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Cost effectiveness of an accurate and rapid assay for serum human chorionic gonadotropin in suspected ectopic pregnancy
CostEffectivenessof an Accurate andRapid Assayfor SerumHumanChorionicGonadotropin in SuspectedEctopicPregnancy PAUL GENNIS, MD,* E. JOHN GALLAGHER, MD,t FRANK ANDERSEN, MD,+ LESLIE HAIN, MD§ Thecost effectiveness and clinical utility of a simple, rapid, and
accurate pregnancy test in the evaluation of suspected ectopic gestation were studied. The Introductionof tfds qualitative serum assay for human chorlonic gonadotropin into our outpatient department during a l-month period was associated with a slgnificant decrease In culdocenteses @ < O.OOl), ultrasound examinations @ < 0.025), and hospital admissions @ < O.Ol), with a net projected lnstltutlonal reduction In health care costs of $123,000 annually. (Am J Emerg Med 1988;8:4-5)
For the emergency physician, the evaluation of suspected ectopic gestation represents a clinical dilemma for several reasons: 1) a reliable pregnancy test is often unavailable on a “stat” basis; 2) culdocentesis is plagued with false-positive test results and nondiagnostic taps’; 3) ultrasound examinations often cannot provide a definitive diagnosis, especially in early ectopic pregnancy*; and 4) admission of all women in whom this diagnosis is a consideration is impractical and cost prohibitive, since fewer than 10% of patients with a clinically suspected ectopic pregnancy actually prove to have one.3 We describe here a rapid and sensitive bedside serum assay for human chorionic gonadotropin (hCG),4 which, when used as a screening test in suspected ectopic pregnancy, can effectively rule out this diagnosis and significantly reduce the number of cul-
From the *Division of Emergency ‘Medicine, Department of Ambulatory Care, Bronx Municipal Hospital Center, and the tDepartments of Medicine, SEpidemiology and Social Medicine, and QObstetrics and Gynecology, Albert Einstein College of Medicine, Bronx, New York. Manuscript May 1987.
received 11 November 1988; revision accepted 8
Sponsored in part by a grant from Hybritech, Inc., San Diego, California. Address reprint requests to Dr. Gennis: Jacobi 1W20, Bronx Municipal Hospital Center, Pelham Parkway South and Eastchester Road, Bronx, NY 10481. Key Words:
Cost effectiveness, pregnancy, testing.
0 1988 W.B. Saunders Company 0735-8757188 $0.00 + .25 4
docenteses, missions.
ultrasound examinations,
and hospital ad-
MATERIALS AND METHODS The study was conducted in the Adult Emergency Department and the Women’s Health Center of the Bronx Municipal Hospital. All women of childbearing age presenting to either clinical site between the hours of 9:00 AM and midnight during July and August 1985 were screened for study eligibility. Entry criteria were a chief complaint of lower abdominal pain and a serum hCG level determination requested by the examining physician. Patients with multiple visits during the study period were entered into the study only on their initial visit. All patients were evaluated by either Emergency Medicine residents or Gynecology residents at the postgraduate year-2 level or above. The study was approved by our Committee for Clinical Investigations. General guidelines for the evaluation and management of patients with pelvic pain in our emergency department are as follows: 1) Culdocentesis is performed to detect free blood, cystic fluid, or pus in the cul-desac. 2) Ultrasound is done to evaluate adnexal masses or to assess the presence and status of an intrauterine gestation. 3) Admission is indicated for the management of possible ectopic pregnancy, moderate to severe pelvic inflammatory disease, spontaneous abortion, or any reasonable possibility of surgical disease of the abdomen (e.g., appendicitis). During the first month of the study, the serum hCG level was measured by the hospital laboratory using the Hybritech Tandem-E hCG serum assay (Hybritech, San Diego, CA), a quantitative two-site solidphase immunoenzymometric assay. Results of this assay compare favorably with those of the standard radioimmunoassay for hCG, and the test has a reported sensitivity of 5 mIU/mL.5 Because our laboratory does not perform this assay on a stat basis, decisions about further evaluation and admission of patients during the first month of the study were made without knowledge of a serum hCG level. During the second month of the study, paired samples of blood were collected from each patient. One sample was sent to the hospital laboratory for
GENNIS ET AL n SERUM hCG IN ECTOPIC PREGNANCY
