1. Implications of ARRIVE Elective Labor Induction in 2019
Brett D. Einerson, MD MPH
Maternal-Fetal Medicine

2. Disclosure
Funding from NICHD / MFMU to study the cost of the ARRIVE trial.

3. The Issues IOL is common IOL takes longer IOL is undesirable to some
Increasing risks after 39 weeks

4. Increasing Risk after 39 wks
Observational studies

5. Fetal Risk
from Greene, NEJM 2018

6. Neonatal Risk Severe neonatal morbidity: 41 vs 39 wks
Birth Trauma Sepsis
Seizures MAS
ICH RDS
41 vs 39 wks
aOR 2.04 (1.5 – 2.8)
40 vs 39 wks
aOR 1.47 (1.1 – 2.0)
Caughey 2005

7. Maternal Risk Operative vaginal delivery
3rd & 4th degree perineal lacerations
Postpartum hemorrhage
Febrile morbidity
Caughey 2007

8. Cesarean Risk
Cheng 2009
Garite 2000

9. …but IOL increases risk of CS
…in non-randomized studies
…compared to spontaneous labor

10. IOL Risk
”Patients undergoing induction of labor should be counseled about a 2 – fold increased risk of cesarean”
ACOG Practice Bulletin #107, 2009

11. A Randomized Trial of Induction Versus Expectant Management (ARRIVE)
Grobman et al. NEJM 2018

12. ARRIVE: Objective
To test the hypothesis that elective induction of labor at 39 weeks compared with expectant management among low-risk nulliparous women reduces the risk of a composite of perinatal mortality and severe neonatal morbidity

13. ARRIVE: Study Design Unmasked randomized trial Inclusion criteria:
Induction of Labor (IOL) at 39w
Expectant management (EM) until 40w5d
Inclusion criteria:
Nulliparous women
Singleton gestations
Reliably dated
Low risk

14. ARRIVE: Perinatal Outcomes*

15. ARRIVE: Maternal Outcomes* *

16. ARRIVE Conclusions Elective IOL in low-risk nullips at 39 wks
Does not increase perinatal risk
Is unlikely to increase cesarean
May decrease cesarean
May reduce hypertensive disorders
“…elective labor induction at 39 weeks did not results in greater frequency of perinatal adverse events…
“… and policies aimed at the avoidance of elective labor induction among low-risk nulliparous women at 39 weeks of gestation are unlikely to reduce the rate of cesarean…”

17. SMFM Recommendations
Reasonable to offer eIOL to ARRIVE- eligible women.
No eIOL for ARRIVE-ineligible women
Do impact studies

18. Joint ACOG/SMFM Guidance
Reasonable to offer eIOL to low risk nullips at 39 weeks
Consider carefully:
Values & preferences of women
Resources available
Protocols for failed inductions
“ACOG and SMFM have reviewed the published results of the ARRIVE Trial and determined that it is reasonable for obstetric care providers to offer an induction of labor to low-risk women after discussing the options thoroughly, as shared decision making is a critical element.  Women eligible for induction must meet the following criteria: 
Women who are planning their first delivery, are healthy and have no medical or obstetrical complications.
Women who are 39 weeks pregnant and had an ultrasound performed early in the pregnancy to confirm dating.
“It is important for all inductions of labor, as was done in this study, to adhere to clinical protocols that optimize the chances of a vaginal delivery. Elective induction of labor should not be offered to women under circumstances that are inconsistent with the study protocol unless performed as part of research or quality improvement. As induction of labor involves coordination between the health care provider and the infrastructure in which induction and delivery will occur, it is critical that personnel and facilities coordinate polices related to the offering of elective induction of labor. 
ACOG Practice Advisory 2018.

