. The Pod activates the Capsule using radio frequency (RF) communication. After activation, the Capsules are taken orally. After a pre-programmed activation delay, the Capsules begin to vibrate. The marketed device will have an activation delay of 14 hours. (The 14 hours activation delay corresponds to Active Mode 1 of the pivotal study described below: the pivotal study also included an Active Mode 2 with a 9 hour activation delay.) As they pass through the gastrointestinal tract, the Capsules vibrate for four pre-programmed periods of 100 min, 120 min, 100 min. 180 min. It takes about three days for the Capsules to pass through the gastrointestinal tract, at which point thev are excreted in a bowel movement.
The Capsule is comprised of a motor that vibrates (2.5 Vdc. 70 ma), electronic card, batteries (2x 1.5V 60 mAh, alkaline/0% Hg coin battery) and connector. The capsule is a two-piece shell made from Polycarbonate Makrolon 2458. The Capsule dimensions are as follows: length: 24.5 ± 0.1 mm; diameter: 11.20 ± 0.05 mm; weight 4.0 ± 0.1 g. The Capsules have a vibration force between 200 and 550 gf, with vibration cycles of 3 seconds on and16 seconds off (190 cycles per hour).
Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The provided text details acceptance criteria for bench testing and clinical effectiveness.
Bench Testing Acceptance Criteria & Results (from Table 1)
| Test | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Mechanical Integrity | No cracks, ruptures, loose particles, or debris are observable following (b)(4) application of (b)(4) | Pass |
| Seal test | No major leak, and the pressure of the test capsule must be less than (b)(4) the control capsule pressure. | Pass |
| pH Resistance | Capsules must not show defects in the seal, no ruptures, no shell cracks, or any other damage to the capsule. The Capsules must also pass the sealing | Pass |
| Mode of Operation | Capsules must meet the predefined specifications for start time, duration, vibrational force, vibrational sequence. | Pass |
| Dimensional | Capsule length must be (b)(4) Capsule diameter must be (b)(4) | Pass |
| Visual Inspection | External surface of Capsule is free of surface defects and extraneous matter. | Pass |
Clinical Effectiveness Acceptance Criteria & Results (from "Effectiveness results" section for mITT analysis set)
| Endpoint | Acceptance Criteria (Study Success Definition) | Reported Device Performance |
|---|---|---|
| Primary Effectiveness Endpoint: | Either CSBM1 or CSBM2 success rate being statistically significantly higher in the active arm (Active Mode 1) than in the control arm, as evaluated in the mITT population. | Met. Both CSBM1 and CSBM2 success rates were statistically significantly higher in the active arm compared to the control. |
| CSBM1 Success Rate | Increase from the run-in period of at least one weekly CSBM during at least 6 of the 8 weeks of treatment, with a statistically significantly higher rate in the active arm vs. control. | 40.51% in Treatment (Active Mode 1) vs. 22.92% in Control. Difference of 17.6% (chi-square p-value = 0.0011). Statistically significant. |
| CSBM2 Success Rate | Increase from the run-in period of at least two weekly CSBM during at least 6 of the 8 weeks of treatment, with a statistically significantly higher rate in the active arm vs. control. | 23.42% in Treatment (Active Mode 1) vs. 11.81% in Control. Difference of 10.0% (chi-square p-value = 0.0085). Statistically significant. |
| Primary Safety Endpoint: All Adverse Events (AEs) | Not explicitly stated as a numerical acceptance criterion, but the study was designed to evaluate all AEs related and unrelated to the treatment. The implication is that the safety profile should be acceptable for the intended use, and risks should be mitigable. | Acceptable. 114 AEs reported (74 in treatment, 40 in control). No SAEs in treatment arms. 49 AEs considered related (41 in treatment, 8 in control). Most common device-related AE was "sensation of vibration" (9.5%). |
| Secondary Endpoints: Straining | Observed reduction in straining in the active arm compared to the control arm. | Observed reduction. Adj. Mean change from baseline: Treatment -1.78, Control -1.32. Diff (Treatment-Control): -0.46 ([-0.95; 0.03]). |
| Stool Consistency (Bristol Stool Scale) | Observed improvement in stool consistency in the active arm compared to the control arm. | Observed improvement. Adj. Mean change from baseline: Treatment 1.03, Control 0.58. Diff (Treatment-Control): 0.45 ([0.19; 0.71]). |
| Bloating Sensation | No difference was observed in the bloating sensation endpoint. (This appears to be an observed finding rather than a strict acceptance criterion for improvement). | No difference observed. Adj. Mean change from baseline: Treatment -0.42, Control -0.37. Diff (Treatment-Control): -0.06 ([-0.42; 0.30]). |
Study Proving Device Meets Acceptance Criteria
The primary study proving the device meets the acceptance criteria is the V270 pivotal study.
