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Caughey AB, Sundaram V, Kaimal AJ, et al. Maternal and Neonatal Outcomes of Elective Induction of Labor. Rockville (MD): Agency for Healthcare Research and Quality (US); 2009 Mar. (Evidence Reports/Technology Assessments, No. 176.)

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

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Maternal and Neonatal Outcomes of Elective Induction of Labor.

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3Decision Analytic Model of Elective Induction of Labor

Given gaps in the available literature on elective induction of labor, we utilized decision and cost-effectiveness analyses to further address Key Questions 1 and 2, which compared elective induction of labor to expectant management of pregnancy. The advantage of utilizing decision analysis is that it allows us to explore some of the possible clinical implications of the information described in the meta-analysis as well as the implicit uncertainty in these data. For example, in decision analytic modeling, one of the first sensitivity analyses performed is the univariate analysis. This technique varies each point estimate in turn to determine what effect this factor has on the overall outcomes. In this setting, if varying the point estimates has little effect on the overall outcomes, one can be reassured that the results produced by the model are robust to uncertainty in these assumptions. Similarly, if a univariate sensitivity analysis produces change in the results, this guides investigators towards the need for greater certainty in the result from clinical studies. Based on these advantages, we utilized decision analysis as a complementary technique to the systematic review and present our methods and results in this chapter.

Decision Analytic Model Methods

We utilized decision analysis to characterize the expected outcomes in a population of pregnant women undergoing either induction of labor or expectant management of the pregnancy at or beyond a particular gestational age. The optimal timing of induction of labor depends on comorbidities of the pregnant patient, overall status of the developing fetus, and the potential complications associated with pursuing an induction of labor. While the clinical constraints of the obstetric population limit the number of management options that can be investigated in a prospective fashion, decision and cost-effectiveness analysis can be used to model the impact of induction strategies on clinical outcomes or cost in certain populations.125, 126 Similar to the way that clinicians integrate the prior probability of clinical outcomes of interest when making a management decision, decision-analytic models consider a hypothetical cohort of patients in a defined clinical scenario who experience the consequences of each management strategy based on their prior probability of each outcome being propagated through the decision tree structure. Correspondingly, the tree structure allows the assessment of multiple clinical outcomes as well as costs and cost-effectiveness.

To address the question of the consequences of induction of labor, we constructed decision trees to simulate clinical scenarios in which elective induction of labor might be considered as an alternative to expectant management of the pregnancy. Three separate models considering the question of elective induction of labor at 41, 40, and 39 weeks of gestation were created. Since expectant management beyond 40 weeks of gestation is usually accompanied by antenatal testing with a combination of a nonstress test (NST) and amniotic fluid index (AFI), we included these interventions in the expectant management arms of the models for the 40 and 41 weeks models, but not between 39 and 40 weeks gestation in the 39 week model. Since the medical comorbidities of pregnant women may lead to an indicated induction of labor at any gestational age, the hypothetical cohort entering the decision tree consisted of women with low risk, singleton, cephalic gestations. In addition, since nulliparous women tend to incur increased costs during labor92 and have a higher likelihood of cesarean delivery in comparison to multiparous patients, we considered all patients to be nulliparous with the attendant increased risks in order to provide the most conservative estimate of the consequences of induction of labor. Decision-analytic models were developed with TreeAgePro 2007 software (TreeAge Software, Inc, Williamstown, MA).

Induction of labor for postterm pregnancy is currently recommended by the American College of Obstetricians and Gynecologists at 42 weeks gestation, so the first strategy assessed was induction of labor at 41 weeks versus expectant management of the pregnancy until 42 weeks (Figure 3.1). The literature shows an increase in intrauterine fetal demise127 and an increase in hypertensive complications of pregnancy with advancing gestational age.99 Thus, women undergoing expectant management could go into spontaneous labor (52 percent of ongoing pregnancies between 41 and 42 weeks), develop preeclampsia requiring induction of labor (1.2 percent), or have an intrauterine fetal demise (0.12 percent). As one of the primary clinical concerns with continuing pregnancy beyond term is the development of placental insufficiency leading to neonatal compromise or death, women undergoing expectant management in the model were subjected to antenatal testing consisting of a nonstress test and measurement of amniotic fluid volume in order to assess fetal well being and placental function. Women undergoing antenatal testing could therefore develop an indication for induction based on antenatal testing (14 percent of ongoing pregnancies 41–42 weeks). Women undergoing spontaneous or induced labor could experience downstream events including: 1) development of fetal macrosomia; 2) epidural placement; 3) mode of delivery, including spontaneous vaginal delivery, operative vaginal delivery, or cesarean delivery with potential for maternal mortality as a consequence (Figure 3.2); 4) severe perineal laceration, defined as a perineal laceration injuring the rectal sphincter; 5) shoulder dystocia with the possibility of brachial plexus injury or neonatal demise; and 6) meconium stained amniotic fluid with the possibility of meconium aspiration syndrome, potentially leading to neonatal demise (Figure 3.3). All women who reached a gestational age of 42 weeks with ongoing pregnancies underwent induction of labor at that time.

Figure 3.1. Schematic of Decision Tree for 41 week model.

Figure 3.1

Schematic of Decision Tree for 41 week model.

Figure 3.2. Mode of delivery for 39, 40, and 41 week models.

Figure 3.2

Mode of delivery for 39, 40, and 41 week models.

Figure 3.3. Maternal and Neonatal outcomes for 39, 40, and 41 week models.

Figure 3.3

Maternal and Neonatal outcomes for 39, 40, and 41 week models.