19. The Response
Critiques, Questions, and Calls for More Evaluation

20. Critiques of ARRIVE Too small to detect differences
Does not reflect (my) reality
Most patients did not enroll
Unmasking introduces bias
A single RCT should not change practice for millions of women

21. Critique
ARRIVE does not reflect reality

22. The ARRIVE Population Self selected (>73% didn’t enroll)
Obese (53%)
Young (24 yo)
Unfavorable cervix (63%)
Few (6%) used midwives
Compliant (94% adhered)
Low-risk: no medical or OB problems

23. The cesarean rate was too low
Median rate in California = 32%
Many hospitals in Florida = 40+%
Average in Utah = 17%
ARRIVE EM = 22.2% IOL = 18.6%
CMQCC 2018
CesareanRates.org

24. A trial is not reality
“it needs to be repeated that the results in this study were obtained in university hospitals with strict labor guidelines”
CMQCC 2018

25. Critique
Most patients did not enroll

26. Most patients didn’t enroll
An ARRIVE Patient was:
Interested in induction
Generally adherent to the protocol
We don’t know why women declined
Induction isn’t for everyone
Many are not interested in induction
Shared decision making is key

27. Critique
Unmasking introduces bias

28. Unmasking and Bias Unconscious bias could alter patient management
Quicker calls for CS in one group?
Direction of bias not clear
Unmasking was unavoidable

29. Critique
A single RCT should not change practice for millions of women each year.

30. “it takes many rigorous studies to establish an acceptable level of evidence to vastly change practice, especially when the implication is an additional and costly intervention.”
Phillippi and King 2018

31. ARRIVE does not stand alone
Retrospective studies of eIOL vs EM with results similar to ARRIVE
Osmundson OBG 2010 (Chicago)
Osmundson OBG 2011 (Chicago)
Cheng AJOG 2012 (California)
Stock BMJ 2012 (Scotland)
Darney OBG 2013 (California)

32. Questions about elective IOL
What about the obese? AMA?
What about the unfavorable cervix?
What about multips?
What is the cost ?!?

33. Obese 53% of ARRIVE participants BMI 30+ No interaction for obesity
Primary Composite RR 0.77 (0.58 – 1.22)
Cesarean RR 0.89 (0.79 – 1.00)
IOL appears to be effective in obese

34. AMA Only 4% of ARRIVE No interaction in subgroup analyses
Walker NEJM 2016
n=619, IOL vs EM in age 35+
Cesarean RR 0.99 (0.87 – 1.14)
No difference in maternal/neonatal outcomes

35. Unfavorable Cervix 63% of ARRIVE had Bishop <5
No interaction in subgroup analysis
Primary Composite RR 0.81 (0.61 – 1.06)
Cesarean RR 0.85 (0.76 – 0.95)
Risk factor for cesarean, but IOL still improved chance for SVD at given Bishop Score in ARRIVE (SMFM Abstract 794)

36. Multips
“it is unknown whether the findings can be extrapolated to multiparous women”
SMFM Consult Series 2018

37. The BIG Question
What will elective induction cost the system?

38. The BIG Question: what cost?
From the trial – IOL resulted in:
Fewer outpatient tests/visits
Shorter hospital stay
Longer L&D time (+6 hours)
Will costs saved be offset by increased use of L&D?

39. SMFM 2019, Abstract No. 2 Tally of resources utilized IOL
Fewer office/triage/ED visits
Fewer inpatient admissions
Longer L&D duration (median 20 vs 14 hr)
More ripening/induction agents
Less MgSO4 & Antibiotics
Less neonatal care
Grobman et al

40. Our Cost Analysis Knowing resources is great. Knowing cost is better.
Cost: not charge, not reimbursement
Measure costs at UT site (IHC + UofU)
N=1,230 (1/5 of entire ARRIVE trial)
Used advanced accounting analytics
Compared cost IOL vs EM

41. Cost of ARRIVE No difference in total cost +4.7% (95% CI -2.1%, 12.0%)
Intrapartum/delivery costs differ
IOL 43% of total costs
EM 34% of total costs
Delivery/newborn costs similar
IOL 31% of total costs
EM 33% of total costs

42. Cost Lessons
Intrapartum/Delivery costs dominate the antenatal and postpartum costs associated with IOL and EM
Costs saved by IOL in antenatal care, neonatal care, and cesarean are offset by increased L&D time costs
Even small changes in time spent on L&D greatly affect the cost equation

43. How shall we proceed?

44. Reasonable Approach Offer elective IOL as an option
Limit to ARRIVE-eligible patients
Elicit & honor patient preferences
Consider your facility resources