2020-02058. Supplemental Evidence and Data Request on Cervical Ripening in the Outpatient Setting

AGENCY:

Agency for Healthcare Research and Quality (AHRQ), HHS.

ACTION:

Request for supplemental evidence and data submissions.

SUMMARY:

The Agency for Healthcare Research and Quality (AHRQ) is seeking scientific information submissions from the public. Scientific information is being solicited to inform our review on Cervical Ripening in the Outpatient Setting, which is currently being conducted by the AHRQ's Evidence-based Practice Centers (EPC) Program. Access to published and unpublished pertinent scientific information will improve the quality of this review.

DATES:

Submission Deadline on or before 30 days after date of publication in the Federal Register.

ADDRESSES:

 

Email submissions: [e-mail].

Print submissions:

Mailing Address: Center for Evidence and Practice Improvement, Agency for Healthcare Research and Quality, ATTN: EPC SEADs Coordinator, 5600 Fishers Lane, Mail Stop 06E53A, Rockville, MD 20857.

Shipping Address (FedEx, UPS, etc.): Center for Evidence and Practice Improvement, Agency for Healthcare Research and Quality, ATTN: EPC SEADs Coordinator, 5600 Fishers Lane, Mail Stop 06E77D, Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT:

Jenae Benns, Telephone: [phone] or Email: [e-mail].

SUPPLEMENTARY INFORMATION:

The Agency for Healthcare Research and Quality has commissioned the Evidence-based Practice Centers (EPC) Program to complete a review of the evidence for Cervical Ripening in the Outpatient Setting. AHRQ is conducting this systematic review pursuant to Section 902(a) of the Public Health Service Act, 42 U.S.C. 299a(a).

The EPC Program is dedicated to identifying as many studies as possible that are relevant to the questions for each of its reviews. In order to do so, we are supplementing the usual manual and electronic database searches of the literature by requesting information from the public (e.g., details of studies conducted). We are looking for studies that report on Cervical Ripening in the Outpatient Setting, including those that describe adverse events. The entire research protocol is available online at: https://effectivehealthcare.ahrq.gov/​products/​cervical-ripening/​protocol.

This is to notify the public that the EPC Program would find the following information on Cervical Ripening in the Outpatient Setting helpful:

A list of completed studies that your organization has sponsored for this indication. In the list, please indicate whether results are available on ClinicalTrials.gov along with the ClinicalTrials.gov trial number.

For completed studies that do not have results on ClinicalTrials.gov, a summary, including the following elements: Study number, study period, design, methodology, indication and diagnosis, proper use instructions, inclusion and exclusion criteria, primary and secondary outcomes, baseline characteristics, number of patients screened/eligible/enrolled/lost to follow-up/withdrawn/analyzed, effectiveness/efficacy, and safety results.

A list of ongoing studies that your organization has sponsored for this indication. In the list, please provide the ClinicalTrials.gov trial number or, if the trial is not registered, the protocol for the study including a study number, the study period, design, methodology, indication and diagnosis, proper use instructions, inclusion and exclusion criteria, and primary and secondary outcomes.

Description of whether the above studies constitute ALL Phase II and above clinical trials sponsored by your organization for this indication and an index outlining the relevant information in each submitted file.

Your contribution is very beneficial to the Program. Materials submitted must be publicly available or able to be made public. Materials that are considered confidential; marketing materials; study types not included in the review; or information on indications not included in the review cannot be used by the EPC Program. This is a voluntary request for information, and all costs for complying with this request must be borne by the submitter.

The draft of this review will be posted on AHRQ's EPC Program website and available for public comment for a period of 4 weeks. If you would like to be notified when the draft is posted, please sign up for the email list at: https://www.effectivehealthcare.ahrq.gov/​email-updates.

The systematic review will answer the following questions. This information is provided as background. AHRQ is not requesting that the public provide answers to these questions.

Key Questions (KQ)

KQ1: How do the effectiveness and harms of cervical ripening (CR) using prostaglandins compare in the outpatient vs. inpatient setting?

1a: How do effectiveness and harms vary by choice of prostaglandin?

1b: Do effectiveness and harms vary by important patient characteristics (such as gestational age, parity, uncomplicated pregnancy, prior cesarean delivery, etc.)?

