Mirena Intrauterine System Timing of Insertion: A Randomized Controlled Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Mirena Intrauterine System Timing of Insertion: A Randomized Controlled Trial (NCT01272960), a randomized na study. The primary outcome is Mirena in Place.

2. Clinical Question

The trial asks whether timing of Mirena insertion after vaginal delivery is associated with the proportion of participants who have the device in place at 6 months. It compares insertion immediately after placental delivery with insertion at a later postpartum visit. The registry describes the study as a randomized, open-label, controlled trial.

3. Trial Design

The registry describes a randomized, parallel-group trial with no masking. Participants were enrolled at 36 weeks gestation and greater. At vaginal delivery, assignment was made to immediate post-placental insertion or interval insertion. Post-placental insertion was specified as within 10 minutes of delivery of the placenta. Interval insertion was described as taking place at 4-8 weeks postpartum after vaginal delivery.

The planned follow-up described in the study summary included visits at 4-6 weeks after insertion and at 6 months postpartum to confirm the position of the device. The primary outcome reported in the registry is Mirena in place at 6 months. Secondary outcomes listed include Mirena expulsion, uterine perforation, and intrauterine infection. The study summary also describes safety, acceptability, and symptoms as secondary interests, but the posted outcome results in the record do not provide estimates for those listed secondary outcomes.

The registry lists Washington University School of Medicine as sponsor, the status as completed, and the phase as NA. The recorded start is 2010-10 and primary completion is 2012-12. The overall enrollment is 53. For the primary outcome, the arm counts are 15 for post-placental insertion and 14 for interval insertion. The record does not explain why these outcome counts differ from the overall enrollment figure, or whether the difference reflects availability of outcome data, eligibility for the analysis, or another reason.

Randomization supports a comparative interpretation, but the record does not report the allocation procedure or details about implementation. It also does not report the trial’s original sample-size justification, the prespecified statistical analysis plan, or whether any interim analyses were planned. These omissions limit how fully the reported comparison can be evaluated against the trial’s intended design.

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.

Before assignment: 53 participants were enrolled but only 29 randomized.

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 Mirena in Place, measured over 6 months.

The primary endpoint is Mirena in place at 6 months, recorded as a count of participants in each arm. It captures whether the device was present in the intended position at the follow-up time, rather than merely whether insertion was attempted or completed. The study summary describes confirmation of correct position at follow-up; the outcome title and description state the endpoint as Mirena in place at 6 months.

This endpoint is relevant to the timing question because the study seeks to compare the proportion of participants with the device in place after immediate post-placental insertion versus interval insertion. The registry reports 10 participants with Mirena in place among 15 in the post-placental arm, and 3 among 14 in the interval arm. Those counts are the observed outcome data behind the posted comparison.

Endpoint interpretation depends on knowing how outcomes were ascertained and how participants without a recorded 6-month result were handled. The registry record does not report those details, nor does it define the endpoint beyond the description of Mirena in place at 6 months. In particular, it does not state whether absence from follow-up was treated as a device not in place, excluded from the calculation, or handled in another way. The endpoint therefore describes the posted outcome counts, while the record leaves important details of outcome ascertainment and missing-result handling unspecified.

7. Results Posted in the Registry

• Interval Insertion: 21.4% (3/14) versus 66.7% (10/15) on control; risk difference -45.2 percentage points (95% CI -77.3 to -13.1), risk ratio 0.32 (0.11–0.93); unadjusted two-proportion z-test p = 0.014.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary result is a binary outcome: each participant is classified according to whether Mirena was in place at 6 months. The registry reports counts for participants with the event and arm denominators. For post-placental insertion, the count is 10 among 15; for interval insertion, it is 3 among 14. A binary outcome can be summarized within each group as an event proportion, then compared between groups using an absolute contrast or a relative measure. The posted record includes a risk difference, risk ratio, and odds ratio.

What does the risk difference express?

The risk difference subtracts the outcome proportion in one group from the outcome proportion in the other, with the order of groups determining the sign. The registry comparison is interval insertion relative to the post-placental control arm. Its reported risk difference is -0.452. A negative value means the recorded outcome proportion is lower in the interval arm under that comparison order. The confidence interval is -0.773 to -0.131. The estimate is on an absolute scale: it describes a difference in proportions, rather than a ratio between them.

How do relative measures differ?

The risk ratio compares the outcome proportions as a ratio, while the odds ratio compares the odds of the outcome. They use different scales and should not be interpreted as interchangeable quantities. The posted risk ratio is 0.321, with an interval from 0.111 to 0.932. The posted odds ratio is 0.136, with an interval from 0.026 to 0.723. The direction of both measures indicates a lower observed outcome in the interval group relative to the post-placental group. A ratio’s numerical distance from its reference value does not translate directly into an absolute difference; the underlying event frequency also matters.

