(872 days)
The QIAstat-Dx Gastrointestinal Panel 2 is a multiplexed nucleic acid test intended for use with the QIAstat-Dx Analyzer 1.0. for the simultaneous in vitro qualitative detection of nucleic acids from multiple viruses, bacteria. and parasites directly from preserved stool samples (Para-Pak C&S or FecalSwab) obtained from individuals with signs and/or symptoms of gastrointestinal infection. The following viruses, bacteria (including several diarrheagenic E. col/ Shigella pathotypes), and parasites are identified with the QIAstat-Dx Gastrointestinal Panel 2 :
• Adenovirus F40/F41
• Astrovirus
• Norovirus GI/GII
• Rotavirus A
• Campylobacter (C. jejuni, C. coli and C. upsaliensis)
• Shigella/Enteroinvasive Escherichia coli (EIEC)
• Enteropathogenic Escherichia coli (EPEC)
• Enterotoxigenic Escherichia coli (ETEC) lt/st
• Shiga-like toxin-producing Escherichia coli (STEC) stx1/stx2
(including specific identification of E. coli O157 serogroup within STEC)
• Salmonella
• Plesiomonas shigelloides
• Yersinia enterocolitica
• Cryptosporidium
• Cyclospora cayetanensis
• Entamoeba histolytica
• Giardia lamblia*
*(Also known as Giardia intestinalis and Giardia duodenalis)
Concomitant culture is necessary for organism recovery and further typing of bacterial agents.
The QIAstat-Dx Gastrointestinal Panel 2 is indicated as an aid in the diagnosis of specific agents of gastrointestinal illness, in conjunction with other clinical, laboratory, and epidemiological data. Positive results do not rule-out coinfection with organisms not detected by the QIAstat-Dx Gastrointestinal Panel 2. The organisms detected may not be the sole or definitive cause of the disease.
Negative QIAstat-Dx Gastrointestinal Panel 2 results in the setting of clinical illness compatible with gastroenteritis may be due to infection by pathogens that are not detected by this assay test or non-infectious causes such as ulcerative colitis, irritable bowel syndrome, or Crohn's disease.
QIAstat-Dx is based on single-test cartridges with pre-packaged reagents including both wet and dry chemistry to handle the sample preparation and detection steps for the presence of a range of selected analytes by PCR technology. After insertion of the sample, the OIAstat-Dx assay cartridge is processed by the OIAstat-Dx Analyzer 1.0.
Here's a summary of the acceptance criteria and study details for the QIAstat-Dx Gastrointestinal Panel 2, extracted from the provided text:
Acceptance Criteria and Device Performance for QIAstat-Dx Gastrointestinal Panel 2
The acceptance criteria for the QIAstat-Dx Gastrointestinal Panel 2 can be inferred from the performance metrics (Positive Percentage Agreement - PPA and Negative Percentage Agreement - NPA) reported for both prospective and retrospective clinical studies. While explicit 'acceptance criteria' values are not provided as a separate table, the reported performance demonstrates the device's ability to meet the necessary accuracy for clinical utility. The FDA's substantial equivalence determination implies these performance characteristics were found acceptable.
Implied Acceptance Criteria (based on reported performance):
- High PPA: The device should accurately detect the target pathogens when they are present. Most reported PPA values are above 90%, with many at 100%. Even lower values like 75% for Giardia lamblia in FecalSwab are within a statistically acceptable range given the confidence intervals.
- High NPA: The device should accurately report the absence of target pathogens when they are not present, minimizing false positives. Most reported NPA values are very high, often 99% or 100%.
Table of Acceptance Criteria (Implied) and Reported Device Performance
Given that specific numerical acceptance criteria (e.g., "PPA > X%") are not explicitly stated in the document, the table below showcases the reported clinical performance which serves as evidence of meeting the implicit acceptance criteria for reliable detection and non-detection of pathogens.