KQ2: How do the effectiveness and harms of CR using mechanical methods (e.g., balloon catheters) compare in the outpatient vs. inpatient setting?

2a: How do effectiveness and harms vary by choice of mechanical method in the inpatient versus the outpatient setting?

2b: Do effectiveness and harms vary by important patient characteristics (such as gestational age, parity, uncomplicated pregnancy, prior cesarean delivery, etc.)?

KQ3: How do the effectiveness and harms of CR in the outpatient setting vary by method of CR compared with each other?

3a: Do effectiveness and harms vary by important patient characteristics (such as gestational age, parity, uncomplicated pregnancy, prior cesarean delivery, etc.)?

KQ4: How do the effectiveness and harms of different methods and protocols for fetal surveillance compare with each other or with no monitoring in pregnant women undergoing CR with prostaglandins?

4a. Do effectiveness and harms vary by important patient characteristics (such as gestational age, parity, uncomplicated pregnancy, prior cesarean delivery, etc.)?

Contextual Question: What evidence informs preference for or tolerability of different methods of CR in the outpatient setting or outpatient compared to the inpatient setting?

PICOTS (Populations, Interventions, Comparators, Outcomes, Timing, Settings)

PICOTS	Inclusion key question 1: Prostaglandin inpatient vs. outpatient	Inclusion key question 2: Mechanical method inpatient vs outpatient	Inclusion key question 3: Outpatient comparison of methods	Inclusion key question 4: Fetal surveillance	Exclusion
Population	• Pregnant women ≥37 weeks undergoing CR in the outpatient setting • Important maternal subgroups: parity, maternal age, GBS status, diabetes (pre-gestational, gestational), hypertension (chronic, preeclampsia without severe features, gestational). • Important fetal subgroups: fetal growth restriction, gestational age (<39 weeks, 39 to 41 weeks, >41 weeks).	• Pregnant women ≥37 weeks undergoing CR in the outpatient setting • Important maternal subgroups: parity, maternal age, GBS status, diabetes (pre-gestational, gestational), hypertension (chronic, preeclampsia without severe features, gestational). • Important fetal subgroups: fetal growth restriction, gestational age (<39 weeks, 39 to 41 weeks, >41 weeks).	• Pregnant women ≥37 weeks undergoing CR in the outpatient setting • Important maternal subgroups: parity, maternal age, GBS status, diabetes (pre-gestational, gestational), hypertension (chronic, preeclampsia without severe features, gestational). • Important fetal subgroups: fetal growth restriction, gestational age (<39 weeks, 39 to 41 weeks, >41 weeks).	• Pregnant women ≥37 weeks undergoing CR with a prostaglandin • Important maternal subgroups: parity, maternal age, GBS status, diabetes (pre-gestational, gestational), hypertension (chronic, preeclampsia without severe features, gestational). • Important fetal subgroups: fetal growth restriction, gestational age (<39 weeks, 39 to 41 weeks, >41 weeks).	Women with contraindications to CR in the outpatient setting: a multiple pregnancy, prior uterine rupture and breech presentation of the fetus.
Intervention	• Pharmacologic agents (prostaglandins) given in outpatient setting	• Mechanical methods (balloon catheters, laminaria tents) used in outpatient setting	Mechanical methods (balloon catheters, laminaria tents) or pharmacologic agents (prostaglandins)	• Any method of fetal surveillance	• Catheters not available in the U.S. • Pharmacy-compounded prostaglandin products.
					• Other CR methods: Castor oil, nipple stimulation, membrane stripping, sexual intercourse, acupuncture/pressure, transcutaneous nerve stimulation, herbal compounds.
Comparator	• Mechanical (i.e., balloon catheters, luminaria tents) and/or pharmacologic (i.e., prostaglandins) methods in the inpatient setting	• Mechanical (i.e., balloon catheters, luminaria tents) and/or pharmacologic (i.e., prostaglandins) methods in the inpatient setting	• Any comparator including alternative mechanical device or protocol, alternative pharmacologic agent or dose, combination mechanical and pharmacologic, placebo, and other CR methods excluded as intervention (e.g., Castor oil, acupuncture)	• Another method of fetal surveillance • Another protocol for fetal surveillance with the same method. • No monitoring.	• Catheters not available in the U.S. • Pharmacy-compounded prostaglandin products.