The V270 study was described as:
- Design: Prospective, randomized, multi-center, double-blinded, placebo-controlled pivotal study.
- Arms: Initially two active treatment arms (Active Mode 1 and Active Mode 2) and a control arm. Active Mode 2 was dropped after interim analysis, continuing with Active Mode 1 and control.
- Treatment Duration: 8 weeks.
- Population: Adults with chronic idiopathic constipation (CIC) refractory to existing OTC or Rx treatments or intolerant of side effects.
Additional Information:
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set (Clinical Study - V270):
- Consented and Screened: 904 subjects
- Randomized (ITT analysis set): 349 subjects (Active Mode 1: 163, Active Mode 2: 37, Control: 149)
- Modified Intent-to-Treat (mITT) analysis set: 336 subjects (Active Mode 1: 158, Active Mode 2: 34, Control: 144) - This was the primary effectiveness analysis population.
- Per Protocol (PP) analysis set: 333 subjects (Active Mode 1: 155, Active Mode 2: 34, Control: 144)
- Primary Safety Analysis Set (ITT): 349 subjects (Active Mode 1 & 2 combined: 200, Control: 149)
- Data Provenance: The document does not explicitly state the country of origin for the clinical study data but mentions the sponsor information is Vibrant Ltd. Hakochav P.O. Box 516 Yokneam, Israel. Given it's a pivotal FDA study, it often involves sites in the US and potentially other regions, but this is not specified. The study was prospective.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications
- For this type of device (orally ingested capsule for constipation), the "ground truth" for effectiveness endpoints (CSBMs, straining, stool consistency, bloating) is patient-reported outcomes (PROs) based on diary entries. These outcomes are not typically established by "experts" in the sense of image readers or diagnosticians.
- For safety, adverse events were reported by subjects and assessed by study investigators, who are implicitly qualified medical professionals overseeing the clinical trial. The document doesn't specify the number or specific qualifications (e.g., years of experience) of these investigators beyond them being the "study investigators."
4. Adjudication Method for the Test Set
- The text does not mention an "adjudication method" in the context of expert review for establishing ground truth, as the primary effectiveness endpoints are patient-reported.
- For adverse events, "study investigators" classified AEs as "possibly, probably, or definitely related to the study treatment or procedure" (Table 8), implying an internal review process, but no specific multi-reviewer adjudication method (like 2+1 or 3+1) is described.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance
- No, an MRMC comparative effectiveness study was not done. This device is a therapeutic capsule, not an AI-assisted diagnostic tool that would involve human readers interpreting cases. Therefore, the concept of improving human readers with AI assistance does not apply.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
- This device is a physical, orally ingested capsule with pre-programmed vibration patterns. It does not involve an "algorithm" in the sense of AI performing a diagnostic task. The "algorithm" here refers to the embedded software controlling the capsule's operation (vibration start time, duration, sequence, rest time). The performance of this software in controlling the physical device was assessed via bench testing ("Mode of Operation" test).
7. The Type of Ground Truth Used
- The primary ground truth for effectiveness was patient-reported outcomes (PROs) from daily diaries (e.g., number of CSBMs, straining levels, Bristol Stool Scale scores, bloating).
- The ground truth for safety was adverse events reported by subjects and assessed by investigators.
8. The Sample Size for the Training Set
- This is not an AI/machine learning device that typically has a separate "training set" for model development. The "training" for this device would be its design, engineering, and iterative testing, not data-driven model training.
- The various non-clinical (bench) and animal studies served as early development and validation steps prior to the pivotal human clinical trials. Five smaller clinical trials involving a total of 499 subjects were conducted prior to V270, but these did not fully support effectiveness and are mentioned as providing cumulative safety data, not as a "training set" for an algorithm.
9. How the Ground Truth for the Training Set Was Established
- As this is not an AI/machine learning device with a typical "training set," this question is not directly applicable. The "ground truth" for the development and bench testing of the capsule's physical and functional properties would be established through engineering specifications, physical measurements, and adherence to biological/physiological parameters (e.g., pH conditions, vibration specifications).
- For the earlier clinical trials (499 subjects), the ground truth for safety and preliminary effectiveness would have been established similarly to the pivotal study – patient-reported outcomes and investigator assessment of adverse events.
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