Multifactorial Approach to Emergent Cerclage: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Multifactorial Approach to Emergent Cerclage (NCT01114516), a randomized na study. The primary outcome is Gestational Latency Achieved Between Cerclage Placement and Time of Delivery.

2. Clinical Question

3. Trial Design

NCT01114516, titled Multifactorial Approach to Emergent Cerclage, is a completed randomized parallel-group trial sponsored by Northwestern University. Its official title is Role in Emergent Cerclage of Indomethacin and Antibiotics. The registry lists the phase as not applicable, enrollment of 53, and no masking. The recorded start was 2010-03 and primary completion was 2013-03.

The comparison involved emergent cerclage alone versus emergent cerclage with perioperative indomethacin and antibiotics. The registry identifies cefazolin or clindamycin as antibiotic options for the combined-treatment group. It does not report the specific allocation procedure, allocation concealment, the treatment schedule in further detail, or whether treatment adherence was assessed.

The primary outcome was median gestational latency in days from cerclage placement to delivery, with an outcome timeframe recorded as 24 weeks. The registry also names gestational latency of more than 28 days, gestational age at delivery, neonatal morbidity and mortality, and birthweight as secondary outcomes. Results are included for gestational latency of more than 28 days; detailed estimates for the other named outcomes are not reported in the registry record.

For the primary outcome, the posted results include 24 control participants and 26 participants in the intervention group. Those outcome counts do not account for all 53 enrolled participants, and the reason for the difference is not reported in the registry record. The analysis population, participant flow after enrollment, and handling of missing outcome data are also not reported in the registry record. These omissions limit assessment of how closely the analyzed groups correspond to everyone enrolled.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Gestational Latency Achieved Between Cerclage Placement and Time of Delivery, measured over 24 weeks.

The primary endpoint, gestational latency achieved between cerclage placement and delivery, measures the interval from the procedure to delivery. It is recorded in days and summarized with a median and an inter-quartile range. In this clinical setting, the endpoint expresses the duration of pregnancy after the emergent cerclage, rather than an outcome measured at a single scheduled visit.

A time-to-event outcome is useful when the event of interest can occur at different times for different participants. Here, delivery is the event, and the elapsed time from cerclage to delivery is the outcome. A median describes the point at which half of the observed time-to-event distribution lies on either side; the inter-quartile range describes the middle portion of that distribution. These summaries convey both a central value and how widely observed times vary, but they do not by themselves describe the full event pattern.

The registry reports medians of 80 days in the control group and 97 days in the indomethacin-and-antibiotics group. The corresponding inter-quartile ranges are 15 to 122 days and 57 to 125 days. The reported timeframe is 24 weeks. A log-rank test is reported for the group comparison, which uses information about the timing of events rather than treating the medians as the only data. The registry does not report confidence intervals for the medians or a hazard ratio for the primary outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted analysis combines descriptive summaries for a time-to-event endpoint with a formal comparison between randomized groups. These methods answer related but different questions: the summaries describe the observed latency distributions, while the test evaluates evidence against a statistical null hypothesis of no group difference under its assumptions.

What does the median describe?

The median is a measure of the center of a distribution. For gestational latency, it is the time by which half of the observed event times fall at or before that point and half fall at or after it, subject to the way time-to-event observations are handled. The registry gives medians of 80 days for control and 97 days for indomethacin and antibiotics. A median is relatively resistant to unusually early or late values, but it compresses a distribution into a single summary. It does not show every participant's time or the shape of the event pattern.

The inter-quartile range describes the span from the lower quartile to the upper quartile, containing the middle half of a distribution. The posted inter-quartile ranges are 15 to 122 days for control and 57 to 125 days for indomethacin and antibiotics. These ranges indicate substantial variation in observed latency. Overlap between inter-quartile ranges does not by itself determine whether a group comparison is statistically significant; the test uses the available time-to-event information under its method.

Why use a log-rank test?

