Abstract：
BACKGROUND: Persistent pregnancies of unknown location are defined by abnormally trending serum human chorionic gonadotropin with nondiagnostic ultrasound. There is no consensus on optimal management.
OBJECTIVE: This study aimed to assess the cost-effectiveness of 3 primary management strategies for persistent pregnancies of unknown location: (1) expectant management, (2) empirical 2-dose methotrexate, and (3) uterine evacuation followed by methotrexate, if indicated.
METHODS: This was a prospective economic evaluation performed concurrently with the Expectant versus Active Management for Treatment of Persistent Pregnancies of Unknown Location multicenter randomized trial that was conducted from July 2014 to June 2019. Participants were randomized 1:1:1 to expectant management, 2-dose methotrexate, or uterine evacuation. The analysis was from the healthcare sector perspective with a 6-week time horizon after randomization. Costs were expressed in 2018 US dollars. Effectiveness was measured in quality-adjusted life years and the rate of salpingectomy. Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were generated. Sensitivity analyses were performed to assess the robustness of the analysis.
RESULTS: Methotrexate had the lowest mean cost ($875), followed by expectant management ($1085) and uterine evacuation ($1902) (P=.001). Expectant management had the highest mean quality-adjusted life years (0.1043), followed by methotrexate (0.1031) and uterine evacuation (0.0992) (P=.0001). The salpingectomy rate was higher for expectant management than for methotrexate (9.4% vs 1.2%, respectively; P=.02) and for expectant management than for uterine evacuation (9.4% vs 8.1%, respectively; P=.04). Uterine evacuation, with the highest costs and the lowest quality-adjusted life years, was dominated by both expectant management and methotrexate. In the base case analysis, expectant management was not cost-effective compared with methotrexate at a willingness to pay of $150,000 per quality-adjusted life year given an incremental cost-effectiveness ratio of $175,083 per quality-adjusted life year gained (95% confidence interval, -$1,666,825 to $2,676,375). Threshold analysis demonstrated that methotrexate administration would have to cost $214 (an increase of $16 or 8%) to favor expectant management. Moreover, expectant management would be favorable in lower-risk patient populations with rates of laparoscopic surgical management for ectopic pregnancy not exceeding 4% of pregnancies of unknown location. Based on the cost-effectiveness acceptability curves, the probability of expectant management being cost-effective compared with methotrexate at a willingness to pay of $150,000 per quality-adjusted life year gained was 50%. The results were dependent on the cost of surgical intervention and the expected rate of methotrexate failure.
CONCLUSIONS: The management of pregnancies of unknown location with a 2-dose methotrexate protocol may be cost-effective compared with expectant management and uterine evacuation. Although uterine evacuation was dominated, expectant management vs methotrexate results were sensitive to modest changes in treatment costs of both methotrexate and surgical management.
OBJECTIVE: This study aimed to assess the cost-effectiveness of 3 primary management strategies for persistent pregnancies of unknown location: (1) expectant management, (2) empirical 2-dose methotrexate, and (3) uterine evacuation followed by methotrexate, if indicated.
METHODS: This was a prospective economic evaluation performed concurrently with the Expectant versus Active Management for Treatment of Persistent Pregnancies of Unknown Location multicenter randomized trial that was conducted from July 2014 to June 2019. Participants were randomized 1:1:1 to expectant management, 2-dose methotrexate, or uterine evacuation. The analysis was from the healthcare sector perspective with a 6-week time horizon after randomization. Costs were expressed in 2018 US dollars. Effectiveness was measured in quality-adjusted life years and the rate of salpingectomy. Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were generated. Sensitivity analyses were performed to assess the robustness of the analysis.
RESULTS: Methotrexate had the lowest mean cost ($875), followed by expectant management ($1085) and uterine evacuation ($1902) (P=.001). Expectant management had the highest mean quality-adjusted life years (0.1043), followed by methotrexate (0.1031) and uterine evacuation (0.0992) (P=.0001). The salpingectomy rate was higher for expectant management than for methotrexate (9.4% vs 1.2%, respectively; P=.02) and for expectant management than for uterine evacuation (9.4% vs 8.1%, respectively; P=.04). Uterine evacuation, with the highest costs and the lowest quality-adjusted life years, was dominated by both expectant management and methotrexate. In the base case analysis, expectant management was not cost-effective compared with methotrexate at a willingness to pay of $150,000 per quality-adjusted life year given an incremental cost-effectiveness ratio of $175,083 per quality-adjusted life year gained (95% confidence interval, -$1,666,825 to $2,676,375). Threshold analysis demonstrated that methotrexate administration would have to cost $214 (an increase of $16 or 8%) to favor expectant management. Moreover, expectant management would be favorable in lower-risk patient populations with rates of laparoscopic surgical management for ectopic pregnancy not exceeding 4% of pregnancies of unknown location. Based on the cost-effectiveness acceptability curves, the probability of expectant management being cost-effective compared with methotrexate at a willingness to pay of $150,000 per quality-adjusted life year gained was 50%. The results were dependent on the cost of surgical intervention and the expected rate of methotrexate failure.
