Misoprostol With Intrauterine Device Insertion: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Misoprostol With Intrauterine Device Insertion (NCT00613366), a randomized na study. The primary outcome is The Ease of IUD Insertion as Rated by the Provider Using a 100mm Visual Analog Scale (VAS)..

2. Clinical Question

3. Trial Design

The registry record describes a randomized, parallel-group trial with quadruple masking. Participants were assigned to active drug or placebo, with cervical preparation before intrauterine device insertion in both arms. The record lists Oregon Health and Science University as the sponsor and identifies contraception as the condition. The study is marked completed.

Enrollment is recorded as 40. For the primary outcome, the posted arm summaries include 17 participants in the active-drug arm and 18 in the placebo arm. These outcome-specific counts should be read as reported, not as a substitute for an explanation of participant flow. The registry record does not report reasons for any difference between enrollment and the numbers contributing to the outcome summaries.

The study began in 2007-06, and primary completion is recorded as 2010-04. The phase is listed as NA. The registry record does not report the trial's original sample-size justification, allocation ratio rationale, detailed randomization procedure, or the exact masking roles. Although the record identifies quadruple masking, it does not specify which groups of people were masked.

The registry lists misoprostol and magnesium oxide as interventions, while the arm descriptions identify misoprostol and placebo. The relationship between the magnesium oxide listing and the described study arms is not reported in the registry record, so no further role should be inferred. The registry record also does not report detailed information about the dose or timing of the study preparations.

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: Women desiring IUD placement who were nulliparous were enrolled.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent to Treat (ITT)

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 The Ease of IUD Insertion as Rated by the Provider Using a 100mm Visual Analog Scale (VAS)., measured over Time of IUD insertion.

The primary endpoint is provider-rated ease of intrauterine device insertion, recorded at the time of insertion using a 100mm visual analog scale. The registry describes the instrument as a continuous line on which a respondent indicates a position. Its description refers to anchors from 0, labelled No Pain, to 100, labelled Worst Pain of My Life. That wording describes a pain scale, while the named primary outcome concerns provider-rated ease of insertion. The registry record does not clarify this apparent mismatch in the measure description, so the posted outcome should be understood according to its stated title and rating source, with that limitation in mind.

A visual analog scale is used for subjective experiences that cannot be measured directly in the way a physical quantity can. A continuous score preserves more gradation than a small set of response categories, but the meaning of a score depends on the scale anchors and the question asked. The primary measure therefore represents the provider's subjective rating, not an objective measure of insertion time or technical success. The registry reports the mean and standard deviation for each arm. The endpoint is useful for comparing average provider ratings, while the spread of scores helps show how much individual ratings varied within each arm.

7. Results Posted in the Registry

• Active Drug (Misoprostol): mean 24.00 versus 29.00 on control; difference -5.00 (95% CI -18.25 to 8.25), standardized effect d = -0.25; z-test p = 0.460.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Perceived Pain of IUD Insertion by Patient Using a 100mm Visual Analog Scale (VAS).

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Active Drug (Misoprostol): mean 65.00 versus 55.00 on control; difference 10.00 (95% CI -3.92 to 23.92), standardized effect d = 0.48; z-test p = 0.159.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Active Drug (Misoprostol) and the control. The interval gives the range of effects that remain compatible with the data.

The registry reports one secondary outcome: patient-perceived pain of intrauterine device insertion, measured by a 100mm visual analog scale at the time of insertion. This outcome captures the participant's experience, whereas the primary endpoint captures the provider's rating of ease. Considering both perspectives can add context because a provider's procedural assessment and a participant's pain rating are related concepts but not the same outcome.

The overall pattern does not provide clear statistical confirmation of the primary comparison. The secondary comparison is uncertain, and its confidence interval includes no difference. It should not be treated as a repeat measurement of the primary endpoint or as a direct validation of the provider rating. Differences between the measures may reflect that they assess different experiences, as well as sampling variability.

General explanation: secondary outcomes are often useful for describing a broader set of effects, but they commonly carry less evidential weight than a prespecified primary outcome. When multiple outcomes are examined, the chance of finding at least one apparently notable result can increase unless the analysis accounts for multiplicity. The registry record does not report a multiplicity adjustment or a plan for interpreting secondary outcomes. It also reports no secondary analyses, despite posting a group comparison for the secondary outcome. This limits the ability to judge whether the comparison was prespecified and how it fits into the overall analysis strategy.