General explanation: time-to-event methods are designed for outcomes defined by both whether an event occurs and when it occurs. A log-rank test compares event-time patterns between groups, rather than testing only whether their medians differ. It can make use of censored observations, where the event time is not fully observed during follow-up, when those observations and the analysis are handled appropriately. The registry identifies the primary comparison as a log-rank test and reports p = 0.018.

The registry does not report the censoring pattern, the number of events, details of follow-up, or assumptions checks. It also does not report a hazard ratio or confidence interval for the primary analysis. A p-value alone does not provide an estimate of the size of the difference or its precision. Without an effect estimate and interval, readers cannot assess how large a range of time-to-event contrasts remains compatible with the posted primary analysis.

What does the secondary risk ratio mean?

For gestational latency of more than 28 days, the registry reports 62.5% in the control group and 92.3% in the intervention group. The sponsor's posted risk ratio is 1.48, with a 95% confidence interval from 1.06 to 2.05. General explanation: a risk ratio compares the probability of the specified outcome between groups. A value above one indicates a higher observed proportion in the group named in the comparison, but interpretation depends on the outcome definition, the design, and the uncertainty in the estimate.

A confidence interval describes a range of values compatible with the data and the statistical procedure used, under its assumptions. It is not a guarantee that the true effect lies in that particular interval. The posted interval does not include the null value of one for a risk ratio, but this secondary comparison should still be interpreted in context: it is one of several outcomes named in the registry, and no multiplicity adjustment is reported.

A separate unadjusted recalculation is based on the posted event counts and group sizes. General explanation: such a calculation can be a transparent check of a simple comparison, but it does not reproduce any analysis adjustments that may have been applied by the sponsor. The registry does not report an adjustment method for this outcome. The sponsor's reported risk ratio and confidence interval therefore remain the principal reported analysis, and the recalculation should not be presented as an adjusted result.

Why can over-dispersion matter?

General explanation: over-dispersion occurs when observed variability is greater than a statistical model expects. If a model assumes less variability than the data contain, standard errors can be too small and confidence intervals can be too narrow, making statistical evidence appear stronger than it is. The posted primary endpoint is a time-to-event outcome and the named comparison is a log-rank test; the registry does not report an over-dispersion assessment or a model-based variance adjustment. Over-dispersion is therefore a general statistical consideration, not a reported feature of this analysis.

How should planning illustrations be read?

General explanation: sample-size illustrations show how many participants per arm might be needed under specified assumptions to detect a chosen effect with a selected power. They are planning aids, not measurements of trial performance and not observed power. The registry's illustrations use the observed effect as a starting point, equal allocation, a two-sided significance level of 0.05, and a normal approximation. Their rows consider planning for 100%, 75%, and 50% of the observed effect. For 80% power, the stated participants per arm are 30, 60, and 148; for 90% power, they are 40, 80, and 197.

These sample-size illustrations are not evidence that the trial had those numbers planned or achieved those power levels. The registry states that the calculations are planning illustrations and not the trial's own design. The trial's sample-size justification is not reported in the registry record. The illustrations also depend on the assumptions stated for them and on an observed effect that may not represent the effect in another study. They should therefore be read as conditional planning scenarios, not as proof that the trial was adequately or inadequately powered.

10. Analyses Reported by the Sponsor

For the primary endpoint, the registry reports the sponsor's log-rank test with p = 0.018. The posted median and inter-quartile summaries describe the latency distributions, but they are not a recalculation of the sponsor's time-to-event analysis. No primary hazard ratio or confidence interval is reported, and the available information does not support reconstructing those quantities from the medians and inter-quartile ranges alone.

For gestational latency of more than 28 days, the sponsor reports a risk ratio of 1.48 with a 95% confidence interval from 1.06 to 2.05. A separate recalculation from the posted counts is unadjusted. The registry does not flag a discrepancy between that check and the sponsor's analysis. The recalculation is therefore best treated as a simple comparison based on the reported summary data, rather than a substitute for the sponsor's result or evidence about any unreported adjustment.

