Doany 1997.

Methods	Double‐blinded placebo‐controlled study
Participants	Setting: UCLA Medical Center, California, USA Duration of study: not stated Inclusion criteria: “Singleton pregnancy in the cephalic presentation who were referred for fetal surveillance at 287 days of gestation or more”. “Reactive nonstress test, amniotic fluid index (AFI) between 5 cm and 25 cm. Fetal weight between 2500 g and 4500 g and uterine contractions less frequent than every 5 mins” Page 72 Exclusion criteria: “No prenatal care, previous uterine surgery, acute or chronic medical or psychiatric illness or drug use” Page 72 Bishop score: Bishop score ≤ 6 recorded.
Interventions	Women were randomised to 1 of 4 treatment groups The treatments were administered at 287 days (41 weeks) and 294 days (42 weeks) of gestation, then every 3–4 days until 307 days (43 weeks and 6 days) of gestation. The assigned treatment was given at each visit after a reactive NST, a normal AFI and a Bishop score. Page 72 Group 1: n = 28 no membrane stripping and placebo gel Group 2: n = 37 no membrane stripping and 4 mL (0.5 mg/mL PGE2 gel) Group 3: n = 50 membrane stripping or cervical massage and placebo gel Group 4: n = 28 membrane stripping or cervical massage and 4 mL (0.5 mg/mL PGE2 gel) “The examining finger was introduced into the cervical canal and a total of three circumferential sweeps were made between the lower uterine segment and the chorionic membranes.” “When the cervical canal was not accessible, the cervical canal was pulled anteriorly and massaged.” “This was followed by placing 4 mL of an unlabeled gel, containing either a placebo or 2mg of PGE2, via syringe, in the posterior vaginal fornix” “both patients and staff were blinded to the type of gel administered” “After treatment patients underwent continuous external fetal and uterine monitoring….for 1 hour” If there was no sign of fetal distress the patients were allowed to go home. Page 72 “Management of study patients in labour and delivery was not controlled and thus was physician dependent. Physicians managing labour were blinded to the study group assignment.” Patients were admitted to labour ward when they had “clear changes in both effacement and dilatation of the cervix or if they are in the active phase of labour defined by cervical effacement > 80% & cervical dilatation ≥4cm.” Page 72
Outcomes	Spontaneous labour Induction of labour Caesarean section Operative vaginal delivery 5‐minute Apgar < 7 Amnionitis Hemorrhage Probable sepsis (neonate) Oxytocin augmentation Pre‐eclampsia
Notes	Funding: none declared Trial authors’ declaration of interest: none declared Informed consent obtained: not stated Ethical approval: “approval from our institutional Human Subject for Research Committee” Emailed for further information 28 August 2017; 8 January 2018. No reply to date
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	“randomized, by table of random numbers, into one of four treatment groups”. Page 72
Allocation concealment (selection bias)	Unclear risk	No information given on concealment
Blinding of participants and personnel (performance bias) All outcomes	High risk	Participants: unclear risk of bias. “Both patients and staff were blinded to the type of gel administered.” Unclear if blinded to membrane sweep. Personnel: high risk of bias. “Physicians managing labor were blinded to the study group assignment.” Page 72. Personnel blinded to gel administered, however clinician not blinded to membrane sweep. “The mixture, with a final PGE2concentra‐tion of 0.5 mg/mL, was placed in syringes of 4‐mL allocations. The placebo gel consisted of hydroxyethyl cellulose gel mixed with an inert emulsion (Fattibase, Paddock Labs, Inc., Minneapolis, MN) to produce a gel indistinguishable from the PGE2mix, and was similarly placed in syringes of 4‐mL allocations. All gel samples were stored in a freezer at 25to07C, and were updated weekly. The gel samples were thawed at room temperature for 10 min prior to administration” Page 72
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information given to inform judgement.
Incomplete outcome data (attrition bias) All outcomes	Low risk	No evidence of attrition bias.
Selective reporting (reporting bias)	Low risk	No selective reporting bias noted. The following discrepancy was noted “the only complication which was statistically more prevalent was preeclampsia, which occurred in 7/64(11%) of PGE2‐gel‐receiving subjects, groups II and IV” n = 65 in these groups not 64 as stated (10.7% v’s 10.9%). Page 73. However we judged this discrepancy as unlikely to make a clinically important difference
Other bias	High risk	Group sizes are imbalanced: group I = 28 group II = 37 group III = 50 group IV = 28 Unequal number of women in the 4 groups, reasons for imbalance not explained in the methods section. Author contacted, no reply received to date.