Level 1. Screening Form (Titles and Abstracts)

1. Does the record describe a study for which an abstract and/or a full-text article has been published in English?
   • No
   • Yes
   • Unsure
2. Does the record describe a review article?
   • No
   • Yes
   • Unsure
3. Does the record describe a single case study?
   • No
   • Yes
   • Unsure
   • N/A
4. Does the record describe a study that includes pregnant women >24 weeks and <37 weeks gestation?
   • No
   • Yes
   • Unsure
   • N/A
5. Does the record describe a study that includes pregnant women with arrested preterm labor?
   • No
   • Yes
   • Unsure
   • N/A
6. Does the record describe a study that includes at least one treatment group administered subcutaneous (SC) terbutaline by infusion pump as maintenance tocolytic therapy (i.e. not primary tocolytic therapy)?
   • No
   • Yes
   • Unsure
   • N/A
7. Has the study assessed at least one of the following outcomes?
   Neonatal Health Outcomes: bronchopulmonary dysplasia, necrotizing enterocolitis, significant intraventricular hemorrhage (grade III/IV), periventricular leukomalacia, seizures, retinopathy of prematurity, sepsis, stillbirth, death within initial hospitalization, neonatal death.
   Other Health Outcomes: gestational age at delivery, incidence of delivery at <28 weeks, <34 weeks and <37 weeks gestational age, prolongation of pregnancy, birthweight, need for assisted ventilation, need for oxygen per nasal cannula, NICU admission
   Maternal Harms: pulmonary edema, heart failure, arrhythmia, myocardial infarction, refractory hypotension, hypokalemia, hyperglycemia, maternal withdrawal due to adverse effects, maternal discontinuation of therapy
   Neonatal Harms: hypoglycemia, hypocalcemia, ileus
   Pump Failure: missed doses, dislodgment, overdose
   • No
   • Yes
   • Unsure
   • N/A
8. Should this record be excluded for any other reason that has not yet been captured with the above questions? If yes, please describe that reason.
   • No
   • Yes
   • N/A

Level 2. Screening Form (Full-text)

1. Does the record describe a study for which an abstract and/or a full-text article has been published in English?
   • No
   • Yes
   • Can't tell, abstract and/or full-text not available
2. Does the record describe a review article?
   • No
   • Yes
3. Does the record describe a single or multiple (individual) case reports?
   • No
   • Yes
   • N/A because record already excluded by a prior question
4. Does the record describe a study that includes pregnant women >24 weeks and <37 weeks gestation?
   • No
   • Yes
   • N/A because record already excluded by a prior question
5. Does the study include only women with ruptured membranes?
   • No
   • Yes
   • Data not reported
   • N/A because record already excluded by a prior question
6. Does the record describe a study that includes pregnant women with arrested preterm labor after primary tocolytic treatment?
   • No
   • Yes
   • N/A because record already excluded by a prior question
7. Has subcutaneous (SC) terbutaline by infusion pump been administered as a maintenance tocoloytic therapy in at least one treatment group (i.e. not primary tocolytic treatment)?
   • No
   • Yes
   • N/A because record already excluded by a prior question
8. Has the study assessed at least one of the following outcomes?
   • Neonatal Health Outcomes: bronchopulmonary dysplasia, necrotizing enterocolitis, significant intraventricular hemorrhage (grade III/IV), periventricular leukomalacia, seizures, retinopathy of prematurity, sepsis, stillbirth, death within initial hospitalization, neonatal death
   • Other Health Outcomes: gestational age at delivery, incidence of delivery at <28 weeks, <34 weeks and <37 weeks gestational age, prolongation of pregnancy period, birthweight, need for assisted ventilation, need for oxygen per nasal cannula, NICU admission
   • Maternal Harms: pulmonary edema, heart failure, arrhythmia, myocardial infarction, refractory hypotension, hypokalemia, hyperglycemia, maternal withdrawal due to adverse effects, maternal discontinuation of therapy
   • Neonatal Harms: hypoglycemia, hypocalcemia, ileus
   • Harms or adverse events related to the pump device, but not necessarily terbutaline: for example missed doses, pump dislodgment, overdose or infection, allergic reaction or thrombosis at the infection site
   • No
   • Yes
   • N/A because record already excluded by a prior question
9. Should this study be excluded for any other reason that has not yet been captured with above questions?
   • No
   • Yes. If yes, please indicate reason
   • N/A because record already excluded by a prior question