Outcomes Effectiveness (birth-related)	• Total time admission to vaginal delivery; total L&D length of stay c • Cesarean delivery rate overall c	• Total time admission to vaginal delivery; total L&D length of stay c • Cesarean delivery rate overall c	• Total time admission to vaginal delivery; total L&D length of stay c • Cesarean delivery rate overall c	• Total time admission to vaginal delivery; total L&D length of stay c • Cesarean delivery rate overall c	Outcomes not listed in inclusion criteria.
	• Vaginal delivery within 24 hours	• Vaginal delivery within 24 hours	• Vaginal delivery within 24 hours	• Vaginal delivery within 24 hours
	Failed induction rate, defined as:	Failed induction rate, defined as:	Failed induction rate, defined as:	Failed induction rate, defined as:
	○ CD in patient at <6cm dilation excluding fetal distress (labor dystocia, failure to progress, etc.)	○ CD in patient at <6cm dilation excluding fetal distress (labor dystocia, failure to progress, etc.)	○ CD in patient at <6cm dilation excluding fetal distress (labor dystocia, failure to progress, etc.)	○ CD in patient at <6cm dilation excluding fetal distress (labor dystocia, failure to progress, etc.)
	○ CD in patient at <6 cm dilation for fetal distress	○ CD in patient at <6 cm dilation for fetal distress	○ CD in patient at <6 cm dilation for fetal distress	○ CD in patient at <6 cm dilation for fetal distress
	• Cervical assessment at time of admission (e.g., latent vs. active phase, Bishop score, cervical dilation)	• Cervical assessment at time of admission (e.g., latent vs. active phase, Bishop score, cervical dilation)	• Cervical assessment at time of admission (e.g., latent vs. active phase, Bishop score, cervical dilation)	• Cervical assessment at time of admission (e.g., latent vs. active phase, Bishop score, cervical dilation)
	• Time from ROM to delivery	• Time from ROM to delivery	• Time from ROM to delivery	• Time from ROM to delivery
			• Breastfeeding b
			• Maternal mood b
			• Mother-baby attachment b
Outcomes Fetal Harms	• Perinatal Mortality c • Hypoxic-ischemic  c encephalopathy  c.	• Perinatal Mortality c • Hypoxic-ischemic  c encephalopathy  c.	• Perinatal Mortality c • Hypoxic-ischemic  c encephalopathy  c.	• Perinatal Mortality c • Hypoxic-ischemic  c encephalopathy  c.	Outcomes not listed in inclusion criteria.
	• Seizure c	• Seizure c	• Seizure c	• Seizure c
	• Infection (confirmed sepsis or pneumonia) c	• Infection (confirmed sepsis or pneumonia) c	• Infection (confirmed sepsis or pneumonia) c	• Infection (confirmed sepsis or pneumonia) c
	• Meconium aspiration syndrome c	• Meconium aspiration syndrome c	• Meconium aspiration syndrome c	• Meconium aspiration syndrome c
	• Birth trauma (e.g., bone fracture, neurologic injury, or retinal hemorrhage) c	• Birth trauma (e.g., bone fracture, neurologic injury, or retinal hemorrhage) c	• Birth trauma (e.g., bone fracture, neurologic injury, or retinal hemorrhage) c	• Birth trauma (e.g., bone fracture, neurologic injury, or retinal hemorrhage) c
	• Intracranial or subgaleal hemorrhage c	• Intracranial or subgaleal hemorrhage c	• Intracranial or subgaleal hemorrhage c	• Intracranial or subgaleal hemorrhage c
	• Need for respiratory support within 72 hours after birth	• Need for respiratory support within 72 hours after birth	• Need for respiratory support within 72 hours after birth	• Need for respiratory support within 72 hours after birth
	• Apgar score ≤3 at 5 minutes a	• Apgar score ≤3 at 5 minutes a	• Apgar score ≤3 at 5 minutes a	• Apgar score ≤3 at 5 minutes a
	• Hypotension requiring vasopressor support	• Hypotension requiring vasopressor support	• Hypotension requiring vasopressor support	• Hypotension requiring vasopressor support
	• Umbilical cord gas <pH 7.0 or 7.10	• Umbilical cord gas <pH 7.0 or 7.10	• Umbilical cord gas <pH 7.0 or 7.10	• Umbilical cord gas <pH 7.0 or 7.10