The second strategy assessed was induction of labor at 40 weeks versus expectant management of the pregnancy (Figure 3.4). Similar to the 41 week model, women undergoing expectant management incurred a risk of preeclampsia (1.2 percent) and intrauterine fetal demise (0.09 percent), as well as the possibility of spontaneous labor (39 percent). While fewer data exist evaluating or supporting antenatal testing starting at 40 week and given that placental insufficiency with a resultant increase in intrauterine fetal demise remains a clinical concern, women undergoing expectant management at 40 weeks also underwent antenatal testing consisting of a nonstress test and measurement of amniotic fluid volume, and could thereby develop indications for induction based on antenatal testing (5 percent). Women undergoing spontaneous or induced labor experienced the same downstream events as detailed for the 41 week model (Figure 3.2 and Figure 3.3). All women who reached a gestational age of 41 weeks with ongoing pregnancies underwent induction of labor at that time.

Figure 3.4. Schematic of Decision Tree for 40 week model.

Figure 3.4

Schematic of Decision Tree for 40 week model.

The third strategy assessed was induction of labor at 39 weeks (Figure 3.5). Given that it is not routine to perform antenatal testing in women with uncomplicated pregnancies at this gestational age, women undergoing expectant management continued pregnancy with the chance to develop spontaneous labor (24 percent), preeclampsia (0.9 percent), or intrauterine fetal demise (0.05 percent), but did not undergo antenatal testing. Induction of labor at 39 weeks was compared both to ongoing pregnancy until 40 weeks with induction of labor at that time, and to ongoing pregnancy until 40 weeks followed by initiation of antenatal testing at 40 weeks with induction of labor at 41 weeks. All women underwent induction at 41 weeks. Women undergoing spontaneous or induced labor experienced the same downstream events detailed for the models above. Since 39 weeks is the gestational age beyond which ACOG allows elective induction of labor or cesarean delivery without assessment of fetal lung maturity, this is the earliest gestational age that was assessed for entry into the model.

Figure 3.5. Schematic of Decision Tree for 39 week model.

Figure 3.5

Schematic of Decision Tree for 39 week model.

In sum, three different management strategies were investigated: 1) Induction of labor at 41 weeks versus expectant management with antenatal testing until 42 weeks; 2) Induction of labor at 40 weeks versus expectant management with antenatal testing until 41 weeks; 3) Induction of labor at 39 weeks versus expectant management until induction of labor at 40 weeks or antenatal testing at 40 weeks followed by induction of labor at 41 weeks.

Probabilities. We entered probability estimates into the model from the published literature; these are displayed in Table 3.1. We primarily obtained information regarding cesarean delivery rate from the national birth cohort data set, a retrospective cohort of all term, singleton deliveries in the United States in 2003. Earlier studies indicated that induction of labor is associated with an increased risk of cesarean delivery; however, this was not confirmed in more recent meta-analyses,90, 91 the current systematic review, nor has it been observed in the national birth cohort data. Therefore, three separate baseline models were created: (a) a model with a decreased risk of cesarean delivery in women undergoing elective induction of labor; (b) a model with the cesarean delivery risk equivalent in the two groups; and (c) a model with an increased risk of cesarean delivery in women undergoing elective induction of labor. The current meta-analysis found a 22 percent decrease in the risk of cesarean delivery with induction; therefore, we assessed the impact of a 22 percent increase or decrease in cesarean delivery rate with induction. The impact of this assumption was further tested in sensitivity analyses which widely varied the risk of cesarean delivery in the two groups.

Table 3.1. Probability estimates.

Table 3.1

Probability estimates.

Perineal lacerations are a common effect of vaginal deliveries; they are categorized from first to fourth degree based on the vaginal, perineal, or rectal tissues involved. We defined a severe perineal laceration as a third or fourth degree laceration, involving injury to the rectal sphincter. Severe perineal lacerations can lead to increased blood loss, prolonged length of stay, and less certain long term effects on continence and symptoms of vaginal prolapse. We applied the probability of severe perineal laceration based on gestational age. Operative vaginal delivery carried an increased risk of severe perineal laceration at every gestational age.

Macrosomia, a neonatal complication defined as birthweight greater than 4000 grams, carries with it increased risk of operative vaginal delivery, cesarean delivery, and shoulder dystocia.128 As the fetus continues to grow throughout gestation, the likelihood of macrosomia increases with ongoing pregnancy, and therefore we applied gestational age specific estimates. A risk ratio of 1.52 for cesarean section was applied in the case of macrosomia.129 Shoulder dystocia is a clinical diagnosis, made during vaginal delivery when the extraction of the fetal shoulders is difficult. The long term clinical sequelae of shoulder dystocia may include permanent neonatal brachial plexus injury or neonatal demise. The risk of shoulder dystocia increases with increasing birthweight, and is higher in the case of operative vaginal delivery as compared to spontaneous vaginal delivery. We applied baseline estimates of shoulder dystocia based on the likelihood of macrosomia, and we applied a risk ratio of 1.74 for shoulder dystocia in the setting of operative vaginal delivery.129

Meconium is the greenish substance present in the intestinal tract of the developing fetus, comprised primarily of sloughed skin and GI tract cells and breakdown products of hemoglobin. Meconium is usually passed by the fetus at or near the time of delivery. The likelihood of passage of meconium in utero increases with fetal stress such as hypoxia as well as increasing gestational age. As such, the finding of meconium stained fluid increases the clinician's index of suspicion that a fetus may be at risk of neonatal compromise. For the purposes of this model, we report meconium stained fluid as a clinical outcome of interest; the effects of the presence of meconium on the decision making of practitioners cannot be quantified as the effect may be subtle and vary considerably. A small proportion of infants born through meconium stained amniotic fluid will develop meconium aspiration syndrome, which occurs when the fetus breathes in amniotic fluid containing meconium; the meconium results in blockage and irritation of the airways, resulting in respiratory distress, which may resolve or lead to neonatal demise.

