Search Results

AlloMap Molecular Expression Testing is an In Vitro Diagnostic Multivariate Index assay (IVDMIA) test service, performed in a single laboratory, assessing the gene expression profile of RNA isolated from peripheral blood mononuclear cells (PBMC). AlloMap Testing is intended to aid in the identification of heart transplant recipients with stable allograft function who have a low probability of moderate/severe acute cellular rejection (ACR) at the time of testing in conjunction with standard clinical assessment.

Indicated for use in heart transplant recipients:

• l 15 years of age or older
• I At least 2 months (>55 days) post-transplant

AlloMap Molecular Expression Testing is performed in a single laboratory (XDx Laboratories). Blood is drawn from the patient and subsequently processed, packaged and shipped frozen to the XDx Laboratory. At the XDx Laboratory, gene expression levels are determined via real time PCR for each of the test and control genes and converted to the AlloMap Test Score. The AlloMap Test Score is then reported to the physician.

Here's a breakdown of the acceptance criteria and study information for the AlloMap® Molecular Expression Testing device, based on the provided document:

Description of Acceptance Criteria and the Study that Proves the Device Meets the Acceptance Criteria

The AlloMap® Molecular Expression Testing is an In Vitro Diagnostic Multivariate Index assay (IVDMIA) intended to aid in identifying heart transplant recipients with stable allograft function who have a low probability of moderate/severe acute cellular rejection (ACR). The device performance was evaluated through analytical and clinical studies.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are generally implied through the presented experimental findings and the successful classification as a Class II device. The precision/reproducibility and various analytical specificity studies demonstrate the robustness and reliability of the assay. The clinical study established the predictive values for the assay.

2. Sample Size for the Test Set and Data Provenance

• Precision Study (Analytical Performance):

  • Healthy Donor Samples: Four healthy donor samples (D1-D4) evaluated in Arm A (RNA->cDNA->Assay). One healthy donor sample evaluated in Arm C (reagent lot-to-lot, plate-to-plate, section-to-section).
  • Patient Samples: Six individual cardiac transplant recipients (P1-P6 from two CARGO centers: 3 per center). Three samples per patient from one center, and four samples per patient from the second center. One pooled patient sample evaluated in Arm C.
  • Data Provenance: Not explicitly stated for healthy donors, but patient samples are from "CARGO centers," implying data from the Cardiac Allograft Rejection Gene Expression Observational (CARGO) study. The study appears to be prospective in nature for data collection used in precision.

• Analytical Specificity (Interference Studies):

  • Immunosuppression Therapy: 700 CARGO samples (from the XDx Population study).
  • CMV Interference: 61 samples from CARGO (11 CMV+, 50 CMV-).
  • Other Compound Interference: 5 donors for acetaminophen, acetylsalicylic acid, bilirubin, triglycerides; 1 donor for hemoglobin; CPT tubes from volunteer XDx donors and same donors for citrate controls for heparin.
  • Genomic DNA Interference: Not explicitly specified, but appears to be conducted on samples where gDNA was manipulated.
  • Data Provenance: Primarily from the CARGO study (retrospective use of collected samples for specificity analysis) and internal XDx donor/volunteer samples.

• Clinical Study (Clinical Validation):

  • Sample Size: 300 samples from 154 patients.
  • Data Provenance: Derived from the prospective, observational multi-center Cardiac Allograft Rejection Gene Expression Observational (CARGO) study. These samples were explicitly "not used to develop the AlloMap Test algorithm."

3. Number of Experts and Qualifications for Ground Truth (Clinical Test Set)

• Number of Experts: Three panel pathologists.
• Qualifications of Experts: Not specified beyond "panel pathologists." They were responsible for grading local biopsies and confirming rejection diagnoses.

4. Adjudication Method (Clinical Test Set)

• The definition for rejection was "a local biopsy grade ≥3A that was also assigned grade ≥3A by at least one of the three panel pathologists ("confirmed rejection")."
• The "no rejection class" included all samples that did not qualify as rejection.
• This suggests a form of majority or consensus-based adjudication, specifically "local ≥3A confirmed by at least one of three central pathologists."

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

• No, a MRMC comparative effectiveness study involving human readers and AI assistance was not explicitly described in this document. The AlloMap test is presented as a standalone diagnostic aid, not an AI-assisted interpretation tool for human readers.

6. Standalone (Algorithm Only) Performance

• Yes, a standalone performance evaluation was the primary focus of the clinical validation. The "AlloMap Test" (algorithm) generated a score, and its performance (AUC, PPV, NPV) was assessed against the biopsy-confirmed ground truth, without human expert-in-the-loop directly interpreting AlloMap scores to classify cases for the study's primary clinical endpoints. Physicians interpret the final AlloMap score along with other clinical assessments, but the study evaluates the algorithm's performance itself.

7. Type of Ground Truth Used (Clinical Test Set)

• Expert Consensus Pathology: The ground truth for acute cellular rejection (ACR) was defined as a "local biopsy grade ≥3A that was also assigned grade ≥3A by at least one of the three panel pathologists ('confirmed rejection')." This relies on histopathological examination and a form of expert consensus.

8. Sample Size for the Training Set

• The document states that the 300 samples from 154 patients used in the clinical validation study were "not used to develop the AlloMap Test algorithm." This implies there was a separate training set, but the sample size for the training set is not provided in this document.

9. How the Ground Truth for the Training Set was Established

• Since the training set size and specific details are not provided, the method for establishing ground truth for the training set is not explicitly described in this document. However, given the nature of the device and the clinical validation methods, it can be inferred that the training set ground truth would also have been established based on similar histopathological assessments of biopsy samples for acute cellular rejection.

Ask a specific question about this device