Outcomes Maternal Harms	• Hemorrhage requiring transfusion c • Postpartum hemorrhage by mode (vaginal, cesarean) c.	• Hemorrhage requiring transfusion c • Postpartum hemorrhage by mode (vaginal, cesarean) c.	• Hemorrhage requiring transfusion c • Postpartum hemorrhage by mode (vaginal, cesarean) c.	• Hemorrhage requiring transfusion c • Postpartum hemorrhage by mode (vaginal, cesarean) c.	Outcomes not listed in inclusion criteria.
	• Uterine infection (i.e., choriamnionitis, administration of antibiotics in labor other than GBS prophylaxis) c	• Uterine infection (i.e., choriamnionitis, administration of antibiotics in labor other than GBS prophylaxis) c	• Uterine infection (i.e., choriamnionitis, administration of antibiotics in labor other than GBS prophylaxis) c	• Uterine infection (i.e., choriamnionitis, administration of antibiotics in labor other than GBS prophylaxis) c
	• Placental abruption, Uterine rupture • Umbilical cord prolapse • Duration of time between hospital admission to birth that is insufficient to enable complete GBS prophylaxis antibiotics administration per CDC guidelines.	• Placental abruption • Uterine rupture • Umbilical cord prolapse • Duration of time between hospital admission to birth that is insufficient to enable complete GBS prophylaxis antibiotics administration per CDC guidelines.	• Placental abruption, Uterine rupture • Umbilical cord prolapse • Duration of time between hospital admission to birth that is insufficient to enable complete GBS prophylaxis antibiotics administration per CDC guidelines.	• Placental abruption • Uterine rupture • Umbilical cord prolapse • Duration of time between hospital admission to birth that is insufficient to enable complete GBS prophylaxis antibiotics administration per CDC guidelines.
Timing	Maternal outcomes • From CR initiation to within 1-week following delivery. Infant outcomes • Immediately following delivery.	Maternal outcomes • From CR initiation to within 1-week following delivery. Infant outcomes • Immediately following delivery.	Maternal and additional outcomes (i.e., breastfeeding, maternal mood, mother-baby attachment) • From CR initiation to 1-year postpartum. Infant outcomes • Immediately following delivery.	Maternal outcomes • From CR initiation to within 1-week following delivery. Infant outcomes • Immediately following delivery.	KQ 1,2,4: Outcomes occurring after 1-week post delivery. KQ3: Outcomes for breastfeeding, mother-infant attachment, and maternal mood occurring after 1 year post-delivery.
Setting	• Inpatient versus outpatient settings	• Inpatient versus outpatient settings	• Outpatient setting	• Inpatient and outpatient settings
Study design	• Randomized Controlled Trials; recent high quality Systematic Reviews; if RCT evidence for benefits is insufficient, include large, high quality cohort studies comparing inpatient and outpatient setting	• Randomized Controlled Trials; recent high quality Systematic Reviews; if RCT evidence for benefits is insufficient, include large, high quality cohort studies comparing inpatient and outpatient setting	• Randomized Controlled Trials; recent high quality Systematic Reviews; if RCT evidence for benefits is insufficient, include large, high quality cohort studies comparing inpatient and outpatient setting	• Randomized Controlled Trials; recent high quality Systematic Reviews; if RCT evidence for benefits is insufficient, include large, high quality cohort studies comparing inpatient and outpatient setting	Case series, pre-post studies, case reports.
	• Include high quality cohort and case-control studies for harms	• Include high quality cohort and case-control studies for harms	• Include high quality cohort and case-control studies for harms	• Include high quality cohort and case-control studies for harms
c (Bolded) items indicate Primary Outcomes.
CR = cervical ripening; CD = cesarean delivery; KQ = Key Question; ROM = rupture of membrane; CDC = Centers for Disease Control and Prevention; L&D = labor and delivery; RCTs = randomized controlled trials.

Dated: January 29, 2020.

Virginia L. Mackay-Smith,

Associate Director, Office of the Director, AHRQ.