Level 3. Screening Form (Further assessment of study design and outcomes for those citations that passed through Level 2 screening)

1. Which of the following categories of outcomes has the study assessed (check all that apply)?
   • Neonatal Health Outcomes: bronchopulmonary dysplasia, necrotizing enterocolitis, significant intraventricular hemorrhage (grade III/IV), periventricular leukomalacia, seizures, retinopathy of prematurity, sepsis, stillbirth, death within initial hospitalization, neonatal death
   • Other Health Outcomes: gestational age at delivery, incidence of delivery at <28 weeks, <32 weeks, <34 weeks and <37 weeks gestational age, prolongation of pregnancy period, birthweight, need for assisted ventilation, need for oxygen per nasal cannula, NICU admission
   • Maternal Harms: pulmonary edema, heart failure, arrhythmia, myocardial infarction, refractory hypotension, hypokalemia, hyperglycemia, maternal withdrawal due to adverse effects, maternal discontinuation of therapy
   • Neonatal Harms: hypoglycemia, hypocalcemia, ileus
   • Harms or adverse events related to the pump device, but not necessarily terbutaline: for example missed doses, pump dislodgment, overdose or infection, allergic reaction or thrombosis at the infection site
   • N/A – the study has not assessed any of the above outcomes
   • Long-term childhood outcomes such as childhood development, neurobehavioural testing, long-term lung function, long-term vision or other long-term childhood outcomes

Based on the answer to the above question, citations were directed to one of the subsequent Level 3 screening forms:

If option 5 was the only one chosen (i.e harm or adverse events related to the pump device):

1. Are incidence data (versus prevalence) available for any outcome related to pump failure?
   • No
   • Yes

If options 1, 2, 3, or 4 were the only ones chosen (i.e. maternal or neonatal outcomes):

1. Does the study include at least one comparison group receiving placebo, standard trea another intervention?
   • No
   • Yes
2. Please specify the study design:
   • Randomized controlled trial
   • Non-randomized controlled trial
   • Prospective cohort
   • Retrospective cohort
   • Case-control
   • Cross-sectional
   • Other (please specify):
   • N/A - because record already excluded by question 1
3. Does the study design allow for an evaluation of the effectiveness or harms of subcutaneous (SC) terbutaline by infusion pump as the sole maintenance tocoloytic therapy?
   Note: study designs which are (treatment X + terbutaline pump vs. X alone) or (X + terbutaline pump vs. treatment X + treatment Y) arenotto be excluded. Study designs that are (terbutaline pump + treatment X vs. terbutaline pump alone or in conjunction with treatment Y) are to be excluded (unless there is pump failure data)
   • No
   • Yes
   • N/A - because record already excluded by question 1

If a combination of pump related outcomes and maternal/neonatal outcomes were chosen:

1. To be included in the review, either condition (1) and/or (2) below must be met:
   1. For outcomes related to pump failure incidence data (versus prevalence data) must be available
   2. For neonatal or other outcomes, maternal harms or neonatal harms, the study must:
      • include at least one comparison group receiving placebo, standard treatment or another intervention AND
      • be a controlled trial (randomized or non-randomized), a prospective or retrospective cohort study, a case-control study or a cross-sectional study AND
      • allow for an evaluation of the effectiveness or harms of subcutaneous terbutaline by infusion pump as the sole maintenance tocolytic therapy (note: study designs which are (treatment X + terbutaline pump vs. X alone) or (X + terbutaline pump vs. treatment X + treatment Y) are to be included. Study designs that are (terbutaline pump + treatment X vs. terbutaline pump alone or in conjunction with treatment Y) are to be excluded (unless there is incident pump failure data, as above)
   Is condition (1) and/or (2) above met?
   • No
   • Yes
2. Which of the following categories of outcomes has the study assessed AND met the above eligibility criteria (select all that apply)?
   • Neonatal Health Outcomes: bronchopulmonary dysplasia, necrotizing enterocolitis, significant intraventricular hemorrhage (grade III/IV), periventricular leukomalacia, seizures, retinopathy of prematurity, sepsis, stillbirth, death within initial hospitalization, neonatal death
   • Other Health Outcomes: gestational age at delivery, incidence of delivery at <28 weeks, <32 weeks, <34 weeks and <37 weeks gestational age, prolongation of pregnancy period, birthweight, need for assisted ventilation, need for oxygen per nasal cannula, NICU admission
   • Maternal Harms: pulmonary edema, heart failure, arrhythmia, myocardial infarction, refractory hypotension, hypokalemia, hyperglycemia, maternal withdrawal due to adverse effects, maternal discontinuation of therapy
   • Neonatal Harms: hypoglycemia, hypocalcemia, ileus
   • Harms or adverse events related to the pump device, but not necessarily terbutaline: for example missed doses, pump dislodgment, overdose or infection, allergic reaction or thrombosis at the infection site

