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

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

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

Increasing Risk after 39 wks Observational studies

Fetal Risk from Greene, NEJM 2018

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

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

Cesarean Risk Cheng 2009 Garite 2000

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

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

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

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

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

ARRIVE: Perinatal Outcomes *

ARRIVE: Maternal Outcomes * *

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…”

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

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.

The Response Critiques, Questions, and Calls for More Evaluation

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

Critique ARRIVE does not reflect reality

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

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

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

Critique Most patients did not enroll

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

Critique Unmasking introduces bias

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

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

“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

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)

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

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

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

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)

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

The BIG Question What will elective induction cost the system?

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?

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

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

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

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

How shall we proceed?

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