quantitative serum hCG determination as described earlier. The second sample was used to perform a rapid qualitative serum hCG assay at the bedside. Medical students were trained and tested in the use of the Tandem Icon hCG (serum) assay and were able to report a result to the examining physician in 15 minutes. The Tandem Icon hCG (serum) assay is a qualitative immunoenzymometric assay with a reported sensitivity of 25 mIU/mL.4 A detailed description of the assay and its performance characteristics (100% sensitive, 96% specific at a threshold value of 25 mIU/mL) has been reported elsewhere.‘j Daily comparisons of the qualitative and quantitative hCG determinations were made. Follow-up information was obtained for all patients with detectable levels of hCG (>5 mIU/mL). The disposition and final diagnosis were obtained in each case by chart review or direct phone contact with the patient. The chi-square test with Yate’s correction was used for statistical comparisons. Significance was established at the p < 0.05 level. RESULTS A total of 253 patient encounters were initially entered into the study. Sixteen encounters represented repeat visits and were excluded from analysis. The general characteristics of the remaining 237 patients are presented in Table 1. There were significantly fewer culdocenteses (7 vs 22, p < O.OOl), pelvic ultrasound examinations (13 vs 20, p < 0.025), and hospital admissions (15 vs 24, p < 0.01) after introduction of the rapid assay (able 2). As shown in Table 3, this reduction in procedures and admissions occurred primarily in nonpregnant women. DISCUSSION This study demonstrates the clinical utility and cost effectiveness of a simple, rapid, and accurate serum pregnancy test in the evaluation of suspected ectopic gestation. The introduction of this test into our outpaTABLE1. Characteristics of Patients Examined for Possible Etopic Pregnancy
Mean patient age (range) (yr) Normal pregnancies (n) Abnormal pregnancies’ (n) Ectopic pregnancies (n) Total pregnancies (n)
Rapid hCG Assay Not Available (n = 100)
Rapid hCG Assay Available (n = 137)
26.6 (15-46) 18 16 4 38
26.7 (24-44) 17 12 4 33
ABBREVIATION: hCG, human chorionic gonadotropin. Abnormal pregnancies include abortions and molar pregnancies but exclude ectopic pregnancies. l
TABLE2. Occurrence of Procedures and Admissions in Women Examined for Ectopic Pregnancy
Culdocenteses Ultrasound examinations Admissions
Rapid hCG Assay Not Available (n = 100)
Rapid hCG Assay Available (n = 137)
p Value
22
7
20 24
13 15
co.025 co.01
ABBREVIATION: hCG, human chorionic
gonadotropin.
tient department was associated with a significant reduction in the performance of culdocenteses (p < O.OOl), pelvic ultrasound examinations (E, < 0.025), and hospital admissions (p < 0.01). This effect was seen primarily in nonpregnant women. The usefulness of this test appears to be related to the reliability with which a negative result excludes the diagnosis of ectopic pregnancy, i.e., the predictive value of a negative test.‘j Indeed, at the manufacturer’s stated threshold sensitivity of 25 mIU/mL of hCG, the bedside assay correctly identified 99.9% (688 of 689) of a series of standardized serum samples4 and 100% (33 of 33) of pregnancies in this study with no false-negative results. Since completion of this study, physicians in our emergency department have used the rapid qualitative assay in over 1200 women with pelvic pain. We know of no instance in which this test produced a false-negative result. In addition, our hospital laboratory recently began performing the rapid assay on a stat basis for the emergency department. Each qualitative test is now run with a standardized positive (25 mIU/mL) and negative control for color comparison. Among 388 patients tested by the hospital laboratory, there have been no reports of either false-positive or false-negative results. We estimate that the introduction of this rapid hCG assay into our outpatient department at a cost of $2.90 per test would save approximately $123,000 in health care costs at this institution annually. This cost is based on a $150.00 fee per pelvic ultrasound examination and a $639.00/day inpatient rate, assuming a l-day stay. In addition to a decrease in maternal mortality, another benefit that might derive from availability of this test is earlier detection of ectopic gestation prior to rupture. This detection, in turn, could result in a decrease in tubal damage and infertility.7 Conclusions that can be drawn from our study are limited because the analysis did not consider the effect that ready availability of a new pregnancy test might have on the physicians’ requests for such a test. We speculate that increased test utilization may account for the increased number of patients entered into the
AMERICAN
JOURNAL
TABLE 3. Occurrence Pregnancy Status
OF EMERGENCY
of Procedures
MEDICINE
and Admissions
Rapid hCG Test Not Available Culdocentesis No pregnancy Normal pregnancy Abnormal pregnancy Ectopic pregnancy Ultrasound examination No pregnancy Normal pregnancy Abnormal pregnancy Ectopic pregnancy Admission No pregnancy Normal pregnancy Abnormal pregnancy Ectopic pregnancy ABBREVIATION: hCG, human
n Volume 6, Number 1 n January
by
Rapid hCG Test Available
16 1 3 2
2 0 1 4
12 4 4 0
4 5 2 2
11 2 7 4
4 1 6 4
number of culdocenteses, pelvic ultrasound examinations, and hospital admissions with a projected net institutional decrease in health care costs of $123,000 annually. The authors thank Ellen Brand, Steven Fishbane, Sharon Glick, Rosie Newhall, Brad Taylor, and Jeff Yormak for their help in collecting the data; Constance Verutes for her help in preparing the manuscript; and Roslyn Weinstein for her continued support throughout this project.