CONCLUSIONS: The management of pregnancies of unknown location with a 2-dose methotrexate protocol may be cost-effective compared with expectant management and uterine evacuation. Although uterine evacuation was dominated, expectant management vs methotrexate results were sensitive to modest changes in treatment costs of both methotrexate and surgical management.
摘要：
背景：位置未知的持续妊娠（PUL）定义为非诊断性超声下血清人绒毛膜促性腺激素的异常趋势。关于优化管理没有共识。
目的：本研究旨在评估不明部位持续妊娠的三种主要管理策略之间的成本效益：（1）期待管理，(2)经验两剂甲氨蝶呤，（3）子宫排空，然后甲氨蝶呤，如果指示。
方法：我们在2014年7月至2019年6月进行了一项前瞻性经济学评估，同时进行了预期与积极管理治疗位置未知的持续妊娠（ACT或NOT）多中心随机试验。参与者被随机分为1：1：1，以期待管理，两次剂量的甲氨蝶呤,或子宫撤离。该分析是从医疗保健行业的角度进行的，随机化后的时间范围为6周。成本以2018美元表示。以质量调整寿命年（QALYs）和输卵管切除术率来衡量有效性。生成了增量成本效益比（ICER）和成本效益可接受性曲线。进行敏感性分析以评估分析的稳健性。
结果：甲氨蝶呤的平均成本最低，$875，其次是预期管理$1085，子宫排空$1902（p=0.001）。预期治疗的平均QALY最高（0.1043），其次是甲氨蝶呤（0.1031）和子宫排空（0.0992）（p=0.0001）。与甲氨蝶呤相比，期待管理的输卵管切除率更高（9.4％vs1.2％；p=0.02），与子宫排空相比，期待管理的输卵管切除率更高（9.4％vs8.1％；p=0.04）。子宫撤离,具有最高的成本和最低的QALY，以预期管理和甲氨蝶呤为主。在基本情况分析中，与愿意支付150,000美元/QALY的甲氨蝶呤相比，预期管理不具成本效益，考虑到ICER为175,083美元/QALY（95%CI，-1,666,825-2,676,375美元）。阈值分析表明，甲氨蝶呤给药必须花费214美元（增加16美元或8％）才能有利于预期管理。在低风险患者人群中，预期管理也将是有利的，腹腔镜手术治疗异位妊娠的比率不超过位置未知妊娠的4％。根据成本效益可接受性曲线，在支付意愿为$150,000/QALY时,与甲氨蝶呤相比,预期管理具有成本效益的概率为50%.结果取决于手术干预的费用，和预期的甲氨蝶呤失败率。
结论：与期待管理和子宫排空相比，使用两次甲氨蝶呤方案管理位置不明的妊娠可能具有成本效益。虽然子宫撤离占主导地位，预期管理与甲氨蝶呤的结果对甲氨蝶呤和手术管理的治疗费用的适度变化敏感。
目的：本研究旨在评估不明部位持续妊娠的三种主要管理策略之间的成本效益：（1）期待管理，(2)经验两剂甲氨蝶呤，（3）子宫排空，然后甲氨蝶呤，如果指示。
方法：我们在2014年7月至2019年6月进行了一项前瞻性经济学评估，同时进行了预期与积极管理治疗位置未知的持续妊娠（ACT或NOT）多中心随机试验。参与者被随机分为1：1：1，以期待管理，两次剂量的甲氨蝶呤,或子宫撤离。该分析是从医疗保健行业的角度进行的，随机化后的时间范围为6周。成本以2018美元表示。以质量调整寿命年（QALYs）和输卵管切除术率来衡量有效性。生成了增量成本效益比（ICER）和成本效益可接受性曲线。进行敏感性分析以评估分析的稳健性。
结果：甲氨蝶呤的平均成本最低，$875，其次是预期管理$1085，子宫排空$1902（p=0.001）。预期治疗的平均QALY最高（0.1043），其次是甲氨蝶呤（0.1031）和子宫排空（0.0992）（p=0.0001）。与甲氨蝶呤相比，期待管理的输卵管切除率更高（9.4％vs1.2％；p=0.02），与子宫排空相比，期待管理的输卵管切除率更高（9.4％vs8.1％；p=0.04）。子宫撤离,具有最高的成本和最低的QALY，以预期管理和甲氨蝶呤为主。在基本情况分析中，与愿意支付150,000美元/QALY的甲氨蝶呤相比，预期管理不具成本效益，考虑到ICER为175,083美元/QALY（95%CI，-1,666,825-2,676,375美元）。阈值分析表明，甲氨蝶呤给药必须花费214美元（增加16美元或8％）才能有利于预期管理。在低风险患者人群中，预期管理也将是有利的，腹腔镜手术治疗异位妊娠的比率不超过位置未知妊娠的4％。根据成本效益可接受性曲线，在支付意愿为$150,000/QALY时,与甲氨蝶呤相比,预期管理具有成本效益的概率为50%.结果取决于手术干预的费用，和预期的甲氨蝶呤失败率。
结论：与期待管理和子宫排空相比，使用两次甲氨蝶呤方案管理位置不明的妊娠可能具有成本效益。虽然子宫撤离占主导地位，预期管理与甲氨蝶呤的结果对甲氨蝶呤和手术管理的治疗费用的适度变化敏感。