Preeclampsia is defined as elevated blood pressures and proteinuria associated with pregnancy, and is cured by delivery. Complications of preeclampsia include abruption, seizure, stroke, and maternal renal compromise. In pregnancies greater than 37 weeks, the rate of preeclampsia increases with increasing gestational age.99 Once a woman reaches a gestational age greater than 37 weeks, induction of labor is indicated when preeclampsia is diagnosed in order to decrease the likelihood of maternal or neonatal compromise.

Utilities. Outcomes from medical decisions can affect both the quality and quantity of life expected. The quality adjusted life year (QALY) is a measure that has been created in order to combine both of these effects. Essentially, it is the product of life expectancy multiplied by the quality of life of the health states that a person experiences. Utilities are a measure of quality of life, usually expressed on a 0 to 1 scale, which assesses how a patient values a health state. Methods for eliciting the value of particular outcomes are usually based on the idea of trade-offs of either risk or time, with participants being asked what risk of a worse outcome they would take to avoid a particular outcome138 or how many years of health in a certain state they would be willing to give up in order to be in perfect health for a shorter time.139

QALYs were based on maternal life expectancy estimates from the national birth/death statistics, assuming a discount rate of 0.03 (Table 3.2). Women experienced a slight decrement in utility in the case of a cesarean delivery, which was applied over their reproductive life, assuming an average age at menopause of 50. In the case of a neonatal demise or IUFD, maternal utility was decreased to 0.92, an estimate for women who experience a miscarriage.140 As we felt that this was likely an underestimate of the decrement in utility that would be experienced after an intrauterine fetal demise at term, this was applied for the remainder of the woman's life. Due to a paucity of data, the utility of induction of labor, perineal laceration, and neonatal complications not resulting in neonatal demise could not be assessed. Similarly, a decrease in neonatal QALYs based on meconium aspiration and shoulder dystocia could not be assessed. As the neonatal outcomes were all improved in the induction of labor arm, this only made the model more conservative with respect to intervention.

Table 3.2. Utility estimates.

Table 3.2

Utility estimates.

Costs. We included direct costs of hospitalization such as equipment, medication, supplies, and nursing and physician staffing costs, as well as indirect costs for hospital overhead and administration. All costs were obtained from the literature and projected to 2007 dollars by inflation with the medical component of the consumer price index (Table 3.3). Costs were applied for maternal interventions only. The estimated costs were: Vaginal delivery $7213, cesarean delivery $11092, additional cost of induction of labor $1237, and epidural $788. The cost of antenatal testing of $210 was calculated for twice weekly nonstress tests and assessment of amniotic fluid volume.

Table 3.3. Cost estimates.

Table 3.3

Cost estimates.

Analytic approach. We conducted analyses from a societal perspective. Baseline analyses consisted first of generating costs and QALYs for each strategy to determine the strategy that minimized costs, the strategy that maximized utility, and cost effectiveness, the incremental cost required for increased QALYs.143

We evaluated a variety of clinical outcomes including: Cesarean delivery, macrosomia, shoulder dystocia, permanent injury from shoulder dystocia, intrauterine fetal demise, meconium stained fluid, meconium aspiration syndrome, and severe perineal laceration. We calculated each of these outcomes in the setting of either elective induction of labor or expectant management of pregnancy for a theoretical cohort of 10,000 women.

Sensitivity analysis is a technique to investigate how projected outcomes are affected when key assumptions are varied. We performed univariate sensitivity analysis for every input probability and cost; probabilities were varied from 50 to 150 percent of their baseline, and costs were varied from 50 to 400 percent of their baseline. In each case, we evaluated the effect on the model outcomes of varying the input around the original point estimate. Given that one of the potentially contentious assumptions of the model is that induction of labor results in a decrease in cesarean delivery rate, we examined the effect of varying the cesarean delivery rate on cost, utility, cost effectiveness, and clinical outcomes.

After examining the impact of varying one probability across its feasible range while holding other probabilities at their baseline, we examined the impact of simultaneously varying two estimates using two way sensitivity analysis. We identified candidate variables for two-way sensitivity analysis based on theoretical impact and results of one-way sensitivity analysis.

We also tested the impact of simultaneous changes in multiple inputs through Monte Carlo simulation. In this technique, each input probability, utility, and cost is defined by a distribution of possible values, rather than point estimates. We performed 1,000 Monte Carlo trials. In each trial, a different input probability, cost and utility is chosen from the underlying distribution. Analyzing the outcome of these 1,000 trials thus provides an estimate of the stability of our conclusions despite the simultaneous uncertainty in input assumptions.

We used beta distributions for probability and utility input variables. Beta distributions are the multivariate equivalent of binomial distributions, in that they are bounded between zero and one. We used gamma distributions for the costs. Gamma distributions are like normal distributions, except they are right-skewed. Thus, they are an accurate representation of medical cost distributions as some individuals will have costs that far exceed the mean.

Both beta and gamma distributions are defined by their mean and spread. We used the baseline model estimates as the distribution means. To estimate standard deviations, we utilized reasonable assumptions, which in general, allowed for very large spreads. For probabilities, we used +/- 0.05 to +/- 0.2 depending on the size of the baseline probability. Similarly, we allowed for +/- $200 to $1000 for costs depending on the size of the baseline cost.