If option 7 has been chosen (long-term outcomes):

Please indicate which long-term outcomes have been assessed in the study (check all that apply)

• Childhood Development. Please provide details.
• Neurobehavioural Testing. Please provide details
• Long-term Lung Function. Please provide details
• Long-term Vision. Please provide details
• Other. Please describe

Risk of Bias Assessment

1. Are the treatment and comparison groups similar in terms of baseline characteristics and prognostic factors?
   • Yes
   • No. If no, please explain the differences
   • Unclear
   • N/A - there is no comparison group (studies of pump failure only)
2. Did participants in the treatment and comparison groups receive the same (or a similar distribution of) primary tocolytic to control their acute episode of preterm labor?
   • Yes
   • No. If no, please describe the differences.
   • Unclear (data not reported)
   • N/A - there is no comparison group (studies of pump failure only)
3. If this is an experimental study, were patients blinded to treatment allocation?
   • Yes
   • No
   • Unclear (data not reported)
   • N/A (not an experimental study)
4. If this is an experimental study, were healthcare providers blinded to treatment allocation?
   • Yes
   • No
   • Unclear (data not provided)
   • N/A (not an experimental study)
5. If this is an experimental study, were healthcare providers blinded to the frequency and intensity of maternal contractions? (Select all that apply)
   • At initiation of maintenance therapy with the subcutaneous terbutaline pump (at treatment allocation)
   • During maintenance therapy with the subcutaneous terbutaline pump
   • When assessing treatment outcomes (of interest to this review)
   • Health care providers were at no point blinded to the frequency and intensity of maternal contractions
   • Unclear (data not reported)
   • N/A (not an experimental study)
6. If this is an experimental study, was the outcome assessor blinded to treatment allocation?
   • Yes
   • No
   • Unclear (data not reported)
   • N/A (not an experimental study)
7. Was an intention-to-treat analysis conducted?
   Note: An intention-to-treat (ITT) analysis aims to include all participants randomized into a trial irrespective of what happened subsequently. Indicate “yes” if participants were analyzed in the intervention groups to which they were assigned, regardless of the intervention they actually received. To receive a “yes” response, all participants must be included in the analysis (i.e. missing data has been imputed by some means).
   • Yes
   • No
   • Unclear (data not reported)
   • N/A (case series)
8. Was there either: i) a differential loss to followup between the compared groups; or ii) an overall high loss to followup?
   • Yes. If yes, please provide details:
   • No
   • Unclear (data not reported)
9. Was the sample size adequate to determine a difference in outcomes between comparison groups or between pre and post intervention?
   • Yes
   • No
   • Unclear
   • N/A
10. Was there a differential level of care (e.g., home uterine contraction monitoring, education, nurse visits, individualized dosing schedules, other co-interventions) between the treatment and comparison groups?
    • Yes
    • No
    • Unclear (data not reported)
    • N/A - there is no comparison group (studies of pump failure only)
11. Are the study funders likely to have had any influence on study outcomes that might have biased the study results?
    • Yes
    • No
    • Unclear (data not reported)
12. Is there any indication of selective outcome reporting?
    Note: to assess selective outcome reporting, please compare the outcomes listed in the methods section of the report to the reported results. Indicate “yes” if all measured outcomes are accounted for in the results section, and are adequately reported.
    • Yes. If yes, please describe:
    • No
    • Unclear
13. If multiple outcome assessors were used, is it likely there was high reliability in outcome assessment between all assessors? (e.g., inter-rater reliability testing was conducted and adequate)
    • Yes
    • No. If no, please describe
    • Unclear (data not reported)
    • N/A - multiple assessors were not used
14. Was compliance with the study protocol (i.e. treatment or comparator intervention) adequate in all study groups?
    • Yes
    • No. If no, please describe:
    • Unclear (data not reported)
15. If this is a randomized controlled trial, was the allocation sequence adequately generated?