| Analyte (Sample Type) | Implied Acceptance Criterion (High PPA/NPA) | Reported Performance (PPA) | 95% Confidence Interval (PPA) | Reported Performance (NPA) | 95% Confidence Interval (NPA) |
|---|---|---|---|---|---|
| Viruses | |||||
| Adenovirus F40/F41 (FecalSwab) | High PPA, High NPA | 83.3% (5/6) | 43.7-97.0% | 100.0% (1214/1214) | 99.7-100.0% |
| Adenovirus F40/F41 (Para-Pak C&S) | High PPA, High NPA | 50.0% (1/2) | 9.5-90.6% | 99.9% (703/704) | 99.2-100.0% |
| Astrovirus (FecalSwab) | High PPA, High NPA | 100.0% (3/3) | 43.9-100.0% | 100.0% (1219/1219) | 99.7-100.0% |
| Astrovirus (Para-Pak C&S) | High PPA, High NPA | 100.0% (6/6) | 61.0-100.0% | 100.0% (700/700) | 99.5-100.0% |
| Norovirus GI/GII (FecalSwab) | High PPA, High NPA | 93.9% (31/33) | 80.4-98.3% | 99.6% (493/495) | 98.6-100.0% |
| Norovirus GI/GII (Para-Pak C&S) | High PPA, High NPA | 77.8% (14/18) | 54.8-91.0% | 100.0% (399/399) | 99.1-100.0% |
| Rotavirus A (FecalSwab) | High PPA, High NPA | 91.3% (21/23) | 73.2-97.6% | 99.8% (1197/1199) | 99.4-100.0% |
| Rotavirus A (Para-Pak C&S) | High PPA, High NPA | 100.0% (3/3) | 43.9-100.0% | 99.9% (702/703) | 99.2-100.0% |
| Bacteria | |||||
| Campylobacter (FecalSwab) | High PPA, High NPA | 97.0% (65/67) | 89.8-99.2% | 99.7% (1151/1155) | 99.1-99.9% |
| Campylobacter (Para-Pak C&S) | High PPA, High NPA | 96.8% (30/31) | 83.8-99.4% | 99.7% (675/677) | 98.9-99.9% |
| Plesiomonas shigelloides (FecalSwab) | High PPA, High NPA | N/A (0/0) | N/A | 99.8% (1220/1222) | 99.4-100.0% |
| Plesiomonas shigelloides (Para-Pak C&S) | High PPA, High NPA | 83.3% (5/6) | 43.7-97.0% | 99.7% (698/700) | 99.0-99.9% |
| Salmonella (FecalSwab) | High PPA, High NPA | 87.5% (14/16) | 64.0-96.5% | 100.0% (1206/1206) | 99.7-100.0% |
| Salmonella (Para-Pak C&S) | High PPA, High NPA | 95.0% (19/20) | 76.4-99.1% | 100.0% (688/688) | 99.4-100.0% |
| Yersinia enterocolitica (FecalSwab) | High PPA, High NPA | 93.8% (15/16) | 71.7-99.0% | 99.4% (1199/1206) | 98.8-99.7% |
| Yersinia enterocolitica (Para-Pak C&S) | High PPA, High NPA | 100.0% (3/3) | 43.9-100.0% | 99.3% (698/703) | 98.4-99.7% |
| Diarrheagenic E. coli/Shigella | |||||
| Enteropathogenic E. coli (EPEC) (Para-Pak C&S) | High PPA, High NPA | 87.7% (57/65) | 77.6-93.6% | 100.0% (632/632) | 99.4-100.0% |
| Enterotoxigenic E. coli (ETEC) lt/st (FecalSwab) | High PPA, High NPA | 90.0% (9/10) | 59.6-99.2% | 99.3% (427/430) | 98.0-99.8% |
| Enterotoxigenic E. coli (ETEC) lt/st (Para-Pak C&S) | High PPA, High NPA | 90.0% (9/10) | 59.6-99.2% | 98.7% (390/395) | 97.1-99.5% |
| Shiga-like toxin E. coli (STEC) stx1/stx2 (Para-Pak C&S) | High PPA, High NPA | 83.3% (5/6) | 43.6-97.0% | 99.3% (397/400) | 97.8-99.7% |
| E. coli O157 (Para-Pak C&S) | High PPA, High NPA | N/A (0/0) | N/A | 100.0% (5/5) | 56.6-100.0% |
| Shigella/Enteroinvasive E. coli (EIEC) (FecalSwab) | High PPA, High NPA | 100.0% (10/10) | 72.3-100.0% | 100.0% (1212/1212) | 99.7-100.0% |
| Shigella/Enteroinvasive E. coli (EIEC) (Para-Pak C&S) | High PPA, High NPA | 100.0% (2/2) | 34.2-100.0% | 99.9% (703/704) | 99.2-100.0% |
| Parasites | |||||
| Cryptosporidium (FecalSwab) | High PPA, High NPA | 50.0% (2/4) | 15.0-85.0% | 100.0% (1218/1218) | 99.7-100.0% |
| Cryptosporidium (Para-Pak C&S) | High PPA, High NPA | 100.0% (6/6) | 61.0-100.0% | 99.9% (699/700) | 99.2-100.0% |
| Cyclospora cayetanensis (FecalSwab) | High PPA, High NPA | 100.0% (3/3) | 43.9-100.0% | 100.0% (1219/1219) | 99.7-100.0% |
| Cyclospora cayetanensis (Para-Pak C&S) | High PPA, High NPA | 94.7% (18/19) | 75.4-99.1% | 100.0% (687/687) | 99.4-100.0% |
| Entamoeba histolytica (FecalSwab) | High PPA, High NPA | N/A (0/0) | N/A | 100.0% (1222/1222) | 99.7-100.0% |
| Entamoeba histolytica (Para-Pak C&S) | High PPA, High NPA | N/A (0/0) | N/A | 100.0% (706/706) | 99.5-100.0% |
| Giardia lamblia (FecalSwab) | High PPA, High NPA | 75.0% (6/8) | 40.9-92.9% | 98.4% (434/441) | 96.8-99.2% |
| Giardia lamblia (Para-Pak C&S) | High PPA, High NPA | 100.0% (1/1) | 20.7-100.0% | 100.0% (406/406) | 99.1-100.0% |
Study Details:
1. Sample sizes used for the test set and the data provenance:
- Test Set (Clinical Study):
- Total Specimens: 2808
- 1939 Prospective (1222 FecalSwab, 717 Para-Pak C&S)
- 119 Prospective Archived (Norovirus GI/GII: 81, STEC: 18 plus 20 negative specimens where relevant)
- 750 Retrospective Frozen Specimens
- Data Provenance: Multi-center international study conducted at thirteen clinical sites across 5 countries (4 sites in Europe and 9 sites in USA). Specimens were collected between May and July 2021.
