(30 days)
Healgen Secobarbital Test is an immunochromatographic assay for the qualitative determination of Secobarbital in human urine at a Cut-Off concentration of 300 ng/mL. The test is available in a Strip format, a Cassette format, a Dip Card format and a Cup format.
The test may yield preliminary positive results even when the prescription drug Secobarbital is ingescribed doses; it is not intended to distinguish between prescription use or abuse of this drug. There is no uniformly recognized cutoff concentration level for Secobarbital in urine. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.
For in vitro diagnostic use only. It is intended for prescription and for over-the-counter use.
Healgen Buprenorphine Test is an immunochromatographic assay for the qualitative determination of Buprenorplaine in human urine at a Cut-Off concentration of 10 ng/mL. The test is available in a Strip format, a Cassette format, a Dip Card format and a Cup format.
The test may yield preliminary positive results even when the prescription drug Burrenorphine is ingested, at prescribed doses; it is not intended to distinguish between prescription use or abuse of this drug. There is no uniformly recognized cutoff concentration level for Buprenorphine in urine. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.
For in vitro diagnostic use only. It is intended for prescription and for over-the-counter use.
Healgen Methadone Test is an immunochromatographic assay for the qualitative determination of Methadone in human urine at a Cut-Off concentration of 300 ng/mL. The test is available in a Strip format, a Cassette format, a Dip Card format and a Cup format.
The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. For in vitro diagnostic use only. It is intended for prescription and for over-the-counter use.
Healgen Secobarbital Test. Healgen Buprenorphine Test and Healgen Methadone Test are immunochromatographic assays for Secobarbital, Buprenorphine and Methadone. Each assay test is a lateral flow system for the qualitative detection of Secobarbital, Buprenorphine and Methadone (target analyte) in human urine. The products are in vitro diagnostic devices, which come in the form of: Strips, Cassettes, DipCards, or Cups. Each product contains a Test Device (in one of the four formats), and a package insert. Each test device is sealed with a desiccant in an aluminum pouch.
Here's an analysis of the acceptance criteria and study findings for the Healgen Secobarbital, Buprenorphine, and Methadone Tests, structured as requested:
Acceptance Criteria and Device Performance
The provided document describes the analytical and comparison studies performed to demonstrate the substantial equivalence of the Healgen drug tests. The acceptance criteria are implied by the expected performance in these studies, particularly the accuracy relative to GC/MS at and around the cutoff concentrations.
Table of Acceptance Criteria (Implied) and Reported Device Performance
| Test Type | Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (Summary) |
|---|---|---|---|
| Precision | Accuracy at various concentrations around the cutoff | Consistent and correct results (negative below cutoff, positive above) at +/- 50%, +/- 75%, +/- 100% of the cutoff. Mixed results expected only very close to the cutoff (+/- 25%). | For all three drugs and all four formats, tests performed by three different operators over 25 days showed: |
- 100% accuracy (50-/0+ or 50+/0-) at -100%, -75%, -50%, +50%, +75%, +100% of cutoff.
- Mixed results (e.g., 22-/28+, 25-/25+, 20-/30+) within the +/- 25% range of the cutoff, which is expected for qualitative tests at the decision point. |
| Cut-off Verification | Ability to distinguish between drug concentrations at and around the cut-off | All samples at or above +25% cut-off should be positive; all samples at or below -25% cut-off should be negative. | For all three drugs, across three different device lots, and three different operators: - All results were positive at and above +25% cut-off.
- All results were negative at and below -25% cut-off. |
| Interference | Absence of interference from common urine substances | No interference at 100µg/mL for listed substances. | No differences observed across different formats for a comprehensive list of compounds at 100µg/mL for all three drugs. |
| Specificity | Cross-reactivity with related compounds and non-reactivity with unrelated compounds. | Acceptable levels of cross-reactivity for structurally similar compounds and no detection for unrelated compounds (where applicable). | - Secobarbital: 100% cross-reactivity with Amobarbital; varying degrees with Alphenol (40%), Aprobarbital (120%), Butabarbital (12%), Butathal (12%), Butalbital (12%), Cyclopentobarbital (60%), Pentobarbital (12%), Phenobarbital (1%). - Buprenorphine: 100% with Buprenorphine -3-D-Glucuronide; 50% with Norbuprenorphine and Norbuprenorphine-3-D-Glucuronide. No detection of Morphine, Oxymorphone, Hydromorphone at 100,000 ng/mL.
