UOG Journal Club: The QUiPP App: a safe alternative to a treat-all strategy for threatened preterm labor

1. UOG Journal Club: September 2017
The QUiPP App: a safe alternative to a treat-all strategy for threatened
preterm labor
H.A. Watson, J. Carter, P.T. Seed, R.M. Tribe and A.H. Shennan
September 2017; Volume 50, Issue 3, pages 342–346
Journal Club slides prepared by Dr Maddalena Morlando
(UOG Editor for Trainees)

2. The QUiPP App: a safe alternative to a treat-all strategy for threatened preterm labor
Watson et al., UOG 2017
• Women with symptoms of preterm labor have long posed a challenge
for clinicians because of the risk of spontaneous preterm birth (sPTB).
• Recent UK guidance advises a treat-all policy for women presenting
with threatened preterm labor prior to 30 weeks’ gestation, advocating
the use of cervical length measurement or fetal fibronectin (fFN)
assay only after 30 weeks.
• An implication of a treat-all strategy is the loss of the useful long-term
prediction that qfFN provides.
• The authors have developed the QUiPP App, which improves the
prediction of sPTB. The App utilizes quantitative fFN (qfFN) as one of
the predictive criteria.

3. To investigate the impact of using the QUiPP App to
identify women at risk of sPTB, relative to a treat-all
strategy in women with symptoms of preterm labor at
24+0 to 29+6 weeks’ gestation
Objective
The QUiPP App: a safe alternative to a treat-all strategy for threatened preterm labor
Watson et al., UOG 2017

4. Methods
• This was a prospective, observational secondary analysis of women
included in the EQUIPP and PETRA studies between 2010 and 2015.
• Women with a first episode of suspected labor at 24-34 weeks’ gestation
were identified from the databases.
• Women with incomplete outcome data, significant additional diagnoses
at presentation (ruptured membranes, pre-eclampsia), with a blood-
stained swab, or reporting sexual intercourse in the previous 24h, were
excluded owing to known interference with fFN quantification.
• By entering the gestation at examination, qfFN and history of previous
sPTB into the QUiPP App, each episode of threatened preterm labor
was assigned a risk of delivery within 7 days.
The QUiPP App: a safe alternative to a treat-all strategy for threatened preterm labor
Watson et al., UOG 2017

5. Statistical analysis
• The sensitivity, specificity, PPV and NPV of the QUiPP App to predict
sPTB within 7 days of assessment (primary endpoint) were determined
for risk thresholds for intervention of 1%, 5% and 10%, and compared
with the treat-all strategy.
• 95% CIs were calculated in most cases. However, for rates of 0% or
100%, the equivalent one-sided 97.5% CIs are given.
• The performance of the QUiPP App to triage cases with threatened
preterm labor before and after 30 weeks was compared.
• The corresponding rates of sPTB within 7 days, < 30 weeks and < 36
weeks were calculated for five prespecified incremental QUiPP App risk
thresholds (< 0.1%, 0.1–1%, 1–5%, 5–10% and > 10%).
The QUiPP App: a safe alternative to a treat-all strategy for threatened preterm labor
Watson et al., UOG 2017
Methods

6. The QUiPP App: a safe alternative to a treat-all strategy for threatened preterm labor
Watson et al., UOG 2017
a) Screenshot of QUiPP App, which requires data on previous preterm prelabor rupture of
membranes (PPROM), gestational age and fetal fibronectin (fFN), to calculate risk of
spontaneous preterm birth (sPTB). (b) Resulting risk scores are calculated and displayed.
a) b)

7. Results
• A total of 355 women with threatened preterm labor were eligible for
analysis.
• Using a 5% risk of delivery within 7 days as the threshold to treat, 9/9
women who presented with threatened preterm labor <34 weeks
would have been treated correctly, giving a sensitivity of 100% (one-
sided 97.5% CI, 66.4%) and a NPV of 100% (95% CI, 98.9–100%).
• If a risk threshold of 5% had been used to triage women presenting
with threatened preterm labor between 24 and 29 + 6 weeks’
gestation, 89.4% of admissions could have been safely avoided
compared with 0% with a treat-all strategy.
• No true case of preterm labor would have been missed using the
QUiPP App risk thresholds, as no woman with a risk of <10%
delivered within 7 days.
The QUiPP App: a safe alternative to a treat-all strategy for threatened preterm labor
Watson et al., UOG 2017