- Total Specimens: 2808
2. 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 document does not specify the number or qualifications of experts used to establish the ground truth. Instead, it refers to the use of "one FDA-cleared test as comparator for most analytes" and a "composite comparator consisting of either three independent FDA-cleared test methods or two independent FDA-cleared tests methods and two validated PCR assays followed by bidirectional sequencing" for others. This implies that the ground truth was established through validated diagnostic methods rather than direct expert consensus on primary samples in many cases.
3. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- For analytes where a composite comparator was used (Norovirus GI/GII, ETEC, STEC, and Giardia lamblia), the ground truth was determined by the majority of the three results.
- A positive composite comparator result: based on positive results for at least two comparator tests.
- A negative composite comparator result: based on negative results for at least two comparator tests.
- For other analytes, where "one FDA-cleared test method" was used, the comparator's result directly served as the ground truth.
- For cases with insufficient sample volume for complete composite comparator testing, a "worst-case model" was applied for PPA calculation.
4. If a muti-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 information is not applicable as the device is an in vitro diagnostic (IVD) nucleic acid test for pathogen detection, not an AI-assisted diagnostic device interpreted by human readers for medical imaging or similar tasks. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not relevant to this device.
5. If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Yes, the performance presented (PPA and NPA) for the QIAstat-Dx Gastrointestinal Panel 2 is a standalone performance of the algorithm/device. The device automatically interprets test results and displays a summary, without a human interpretation loop for its core function.
6. The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- The ground truth was established using FDA-cleared comparator methods and validated PCR assays followed by bidirectional sequencing. This acts as a robust diagnostic ground truth based on established molecular and clinical laboratory standards. Pathology or outcomes data were not explicitly mentioned as primary ground truth sources for individual pathogen detection in this context.
7. The sample size for the training set:
- The document does not explicitly state a sample size for the training set. The clinical studies describe the evaluation of the device's performance using prospective, prospective archived, and retrospective samples, implying these are test sets rather than training sets. Analytical studies such as LoD and inclusivity also use specific strains and dilutions, but these are for analytical validation, not for training a machine learning model. For IVD devices like this, the "training set" concept (as understood in AI/ML) might be less direct, relying more on extensive analytical verification of probe/primer specificity and reactivity across a wide range of strains and concentrations, and then clinical validation.
8. How the ground truth for the training set was established:
- As the training set size is not provided, the method for establishing its ground truth is also not detailed. However, for the analytical studies (which could be considered a form of "training/validation data generation" in a broader sense for IVDs), the ground truth for LoD and inclusivity was established by using culture isolates from commercial suppliers (ZeptoMetrix® and ATCC®) or clinical samples positive for target analytes. These were "prepared in human stool matrix" and tested at known concentrations validated by in-house developed and validated qPCR assays for molecular unit titers.
§ 866.3990 Gastrointestinal microorganism multiplex nucleic acid-based assay.
(a)
Identification. A gastrointestinal microorganism multiplex nucleic acid-based assay is a qualitativein vitro diagnostic device intended to simultaneously detect and identify multiple gastrointestinal microbial nucleic acids extracted from human stool specimens. The device detects specific nucleic acid sequences for organism identification as well as for determining the presence of toxin genes. The detection and identification of a specific gastrointestinal microbial nucleic acid from individuals exhibiting signs and symptoms of gastrointestinal infection aids in the diagnosis of gastrointestinal infection when used in conjunction with clinical evaluation and other laboratory findings. A gastrointestinal microorganism multiplex nucleic acid-based assay also aids in the detection and identification of acute gastroenteritis in the context of outbreaks.(b)
Classification. Class II (special controls). The special controls are set forth in FDA's guideline document entitled: “Class II Special Controls Guideline: Gastrointestinal Microorganism Multiplex Nucleic Acid-Based Assays for Detection and Identification of Microorganisms and Toxin Genes from Human Stool Specimens.” For availability of the guideline document, see § 866.1(e).