Evaluation of CRB in PROM Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of CRB in PROM Patients (NCT01736852), a randomized na study. The primary outcome is Time of Labor.

2. Clinical Question

3. Trial Design

The registry record identifies this as a randomized, parallel-group study with no masking. It compares the Cook Cervical Ripening Balloon plus Pitocin with Pitocin alone in patients described as having premature rupture of membranes. The brief description focuses on term and near-term patients and the induction of labor. The record lists an enrollment of 129 and identifies the study status as completed. It gives a start date of 2012-11 and a primary completion date of 2018-12-31.

The primary outcome is labeled “Time of Labor.” It is a continuous measure, reported as a mean in minutes with standard deviation as the measure of spread. Its stated timeframe runs from the start of labor induction through delivery. The outcome summaries report 63 participants in the CRB Plus Pitocin arm and 61 in the Pitocin arm. The registry record does not explain why these outcome sample sizes differ from the overall enrollment figure, whether all enrolled participants contributed outcome data, or how missing outcome values were handled.

The sponsor is Cook Group Incorporated. The record lists two outcome measures and one analysis, but it does not provide a full account of the statistical plan or identify the analysis population. The trial’s original sample-size assumptions, planned statistical model, treatment of missing data, and approach to interim analyses are not reported in the registry record. Randomization supports a between-arm comparison in principle, but the available record does not give enough procedural detail to assess the conduct of allocation or the analysis beyond the posted summary statistics.

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

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 Time of Labor, measured over Start of labor induction through delivery, an expected average of 6 hours.

The primary endpoint measures elapsed time, in minutes, from the start of labor induction through delivery. It is a continuous outcome: each observed value represents a duration, and the registry reports each arm’s mean and standard deviation. The record gives the timeframe as the induction start through delivery and describes an expected average of 6 hours. This is a timeframe description, not a result; the posted arm means are the observed summary values available for comparison.

Duration is used to express how long the induction-to-delivery process took in the study population. Comparing arm means addresses an average difference between assigned groups, rather than describing every participant’s experience or the proportion reaching a particular time threshold. The standard deviation describes variability among individual durations around each arm’s mean. A mean difference can be informative about the direction and scale of the group contrast, while the variability and confidence interval indicate how much uncertainty accompanies that estimate.

The registry record does not explain whether the endpoint was assessed using a particular time-origin convention beyond the stated start of induction, how unusual or incomplete durations were treated, or whether the definition was changed during the study. It also does not report a clinical-importance threshold for interpreting a difference in minutes. Therefore, statistical interpretation should remain focused on the observed mean contrast and its uncertainty, without assuming that any particular duration is clinically preferable.

7. Results Posted in the Registry

• Pitocin: mean 1,017 versus 850.40 on control; difference 166.20 (95% CI -15.41 to 347.81), standardized effect d = 0.32; z-test p = 0.073.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a continuous duration measured in minutes. For a continuous outcome, a group mean describes the average observed value, while a standard deviation describes how dispersed individual values are around that average. These are different summaries: the standard deviation reflects variation among participants, whereas uncertainty in a mean contrast also depends on the amount of information available and the analysis assumptions. The posted arm summaries are 850.4 minutes with a standard deviation of 417.6 for CRB Plus Pitocin, and 1017.0 minutes with a standard deviation of 595.7 for Pitocin.

What does the mean difference represent?

The reported contrast is a mean difference of 166.2 minutes, comparing the Pitocin mean with the CRB Plus Pitocin mean. A positive estimate in this stated direction indicates that the posted average was higher in the Pitocin arm. The estimate summarizes the difference between group averages; it does not imply that each participant experienced a difference of that size. Nor does it describe whether the difference was similar across all participants. A mean can be influenced by unusually long or short durations, and the registry record does not provide distributional plots or other summaries such as medians or quantiles.

What do standard deviations tell the reader?

The standard deviations are 417.6 minutes for CRB Plus Pitocin and 595.7 minutes for Pitocin. They indicate substantial variation in observed times in both groups, with greater reported spread in the Pitocin arm. Standard deviation is not the same as a confidence interval for the mean and is not a range containing all participants. It describes the spread of the observed outcome values around the group mean. The registry record does not report the underlying participant-level durations, so the shape of each distribution and the influence of extreme values cannot be evaluated from these summaries alone.

How should the interval be read?

The interval for the mean difference extends from -15.41 to 347.8 minutes. A confidence interval is a range of values compatible with the data under the statistical procedure and its assumptions. Its width communicates precision: a wider interval leaves more uncertainty about the size and direction of the underlying mean contrast. This interval spans the no-difference value for a contrast and includes values in either direction. The confidence level is not stated in the registry record, so it is not appropriate to label the interval with an unstated level or to infer the exact procedure used to construct it.