In general, a sponsor analysis may use methods or adjustments that cannot be recovered from summary counts alone. The registry does not report further details of the secondary analysis method. The primary conclusion should therefore be described using the sponsor-reported log-rank result, and the secondary result using the sponsor-reported risk ratio and interval, with the limits of the posted detail kept in view.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and several secondary outcomes. When investigators test multiple outcomes, repeated testing can raise the chance that one result appears statistically notable by chance alone. General statistical practice may address this through a prespecified hierarchy, an adjustment to the testing threshold, or another multiplicity strategy. The registry does not report whether any such strategy was prespecified or used.

The primary log-rank result is reported as p = 0.018. The sponsor's secondary risk ratio for latency of more than 28 days is reported with a 95% confidence interval. Those results should be distinguished from a single, fully documented confirmatory analysis: details of an overall testing strategy are not reported in the registry record. The registry also does not report whether secondary outcomes were intended as confirmatory or exploratory.

Missing-data handling is not reported in the registry record. The primary outcome results include 24 control participants and 26 intervention-group participants, while the record lists enrollment of 53. The reason the posted group counts do not account for all enrolled participants is not reported. The record does not state whether participants were excluded from the outcome analysis, whether outcome times were unavailable, or how any censored observations were treated.

The analysis population is also not reported in the registry record. It is not stated whether the primary and secondary analyses followed an intention-to-treat principle, included only participants who received treatment, or used another population definition. These distinctions matter because the analysis population and missing-data approach can affect how closely the estimates preserve the randomized comparison. Without these details, the posted results can be described, but the robustness of the analyses to exclusions or unavailable data cannot be evaluated.

The registry does not report interim analyses, stopping rules, a sample-size justification, or a detailed statistical analysis plan. Their absence from the record should not be taken as evidence that such procedures were or were not used. They are simply not reported in the registry record, limiting assessment of the prespecification and conduct of the statistical analyses.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry records zero serious adverse events in the control group among 24 participants at risk and zero in the indomethacin-and-antibiotics group among 26 participants at risk. It also records zero other adverse events in each group, using the same group counts at risk. No serious adverse-event terms are listed.

These entries describe the counts reported in the registry, not proof that no adverse events of any kind occurred. The record does not provide further detail on how adverse events were collected, what observation period applied, or whether events were classified in any additional way. Death counts are not reported in the registry record. The absence of posted event counts should therefore be interpreted as a limitation of the available safety reporting, not as a complete accounting of safety experience.

The group sizes are modest, and an absence of recorded events in these groups cannot establish that an event is impossible or that risks are equivalent. General explanation: safety counts are interpreted in relation to the number of participants observed, the duration and completeness of surveillance, and the event definitions used. Those additional details are not reported in the registry record. The posted figures support only a narrow statement about the adverse-event counts entered for the recorded groups.

13. What the Result Does, and Does Not, Mean

The posted primary results show a later median gestational latency in the indomethacin-and-antibiotics group than in the control group, with medians of 97 days and 80 days, respectively. The sponsor's log-rank test reports p = 0.018. Taken together, these are evidence of a difference in time-to-delivery patterns in the randomized comparison, as analyzed in the registry. The record does not provide a primary effect estimate with a confidence interval, so the size and precision of that difference remain incompletely characterized.

The result does not establish the exact time-to-delivery difference that would apply in another population or setting. A median summarizes the center of observed times, and the log-rank p-value does not give an individual-level prediction or quantify the probability that a treatment effect is true. The inter-quartile ranges also show variation in observed latency. Interpretation should keep both the group summaries and the uncertainty in the analysis in view.

The secondary result for latency of more than 28 days is directionally compatible with the primary summaries, but it is a separate endpoint. It does not resolve the limitations of the primary reporting, and the registry does not report results for the remaining named secondary outcomes. No multiplicity plan is reported, which means the secondary result should be regarded cautiously when considered alongside other outcomes.

The posted safety entries show zero serious and zero other adverse events in both recorded groups, but the record provides limited information about surveillance and does not report death counts. Those figures cannot establish the full safety profile. Nor do the registry results alone answer all questions about eligibility, treatment implementation, missing data, or generalizability. They describe the reported trial comparison and should not be expanded into claims beyond those data.