What does a p-value add?

The registry reports an unadjusted p-value of 0.014. In general, a p-value describes how compatible data are with a specified null model, under the assumptions of the statistical test. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. The registry does not name the test used, give the complete analysis plan, or state the trial’s prespecified decision threshold. The reported p-value should therefore be considered alongside the effect estimate and its interval, rather than as a stand-alone verdict.

Why do the intervals matter?

A confidence interval describes uncertainty around an estimated effect under a statistical procedure. Its width reflects both the amount of information and the variability of the data, among other model assumptions. Here, the arm counts are limited, and the intervals allow a range of effect sizes. The registry does not state the confidence level for the reported intervals, so a particular coverage percentage should not be attributed to them. The intervals do not address uncertainty arising from unreported features such as missing outcomes, choice of analysis population, or possible differences in outcome assessment.

What can randomization support?

In general, random assignment is intended to make treatment groups comparable on average with respect to factors present before assignment. This supports a causal comparison of assigned strategies when randomization is properly implemented, outcome data are sufficiently complete, and the analysis respects the assignment. The registry confirms randomized allocation and a parallel-group design, but does not describe sequence generation, concealment, adherence, crossover, or the primary analysis population. The trial is open-label, and the record does not describe whether outcome assessment was masked. Randomization is therefore an important strength of the design, but the record does not supply enough detail to evaluate every condition needed for a strong causal interpretation.

Why can event counts affect inference?

With binary outcomes, a small number of observed events can make estimates sensitive to a change in classification or a small amount of missing information. Intervals can consequently be wide, and relative measures can be especially difficult to interpret when event counts are sparse. This is a general feature of inference with limited event information, not proof that any particular posted value is wrong. The registry reports 10 and 3 participants with the endpoint in the respective arms, but does not explain how missing follow-up or uncertain device position was handled.

What analysis details are absent?

The registry lists four outcome measures and three secondary outcomes, but records zero posted analyses. It nevertheless contains the primary arm counts and a comparison estimate. The record does not explain the statistical test behind the reported p-value, whether the comparison was prespecified, or whether any adjustment was used. It does not report covariate adjustment, subgroup analyses, interim monitoring, or a multiplicity plan. These omissions do not change the arithmetic interpretation of the posted summary statistics, but they restrict assessment of the analysis choices and their relation to the study protocol.

Overall, the methods can be understood as a comparison of binary outcome counts between randomized arms, with absolute and relative effect summaries and an unadjusted p-value. The statistical summaries describe the posted data. Their interpretation remains conditional on details of trial conduct and analysis that are not reported in the registry record.

10. Confidence Intervals and Precision

The primary risk-difference estimate for interval insertion relative to post-placental insertion is -0.452, with an interval from -0.773 to -0.131. This interval conveys uncertainty around the estimated absolute contrast. Its endpoints span effects that differ substantially in magnitude, so the point estimate should not be treated as an exact value for the underlying effect. The registry record does not state the confidence level or method used to construct the interval.

The relative summaries also have intervals: the risk ratio is 0.321, with an interval from 0.111 to 0.932, and the odds ratio is 0.136, with an interval from 0.026 to 0.723. These intervals are on different scales from the risk-difference interval. They indicate uncertainty in the corresponding relative measures and should not be compared by their widths alone.

In general, a confidence interval is a statistical range produced by a method that, under its assumptions, has a specified long-run coverage property. It is not a range containing a fixed proportion of individual responses, and it does not account automatically for every source of uncertainty. In this trial, the modest outcome counts contribute to uncertainty, while the registry does not report how missing data were handled or how the analysis population was defined. Those unreported features cannot be represented by the posted intervals.

The unadjusted p-value is 0.014, but precision is better judged from the estimates and intervals than from the p-value alone. The intervals provide information about the range of effect values compatible with the reported analysis, while the p-value addresses a different question under a null model. Neither establishes how well the trial’s results generalize beyond its observed participants and follow-up.

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 illustrations based on the observed effect, not the trial’s original design justification. They assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to a stated fraction of the observed effect. The reported figures are participants per arm, not total participants and not total events.

For planning for 100% of the observed effect, the illustration gives 18 participants per arm for 80% power and 24 participants per arm for 90% power. For planning for 75% of the observed effect, it gives 33 participants per arm for 80% power and 44 participants per arm for 90% power. For planning for 50% of the observed effect, it gives 75 participants per arm for 80% power and 100 participants per arm for 90% power.

