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The Technozvm ADAMTS13 Activity assay is an enzyme-linked immunosorbent assay (ELISA) intended for the qualitative determination of ADAMTS13 activity in platelet poor human citrated plasma. The assay is intended to be used in conjunction with other clinical and laboratory findings as an aid in the diagnosis of thrombotic thrombocytopenic purpura (TTP) in adult and pediatric patients being evaluated for thrombotic microangiopathy (TMA).

The Technozym ADAMTS13 Activity assay is an enzyme linked immunosorbent assay (ELISA) used for detection of ADAMTS13 activity in citrated human plasma. The assay contains: ADAMTS13 Activity anti-GST coated test plate microplate coated with anti-GST antibody, ADAMTS13 Activity GST-VWF73 reagent that contains GST tagged peptide of 73 amino acids from the A2 domain of VWF with specific cleavage site for ADAMTS13 and serves as the in vitro substrate for ADAMTS13, ADAMTS13 Activity Calibrators-consists of six vials containing lyophilized plasma, each with a different level of ADAMTS13 activity, ADAMTS13 Activity Controls consists of two vials of lyophilized plasma, each with high or low levels of ADAMTS13 activity, ADAMTS13 Activity Conjugate - reagent that contains horseradish peroxidase (HRP) conjugated monoclonal antibody directed against the neoepitope exposed due to cleavage of GST-VWF73 by ADAMTS13 present in plasma, ADAMTS13 TMB substrate reagent contains tetramethylbenzidine (TMB) substrate for HRP, ADAMTS13 Activity Stop Solution reagent contains 2.5% sulfuric acid for stopping the conversion of TMB substrate.

The Technozym ADAMTS13 Activity assay is a manual enzyme-linked immunosorbent assay (ELISA) intended for the qualitative determination of ADAMTS13 activity in platelet-poor human citrated plasma. It is used in conjunction with other clinical and laboratory findings as an aid in the diagnosis of thrombotic thrombocytopenic purpura (TTP) in adult and pediatric patients being evaluated for thrombotic microangiopathy (TMA). The assay's clinical cutoff for TTP diagnosis is 0.1 IU/mL ADAMTS13 activity.

Acceptance Criteria and Device Performance

The primary acceptance criteria for this device appear to be related to its analytical performance (precision, specificity), and its clinical performance (sensitivity and specificity for TTP diagnosis).

Here's a table summarizing the reported device performance, which implicitly serves as the acceptance criteria based on the successful De Novo grant:

Study Details:

1. Sample sizes used for the test set and the data provenance:

   • Precision/Reproducibility Studies: For each of the nine samples (S1-S9), 30 replicate measurements were performed. This involved human plasma sample pools, prepared by mixing human plasma from normal donors with clinical samples from TTP patients or heat-inactivated plasma. The origin of the normal donors and clinical samples is not explicitly specified beyond being "human plasma." These appear to be laboratory-prepared samples, not directly from patient cohorts.
   • Analytical Specificity/Interference Study: Three base pools (mimicking high, medium, and low ADAMTS13 activity) were used. Each interfering substance was tested with five replicates per sample. The samples were human citrated plasma.
   • Clinical Performance Study: A total of 137 samples were included. These were residual samples selected from a local repository of frozen human citrated plasma from patients diagnosed with thrombotic microangiopathies (TMA), with clinical suspicion of TTP. The study was conducted at two external sites, one in the U.S. and one outside the U.S. This indicates a multi-site validation. The study design ("residual samples from a local repository of frozen human citrated plasma") strongly suggests a retrospective approach.
   • Prozone Effect, Cross-contamination, Reagent Stability, Sample Stability: Sample sizes vary for these specific studies but are generally sufficient for the analytical evaluations (e.g., 8 samples for reagent stability, 6-8 samples for sample stability, various low/high samples for cross-contamination).

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • For the Clinical Performance Study, the ground truth for TTP diagnosis was established by a "board-certified clinician" according to the "local testing algorithm for TMAs." The exact number of clinicians involved is not specified, but it implies at least one per site or a consensus from a group. Their qualification as "board-certified clinician" indicates expertise in diagnosing TMAs.
   • For the Precision/Reproducibility and Analytical Specificity/Interference studies, the ground truth for sample concentrations (e.g., "normal donors," "TTP patient plasma," "heat inactivated plasma") was established by how the samples were prepared or selected based on known clinical status. These are analytical ground truths, not clinical diagnoses requiring expert adjudication of individual cases.

3. Adjudication method (e.g., 2+1, 3+1, none) for the test set:

   • For the Clinical Performance Study, the ground truth was established by "board-certified clinician" according to "local testing algorithm for TMAs." There is no explicit mention of an adjudication method like 2+1 or 3+1 for resolving discrepancies in the clinical diagnosis or establishing the final ground truth from multiple experts. The clinical diagnosis was the established baseline for comparison.

4. 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 is an in-vitro diagnostic (IVD) assay, not an AI-assisted diagnostic device that involves human readers interpreting images or complex data aided by AI. Therefore, an MRMC comparative effectiveness study, as typically understood in medical imaging AI, was not performed, nor is it applicable. The study evaluates the performance of the assay itself in providing a quantitative measurement (ADAMTS13 activity) leading to a qualitative TTP diagnosis (positive/negative). Human involvement is in performing the ELISA steps and interpreting the quantitative result against a defined cutoff, not in interpreting complex visual data.

5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

   • The Technozym ADAMTS13 Activity assay is a manual ELISA kit, not an algorithm or AI system. Its performance is evaluated based on its accuracy in producing a quantitative result that is then interpreted qualitatively based on a predefined cutoff. Therefore, the concept of "standalone algorithm performance" (without human-in-the-loop) is not applicable in the context of this device. The device's performance metrics (precision, sensitivity, specificity) reflect its inherent analytical capabilities when properly executed.

6. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

   • For the Clinical Performance Study, the ground truth for TTP diagnosis was based on the "clinical diagnosis of TTP" by "board-certified clinician(s)" according to "local testing algorithm for TMAs." This implies a combination of clinical findings, laboratory results, and potentially outcomes, but the primary reference is the established clinical diagnosis. It's akin to "expert clinical diagnosis" as the ground truth.
   • For the Analytical Performance studies (Precision, Interference), the ground truth was based on known concentrations or characteristics of the prepared samples (e.g., specific concentrations, the presence/absence of interfering substances, known ADAMTS13 deficiency from TTP patient plasma or heat inactivation).

7. The sample size for the training set:

   • This document describes the performance evaluation of a diagnostic assay kit, not a machine learning or AI model. Therefore, there is no "training set" in the context of developing a data-driven model. The assay's "training" or development would involve biochemical and reagent optimization, calibration curve establishment, and analytical validation steps, not a distinct data-driven training set as understood in AI/ML.

8. 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. The "ground truth" during the development of the assay would correspond to reference materials, known concentrations, and established clinical samples used for initial assay development and calibration. The calibrators themselves are traceable to the first International Standard for ADAMTS13 Activity and Antigen in Plasma (NIBSC WHO 1st international Standard ADAMTS13 Plasma 12/252), establishing a form of objective analytical ground truth for calibration.

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