Decision Analytic Model Results

Induction of labor at 41 weeks versus expectant management from 41–42 weeks

Decision analytic results. Induction of labor at 41 weeks was superior to expectant management with an average of 56.910 total QALYs with an induction of labor at 41 weeks versus an average of 56.876 total QALYS with expectant management: An incremental gain of 0.033 QALYs. Table 3.4 shows the maternal, neonatal, and total QALYs for each strategy.

Table 3.4. Decision analytic results for induction of labor at 41 weeks versus expectant management.

Table 3.4

Decision analytic results for induction of labor at 41 weeks versus expectant management.

Clinical outcomes. In terms of clinical outcomes, induction of labor at 41 weeks as opposed to expectant management results in lower rates of neonatal demise, pre-eclampsia, macrosomia, shoulder dystocia, meconium-stained amniotic fluid, meconium aspiration syndrome, severe perineal laceration and operative vaginal delivery. Table 3.5 demonstrates the clinical outcomes associated with each strategy for a cohort of 10,000 women.

Table 3.5. Clinical outcomes per 10,000 women for induction of labor at 41 weeks versus expectant management.

Table 3.5

Clinical outcomes per 10,000 women for induction of labor at 41 weeks versus expectant management.

Cost and cost-effectiveness results. Induction of labor at 41 weeks is more expensive as compared to expectant management. The average cost per woman of an induction at 41 weeks is $10,139 as compared to $9770 for expectant management for an average incremental cost of $368 per induction. In terms of cost-effectiveness, we find that it would cost an additional $10,789 per additional QALY. Typically, interventions are considered cost-effective if they are less than $50,000 to $100,000 per QALY. Thus, induction of labor at 41 weeks is a cost-effective intervention by conventional thresholds for cost effectiveness.

Impact of the cesarean delivery rate on outcomes. One of the key and potentially controversial assumptions in the model is that induction of labor leads to a lower cesarean delivery rate as compared to expectant management. To fully appreciate the impact of this assumption on model outcomes, we ran the model under three separate assumptions: (1) cesarean delivery rates are equal in the induction as compared to expectant management group [our baseline assumption] (2) cesarean delivery rates are 22 percent less in the induction as compared to the expectant management group [Chapter 2] (3) cesarean delivery rates are 22 percent more in the induction as compared to the expectant management group.

In terms of decision analytic results, the cesarean delivery rate has only a marginal impact (Table 3.6). In our baseline model, induction of labor leads to an incremental QALY gain of 0.033 QALYs. Based on the meta-analysis presented in Chapter 2, it appears that induction of labor is associated with a 22 percent decrease in cesarean delivery rate; this would lead to an increase in the incremental QALYs gained to 0.046. Conversely, assuming that induction of labor was associated with a 22 percent increase in the cesarean delivery rate led to a decrease in the incremental QALYs gained to 0.023 QALYs.

Table 3.6. Decision analytic results with varying assumptions in cesarean delivery rates.

Table 3.6

Decision analytic results with varying assumptions in cesarean delivery rates.

Similarly, we tested the impact of cesarean delivery rates on clinical outcomes. Table 3.7 shows the clinical outcomes per 10,000 women for induction versus expectant management at 41 weeks under the same variations in cesarean delivery rate. As shown, the cesarean delivery rate had no effect on most outcomes, and only a very modest impact on shoulder dystocia and perineal laceration. Because the incidence of these complications increases with gestational age, induction of labor is always beneficial in terms of shoulder dystocia and perineal lacerations; interestingly, since varying the relative risk of cesarean delivery affects the number of women at risk for these complications, the relative benefit increases as the likelihood of cesarean delivery with induction increases.

Table 3.7. Clinical outcomes with various assumptions in the cesarean delivery rate.

Table 3.7

Clinical outcomes with various assumptions in the cesarean delivery rate.

Finally, we tested the impact of cesarean delivery rates on the cost and cost-effectiveness calculations. Under all three assumptions, induction of labor at 41 weeks as compared to expectant management was a cost-effective strategy. Using our baseline assumption that the cesarean delivery rate is equal in either scenario, the incremental cost per QALY is $10,789. Based on the review of the literature performed in this report, the cesarean delivery rate is 22 percent lower with an induction; under that assumption, the incremental cost per QALY is $3023. Next, we assumed that the cesarean delivery rate is 22 percent higher with an induction, and the incremental cost per QALY increased to $26,450. Table 3.8 shows the cost and cost-effectiveness outcomes under the various cesarean delivery rate assumptions.

Table 3.8. Cost-effectiveness of an induction versus expectant management at 41 weeks under various cesarean delivery rate assumptions.

Table 3.8

Cost-effectiveness of an induction versus expectant management at 41 weeks under various cesarean delivery rate assumptions.

Univariate sensitivity analysis. Univariate sensitivity analysis was performed on each input variable in the model. We varied all probabilities from 50 percent to 150 percent of baseline. We varied costs from 50 percent to 400 percent of baseline. Below are highlighted some of the important findings.

Probabilities. As described above, the relative cesarean delivery rate for expectant management versus induction is both important and uncertain. Figure 3.6 demonstrates the impact of varying the relative rate over a wide range. Induction is cost-effective up to 148 percent of baseline cesarean risk with induction of labor at a willingness to pay threshold of $100,000.

Figure 3.6. Sensitivity analysis varying relative risk of cesarean delivery with induction.