14. Why This Trial Matters Statistically

This trial is statistically informative because it frames gestational latency as a time-to-event outcome. The endpoint is not simply a measurement taken once: it records the time from cerclage placement until delivery. Comparing time-to-event patterns with a log-rank test is therefore conceptually different from comparing only a pair of medians. The registry provides both median summaries and a sponsor-reported test, allowing readers to see a descriptive contrast alongside an inferential result.

The record also illustrates why an effect estimate and its precision matter. The reported primary p-value indicates evidence against a null comparison under the test, but no primary hazard ratio or confidence interval is posted. Readers can observe the medians and inter-quartile ranges, yet cannot use those summaries alone to assess a full effect scale or the uncertainty around it. More complete reporting would make the magnitude and precision of the primary result easier to evaluate.

The secondary binary outcome offers a different summary of latency, while also illustrating the limits of multiple-outcome interpretation. Its sponsor-reported risk ratio and confidence interval add context, but other named secondary results and a multiplicity strategy are not reported. This makes the distinction between a primary analysis and secondary evidence important.

Finally, the difference between enrollment and the posted primary outcome group counts highlights the value of participant-flow and analysis-population reporting. Without an explanation of who contributed outcome data and how missing information was handled, readers cannot fully judge the basis of the analysis. The sample-size illustrations also emphasize that planning scenarios based on an observed effect are not the same as the trial's original design justification or an assessment of observed power.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record leaves several trial-specific details unavailable. Although it identifies a randomized, unmasked, parallel-group design, it does not report how the randomization sequence was generated, how allocation was concealed, or how treatment was implemented. The record also does not provide detailed eligibility criteria or participant characteristics, limiting assessment of which patients the results describe.

For the primary endpoint, the record provides medians, inter-quartile ranges, and a log-rank p-value, but not a hazard ratio, confidence interval, event count, or detailed time-to-event analysis. The timing and completeness of follow-up, censoring information, and assumptions checks are not reported. These omissions restrict evaluation of the estimated contrast and its precision.

Enrollment was 53, while the posted primary outcome groups include 24 and 26 participants. The reason for the difference is not reported in the registry record. Participant flow, analysis populations, missing-data methods, and the handling of unavailable outcome times are also not reported. Without these details, the impact of exclusions or incomplete observations cannot be assessed.

The registry names multiple secondary outcomes, but detailed results are reported for gestational latency of more than 28 days. Results for gestational age at delivery, neonatal morbidity and mortality, and birthweight are not reported in the registry record. Multiplicity handling and the status of secondary analyses as confirmatory or exploratory are likewise not reported. Safety reporting is limited to adverse-event counts, without further collection or follow-up details, and death counts are not reported.

The record does not report the trial's sample-size justification or detailed statistical analysis plan. The posted sample-size illustrations are explicitly planning scenarios based on the observed effect, not the trial's own design. These reporting gaps do not determine what happened in the trial, but they constrain what can be concluded from the registry results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Multifactorial Approach to Emergent Cerclage — NCT01114516.
• Registry record last updated 2014-11-07; status last verified 2014-11.
• Results first posted 2014-10-10.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT01114516 was a completed randomized, unmasked, parallel-group trial sponsored by Northwestern University. It enrolled 53 participants and compared emergent cerclage alone with emergent cerclage plus perioperative indomethacin and antibiotics, identified as cefazolin or clindamycin.

The primary outcome was median gestational latency from cerclage placement to delivery. The registry reports medians of 80 days for control and 97 days for the intervention group, with a sponsor-reported log-rank p-value of 0.018. A secondary outcome, gestational latency of more than 28 days, was reported with a sponsor risk ratio of 1.48 and a 95% confidence interval from 1.06 to 2.05.

The record also lists secondary outcomes for gestational age at delivery, neonatal morbidity and mortality, and birthweight, but detailed results for these are not reported in the registry record. Adverse-event entries show zero serious and zero other events in each recorded group; death counts are not reported. Analysis populations, missing-data handling, and the sample-size justification are not reported in the registry record.