(225 days)
The IB-Stim is a percutaneous electrical nerve field stimulator (PENFS) system intended to be used in patients 11-18 years of age with functional abdominal pain associated with irritable bowel syndrome (IBS). The IB-Stim is intended to be used for 120 hours per week up to 3 consecutive weeks, through application to branches of Cranial Nerves V, VII, IX and X, and the occipital nerves identified by transillumination, as an aid in the reduction of pain when combined with other therapies for IBS.
The IB-Stim is a device that delivers electrical stimulation through percutaneous electrodes to areas usually innervated by branches of occipital nerves and cranial nerves V, VII, IX and X that are located by transillumination. The device consists of (1) a percutaneous electrical nerve field stimulator (PENFS), (2) a multi-pin wire harness percutaneous electrode array, and (3) a pen light for use in the transillumination technique that aids in positioning of the percutaneous electrodes (Figure 1).
The wire harness percutaneous electrode array consists of 4 leads. The 1-1-1-4 configuration consists of three single-needle leads, and one 4-needle array (Figure 2).
The stimulator is placed behind the ear and the percutaneous electrodes are positioned utilizing the transillumination function of the device (Figure 1). The transillumination technique assists in the visualization of the vasculature of the ear to aid in the placement of the percutaneous electrodes near the nerve branches in the ear.
The provided text describes the regulatory evaluation of the IB-Stim device, a non-implanted nerve stimulator for functional abdominal pain relief associated with Irritable Bowel Syndrome (IBS) in adolescents. The document outlines the studies conducted to establish the device's safety and effectiveness.
It is important to note that the IB-Stim is a medical device performing nerve stimulation, not an AI/ML powered device. Therefore, typical acceptance criteria and study designs for AI/ML devices (e.g., mMRMC studies, stand-alone algorithm performance, ground truth establishment through expert consensus or pathology for image classification, separate training and test sets the way an AI/ML device would need them, etc.) are NOT directly applicable to this device.
The "acceptance criteria" for the IB-Stim are essentially the demonstration of safety and clinical effectiveness as outlined by the FDA's De Novo classification process, largely evidenced through a randomized, double-blind, sham-controlled clinical trial and various non-clinical tests.
Here's an attempt to structure the information according to your request, adapting the concepts to fit a medical device rather than an AI/ML system:
Acceptance Criteria and Device Performance for IB-Stim
The acceptance criteria for the IB-Stim device are based on demonstrating its safety and effectiveness for its intended use, as required by FDA for a De Novo classification. This is primarily achieved through non-clinical testing and a pivotal clinical trial.
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria Category | Specific Criteria/Tests | Reported Device Performance/Results |
|---|---|---|
| Safety - Non-Clinical | Biocompatibility (for patient-contacting materials) | All results demonstrated acceptable performance for cytotoxicity, sensitization, and irritation, leveraging prior evaluations for identical materials in similar devices (DEN170018, K140530). |
| Sterility (for percutaneous electrode array) | Achieved a sterility assurance level of 10^-6 kGy using VDMAX25 method (ISO 11137-2:2007). | |
| Shelf Life (sterility, package integrity, functionality) | Validated for a labeled shelf life of (b)(4) using accelerated-aged samples (ISO 11607-1:2009, ASTM F1980-07:2011). | |
| Electromagnetic Compatibility (EMC) | Conformed to IEC 60601-1-2. | |
| Electrical Safety | Conformed to IEC 60601-1 and IEC 60601-2-10. | |
| Software Verification and Validation | Documentation provided in K140530; software classified as "Minor" level of concern. | |
| Electrical Bench Performance (verification of pulse train, duty cycle, max operating time) | Validated that electrical performance met device specifications (leveraged from K140530). | |
| Safety - Clinical | Absence of Serious Adverse Events (SAEs) | No SAEs recorded in any subject during the clinical study. |
| Incidence of Non-Serious Adverse Events (AEs) | Ten patients reported AEs: Ear discomfort (n=6), Adhesive allergy (n=3), Syncope (n=1). These were considered typical for the device type. | |
| Effectiveness (Clinical Trial) | Primary Outcome: Change from baseline to end of Week 3 in worst abdominal pain (IBS subgroup) | IB-Stim group had a significantly lower worst pain score (median 5.0, IQR 4.0-7.0) compared to sham group (median 7.0, IQR 5.0-9.0). 59% of IB-Stim vs. 26% of sham patients showed >30% reduction. |
| Primary Outcome: Change from baseline to end of Week 3 in composite Pain Frequency-Severity-Duration (PFSD) score (IBS subgroup) | IB-Stim group had a significantly lower PFSD score (median 7.5, IQR 3.6-14.4) compared to sham group (median 14.4, IQR 4.5-39.2). | |
| Secondary Outcome: Global symptom improvement based on Symptom Response Scale (SRS), Week 3 (IBS subgroup) | Median SRS score of 3 (IQR: 2-4) in IB-Stim group vs. 0 (IQR: 0-2) in sham group. 81% of IB-Stim vs. 26% of sham patients reported overall symptom improvement (SRS ≥ 2). | |
| Secondary Outcome: ≥30% improvement in usual abdominal pain, Week 3 (IBS subgroup) | 52% of IB-Stim vs. 30% of sham patients had >30% reduction in usual abdominal pain. | |
| Risk Mitigation | Implementation of Special Controls (e.g., biocompatibility standards, electrical safety, labeling warnings) | Special controls were deemed sufficient to mitigate identified risks, as evidenced by the granting of the De Novo request. |
2. Sample Size and Data Provenance
- Clinical Trial Test Set Sample Size:
- Total randomized: 115 subjects (60 active treatment, 55 sham treatment).
