Qualitative Point-of-Care Human Chorionic Gonadotropin Testing: Can We Defuse This Ticking Time Bomb?

Abstract

Qualitative point-of-care (POC) 2 human chorionic gonadotropin (hCG) testing is routinely performed on urine samples obtained in the Emergency Department (ED) or before surgery to rule out pregnancy and prevent fetal injury or death. Because potentially harmful treatments are allowed to proceed on the basis of a negative hCG test result, falsenegative results can have disastrous consequences.We recently evaluated the performance of 11 common qualitative POC hCG devices and determined that 9 of the 11 devices were susceptible to false-negative results caused by hCG ␤ core fragment (hCG␤cf) (1 ). Although that study highlighted important limitations of these devices in a research laboratory setting, it was unclear whether users experience false negatives in clinical practice. We performed a search of the FDA's Manufacturer and User Facility Device Experience (MAUDE) database using the search term "MAUDE pregnancy false negative" (2 ). Our findings are shown in Figure 1. Seven hundred seven reports described false-negative POC hCG results in women shown to be pregnant at the time of testing. Ninety-one different POC hCG devices were described from 14 manufacturers, including 10 of the 11 devices evaluated in our initial screening study.On the basis of the descriptions in the MAUDE report, false negatives were subdivided by potential cause unknown, likely hCG␤cf hook effect, and likely limit of detection. One hundred forty-two reports were likely due to hCG␤cf hook effect, and 10 (7%) of those were associated with adverse outcomes. Although the exact cause of the false-negative results cannot be conclusively established, interference by high concentrations of hCG␤cf potentially occurred in Ͼ200 patients.It is virtually certain that many more false-negative test results have adversely affected patient management but have gone unreported. Furthermore, these falsenegative results occurred with many of the currently available devices, indicating that this problem is not limited to a single manufacturer or a period of time in the past but represents a much larger public health issue that must be addressed. To reduce the frequency of falsenegative POC hCG test results, coordinated efforts from multiple parties are required. Manufacturers and the FDAThe FDA and device manufacturers should take steps to market products with improved performance characteristics. In defense of their products, manufacturers often point to the fact that their devices are intended for use in early pregnancy, when urine hCG␤cf concentrations are not high enough to interfere with device performance (3 ). This may be the manufacturers' recommendation, but it is no secret that the current clinical practice, at most institutions, is to perform urine hCG testing on all women who present to the ED, regardless of symptoms or likelihood of advanced pregnancy. Therefore, POC hCG devices are regularly used to guide clinical management of pregnant women with high concentrations of hCG␤cf, and thus POC hCG devices must reliably generate a positive signal in ...

False negative point‐of‐care urine pregnancy tests in an urban academic emergency department: a retrospective cohort study

“…6,9,22 However, we also found a broad range of serum values, consistent with prior study of the FDA's Manufacturer and User Facility Device Experience (MAUDE) database, which showed that most false negative results could not be attributed to the lower limit of detection or the hook effect. 23 Although some false negative results may reflect process errors, such as faulty documentation or deviations from assay procedures, previous studies have shown equivalent false negative rates between POC and laboratory urine testing. 4 Clinical decisions around pregnancy testing should incorporate the indication for the test, the implications of a false negative result, the pre-test suspicion for pregnancy, as well as test characteristics.…”

Characterizing urinary hCGβcf patterns during pregnancy

“…High concentrations of hCGβcf (≥500,000 pmol/L) have previously been shown to cause false-negative results in certain qualitative POC hCG devices [4][5][6]. Previous studies have not carefully examined results from samples with hCGβcf concentrations between 50,000 and 500,000 pmol/L.…”

“…High concentrations of hCGβcf (≥500,000 pmol/L) have been shown to cause false-negative results in certain pregnancy tests i.e. qualitative point-of-care (POC) hCG devices [4][5][6]. These pregnancy tests are often used to exclude pregnancy in women subjected to administration of radioactive isotopes for therapeutic or diagnostic purposes.…”

Significance of pregnancy test false negative results due to elevated levels of β-core fragment hCG

“…Collectively, these studies call for further testing and/or modification of POC/ OTC pregnancy tests to ensure they are not susceptible to the excess βcf-hCG hook effect, [6] but it is important that the testing conducted is representative of true clinical scenarios that the assays might encounter. The studies discussed above have clearly demonstrated the hook effect can lead to false negative results and this effect has also been observed in clinical samples.…”