- Methadone: 6% cross-reactivity with Doxylamine. No detection of EDDP, EMDP, LAAM HCI, Alpha Methadol at 100,000 ng/mL. |
| Effect of Urine Specific Gravity and pH | Consistent results across physiological ranges of specific gravity and pH. | All samples at or above +25% cut-off should be positive; all samples at or below -25% cut-off should be negative. | For all three drugs, across various specific gravity (1.000-1.035) and pH (4-9) levels: - All results were positive for samples at and above +25% cut-off.
- All results were negative for samples at and below -25% cut-off. |
| Method Comparison (Clinical Samples) | Agreement with GC/MS results for negative, low negative, near cutoff negative/positive, and high positive samples. | High agreement expected, especially for definitive negative and high positive samples. Discordant results are noted and acceptable near the cutoff. | Across all three drugs and all four formats, for each of three viewers: - 100% agreement for negative, low negative, and high positive samples.
- Discordant results (some positives read as negative, or vice versa) observed mainly in the "Near Cutoff Negative" and "Near Cutoff Positive" categories, which is expected for qualitative tests near their decision point. Specific discordant sample numbers and GC/MS values (e.g., 302 ng/mL, 303 ng/mL for Secobarbital, 10.2 ng/mL for Buprenorphine with a 10 ng/mL cutoff) are provided, showing the device performs qualitatively as expected around the cutoff. |
| Lay-User Study | High percentage of correct results by untrained users, ease of understanding instructions. | High accuracy across various concentrations, especially for definitive positive/negative samples. Instructions should be easily understood. | For all three drugs and all four formats, performed by over 1680 lay persons (560 per drug): - 90-100% correct results for samples at -25% Cutoff, +25% Cutoff.
- 100% correct results for samples at -100%, -75%, -50% Cutoff, and +50%, +75% Cutoff.
- Package insert instructions were easily followed, and Flesch-Kincaid read-out at Grade Level 7. |
Study Details
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Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective)
- Precision Studies:
- For each of the three drugs (Secobarbital, Buprenorphine, Methadone) and each of the four device formats (Strip, Cassette, Dip Card, Cup): 9 drug concentrations (including the cutoff, +/-25%, +/-50%, +/-75%, +/-100%) were tested with 50 replicates per concentration per lot.
- This means (9 concentrations * 50 replicates * 3 lots) = 1350 tests per format.
- Total precision tests per drug: 1350 tests/format * 4 formats = 5400 tests.
- Total precision tests for all three drugs: 5400 tests * 3 drugs = 16,200 individual tests.
- Data Provenance: Not explicitly stated, but the study was "carried out for samples... prepared by spiking drug in negative samples." This suggests a controlled laboratory setting, likely prospective. The country of origin is not mentioned.
- Cut-off Verification Studies:
- For each drug: 150 samples (equally distributed across -50%, -25%, cut-off, +25%, +50% cut-off) per drug. These were tested using three different lots of each device by three different operators.
- Total samples per drug: 150.
- Total cut-off verification tests for all three drugs: 150 * 3 drugs = 450 samples.
- Data Provenance: Controlled laboratory setting, prepared by spiking drugs into negative samples; likely prospective. Country of origin not mentioned.
- Interference Studies:
- Test Set Description: Drug-free urine and target drug urine (at 25% above cut-off) spiked with various potential interfering substances at 100 µg/mL.
- Sample Size: Not explicitly stated as a number of individual samples, but tested "three batches of each device for all formats" against a comprehensive list of compounds.
- Data Provenance: Controlled laboratory setting; likely prospective. Country of origin not mentioned.
- Specificity Studies (Cross-Reactivity):
- Test Set Description: Related drug metabolites and other components.
- Sample Size: Not explicitly stated as a number of individual samples, but tested "three batches of each device for all formats."
- Data Provenance: Controlled laboratory setting; likely prospective. Country of origin not mentioned.
- Effect of Urine Specific Gravity and pH Studies:
- Test Set Description: Urine samples with specific gravity of 1.000 to 1.035, or pH 4 to 9, spiked with target drugs at 25% below and 25% above cut-off levels.