In general, power is the probability that a planned study will detect an effect of a specified size under its assumptions if that effect is real. The 80% and 90% columns describe different target probabilities for detecting the chosen effect, not certainty that a future study will reach a result. Detecting a smaller effect generally requires more participants, as reflected by the increasing planning figures for smaller fractions of the observed effect. These figures are not observed power and should not be read as a retrospective measure of what the completed trial achieved. The trial’s own original sample-size assumptions are not reported in the registry record.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.667; treatment proportion p₁ = 0.214; average p̄ = 0.440.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7021 = 1.3760.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6250 = 0.5260.
4. n = (1.3760 + 0.5260)² / (-0.4524)² = 17.7, rounded up to 18 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
p0 <- 0.666666666666667                          # control proportion
p1 <- 0.214285714285714                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(1272960)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 18 (80% power), 24 (90% power)
 75% of observed effect: n per arm = 33 (80% power), 44 (90% power)
 50% of observed effect: n per arm = 75 (80% power), 100 (90% power)
power.prop.test: 17.7 
Simulated power at n = 18 per arm: 0.839 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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 lists the primary endpoint of Mirena in place at 6 months and three secondary outcomes: Mirena expulsion, uterine perforation, and intrauterine infection. The study summary also refers to acceptability and symptoms as secondary interests. The record lists four outcome measures overall, but it posts zero analyses. As a result, the primary comparison is accompanied by no posted statistical analyses for the listed secondary outcomes.

Multiplicity arises when several hypotheses or outcomes are examined. In general, the more comparisons considered, the more likely it becomes that at least one result appears unusual by chance if no adjustment or other plan is used. Whether an adjustment is appropriate depends on the trial’s prespecified objectives and analysis strategy. The registry does not report a multiplicity plan, a hierarchy of outcomes, or which analyses were intended to be confirmatory. It is therefore not possible to determine from the record whether the primary result was interpreted within a prespecified family of tests or whether any adjustment was planned.

The record also does not report a missing-data method or the analysis population. It does not state how participants without a 6-month assessment were treated, whether all randomized participants were included in the primary comparison, or whether any participants were excluded after randomization. The overall enrollment is 53, while the primary outcome counts are 15 and 14; the registry does not explain the relationship between these figures. This difference should not be assigned a cause without further information.

These omissions affect interpretation because missing outcomes can change the group proportions, while analysis-population choices can affect how closely the reported estimate reflects the randomized comparison. They also limit assessment of whether the statistical analysis followed the original protocol. The posted outcome counts and estimates remain interpretable as recorded results, but conclusions about completeness, prespecification, and multiplicity control are not reported in the registry record.

14. 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.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: infection (6.7%).

The serious adverse event record lists 1 affected participant among 15 at risk in the post-placental insertion group, and 0 among 14 at risk in the interval insertion group. The record separately lists 0 other affected participants among 15 at risk in the post-placental group and 0 among 14 at risk in the interval group. Death counts are not reported in the registry record.

In general, an adverse-event count is a descriptive safety result for the recorded follow-up and event definitions. It does not, by itself, establish whether an event was caused by the intervention. The registry lists Infection as a top serious term at 6.7%, but does not provide the context or denominator for that term in the posted adverse-event summary. It should not be assumed from this entry alone that the term accounts for a particular group’s serious event.

The figures are limited by the small recorded at-risk groups and the lack of additional detail about event ascertainment, timing, severity, relatedness, or follow-up duration. The listed counts should be read as the registry’s reported safety information, not as a complete comparison of every possible harm or a definitive estimate of risk.

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

The result describes the primary endpoint recorded by the trial: Mirena in place at 6 months. The observed count was 10 of 15 after post-placental insertion and 3 of 14 after interval insertion. The posted comparison, expressed as interval insertion relative to post-placental insertion, has a risk difference of -0.452, with an interval from -0.773 to -0.131. The risk ratio, odds ratio, and unadjusted p-value provide additional summaries of the same comparison.

These statistics do not establish that the observed contrast will occur in every clinical setting or for every participant. They do not answer questions about outcomes beyond the registry’s stated follow-up, and they do not establish a difference in acceptability, symptoms, or the listed secondary outcomes. The registry record does not post analyses for those outcomes. Nor do the primary outcome figures alone establish comparative safety; the adverse-event record is limited and does not provide detailed event context.

The trial was randomized, which is a meaningful design feature for comparing assigned insertion strategies. However, the record does not provide enough information to assess randomization procedures, missing outcome handling, analysis populations, or outcome assessment in detail. The difference between overall enrollment and primary outcome arm counts is unexplained. The posted estimates therefore need to be interpreted in light of those reporting gaps.

