Definitions of the levels of evidence (I—III) and grades of the recommendation (A, B, C, I) are presented at the end of the "Major Recommendations" field.
Note from the National Academy of Clinical Biochemistry (NACB) and the National Guideline Clearinghouse (NGC): The Laboratory Medicine Practice Guidelines (LMPG) evidence-based practice for point-of-care testing sponsored by the NACB have been divided into individual summaries covering disease- and test-specific areas. In addition to the current summary, the following are available:
Urine/Serum Human Chorionic Gonadotropin Hormone (hCG) Testing
Does the use of urine hCG point-of-care testing (POCT) as an aid in the diagnosis of pregnancy improve outcomes (i.e., reduce clinic visits or reduce length of stay [LOS] in the emergency department or reduce number of contraindicated drugs or therapies) compared to serum core laboratory hCG? (Literature Search 95 - Refer to Appendix B - see the "Availability of Companion Documents" field)
Guideline 171. The guideline developers note that the use of rapid urine/serum hCG devices may have utility in settings such as the emergency department or urgent care centers, but remarkably, no studies have been published that examine outcomes such as LOS, number of clinic visits, or the number of contraindicated drugs or procedures. Therefore, there is not sufficient evidence to make any recommendation for or against the use of rapid urine/serum hCG tests. The guideline developers note that the use of home urine hCG devices may have utility and reduce adverse social behaviors, but no studies have been published that examine outcomes in this setting either. Therefore, there is not sufficient evidence to make any recommendation for or against the use of home urine hCG tests.
Strength/consensus of recommendation: I
Level of evidence: III (no studies, clinical experience)
Is the diagnostic accuracy of urine hCG POCT equivalent to serum core laboratory hCG? (Literature Search 96 - Refer to Appendix B - see the "Availability of Companion Documents" field)
Guideline 172. Early studies have indicated much brand-by-brand variation in point-of-care (POC) laboratory hCG devices. Recent studies (after 1990) have not been conducted, making a recommendation difficult. According to the published data available, caution should be used with POC hCG devices. Since new novel technologies have significantly enhanced these earlier tests, further studies are needed to determine which devices are most accurate and consistent in performance. POC hCG devices may have utility as an aid in the diagnosis of ectopic pregnancy, although this utility has not been adequately compared to the use of in-lab testing. Therefore, there is not sufficient evidence to make any recommendation for or against the use of POC urine hCG devices for the diagnosis of ectopic pregnancy. Studies also indicate brand-by-brand variation in rapid home hCG devices. However, recent studies (after 1989) have not been conducted, making a recommendation difficult. According to the published data available, caution should be used with home hCG devices. Further studies are needed to determine which devices are most accurate.
Strength/consensus of recommendation: I
Level of evidence: II (observational and retrospective cohort studies)
How early in gestation does urine hCG POCT diagnose pregnancy accurately and how does this compare to serum core laboratory hCG? (Literature Search 97 - Refer to Appendix B - see the "Availability of Companion Documents" field)
Guideline 173. The guideline developers note that it is unclear how early all home urine hCG devices can detect pregnancy. It is clear that there are brand-by-brand differences. Recent studies (after 1989) have not been conducted, making a recommendation difficult. According to the published data available, caution should be used in interpreting home hCG devices early after missed menses. Further studies are needed to determine which newer over-the-counter devices are best able to detect early pregnancy.
Strength/consensus of recommendation: I
Level of evidence: III (single retrospective cohort studies)
What is the diagnostic accuracy of urine hCG POCT when performed by a layperson compared to the diagnostic accuracy of serum or urine core laboratory hCG? (Literature Search 98 - Refer to Appendix B - see the "Availability of Companion Documents" field)
Guideline 174. No studies have been published that compare the accuracy of hCG POC devices when performed by a layperson versus the accuracy of a core laboratory. Therefore, there is not sufficient evidence to make any recommendation about laypersons and the use of home urine hCG tests.