REFERENCES 1.Romero 2.
chorionic
3.
gonadotropin. 4.
study during the time when the assay was available. If this is correct, women with a low pretest probability of ectopic pregnancy may be overrepresented in the larger group, leading to an alpha or type I error. We conclude that the rapid bedside hCG serum assay is a clinically useful and cost-effective tool in the evaluation of suspected ectopic pregnancy. By excluding ectopic gestation in women with negative pregnancy tests, this assay significantly reduced the
6
1988
5.
6.
7.
R, Cope1 JA, Kadar M, et al: Value of culdocentesis in the diagnosis of ectopic pregnancy. Obstet Gynecol 1985;65:519-522 Robinson HB, decrespigny LJCh, Harvey J, et al: Ectopic pregnancy-potentials for diagnosis using ultrasound and urine and serum pregnancy tests. Aust NZ J Obstet Gynaecol 1985;25:49-53 Schwartz RO, DiPietro DL: P-hCG as a diagnostic aid for suspected ectopic pregnancy. Obstet Gynecol 1980;56: 197-203 Valkirs G, Chisum D, Barton R: Qualitative two-site IEMA immunoconcentration technology. Clin Chem 1985;31: 960 Bock JL, Furguiele J, Segen J: Choriogonadotropin measured with the tandem-E immunoenzymetric assay system. Clin Chem 1985;31:441-444 Gennis P, Hain L, Anderson HF, et al: Utility of a sensitive bedside serum pregnancy test in the evaluation of suspected ectopic pregnancy. Ann Emerg Med 1987;16:659661 Sherman D, Langer R, Sadowski G, et al: Improved fertility following ectopic pregnancy. Fertil Steril 1982;37:497
accurate pregnancy test in the evaluation of suspected ectopic gestation were studied. The Introductionof tfds qualitative serum assay for human chorlonic gonadotropin into our outpatient department during a l-month period was associated with a slgnificant decrease In culdocenteses @ < O.OOl), ultrasound examinations @ < 0.025), and hospital admissions @ < O.Ol), with a net projected lnstltutlonal reduction In health care costs of $123,000 annually. (Am J Emerg Med 1988;8:4-5)
For the emergency physician, the evaluation of suspected ectopic gestation represents a clinical dilemma for several reasons: 1) a reliable pregnancy test is often unavailable on a “stat” basis; 2) culdocentesis is plagued with false-positive test results and nondiagnostic taps’; 3) ultrasound examinations often cannot provide a definitive diagnosis, especially in early ectopic pregnancy*; and 4) admission of all women in whom this diagnosis is a consideration is impractical and cost prohibitive, since fewer than 10% of patients with a clinically suspected ectopic pregnancy actually prove to have one.3 We describe here a rapid and sensitive bedside serum assay for human chorionic gonadotropin (hCG),4 which, when used as a screening test in suspected ectopic pregnancy, can effectively rule out this diagnosis and significantly reduce the number of cul-
From the *Division of Emergency ‘Medicine, Department of Ambulatory Care, Bronx Municipal Hospital Center, and the tDepartments of Medicine, SEpidemiology and Social Medicine, and QObstetrics and Gynecology, Albert Einstein College of Medicine, Bronx, New York. Manuscript May 1987.
received 11 November 1988; revision accepted 8
Sponsored in part by a grant from Hybritech, Inc., San Diego, California. Address reprint requests to Dr. Gennis: Jacobi 1W20, Bronx Municipal Hospital Center, Pelham Parkway South and Eastchester Road, Bronx, NY 10481. Key Words:
Cost effectiveness, pregnancy, testing.