- Sample Size: Not explicitly stated but tested "three batches of each device for all formats."
- Data Provenance: Controlled laboratory setting; likely prospective. Country of origin not mentioned.
- Method Comparison (Clinical Samples):
- For each of the three drugs and each of the four device formats: 80 unaltered clinical samples (40 negative and 40 positive).
- Total clinical samples: 80 samples/format * 4 formats * 3 drugs = 960 samples.
- Each sample was run by three different laboratory assistants.
- Data Provenance: "unaltered clinical samples," blind labeled. The origin (country, retrospective/prospective) is not specified.
- Lay-User Study:
- Sample Size: 560 lay persons for each drug test (Secobarbital, Buprenorphine, Methadone). Total individuals performing the study: 1680.
- For each drug, urine samples were prepared at 7 different concentrations per drug: negative, +/-25%, +/-50%, +/-75%, +/-100% of the cutoff. Each concentration had 20 samples. (7 concentrations * 20 samples = 140 samples per drug tested by lay users).
- Data Provenance: Conducted at "three intended user sites." The demographic breakdown (age, gender, educational/professional backgrounds) is provided for the participants. Likely a prospective study. Country of origin not mentioned.
- Precision Studies:
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience)
- The ground truth for all analytical and comparison studies was established by GC/MS (Gas Chromatography/Mass Spectrometry). This is a highly accurate and widely accepted "gold standard" analytical method for drug detection and quantification in urine.
- The document implies that the GC/MS results themselves serve as the ground truth, rather than human experts interpreting the GC/MS. The qualifications of the individuals operating the GC/MS are not specified, but they would typically be trained laboratory technicians or chemists.
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Adjudication method (e.g., 2+1, 3+1, none) for the test set
- For the Method Comparison (Clinical Samples), the samples were "blind labeled and compared to GC/MS results." The results from the three "Viewer" (laboratory assistants) were individually recorded and compared to the GC/MS. There is no explicit "adjudication method" described where multiple human readers' opinions are combined to form a consensus before comparison to ground truth. Instead, individual human readings (referred to as "Viewer A, B, C") were directly compared to the GC/MS ground truth.
- For the Lay-User Study, each participant interpreted their own test and results were compared to GC/MS. No adjudication method among lay users is mentioned.
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If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
- This document describes the performance of immunochromatographic assay devices for drug detection, which are qualitative diagnostic tests, not AI-powered image analysis tools.
- Therefore, an MRMC comparative effectiveness study comparing human readers with and without AI assistance was NOT performed or applicable for this device type. The "Viewers" mentioned in the method comparison are human operators reading a physical test strip/cassette/cup/dip card.
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If a standalone (i.e. algorithm only without human-in-the loop performance) was done
- This device is an immunochromatographic assay. It is a physical test that produces a visual result (colored lines) which is then interpreted by a human. There is no "algorithm only" performance component. The device's performance is intrinsically linked to human interpretation of its visual output.
- The closest to "standalone" performance are the analytical studies (precision, cut-off, interference, specificity) where the chemical reaction and visual readout are evaluated, but even then, a human reads the result.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc)
- The primary ground truth used for all performance evaluations (precision, cut-off, interference, specificity, method comparison, lay-user study) was GC/MS (Gas Chromatography/Mass Spectrometry). This is a highly accurate analytical measurement of drug concentration.
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The sample size for the training set
- This document describes the performance evaluation of a rapid diagnostic test (immunochromatographic assay). These types of tests are typically developed through chemical and biological engineering, not through machine learning models that require "training sets" in the computational sense.
- Therefore, there is no "training set" sample size listed in this context.
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How the ground truth for the training set was established
- As there is no "training set" for a machine learning model, this question is not applicable to the described device.
§ 862.3150 Barbiturate test system.
(a)
Identification. A barbiturate test system is a device intended to measure barbiturates, a class of hypnotic and sedative drugs, in serum, urine, and gastric contents. Measurements obtained by this device are used in the diagnosis and treatment of barbiturate use or overdose and in monitoring levels of barbiturate to ensure appropriate therapy.(b)
Classification. Class II (special controls). A barbiturate test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (e.g., programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).