Strength/consensus of recommendation: I
Level of evidence: III (no studies, clinical experience)
What is the diagnostic accuracy of urine hCG POCT when performed by a layperson compared to the diagnostic accuracy of urine POCT in a core laboratory? (Literature Search 99 - Refer to Appendix B - see the "Availability of Companion Documents" field)
Guideline 175. Studies have clearly shown decreased accuracy of urine POCT devices when performed by laypersons. The guideline developers recommend that manufacturers provide clear concise instructions for use and adequate (easy to interpret) quality-control measures to maximize the proper use and interpretation of these devices. The guideline developers recommend that physicians confirm results with quantitative serum hCG.
Strength/consensus of recommendation: I
Level of evidence: III (observational cohorts and blind randomized cohort)
Urine Luteinizing Hormone (LH) Ovulation Tests
Is the diagnostic accuracy of urine LH tests sufficient for detecting ovulation using progesterone or ultrasound as a gold standard for confirming ovulation? (Literature Search 100 - Refer to Appendix B - see the "Availability of Companion Documents" field)
Guideline 176. The guideline developers note that POC tests have excellent diagnostic sensitivity for the detection of ovulation. They can strongly recommend the use of these devices when the purpose of using them is to detect ovulation.
Strength/consensus of recommendation: A
Level of evidence: II (cohort studies)
Is the diagnostic accuracy of urine LH tests sufficient for predicting ovulation using progesterone or ultrasound as a gold standard for confirming ovulation? (Literature Search 101 - Refer to Appendix B - see the "Availability of Companion Documents" field)
Guideline 177. The guideline developers recommend the use of urine LH tests to predict ovulation within 48 h of a positive test.
Strength/consensus of recommendation: B
Level of evidence: II (cohort studies)
Does the use of urine LH tests for predicting ovulation in women not treated in a fertility clinic improve outcomes (i.e., increase conception rates, decrease number of clinic visits, or number of unwanted pregnancies) compared to no use of prediction tests? (Literature Search 102 - Refer to Appendix B - see the "Availability of Companion Documents" field)
Guideline 178. There is insufficient evidence to make any recommendation for or against the use of home urine LH testing to improve conception rates in women not seeking fertility treatments.
Strength/consensus of recommendation: I
Level of evidence: III
Does the use of urine LH tests for predicting ovulation in women undergoing fertility treatment improve outcomes (i.e., increase conception rates, decrease number of clinic visits, number of fertility treatment cycles) compared to no use of prediction tests? (Literature Search 103 - Refer to Appendix B - see the "Availability of Companion Documents" field)
Guideline 179. The guideline developers can make no recommendation for or against routinely providing urine LH tests to improve outcomes. There are limited data available to adequately assess the utility of the test to improve conception rates, clinic visit frequency, or fertility treatment cycles. Although these questions are certainly of considerable interest, clear-cut answers remain elusive and additional studies need to be performed.
Strength/consensus of recommendation: I
Level of evidence: I (at least 1 randomized controlled trial)
What is the diagnostic accuracy of urine LH POCT ovulation tests when performed/interpreted by a layperson as compared to the diagnostic accuracy of urine LH in a core laboratory (performed by Clinical Laboratories Improvement Act [CLIA]-approved laboratory staff)? (Literature Search 104 - Refer to Appendix B - see the "Availability of Companion Documents" field)
Guideline 180. There is insufficient evidence to evaluate the diagnostic accuracy of results obtained from layperson- or laboratory-performed "urine" LH testing.
Strength/consensus of recommendation: I
Level of evidence: III (descriptive studies)
What is the diagnostic accuracy of urine LH POCT ovulation tests when performed/interpreted by a layperson as compared to the diagnostic accuracy of serum LH in a core laboratory (performed by CLIA-approved laboratory staff)? (Literature Search 105 - Refer to Appendix B - see the "Availability of Companion Documents" field)
Guideline 181. There is insufficient evidence to evaluate the diagnostic accuracy of results obtained from layperson-performed urine LH tests compared to laboratory-performed "serum" LH testing.