0 1988 W.B. Saunders Company 0735-8757188 $0.00 + .25 4
docenteses, missions.
ultrasound examinations,
and hospital ad-
MATERIALS AND METHODS The study was conducted in the Adult Emergency Department and the Women’s Health Center of the Bronx Municipal Hospital. All women of childbearing age presenting to either clinical site between the hours of 9:00 AM and midnight during July and August 1985 were screened for study eligibility. Entry criteria were a chief complaint of lower abdominal pain and a serum hCG level determination requested by the examining physician. Patients with multiple visits during the study period were entered into the study only on their initial visit. All patients were evaluated by either Emergency Medicine residents or Gynecology residents at the postgraduate year-2 level or above. The study was approved by our Committee for Clinical Investigations. General guidelines for the evaluation and management of patients with pelvic pain in our emergency department are as follows: 1) Culdocentesis is performed to detect free blood, cystic fluid, or pus in the cul-desac. 2) Ultrasound is done to evaluate adnexal masses or to assess the presence and status of an intrauterine gestation. 3) Admission is indicated for the management of possible ectopic pregnancy, moderate to severe pelvic inflammatory disease, spontaneous abortion, or any reasonable possibility of surgical disease of the abdomen (e.g., appendicitis). During the first month of the study, the serum hCG level was measured by the hospital laboratory using the Hybritech Tandem-E hCG serum assay (Hybritech, San Diego, CA), a quantitative two-site solidphase immunoenzymometric assay. Results of this assay compare favorably with those of the standard radioimmunoassay for hCG, and the test has a reported sensitivity of 5 mIU/mL.5 Because our laboratory does not perform this assay on a stat basis, decisions about further evaluation and admission of patients during the first month of the study were made without knowledge of a serum hCG level. During the second month of the study, paired samples of blood were collected from each patient. One sample was sent to the hospital laboratory for
GENNIS ET AL n SERUM hCG IN ECTOPIC PREGNANCY
quantitative serum hCG determination as described earlier. The second sample was used to perform a rapid qualitative serum hCG assay at the bedside. Medical students were trained and tested in the use of the Tandem Icon hCG (serum) assay and were able to report a result to the examining physician in 15 minutes. The Tandem Icon hCG (serum) assay is a qualitative immunoenzymometric assay with a reported sensitivity of 25 mIU/mL.4 A detailed description of the assay and its performance characteristics (100% sensitive, 96% specific at a threshold value of 25 mIU/mL) has been reported elsewhere.‘j Daily comparisons of the qualitative and quantitative hCG determinations were made. Follow-up information was obtained for all patients with detectable levels of hCG (>5 mIU/mL). The disposition and final diagnosis were obtained in each case by chart review or direct phone contact with the patient. The chi-square test with Yate’s correction was used for statistical comparisons. Significance was established at the p < 0.05 level. RESULTS A total of 253 patient encounters were initially entered into the study. Sixteen encounters represented repeat visits and were excluded from analysis. The general characteristics of the remaining 237 patients are presented in Table 1. There were significantly fewer culdocenteses (7 vs 22, p < O.OOl), pelvic ultrasound examinations (13 vs 20, p < 0.025), and hospital admissions (15 vs 24, p < 0.01) after introduction of the rapid assay (able 2). As shown in Table 3, this reduction in procedures and admissions occurred primarily in nonpregnant women. DISCUSSION This study demonstrates the clinical utility and cost effectiveness of a simple, rapid, and accurate serum pregnancy test in the evaluation of suspected ectopic gestation. The introduction of this test into our outpaTABLE1. Characteristics of Patients Examined for Possible Etopic Pregnancy
Mean patient age (range) (yr) Normal pregnancies (n) Abnormal pregnancies’ (n) Ectopic pregnancies (n) Total pregnancies (n)
Rapid hCG Assay Not Available (n = 100)
Rapid hCG Assay Available (n = 137)
26.6 (15-46) 18 16 4 38
26.7 (24-44) 17 12 4 33
ABBREVIATION: hCG, human chorionic gonadotropin. Abnormal pregnancies include abortions and molar pregnancies but exclude ectopic pregnancies. l
TABLE2. Occurrence of Procedures and Admissions in Women Examined for Ectopic Pregnancy
Culdocenteses Ultrasound examinations Admissions
Rapid hCG Assay Not Available (n = 100)
Rapid hCG Assay Available (n = 137)
p Value
22
7
20 24
13 15
co.025 co.01
ABBREVIATION: hCG, human chorionic
gonadotropin.