Confidence intervals do not assign a probability to the true effect being inside the particular interval after the data have been observed. Their interpretation concerns the long-run behavior of the method under repeated use and its assumptions. In practical reading, the interval is useful for seeing which effect sizes remain consistent with the posted estimate and method. It does not answer whether those values are clinically important, because a clinical-importance threshold is not reported.

What does the p-value convey?

The posted unadjusted p-value is 0.073. In general, a p-value measures how unusual results at least as incompatible with a null hypothesis would be if that null hypothesis and the statistical model were true. It is not the probability that the null hypothesis is true, nor is it a measure of the magnitude or clinical importance of a difference. “Unadjusted” indicates that the reported value is not presented as adjusted for multiplicity; the registry record does not describe other adjustments or the exact test used. The trial’s primary significance threshold and full analysis plan are not reported. The two-sided significance level of 0.05 belongs to the planning illustration assumptions, not necessarily to the trial’s original analysis.

Why do outcome sample sizes matter?

The posted summaries list 63 participants for CRB Plus Pitocin and 61 for Pitocin. Sample size affects the precision of a group mean and the comparison between groups, but the number alone does not determine precision: variability and the analysis method also matter. The record lists overall enrollment as 129 but does not explain the relationship between enrollment and the arm-specific endpoint counts. It does not state whether any participants lacked an outcome value, were excluded, or were analyzed under a particular population definition. These points should therefore remain unresolved rather than being inferred from the summary counts.

What assumptions are not documented?

The registry record does not report the statistical model used for the primary comparison, any adjustment for covariates, a method for handling missing values, or details about the analysis population. It also does not state the confidence level or interval-construction method. General methods for analyzing continuous outcomes may rely on assumptions about independent observations and the sampling distribution of the estimate; whether specific assumptions were checked or whether another method was used is not reported in the registry record. The posted summaries can be interpreted descriptively, but reconstructing the trial’s analysis from them would require details that are not available.

The sample-size illustrations are separate planning calculations based on the observed effect under stated assumptions. They use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Their effect targets are stated as fractions of the observed effect. The registry record does not report whether those assumptions match the study’s original planning or whether its investigators used another approach. Consequently, the illustrations can explain planning trade-offs, but they should not be treated as a record of the trial’s design calculation or analysis procedure.

10. Confidence Intervals and Precision

The mean-difference estimate is 166.2 minutes, and its interval extends from -15.41 to 347.8 minutes. The interval is broad relative to the point estimate and includes both a modest difference in the opposite direction and larger differences in the reported direction. This means the point estimate alone gives an incomplete account: the interval makes visible that the underlying average contrast remains uncertain. The record does not state the interval’s confidence level or construction method, so neither should be assumed.

The arm means are 850.4 minutes for CRB Plus Pitocin and 1017.0 minutes for Pitocin. Their standard deviations, 417.6 and 595.7 minutes, respectively, describe participant-level spread, not uncertainty in the estimated difference. The reported spread is sizable, and the Pitocin arm has the larger standard deviation. Without the outcome distribution or participant-level records, it is not possible to determine whether the means are affected by skewness or unusually long durations.

The unadjusted p-value is 0.073, but it should be read alongside the estimate and interval rather than as a stand-alone verdict. The registry record does not provide a prespecified primary-analysis threshold, the confidence level, the statistical model, or details of missing-data handling. These unknowns constrain precision assessment. The interval conveys uncertainty under an analysis procedure, but the record does not identify that procedure in enough detail to evaluate its assumptions. The clinical importance of the range also cannot be determined because no threshold for a meaningful difference in minutes is reported.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total event counts. They illustrate the number of participants per arm for 80% power and participants per arm for 90% power under the stated planning assumptions. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The target effect is expressed as the stated fraction of the observed effect. These are planning illustrations based on the observed effect, not the trial’s original design assumptions; the original design assumptions are not reported in the registry record.

The 80% power column gives an illustrative per-arm sample size for a future comparison designed to have 80% power to detect the target effect under those assumptions. The 90% power column gives the corresponding illustration for a design targeting 90% power. Power is a feature of a study design under an assumed effect and model; it is not a guarantee that a result will be detected or that the assumed effect is true. The listed values are not observed power.