Strength/consensus of recommendation: I
Level of evidence: III (expert opinion)
Nonurine Ovulation Tests
Is the diagnostic accuracy of nonurine POCT ovulation tests sufficient to predict ovulation using progesterone or ultrasound as a gold standard for confirming ovulation? (Literature Search 106 - Refer to Appendix B - see the "Availability of Companion Documents" field)
Guideline 182. The guideline developers note that there is limited useful evidence to support the use of nonurine POCT for predicting ovulation, and the available evidence is generally of poor quality. They therefore can make no recommendation for or against the use of nonurine POCT for ovulation prediction.
Strength/consensus of recommendation: I
Level of evidence: III (descriptive studies)
pH/Nitrazine Tests for Premature Rupture of Membranes
Does the pH/nitrazine test accurately predict preterm premature rupture of membranes? (Literature Search 107 - Refer to Appendix B - see the "Availability of Companion Documents" field)
Guideline 183. The guideline developers note that the evidence is insufficient to recommend for or against providing pH/nitrazine tests for the prediction of preterm premature rupture of membranes.
Strength/consensus of recommendation: I
Level of evidence: III (descriptive studies)
Does the pH/nitrazine test accurately identify women with ruptured membranes and/or women whose membranes have not ruptured? (Literature Search 108 - Refer to Appendix B - see the "Availability of Companion Documents" field)
Guideline 184. The guideline developers note that the pH/nitrazine test is sensitive only when used in women for whom membrane status is known. When applied to patients suspected of having premature rupture of the membranes (PROM), the test does not appear to be sufficiently sensitive or specific enough for diagnostic determination of premature rupture of membranes. Accordingly, the guideline developers do not recommend the use of pH/nitrazine testing alone for the detection of premature rupture of membranes.
Strength/consensus of recommendation: C
Level of evidence: II (case-controlled studies)
Does the pH/nitrazine test improve outcomes (number of admissions, use of antibiotics, neonatal morbidity/mortality) compared to the fern test in women suspected of having PROM? (Literature Search 109 - Refer to Appendix B - see the "Availability of Companion Documents" field)
Guideline 185. The guideline developers note that the evidence is insufficient to recommend for or against providing pH/nitrazine tests for the prediction of preterm premature rupture of membranes.
Strength/consensus of recommendation: I
Level of evidence: III (descriptive studies)
Fern Tests for Premature Rupture of Membranes
Does the fern test accurately identify women with ruptured membranes and/or women whose membranes have not ruptured? (Literature Search 110 - Refer to Appendix B - see the "Availability of Companion Documents" field)
Guideline 186. The guideline developers note that the fern test is neither sensitive nor specific enough for diagnostic determination of premature rupture of membranes. They recommend against routinely providing fern testing alone for the detection of ruptured membranes
Strength/consensus of recommendation: C
Level of evidence: III (case-controlled studies)
Fetal Fibronectin (fFN) Testing for Premature Delivery
Does performing a single rapid fFN assay improve outcomes (such as number of patient admissions, LOS, use of tocolytic medications, cost, neonatal morbidity/mortality, maternal morbidity because of adverse effects of intervention therapy) compared to cervical dilation, Bishop score, contraction number, or cervical length by ultrasound in women with symptoms of preterm labor, intact membranes, and cervical dilation <3 cm? (Literature Search 111 - Refer to Appendix B - see the "Availability of Companion Documents" field)
Guideline 187. There are no studies that directly compared rapid fFN to any other method to predict preterm birth. There are several noncomparison studies, but none are available that investigated the role of rapid fFN in decreasing neonatal morbidity or mortality. There are 3 outcome studies available that investigated length of maternal stay, maternal transfers to a tertiary-care facility, and need for tocolysis. Two of the 3 studies demonstrated that rapid fFN decreases the need for tocolysis and the need for maternal transfer to a tertiary-care facility. It is important to note that these studies used historical controls for comparison. The third study, the only investigation that used a randomized study design, was not powered to detect a difference in the number of maternal transfers to a tertiary-care facility (primary outcome measure) and did not demonstrate an overall difference in length of maternal hospitalization in patients with symptoms of preterm labor (secondary outcome measure). Therefore, additional well-designed studies are needed to determine the true efficacy of fFN testing.