8. Results
The QUiPP App: a safe alternative to a treat-all strategy for threatened preterm labor
Watson et al., UOG 2017
Sensitivity Specificity NPV
Discharged
inappropriately
PPV
Pre-emptive
hospital
admission
Negative result
(admissions
avoided)
Parameter (%) (%) (%) (n) (%) (n) (%)
Treat-all
strategy
100 0 100 0 3 188 0
QUiPP App risk thresold
1%
100
(54.1-100)
83.5
(77.3-88.6)
100
(97.8-100)
0 17 36 81.0
5%
100
(54.1-100)
92.3
(87.4-95.7)
100
(97.8-100)
0 30 20 89.4
10%
100
(54.1-100)
95.0
(90.8-97.7)
100
(97.8-100)
0 40 15 86.7
NPV, negative predictive value; PPV, positive predictive value.
Performance of treat-all strategy vs intervention at risk thresholds of 1%, 5% and
10% for delivery within 7 days according to QUiPP App before 30 weeks’ gestation

9. The QUiPP App: a safe alternative to a treat-all strategy for threatened preterm labor
Watson et al., UOG 2017
Results
Sensitivity Specificity NPV PPV
sPTB
within 7
days
Pre-emptive
hospital
admission
Negative
result
(admissions
avoided)
GA at
presentation
(%) (%) (%) (%) (n) (n) (%)
24+0
to 29+6 100
(54.1-100)
92.3
(87.4-95.7)
100
(97.8-100)
30
(11.9-54.3)
36 81.0
30+0
to 34+0 100
(29.2-100)
92.7
(87.6-96.2)
100
(97.6-100)
20
(12.7-30.1)
20 89.4
GA, gestational age; NPV, negative predictive value; PPV, positive predictive value.
Prediction of spontaneous preterm birth (sPTB) using QUiPP App in women
presenting with threatened preterm labor before and after 30 weeks’ gestation

10. Conclusions
• The QUiPP App can safely and accurately inform clinicians on the
management of women with threatened preterm labor, allowing
outpatient management for the vast majority of cases.
• This holds true irrespective of whether a 1%, 5% or 10% risk of delivery
within 7 days is used as the threshold for admission.
• The QUiPP App confers advantage over NICE’s recommended treat-all
strategy, which allows no woman to be managed as an outpatient.
• Using the 5% risk threshold in this study, 9x-fewer women would have
received intervention, and all true cases of preterm labor would have
been identified correctly to benefit from intervention.
• The accuracy of the QUiPP App was similar in women presenting before
and after 30 weeks.
The QUiPP App: a safe alternative to a treat-all strategy for threatened preterm labor
Watson et al., UOG 2017

11. Strengths
This study projects risk thresholds for intervention onto a large prospectively
collected cohort of women who experienced threatened preterm labor. It
provides important new insight into the impact of these management
strategies. Lacking such evidence, UK national guidelines have previously
been based on a cost – utility analysis alone.
Limitations
A larger sample would have probably revealed false negatives. However, the
rate of delivery within 7 days in the study cohort (3%) is consistent with that in
previous studies. The data from a minority of women included in the study
were used in developing the QUiPP model. While this study provides useful
insight into the properties of the App, a new and preferably external dataset is
required for further validation.
The QUiPP App: a safe alternative to a treat-all strategy for threatened preterm labor
Watson et al., UOG 2017

12. Discussion Points
• Would it be possible to replace the recommended treat-all policy with
a new policy based on risk thresholds for intervention?
• Can we assume that every clinician and patient will accept the use
and findings of the App?
• Which risk of delivery should be used as a threshold for admission?
• Should the same threshold be used at different gestational ages?
• Would it be possible to improve the accuracy of this model by adding
information regarding the cervical length?
The QUiPP App: a safe alternative to a treat-all strategy for threatened preterm labor
Watson et al., UOG 2017