tient department was associated with a significant reduction in the performance of culdocenteses (p < O.OOl), pelvic ultrasound examinations (E, < 0.025), and hospital admissions (p < 0.01). This effect was seen primarily in nonpregnant women. The usefulness of this test appears to be related to the reliability with which a negative result excludes the diagnosis of ectopic pregnancy, i.e., the predictive value of a negative test.‘j Indeed, at the manufacturer’s stated threshold sensitivity of 25 mIU/mL of hCG, the bedside assay correctly identified 99.9% (688 of 689) of a series of standardized serum samples4 and 100% (33 of 33) of pregnancies in this study with no false-negative results. Since completion of this study, physicians in our emergency department have used the rapid qualitative assay in over 1200 women with pelvic pain. We know of no instance in which this test produced a false-negative result. In addition, our hospital laboratory recently began performing the rapid assay on a stat basis for the emergency department. Each qualitative test is now run with a standardized positive (25 mIU/mL) and negative control for color comparison. Among 388 patients tested by the hospital laboratory, there have been no reports of either false-positive or false-negative results. We estimate that the introduction of this rapid hCG assay into our outpatient department at a cost of $2.90 per test would save approximately $123,000 in health care costs at this institution annually. This cost is based on a $150.00 fee per pelvic ultrasound examination and a $639.00/day inpatient rate, assuming a l-day stay. In addition to a decrease in maternal mortality, another benefit that might derive from availability of this test is earlier detection of ectopic gestation prior to rupture. This detection, in turn, could result in a decrease in tubal damage and infertility.7 Conclusions that can be drawn from our study are limited because the analysis did not consider the effect that ready availability of a new pregnancy test might have on the physicians’ requests for such a test. We speculate that increased test utilization may account for the increased number of patients entered into the
AMERICAN
JOURNAL
TABLE 3. Occurrence Pregnancy Status
OF EMERGENCY
of Procedures
MEDICINE
and Admissions
Rapid hCG Test Not Available Culdocentesis No pregnancy Normal pregnancy Abnormal pregnancy Ectopic pregnancy Ultrasound examination No pregnancy Normal pregnancy Abnormal pregnancy Ectopic pregnancy Admission No pregnancy Normal pregnancy Abnormal pregnancy Ectopic pregnancy ABBREVIATION: hCG, human
n Volume 6, Number 1 n January
by
Rapid hCG Test Available
16 1 3 2
2 0 1 4
12 4 4 0
4 5 2 2
11 2 7 4
4 1 6 4
number of culdocenteses, pelvic ultrasound examinations, and hospital admissions with a projected net institutional decrease in health care costs of $123,000 annually. The authors thank Ellen Brand, Steven Fishbane, Sharon Glick, Rosie Newhall, Brad Taylor, and Jeff Yormak for their help in collecting the data; Constance Verutes for her help in preparing the manuscript; and Roslyn Weinstein for her continued support throughout this project.
REFERENCES 1.Romero 2.
chorionic
3.
gonadotropin. 4.
study during the time when the assay was available. If this is correct, women with a low pretest probability of ectopic pregnancy may be overrepresented in the larger group, leading to an alpha or type I error. We conclude that the rapid bedside hCG serum assay is a clinically useful and cost-effective tool in the evaluation of suspected ectopic pregnancy. By excluding ectopic gestation in women with negative pregnancy tests, this assay significantly reduced the
6
1988
5.
6.
7.
R, Cope1 JA, Kadar M, et al: Value of culdocentesis in the diagnosis of ectopic pregnancy. Obstet Gynecol 1985;65:519-522 Robinson HB, decrespigny LJCh, Harvey J, et al: Ectopic pregnancy-potentials for diagnosis using ultrasound and urine and serum pregnancy tests. Aust NZ J Obstet Gynaecol 1985;25:49-53 Schwartz RO, DiPietro DL: P-hCG as a diagnostic aid for suspected ectopic pregnancy. Obstet Gynecol 1980;56: 197-203 Valkirs G, Chisum D, Barton R: Qualitative two-site IEMA immunoconcentration technology. Clin Chem 1985;31: 960 Bock JL, Furguiele J, Segen J: Choriogonadotropin measured with the tandem-E immunoenzymetric assay system. Clin Chem 1985;31:441-444 Gennis P, Hain L, Anderson HF, et al: Utility of a sensitive bedside serum pregnancy test in the evaluation of suspected ectopic pregnancy. Ann Emerg Med 1987;16:659661 Sherman D, Langer R, Sadowski G, et al: Improved fertility following ectopic pregnancy. Fertil Steril 1982;37:497