Strength/consensus of recommendation: I
Level of evidence: II (cohort studies)
Does performing a single rapid fFN assay improve outcomes (such as number of patient admissions, LOS, use of tocolytic medications, cost, neonatal morbidity/mortality, maternal morbidity because of adverse effects of intervention therapy) compared to fFN enzyme-linked immunosorbent assay (ELISA) in women with symptoms of preterm labor, intact membranes, and cervical dilation <3 cm? (Literature Search 112 - Refer to Appendix B - see the "Availability of Companion Documents" field)
Guideline 188. No studies performed a direct comparison of rapid fFN (rfFN) to the ELISA fFN and reported any of the outcomes of interest. Validation of this test appears to be limited to studies that looked at the sensitivity, specificity, and negative and positive predictive values for predicting preterm birth and then compared these results to previous published results of fFN determined by an ELISA microtiter plate. No study used the same sample that was measured using the 2 different methods. Therefore, there is insufficient evidence to compare clinical outcomes between the rfFN and the ELISA fFN.
Strength/consensus of recommendation: I
Level of evidence: III (no studies)
Do repeated rapid fFN tests decrease costs and improve clinical outcomes? At what testing interval? (Literature Search 113 - Refer to Appendix B - see the "Availability of Companion Documents" field)
Guideline 189. There were no studies available that addressed the issue of the utility of repeated rapid fFN testing. In addition, there were no studies available to determine the appropriate interval between samplings. Therefore, there is insufficient evidence to make recommendations about repeated sampling or the appropriate interval between sampling.
Strength/consensus of recommendation: I
Level of evidence: III (no studies)
What are rapid fFN positive predictive values (PPV) and negative predictive values (NPV) for preterm delivery? Does rapid fFN reliably identify women at risk of preterm delivery and/or women at no risk of preterm delivery? (Literature Search 114 - Refer to Appendix B - see the "Availability of Companion Documents" field)
Guideline 190. The major strength of this test is the strong NPV. Studies have clearly demonstrated the high NPV of rapid fFN, with NPVs > 95% to predict preterm birth within 7 days of testing. A negative rapid fFN result in symptomatic patients is a reliable test to place women at low risk of preterm birth within 7 days of testing. However, the PPV of rapid fFN is a poor predictor of preterm birth. Therefore, a positive rapid fFN should not be used as the primary guide for therapeutic decisions related to the imminent prevention of preterm birth.
Strength/consensus of recommendation: I
Level of evidence: II (cohort studies)
Definitions:
Levels of Evidence
- Evidence includes consistent results from well-designed, well-conducted studies in representative populations.
- Evidence is sufficient to determine effects, but the strength of the evidence is limited by the number, quality, or consistency of the individual studies; generalizability to routine practice; or indirect nature of the evidence.
- Evidence is insufficient to assess the effects on health outcomes because of limited number or power of studies, important flaws in their design or conduct, gaps in the chain of evidence, or lack of information.
Strength of Recommendations
A - The National Academy of Clinical Biochemistry (NACB) strongly recommends adoption; there is good evidence that it improves important health outcomes and concludes that benefits substantially outweigh harms.
B - The NACB recommends adoption; there is at least fair evidence that it improves important health outcomes and concludes that benefits outweigh harms.
C - The NACB recommends against adoption; there is evidence that it is ineffective or that harms outweigh benefits.
I - The NACB concludes that the evidence is insufficient to make recommendations; evidence that it is effective is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.