Figure 3.6

Sensitivity analysis varying relative risk of cesarean delivery with induction.

Figure 3.7 shows the impact of the spontaneous labor rate. If the rate of spontaneous labor between 41 and 42 weeks is 25 percent or less, induction of labor at 41 weeks is the dominant option. It remains cost-effective for the entire range; at 150 percent of baseline (78 percent) it costs $24,710 per additional QALY.

Figure 3.7. Sensitivity analysis varying probability of spontaneous labor before 42 weeks.

Figure 3.7

Sensitivity analysis varying probability of spontaneous labor before 42 weeks.

Costs. The model was slightly more sensitive to changes in cost inputs. However, as stated above, induction of labor was always the cost-effective strategy.

Induction of labor is cost-effective at an antenatal testing cost of $105 (50 percent of baseline) at $13,839 per QALY. At an antenatal testing cost of $600 (300 percent of baseline), induction of labor becomes the dominant option. As the cost of labor induction increases, the cost-effectiveness of labor induction decreases to $59,316 per QALY at 400 percent of baseline estimates (an additional $5000 per IOL).

Two-way sensitivity analysis. Two-way sensitivity analysis was also performed to examine the effect of simultaneously varying two inputs. First, we investigated the impact of varying the probability of spontaneous labor within the next week along with the relative risk of cesarean delivery with induction of labor. Clinically, the determinants of successful induction may be similar to the predictors of spontaneous labor in the following week. However, sensitivity analysis shows that even when the likelihood of spontaneous labor is high, as long as the cesarean delivery rate is at least equal in the expectant management and induction arms, induction remains a cost effective intervention. Next, we explored the effect of varying the relative risk of cesarean delivery and the additional cost of labor induction. In women with the lowest likelihood of successful induction, additional costs may be incurred as the induction process may be prolonged. Induction remained cost effective across all cost estimates. Examining this from a different perspective, the additional cost of labor induction may be varied with the likelihood of spontaneous labor in the next week. Given that the baseline estimate of spontaneous labor is 52 percent, induction of labor remains cost effective even if the additional cost is increased to 400 percent of the baseline, with the likelihood of spontaneous labor increasing to 150 percent of the baseline.

Monte Carlo simulation

Multivariate sensitivity analysis, or Monte Carlo simulation, is performed to test the robustness to simultaneous changes in multiple input variables. We found that in 24 percent of the trials induction of labor at 41 weeks was the dominant strategy (i.e., less expensive and more effective). In all remaining trials it was more effective, but also more expensive. Figure 3.8 illustrates the distribution of incremental costs and effectiveness for induction of labor compared to expectant management at 41 weeks. Each trial is represented by a different dot. The 95 percent confidence interval is shown by the elliptical borders (i.e., 95 percent of all trials fall within this boundary).

Figure 3.8. Incremental cost effectiveness for induction of labor compared with expectant management at 41 weeks.

Figure 3.8

Incremental cost effectiveness for induction of labor compared with expectant management at 41 weeks.

Figure 3.9 shows the acceptability curve which illustrates the proportion of all trials in which each strategy is cost-effective at various willingness-to-pay thresholds. Using a willingness-to-pay threshold of $100,000, induction of labor at 41 weeks is cost-effective in 98.5 percent of the trials. At a willingness to pay of $50,000, it is cost-effective in 95.1 percent of trials. In other words, we can be 95 percent confident that if women are willing to pay at least $50,000 for one additional QALY, then induction of labor at 41 weeks would be a cost-effective intervention.

Figure 3.9. Acceptability curve.

Figure 3.9

Acceptability curve.

Induction of labor at 40 weeks versus expectant management from 40–41 weeks

Decision analytic results. Induction of labor at 40 weeks is superior to expectant management until 41 weeks, with an average of 56.916 total QALYs for an induction of labor at 40 weeks versus an average of 56.889 total QALYS for expectant management: An incremental gain of 0.027 QALYs. Table 3.9 shows the maternal, neonatal, and total QALYs for each strategy.

Table 3.9. Decision analytic results for induction of labor at 41 weeks versus expectant management.

Table 3.9

Decision analytic results for induction of labor at 41 weeks versus expectant management.

Clinical outcomes. In terms of clinical outcomes, induction of labor at 40 weeks compared to expectant management results in a lower rate of all adverse obstetric outcomes, including neonatal demise, pre-eclampsia, macrosomia, shoulder dystocia, meconium-stained amniotic fluid, meconium aspiration syndrome, severe perineal lacerations, and operative vaginal deliveries. Table 3.10 demonstrates the clinical outcomes associated with each strategy for a cohort of 10,000 women.

Table 3.10. Clinical outcomes per 10,000 women for induction of labor at 40 weeks versus expectant management until 41 weeks.

Table 3.10

Clinical outcomes per 10,000 women for induction of labor at 40 weeks versus expectant management until 41 weeks.

Cost and cost-effectiveness results. Induction of labor at 40 weeks is more expensive as compared to expectant management. The average cost per woman of an induction at 40 weeks is $10,030 compared to $9760 for expectant management, for an average incremental cost of $269 per induction. In terms of cost-effectiveness, it would cost an additional $9932 per added QALY; thus, induction of labor at 40 weeks is a cost-effective intervention.

Impact of the cesarean delivery rate on outcomes. Similar to the 41 week model, we performed the 40 week model under three separate assumptions about the cesarean delivery rate: (1) cesarean delivery rates are equal in the induction as compared to expectant management group [our baseline assumption] (2) cesarean delivery rates are 22 percent less in the induction as compared to the expectant management group, as would be expected based on the meta-analysis presented in Chapter 2; and (3) cesarean delivery rates are 22 percent higher in the induction as compared to the expectant management group.

