The Clinical Chemistry and Clinical Toxicology Devices Panel met on Friday, March 24, 2000 to provide advice and recommendations to the Agency regarding a premarket approval application (P990082) for the Triage® B-Type Natriuretic Peptide (BNP) Test, manufactured by Biosite Diagnostics. This test measures BNP in whole blood and EDTA plasma as an aid in the diagnosis of congestive heart failure (CHF) and is intended for use in patients who already exhibit mild symptoms of CHF such as, shortness of breath. This device could potentially be used as a screening test for left ventricular dysfunction and ventricular remodeling following acute myocardial infarction as well, according to one of the clinical investigators.
The BNP test consists of a reagent strip housed in a small plastic cartridge, which is used on the Biosite Diagnostics Triage® Analyzer. A small sample of the patient’s blood or plasma is added to the well, and BNP in the sample and the antibody reagents react and produce a signal that is measured by the Triage® analyzer. The analyzer converts this signal to a digital readout of the BNP measurement, which is used in conjunction with other clinical factors and laboratory tests to evaluate the patient’s condition.
The sponsor presented data from a multi-center evaluation on 430 apparently healthy individuals, 167 hypertensive individuals, and 412 patients diagnosed with CHF. The clinical study was designed to determine whether there is a relationship between blood B-type natriuretic peptide concentration and stage of heart failure as classified by the New York Heart Association (class I, II, III, and IV).
The Panel had major concerns with the clinical data, noting that the control group (predominantly men around 36 years of age) was not adequate, the percentage of patients with myocardial infarction was atypical of normal CHF patients, not enough women were studied when women are known to have more CHF than males, and there was insufficient information regarding the relationship between BNP and other variables, e.g., ejection fraction and changes in renal function. In addition, several technical issues were raised during deliberations. Examples included lack of method comparison data; insufficient information on assay standardization and calibration verification, calibration and control stability, and interferences; and lack of linearity data.
In response to the FDA questions, the Panel provided some labeling recommendations but was unable to determine an appropriate cutoff. Some panelists had concerns with the age-matched data and ROC curves used by the FDA to evaluate the cut-off, since they were based on an inappropriate population.
The Panel voted 6-to-3 recommending that the device was "not approvable" and provided guidance on how the sponsor could bring the PMA into an approvable form. The three panelists who were opposed felt the device could have been found approvable with conditions such as, cautious wording in the labeling, limited indications for use, and performance of some additional studies.
The sponsor stated that they could evaluate the different groups as suggested but emphasized that the device is not a stand-alone test.
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