- Completed the trial (primary analysis cohort): 104 subjects (57 active, 47 sham).
- IBS Subgroup Analysis (post-hoc, for final indication): 51 subjects met Rome III criteria for IBS at baseline. 50 of these completed the study (27 active IB-Stim, 23 sham). This IBS subgroup formed the basis for the specific indication granted.
- Data Provenance: The study was a randomized, double-blind, sham-controlled clinical trial. It is stated to be published in Lancet Gastroenterol Hepatol in 2017, suggesting it was a prospective clinical trial. The location of the clinical trial (country of origin) is not explicitly stated in the provided text, but the authors listed (K. Kovacic, etc.) typically indicate US-based research centers.
3. Number of Experts and Qualifications for Ground Truth
- The "ground truth" in this context refers to the patient-reported outcomes of pain and symptom scores (e.g., worst pain, PFSD, SRS). These are direct measures from the participants themselves, not interpretations by experts.
- The diagnosis of functional abdominal pain, including IBS, was based on established clinical criteria (Rome III criteria for IBS) by the clinicians conducting the study. The number or specific qualifications of these clinicians are not detailed as "experts establishing ground truth" in the way it would be for, e.g., image annotation.
4. Adjudication Method for the Test Set
- Adjudication methods (e.g., 2+1, 3+1) are typically used for establishing ground truth in AI/ML model training or evaluation where human reviewers provide labels or assessments that need to be reconciled.
- This was a clinical trial with patient-reported outcomes. While there would be standard operating procedures for data collection and monitoring, there was no "adjudication" in the sense of reconciling disagreeing expert labels. The "ground truth" was the direct patient report and clinical diagnosis.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- An MRMC study evaluates the performance of multiple human readers on multiple cases, often comparing performance with and without AI assistance.
- No MRMC study was performed as this is a medical device for direct patient treatment, not an AI-based diagnostic tool that assists human readers in interpreting data or images. The study design was a standard randomized controlled trial comparing the device to a sham control.
6. Standalone (Algorithm Only) Performance
- "Standalone performance" refers to the performance of an algorithm without human-in-the-loop.
- Not applicable to this device. The IB-Stim is a physical medical device that delivers electrical stimulation to a patient. Its functionality is inherently tied to its application to a patient's body under clinical guidance. There is no "algorithm only" component that could be evaluated for standalone performance.
7. Type of Ground Truth Used
- The primary ground truth for effectiveness was patient-reported outcome data (pain scores, symptom improvement) collected during the clinical trial.
- The patient cohort was defined by clinical diagnostic criteria (Rome III for IBS) established by medical professionals.
8. Sample Size for the Training Set
- Not applicable in the context of AI/ML. The IB-Stim design and functionality are based on medical principles and prior devices, not on machine learning from a "training set." The clinical trial data (the "test set" in your original framework) was used to demonstrate safety and effectiveness for regulatory approval.
9. How Ground Truth for Training Set was Established
- Not applicable as there is no "training set" for an AI/ML model. The device's design and parameters (e.g., electrical characteristics, duty cycle) were based on existing medical understanding of nerve stimulation and were verified through bench testing. The clinical trial then assessed the device's efficacy in a target patient population.
§ 876.5340 Nonimplanted nerve stimulator for functional abdominal pain relief.
(a)
Identification. A nonimplanted nerve stimulator for functional abdominal pain relief is a device that stimulates nerves remotely from the source of pain with the intent to relieve functional abdominal pain. This generic type of device does not include devices designed to relieve pelvic pain.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The patient-contacting components of the device must be demonstrated to be biocompatible.
(2) Electromagnetic compatibility and electrical, mechanical, and thermal safety testing must be performed.
(3) Electrical performance testing of the device and electrodes must be conducted to validate the specified electrical output and duration of stimulation of the device.
(4) Software verification, validation, and hazard analysis must be performed.
(5) Sterility testing of the percutaneous components of the device must be performed.
(6) Shelf life testing must be performed to demonstrate continued sterility, package integrity, and device functionality over the labeled shelf life.
(7) Labeling must include the following:
(i) A detailed summary of the device technical parameters;
(ii) A warning stating that the device is only for use on clean, intact skin;
(iii) Instructions for use, including placement of the device on the patient; and
(iv) A shelf life.