As with the 41 week model, the cesarean delivery rate had only a marginal impact (Table 3.11). In our baseline model, induction of labor leads to an incremental QALY gain of 0.027 total QALYs. Assuming a 22 percent decrease in the cesarean delivery rate with induction of labor, the incremental QALY gain increases to 0.037. Assuming that induction of labor was associated with a 22 percent increase in the cesarean delivery rate, the incremental QALY gain decreases to 0.016 QALYs.

Table 3.11. Decision analytic results with varying assumptions in cesarean delivery rates.

Table 3.11

Decision analytic results with varying assumptions in cesarean delivery rates.

Table 3.12 shows the clinical outcomes per 10,000 women for induction versus expectant management at 40 weeks under the same variations in cesarean delivery rate assumptions. The categories with any change in the cesarean delivery rate are displayed in bold text.

Table 3.12. Clinical outcomes with various assumptions in the cesarean delivery rate.

Table 3.12

Clinical outcomes with various assumptions in the cesarean delivery rate.

The impact of cesarean delivery rates on the cost and cost-effectiveness calculations are shown below. Under all three assumptions, induction of labor at 40 weeks is a cost-effective strategy as compared to expectant management. Using the baseline assumption that the cesarean delivery rate is equal, the incremental cost is $9932 per QALY. If the cesarean delivery rate is 22 percent lower for induction of labor at 40 weeks, the incremental cost is $1692 per QALY. Table 3.13 shows the cost and cost-effectiveness outcomes under the various cesarean delivery rate assumptions.

Table 3.13. Cost and Cost-Effectiveness for induction versus expectant management under various cesarean delivery rate assumptions.

Table 3.13

Cost and Cost-Effectiveness for induction versus expectant management under various cesarean delivery rate assumptions.

Univariate sensitivity. Univariate sensitivity analysis was performed on each input variable in the 40 week model. Again, all probabilities were varied from 50 percent to 150 percent of baseline. We varied costs from 50 percent to 400 percent of baseline.

Probabilities. Figure 3.10 demonstrates the impact of varying the relative rate of cesarean delivery for an induction compared to expectant management over a wide range. As shown, induction of labor is the dominant strategy if the relative risk of cesarean delivery in the induction group is less than 76 percent of the rate of cesarean delivery in the expectant management group. Induction is cost-effective up to 144 percent of the baseline.

Figure 3.10. Sensitivity analysis varying relative risk of cesarean delivery with induction.

Figure 3.10

Sensitivity analysis varying relative risk of cesarean delivery with induction.

Figure 3.11 illustrates the impact of the spontaneous labor rate. If the rate of spontaneous labor between 40 and 41 weeks is 20 percent or less, induction of labor at 40 weeks is the dominant option. It remains cost-effective all the up to 200 percent of baseline (78 percent) at $31,368 per QALY.

Figure 3.11. Sensitivity analysis varying probability of spontaneous labor.

Figure 3.11

Sensitivity analysis varying probability of spontaneous labor.

Costs. The model was more sensitive to changes in cost inputs. However, induction of labor was always the cost-effective strategy. Induction of labor is cost-effective at $12,635 per QALY to an antenatal testing cost of $105 (50 percent of baseline). At an antenatal testing cost of $450 (200 percent of baseline estimates) induction of labor becomes the dominant option. As the cost of labor induction increases, the cost-effectiveness of labor induction decreases to $56,218 per QALY at the 400 percent of baseline estimates (an additional $5000 per induction).

Two-way sensitivity analysis. Similar to the results in the 41 week model, even if the likelihood of spontaneous labor is higher than expected, and the cesarean delivery rate is at least equal in the expectant management and induction arms, induction remains a cost effective intervention. In women with the lowest likelihood of successful induction, additional costs may be incurred as the induction process may be prolonged. If induction continues to confer either an equal or a decreased risk of cesarean delivery in comparison to expectant management, even if the additional cost of induction of labor increases to twice the baseline estimate, induction of labor remains cost effective.

Monte Carlo simulation. We performed multivariate sensitivity analysis, or Monte Carlo simulation, to test the robustness to simultaneous changes in multiple input variables. Figure 3.12 demonstrates the distribution of incremental costs and effectiveness for induction of labor as compared to expectant management at 40 weeks. Each trial is represented by a different dot. The 95 percent confidence interval is shown by the elliptical line (i.e. 95 percent of all trials fall within this boundary). In this multivariate sensitivity analysis, elective induction of labor is only cost-effective in approximately 55 percent of trials (Figure 3.13) as compared to well over 95 percent of the trials in the 41 week model and is even dominated by expectant management in a proportion of cases.

Figure 3.12. Monte Carlo simulation of induction of labor versus expectant management at 40 weeks of gestation.

Figure 3.12

Monte Carlo simulation of induction of labor versus expectant management at 40 weeks of gestation.

Figure 3.13. Acceptability curve.

Figure 3.13

Acceptability curve. Figure 3.13 is the acceptability curve which demonstrates the proportion of all trials in which each strategy is cost-effective at various willingness-to-pay thresholds. Using a willingness-to-pay threshold of $100,000, induction (more...)