Statistical uncertainty is also important. The effect estimate is a single summary of the observed data, while its interval indicates a range of values compatible with the analysis method. The registry does not report the confidence level or interval method. Neither the point estimate nor the p-value captures all uncertainty from trial conduct, incomplete follow-up, or limitations on generalizability.

The result supports a careful descriptive statement: the recorded proportion with Mirena in place at 6 months was higher in the post-placental group than in the interval group, and the registry’s unadjusted comparison quantified that difference. It does not, on its own, establish the magnitude that would be expected in another population or resolve the unreported aspects of the trial’s conduct and analysis.

16. Why This Trial Matters Statistically

This trial illustrates how a randomized comparison can be interpreted through an absolute effect estimate, relative measures, event counts, and uncertainty intervals. The risk difference describes the contrast in proportions on an absolute scale, while the risk ratio and odds ratio describe relative contrasts. Each measure answers a related but distinct statistical question, and their interpretation depends on the group order and outcome frequency.

The study also demonstrates why counts and denominators matter. The primary result is based on 10 participants with the endpoint among 15 in the post-placental arm and 3 among 14 in the interval arm. A point estimate alone can sound definitive, but limited outcome information leaves uncertainty about the size of the underlying contrast. The interval estimates help show that uncertainty, although their method and confidence level are not stated in the registry record.

Design and reporting details are part of statistical interpretation, not administrative extras. Randomization is reported, but the registry does not describe allocation implementation, missing-data handling, outcome assessment, or the primary analysis population. The overall enrollment figure is not reconciled with the primary outcome counts. These details are necessary to evaluate how completely the posted estimate reflects the randomized comparison.

The record also lists secondary outcomes without posted analyses. This makes multiplicity and selective emphasis difficult to assess. The planning illustration offers a separate lesson: sample-size requirements depend on the effect size chosen for planning, and smaller target effects call for larger participant counts under the stated assumptions. Such calculations are planning aids, not evidence about the power achieved by the completed trial.

Together, these features show why statistical significance, effect size, precision, completeness of follow-up, and analysis transparency should be considered as distinct parts of evidence. The primary result is interpretable, but its scope is limited by the information documented in the registry.

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.

The outcome counts for the primary comparison are smaller than the overall enrollment figure of 53, and the registry does not explain the relationship. It is not possible to tell from the record whether this reflects missing follow-up, exclusions, a defined analysis subset, or another reason. The record also does not specify how participants without outcome measurements were handled. This leaves uncertainty about the completeness and representativeness of the posted primary comparison.

The trial is listed as open-label, and no detail is reported about masking of outcome assessors or the method used to confirm device position. The study summary describes follow-up intended to confirm position, but the registry does not give the outcome-assessment procedures or missing-visit rules. These omissions limit evaluation of possible measurement or follow-up differences between groups.

Although randomization is recorded, sequence generation, allocation concealment, adherence to assigned timing, crossover, and analysis by assigned group are not described. The original sample-size justification and trial statistical plan are also not reported. The planning illustration based on the observed effect cannot substitute for the trial’s original design rationale.

The registry lists secondary outcomes but provides no analyses for them. It does not report a multiplicity approach, subgroup results, adjusted analyses, or interim analyses. Adverse-event detail is limited: the registry gives affected counts and a top serious term but does not describe event timing, severity, relatedness, or the context for the listed infection percentage. The resulting interpretation is restricted to the posted primary outcome and the limited safety counts, rather than a comprehensive assessment of all trial outcomes.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Mirena Intrauterine System Timing of Insertion: A Randomized Controlled Trial — NCT01272960.
• Registry record last updated 2017-12-02; status last verified 2017-10.
• Results first posted 2017-12-02.
• 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

NCT01272960 is a completed, randomized, open-label, parallel-group trial sponsored by Washington University School of Medicine. It compared post-placental Mirena insertion within 10 minutes of placental delivery with interval insertion at 4-8 weeks postpartum after vaginal delivery. The registry records an enrollment of 53 and primary completion in 2012-12.

The primary endpoint was Mirena in place at 6 months. The posted counts are 10 of 15 in the post-placental arm and 3 of 14 in the interval arm. The comparison reports a risk difference of -0.452, with an interval from -0.773 to -0.131, and an unadjusted p-value of 0.014. The registry also lists secondary outcomes and limited adverse-event counts, but posts no secondary analyses.

The record does not explain the difference between enrollment and primary outcome counts or report missing-data handling, the analysis population, the original sample-size justification, or the complete statistical plan. These gaps qualify interpretation of the posted estimates.