The rows vary the target from 100% of the observed effect to 75% and 50% of the observed effect. The displayed per-arm requirements increase as the target effect becomes smaller. This reflects a general statistical principle: when a study aims to detect a smaller difference, more information is needed to distinguish that difference from random variation, all else held constant. The plotted planning curve visualizes that relationship. It does not show participant enrollment in the completed trial or establish what sample size the trial originally planned. The figures should be read as assumption-dependent illustrations rather than recommendations or evidence about the trial’s achieved power.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 166.200; pooled standard deviation σ = 512.976.
2. n = 2 × (1.96 + 0.842)² × 512.976² / 166.200² = 149.5, rounded up to 150 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 166.2                      # observed difference in means
sigma <- 512.976483978315                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1736852)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 150 (80% power), 201 (90% power)
 75% of observed effect: n per arm = 266 (80% power), 356 (90% power)
 50% of observed effect: n per arm = 599 (80% power), 801 (90% power)
power.t.test: 150.5 
Simulated power at n = 150 per arm: 0.798 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures and one analysis, and it identifies Time of Labor as the primary outcome. It reports no secondary outcomes posted. The record does not describe whether other outcomes were collected, whether additional analyses were conducted, or how the primary outcome was selected in relation to any other planned outcomes. The number of listed outcomes alone does not establish the full scope of analyses performed.

Multiplicity arises when several outcomes, comparisons, subgroups, or analytic choices are tested. In general, conducting multiple tests can increase the chance of obtaining an apparently unusual result by chance if each test is interpreted in isolation. Adjustment procedures or a prespecified hierarchy can address this issue, but the registry record does not report a multiplicity strategy. The posted p-value is identified as unadjusted. It should therefore be read as an unadjusted result, without assuming that it accounts for other comparisons or analyses.

Missing-data handling is also not reported in the registry record. The endpoint summaries give 63 participants in the CRB Plus Pitocin arm and 61 in the Pitocin arm, while overall enrollment is listed as 129. The record does not explain this relationship or state whether missing endpoint values occurred, how many values were missing, why any values were unavailable, or how missingness was handled. Without those details, the impact of missing outcome information on the comparison cannot be assessed.

The analysis population is not described. The registry record does not say whether the primary analysis followed randomized assignment, included only participants who received assigned treatment, or used another population definition. It also does not report exclusions after randomization or an intention-to-treat approach. These are important distinctions because analysis populations can affect how a randomized comparison is interpreted. No particular population or missing-data method should be inferred from the posted summaries.

More generally, the trial’s statistical analysis plan, interim-analysis approach, and handling of protocol deviations are not reported in the registry record. This absence does not prove that no such procedures existed; it means they cannot be characterized from the record. The primary comparison can be described using the posted means, standard deviations, interval, and unadjusted p-value, while conclusions about multiplicity control, missingness, and the analysis set must remain limited.

14. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: postpartum hemorrhage (3.2%), jaundice neonatal (1.6%), neonatal hypoxia (1.6%), infantile apnea (1.6%), arrested labor (1.6%).

The serious adverse event summaries list 5 affected participants among 63 at risk in the CRB Plus Pitocin arm and 4 among 61 at risk in the Pitocin arm. For other adverse events, the record lists 27 affected among 63 at risk for CRB Plus Pitocin and 21 among 61 at risk for Pitocin. The death count is 0 in each arm. These are reported counts and at-risk group sizes; they should not be converted into unreported comparisons or treated as evidence that every event had the same severity or clinical significance.

The registry record lists postpartum hemorrhage at 3.2%, followed by Jaundice Neonatal, Neonatal Hypoxia, Infantile Apnea, Arrested Labor, and Neonatal respiratory distress syndrome, each at 1.6%, among the top serious-event terms. The listed terms are not accompanied by arm-specific counts in the available record, so they cannot be assigned to either group from these summaries. The record does not provide event definitions, timing, seriousness criteria, relatedness assessments, or details about how repeated events in a participant were counted. The counts describe the posted safety summaries and do not establish a causal relationship with an intervention.

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

The posted results describe a randomized comparison of CRB plus Pitocin with Pitocin alone for the primary outcome of time from induction start through delivery. The observed mean was 850.4 minutes in the CRB Plus Pitocin arm and 1017.0 minutes in the Pitocin arm. The reported mean contrast is 166.2 minutes in the direction of the higher Pitocin-arm mean. The interval from -15.41 to 347.8 minutes indicates uncertainty about the size and direction of the underlying average difference. The unadjusted p-value is 0.073.

These statistics do not establish that one approach works or does not work. They characterize the posted outcome summaries and the uncertainty attached to a mean comparison. The interval includes values on either side of the no-difference point, and the record does not report the confidence level, the trial’s prespecified significance threshold, or a clinical-importance threshold. A statistical estimate is not a direct measure of patient benefit, and a mean duration does not capture all aspects of labor or delivery.