Induction of labor at 39 weeks versus expectant management from 39–40 weeks and expectant management from 39–41 weeks

Decision analytic results. Induction of labor at 39 weeks is superior to expectant management until 40 or 41 weeks, with an average of 56.920 total QALYs for induction at 39 weeks versus an average of 56.903 total QALYS for expectant management until 40 weeks and 56.877 for expectant management until 41 weeks. This represents an incremental gain of 0.017 QALYs for induction at 39 weeks compared to expectant management until 40 weeks and an incremental gain of 0.033 QALYs for an induction as compared to expectant management until 41 weeks. Table 3.14 shows the maternal, neonatal, and total QALYs for each strategy;

Table 3.14. Decision analytic results for induction of labor at 39 weeks versus expectant management.

Table 3.14

Decision analytic results for induction of labor at 39 weeks versus expectant management.

Clinical outcomes. In terms of clinical outcomes, induction of labor at 39 weeks compared to expectant management until either 40 or 41 weeks leads to a lower rate of all adverse obstetric outcomes, including neonatal demise, pre-eclampsia, macrosomia, shoulder dystocia, meconium-stained amniotic fluid, meconium aspiration syndrome, severe perineal lacerations, and operative vaginal deliveries. Table 3.15 shows the clinical outcomes associated with each strategy for a cohort of 10,000 women.

Table 3.15. Clinical outcomes per 10,000 women for induction of labor at 39 weeks versus expectant management until 40 or 41 weeks.

Table 3.15

Clinical outcomes per 10,000 women for induction of labor at 39 weeks versus expectant management until 40 or 41 weeks.

Cost and cost-effectiveness results. Induction of labor at 39 weeks is more expensive compared to expectant management until either 40 or 41 weeks. The average cost per woman of an induction at 39 weeks is $9,568 versus $9253 for expectant management until 40 weeks and $8915 for expectant management until 41 weeks. Thus, the incremental cost per woman induced is $316 compared to expectant management to 40 weeks and $338 per woman expectantly managed to 40 weeks compared to expectant management until 41 weeks. In terms of cost-effectiveness, it costs an additional $20,222 per additional QALY compared to expectant management until 40 weeks and an additional $13,900 per additional QALY as compared to expectant management until 41 weeks. Thus, induction of labor at 39 weeks is the most cost-effective strategy at any reasonable willingness-to-pay threshold.

Considering maternal QALYs alone, however, induction of labor at 39 weeks is not cost effective, as induction costs an additional $269,151 per QALY compared to induction at 40 weeks, and is more expensive and only equally effective compared to induction at 40 weeks (see table 3.18 below).

Table 3.18. Cost and cost-effectiveness for induction versus expectant management under various cesarean delivery rate assumptions.

Table 3.18

Cost and cost-effectiveness for induction versus expectant management under various cesarean delivery rate assumptions.

Impact of the cesarean delivery rate on outcomes. As with the previous models, we examined the 39 week model under three separate assumptions about the cesarean delivery rate: (1) cesarean delivery rates are equal in the induction and expectant management groups [our baseline assumption] (2) cesarean delivery rates are 22 percent less in the induction compared to the expectant management group; and (3) cesarean delivery rates are 22 percent more in the induction as compared to the expectant management groups.

In our baseline model, induction of labor leads to an incremental QALY gain of 0.017 QALYs for an induction compared to expectant management until 40 weeks and an incremental gain of 0.033 QALYs for an induction as compared to expectant management until 41 weeks. Assuming that induction of labor led to a 22 percent decrease in cesarean delivery rate, the incremental QALY gain increases to 0.027 and 0.043, respectively. If induction of labor is associated with a 22 percent increase in the cesarean delivery rate the incremental QALY gain decreases to 0.007 and 0.023 QALYs, respectively (Table 3.16).

Table 3.16. Decision analytic results with varying assumptions in cesarean delivery rates.

Table 3.16

Decision analytic results with varying assumptions in cesarean delivery rates.

Similarly, we tested the impact of cesarean delivery rates on clinical outcomes. Table 3.17 displays the clinical outcomes per 10,000 women for induction versus expectant management until 40 and 41 weeks under the same variations in cesarean delivery rate.

Table 3.17. Clinical outcomes with various assumptions in the cesarean delivery rate.

Table 3.17

Clinical outcomes with various assumptions in the cesarean delivery rate.

The impact of cesarean delivery rates on the cost and cost-effectiveness calculations are shown in Table 3.18. Unlike the previous models, the cesarean delivery rate assumptions impact the cost-effectiveness conclusions for this model. While induction of labor is cost-effective as compared to expectant management, the cost per QALY has increased. Additionally, when examining maternal QALYs, with an increased in the cesarean delivery rate of 22 percent per induction, induction of labor is both more expensive and less effective (hence dominated) as compared to expectant management until 40 weeks.

Univariate sensitivity. Univariate sensitivity analysis was performed on each input variable in the 39 week model. Again, all probabilities were varied from 50 percent to 150 percent of baseline. Similarly, costs were varied from 50 percent to 400 percent of baseline. Given the findings of the previous models showing cost-effectiveness of induction of labor at 40 weeks, induction of labor at 39 weeks was compared to expectant management until 40 weeks. Unlike the previous models, however, this model was not uniformly robust. Highlighted below are the key findings.

Probabilities. Figure 3.14 demonstrates the impact of varying the relative rate of cesarean delivery for an induction at 39 weeks compared to expectant management until 40 weeks over a wide range. As shown, the model is quite sensitive to the risk of cesarean delivery with induction compared to expectant management until 40 weeks. Induction of labor is the dominant strategy if the rate of cesarean delivery is less than 75 percent of the cesarean rate with expectant management. Induction is cost-effective at $50,000 until the risk of cesarean delivery is 14 percent higher with an induction. Induction is cost-effective at $100,000 until the risk of cesarean delivery is 22 percent higher with induction, and at an increased risk of 35 percent or higher, induction of labor is dominated (more expensive and less effective) as compared to expectant management until 40 wks.