    Note: Indicate “yes” if the method of randomization to treatment groups is likely to produce comparable groups, for example through use of a random number table or a computerized random number generator.
    • Yes
    • No
    • Unclear (data not reported)
    • N/A - this is not a randomized controlled trial
16. If this is a randomized controlled trial, was the process of concealing the random allocation sequence adequate?
    Note: Indicate “yes” if a process was in place to adequately conceal future intervention allocations from study personnel, for example through pharmacy controlled randomization, or the use of sequentially numbered, sealed and opaque envelopes.
    • Yes
    • No
    • Unclear (data not reported)
    • N/A - this is not a randomized controlled trial
17. If this is a randomized controlled trial, at the time of study enrollment is there any indication that study personnel were able to predict future intervention assignments?
    Note: Indicate “yes” if any reported baseline imbalances are likely to have resulted from study personnel selectively enrolling patients into the study based on their prediction of future intervention assignments.
    • Yes
    • No
    • Unclear (data not reported)
    • N/A - this is not a randomized controlled trial
18. If this is an observational study or a nonrandomized trial, is the sample population from which the comparison group(s) was drawn the same as the sample population from which the treatment group was drawn?
    • Yes
    • No. If no, please describe:
    • Unclear
    • N/A - this is not an observational study/nonrandomized trial or there is no comparison group (studies of pump failure only)
19. If this is an observational study or a nonrandomized trial, were appropriate methods undertaken to control for important confounders (e.g., matching)?
    • Yes
    • No
    • Unclear
    • N/A - this is not an observational study/nonrandomized trial or there is no comparison group (studies of pump failure only)
20. If this is a retrospective study that used multiple data sources, is it likely there was consistency in outcome definition across those data sources?
    • Yes
    • No. If no, please describe:
    • Unclear (data not reported)
    • N/A - this is not a retrospective study that uses multiple data sources
21. For studies assessing maternal or neonatal harms: If the harm outcomes assessed in the study are not generally known to have standard definitions, then were these harms pre-defined using standardized or precise definitions?
    • Yes
    • No
    • Unclear (data not reported)
    • N/A - this is not a study assessing maternal or neonatal harms
    • N/A - this study measured harms with standardized definitions. If so, please specify these harms
22. If this is a study assessing maternal or neonatal harms, was the mode of harms collection specified as active (versus passive)?
    Note: Active harms assessment is when participants are asked about the occurrence of specific harms in structured questionnaires or interviews or pre-defined laboratory or diagnostic tests, usually performed at pre-specified time intervals.
    Passive assessment of harms occurs when study participants spontaneously report (on their own initiative) or are allowed to report harmful events not probed with active ascertainment.
    • Yes
    • No
    • Unclear (data not reported)
    • N/A - this is not a study assessing maternal or neonatal harms
23. If this is a study assessing maternal or neonatal harms, did the report specify who collected harms data, including their training and background?
    • Yes
    • No
    • Unclear
    • N/A - this is not a study assessing maternal or neonatal harms
24. Were the subjects who were included in the study representative of the source population? For instance, subjects would be representative if the entire source population was recruited for the study, if a sample of consecutive patients was recruited, or if a random sample was obtained.
    • Yes. Please explain
    • No. Please explain
    • Unclear (e.g. sampling methodology is not reported). Please explain
25. Were the primary outcomes in the study defined by either prespecified or standardized clinical definitions?
    • Yes. Please list what these outcomes are and any definitions provided in paper
    • No. Please list what these outcomes are
    • Unclear
    • N/A - the study does not list any primary outcomes

Applicability Assessment Form