The results also do not show the experiences of every participant. Group means and standard deviations compress individual observations into summary measures. The record does not provide outcome distributions, detailed baseline characteristics, the analysis population, missing-data methods, or enough information to assess the primary model. The overall enrollment and outcome-specific arm counts are both stated, but their relationship is not explained.

Safety counts are reported separately and should not be interpreted as proof that events were caused by either assigned intervention. The top serious-event terms are listed with percentages but without arm-specific counts in the available record. The record’s description of the study population and interventions also does not substitute for detailed eligibility or treatment-procedure information. Accordingly, interpretation should stay with the registered population description, assigned-group comparison, endpoint summaries, and stated limitations rather than extending to unreported outcomes or clinical conclusions.

16. Why This Trial Matters Statistically

This trial illustrates why a point estimate should be read together with its uncertainty. The mean contrast is 166.2 minutes, but its interval runs from -15.41 to 347.8 minutes. Readers can see both the direction of the point estimate and the range of values still compatible with the reported analysis. The interval does not support treating the point estimate as a precise description of the underlying difference.

The endpoint also highlights the distinction between variability among participants and precision of a group comparison. Standard deviations of 417.6 minutes and 595.7 minutes show considerable spread in observed durations, while the interval for the contrast represents uncertainty about the comparison. Neither statistic answers whether a difference is important to patients. The registry record does not state a threshold for clinical importance, making that distinction especially relevant.

The sample-size illustrations demonstrate how planning depends on the effect a future study aims to detect. Their assumptions are explicitly described, but the registry record does not provide the trial’s original design assumptions. The planning figures therefore illustrate a general design trade-off rather than documenting the basis for this study’s enrollment. Keeping these two purposes separate prevents planning calculations from being mistaken for evidence about the completed trial’s power.

Finally, the record shows how reporting details shape statistical interpretation. The primary outcome summaries and unadjusted p-value are available, while the analysis plan, missing-data methods, analysis population, and multiplicity approach are not reported. Recognizing what can be learned from the posted estimates—and what remains unknown—is central to a careful reading of a clinical-trial result.

17. 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.

Several limitations arise from what the registry record does not report. The trial is labeled randomized and parallel, but the record does not describe sequence generation, allocation concealment, or procedural details. Masking is listed as none, while the record does not specify whether outcome assessment or data analysis was masked. These details matter when evaluating the potential for bias, but their absence from the record does not establish how the procedures were conducted.

The registry describes the population as term and near-term patients with PROM, but detailed eligibility criteria and participant characteristics are not reported. The arm descriptions contain no additional treatment details. The record does not state dose, timing, adherence, co-interventions, or how deviations from assigned treatment were handled. Consequently, the treatment contrast cannot be characterized beyond the registered intervention labels.

The outcome is reported as a mean and standard deviation, without participant-level data or distributional summaries. The interval’s confidence level and statistical construction are not stated. The primary analysis model, analysis population, missing-data approach, and prespecified threshold are also not reported. Overall enrollment is 129, while outcome summaries list 63 participants for CRB Plus Pitocin and 61 for Pitocin; the registry record does not explain the relationship between these figures.

Safety information is limited to the posted counts, at-risk group sizes, death counts, and listed serious-event terms. Definitions, event timing, relatedness, and arm-specific detail for the listed terms are not reported. These limits constrain interpretation of both the primary outcome and safety summaries. They should be treated as gaps in the registry record, not resolved through assumptions about the study.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Evaluation of CRB in PROM Patients — NCT01736852.
• Registry record last updated 2020-10-20; status last verified 2020-10.
• Results first posted 2020-10-20.
• 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.

21. Record Summary

The registry record describes a completed randomized, parallel-group study with no masking, sponsored by Cook Group Incorporated. It compares CRB plus Pitocin with Pitocin alone for induction of labor in term and near-term patients with PROM. The primary outcome is time from induction start through delivery, measured in minutes and summarized as a mean with standard deviation. The record lists enrollment of 129, a start date of 2012-11, and primary completion on 2018-12-31.

The posted means are 850.4 minutes for CRB Plus Pitocin and 1017.0 minutes for Pitocin, with a reported mean difference of 166.2 minutes and an interval from -15.41 to 347.8 minutes. The unadjusted p-value is 0.073. Safety summaries list serious and other adverse-event counts, with 0 deaths in each arm. The registry record does not report the full statistical plan, analysis population, missing-data methods, or original sample-size assumptions.