Figure 3.14. Sensitivity analysis on relative rate of cesarean delivery with IOL at 39 weeks.

Figure 3.14

Sensitivity analysis on relative rate of cesarean delivery with IOL at 39 weeks.

Figure 3.15 shows the impact of the spontaneous labor rate. Induction of labor is cost-effective compared to expectant management until 40 weeks over the entire range. If the rate of spontaneous labor is half of the baseline rate (12 percent) then induction of labor at 39 weeks costs $9337 per addition QALY. If the rate of spontaneous labor is 2 times baseline (48 percent) then induction of labor costs $39,013 per QALY.

Figure 3.15. Sensitivity analysis on probability of Spontaneous Labor 39–40 weeks.

Figure 3.15

Sensitivity analysis on probability of Spontaneous Labor 39–40 weeks.

Costs. Induction of labor is the cost effective option down to 50 percent of the baseline cesarean delivery costs. As the cost of labor induction increases, the cost-effectiveness of labor induction decreases. Induction of labor is cost-effective at a willingness-to-pay threshold of $100,000 over the entire range. At a threshold of $50,000 per QALY, it is cost-effective to $4123 (330 percent of baseline).

Two-way sensitivity analysis. Figure 3.16 illustrates the impact of varying the probability of spontaneous labor within the next week along with the relative risk of cesarean delivery with induction of labor. Of note, all two-way sensitivity analyses for this model use a willingness to pay threshold of $50,000. Unlike the previous models, this model was not as robust. Figure 3.20 illustrates that when the likelihood of spontaneous labor is higher than expected, induction of labor remains cost-effective only if the probability of cesarean delivery with an induction is the same as the likelihood of cesarean delivery with expectant management (relative risk of cesarean delivery with induction of 1).

Figure 3.16. Net monetary benefit (willingness to pay=50000) sensitivity analysis on relative risk of cesarean delivery IOL at 39 weeks and probability of spontaneous labor at 39 weeks.

Figure 3.16

Net monetary benefit (willingness to pay=50000) sensitivity analysis on relative risk of cesarean delivery IOL at 39 weeks and probability of spontaneous labor at 39 weeks.

Figure 3.20. Acceptability Curve.

Figure 3.20

Acceptability Curve.

Figure 3.17 illustrates the effect of varying the relative risk of cesarean delivery and the additional cost of labor induction. In women with the lowest likelihood of successful induction, additional costs may be incurred as the induction process may be prolonged. As demonstrated, if an induction of labor costs an additional $2000, then induction of labor is cost-effective only if the relative risk of cesarean delivery with an induction is less than one.

Figure 3.17. New monetary benefit (willingness to pay=50000) sensitivity analysis on relative risk of cesarean delivery IOL and additional cost of labor induction.

Figure 3.17

New monetary benefit (willingness to pay=50000) sensitivity analysis on relative risk of cesarean delivery IOL and additional cost of labor induction.

Examining this from a different perspective, the additional cost of induction of labor may be varied with the likelihood of spontaneous labor in the next week, as seen in Figure 3.18. If the probability of spontaneous labor in the next week is low, then an induction of labor is cost-effective even at a higher additional cost.

Figure 3.18. Net monetary benefit (willingness to pay = 50000) sensitivity analysis on probability of spontaneous labor and additional cost of labor induction.

Figure 3.18

Net monetary benefit (willingness to pay = 50000) sensitivity analysis on probability of spontaneous labor and additional cost of labor induction.

Monte Carlo simulation. Multivariate sensitivity analysis, or Monte Carlo simulation, was performed to test the robustness to simultaneous changes in multiple input variables. In 29.5 percent of the trials, induction of labor at 39 weeks was the dominant strategy (less expensive and more effective). In 25.7 percent of trials it was more effective but more costly, and in 44.8 percent of the trials it was dominated (less effective and more costly). Figure 3.19 shows the distribution of incremental costs and effectiveness for induction of labor as compared to expectant management at 39 weeks. Each trial is represented by a different dot. The 95 percent confidence interval is shown by the elliptical line (i.e. 95 percent of all trials fall within this boundary).

Figure 3.19. Cost-Effectiveness Induction of labor at 39 weeks versus expectant management until 40 weeks.

Figure 3.19

Cost-Effectiveness Induction of labor at 39 weeks versus expectant management until 40 weeks.

Figure 3.20 is the acceptability curve, which demonstrates the proportion of all trials in which each strategy is cost-effective at various willingness-to-pay thresholds. Using a willingness-to-pay threshold of $100,000, induction of labor at 39 weeks is cost-effective in 52.5 percent of the trials. At a willingness to pay of $50,000, it is cost-effective in 49.5 percent of trials. As induction of labor is dominated by expectant management in 44.8 percent of trials, we can never be greater than 55.2 percent confident that induction of labor is cost-effective at any willingness to pay threshold.

In summary, our cost-effectiveness analysis suggests that elective induction of labor at 41 weeks improves maternal and fetal outcomes and is cost effective. Our analyses also suggest that elective induction of labor prior to 41 weeks may improve outcomes and could reach conventional thresholds for cost effectiveness. However, there is additional uncertainty about outcomes prior for elective induction prior to 41 weeks because less evidence is available. All of our model-based analyses should be considered exploratory and hypothesis generating, rather than definitive, because the strength of evidence for model inputs is generally low.

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