The secondary result is best read as supportive descriptive information rather than as a standalone conclusion. It neither resolves the uncertainty in the primary result nor establishes a consistent pattern across distinct outcome perspectives. The registry record does not report additional secondary endpoints that would allow a broader assessment of consistency.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Perceived Pain of IUD Insertion by Patient Using a 100mm Visual Analog Scale (VAS).

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean difference describe?

For a continuous outcome, the mean is the arithmetic average of participants' recorded scores in an arm. The primary outcome is reported in millimeters on a 100mm visual analog scale, with a mean of 24.0 mm for misoprostol and 29.0 mm for placebo. The posted mean difference is -5.0 mm, expressed as active drug relative to placebo. A negative difference therefore indicates that the active-arm mean was lower than the placebo-arm mean on the recorded scale. Whether a lower score represents greater ease depends on how the scale was actually anchored; the registry's stated scale description refers to pain anchors even though the outcome title refers to ease.

What does the standard deviation add?

The standard deviation describes variation in individual scores around an arm's mean. It is not the uncertainty interval for the mean difference and does not tell how many participants had a particular score. The primary-outcome standard deviations are 19.0 mm in the misoprostol arm and 21.0 mm in the placebo arm. General statistical explanation: when individual observations vary widely, the mean may be estimated less precisely than when observations cluster more closely, although precision also depends on the number of observations and the analysis model. The posted standard deviations give a sense of within-arm variability, but they do not reveal the full score distributions.

How should the comparison be understood?

The reported comparison is an unadjusted mean difference between the active and placebo arms. General explanation: an unadjusted comparison uses the group summaries without accounting for additional covariates in a regression or other adjustment model. This makes the estimate relatively direct to interpret, but it does not account for any chance imbalance in participant characteristics. The registry record does not report an adjusted primary analysis. The posted p-value is unadjusted as well, so it should not be interpreted as evidence that any adjustment or multiplicity correction was applied.

What does the p-value say?

The primary unadjusted p-value is 0.46. General explanation: a p-value measures how unusual data at least as incompatible with a specified null model would be if that model and the analysis assumptions were correct. It is not the probability that the null hypothesis is true, nor the probability that the observed result arose by chance. A p-value above a conventional threshold does not prove no effect, and a p-value below a threshold would not by itself establish clinical importance. The registry record does not state an analysis threshold or a decision rule for the primary comparison.

Why are the confidence interval and p-value considered together?

The primary 95% confidence interval extends from -18.25 to 8.255 mm. General explanation: a confidence interval presents a range of values compatible with the observed data under the method's assumptions, and its width conveys uncertainty. In repeated use of a valid method, intervals constructed at a stated confidence level have a long-run coverage interpretation. It is not correct to treat a single interval as assigning a probability to each possible true effect. Here, the interval crosses zero and also spans effects in both directions, emphasizing that the estimate is not precise enough to rule out a range of possibilities.

What can be inferred from the trial structure?

Random allocation is intended to make treatment groups comparable on average, while masking is intended to reduce bias in care, measurement, or reporting. The registry identifies randomization, a parallel model, and quadruple masking. General explanation: these design features can strengthen an arm-to-arm comparison, but they do not eliminate uncertainty from a small evidence base, missing outcome data, or limitations in measurement. The exact randomization and masking procedures are not reported in the registry record, so their implementation cannot be evaluated from the record alone.

What remains unknown about the analysis?

The registry reports zero analyses in its analysis count and no reported secondary analyses. It does, however, post group summaries and comparison statistics for the outcomes described. The record does not report a detailed statistical analysis plan, assumptions about the outcome distribution, handling of missing data, covariate adjustment, or whether any interim analyses took place. General explanation: these details matter because they define how the data were processed and which comparisons were intended before results were known. Their absence means the posted summaries can be described, but important aspects of the prespecified analysis cannot be verified.

11. Confidence Intervals and Precision

The primary mean difference is -5.0 mm, and its 95% confidence interval runs from -18.25 to 8.255 mm. This interval includes zero and extends to estimates in both directions. It therefore does not isolate a single direction of difference with precision. The interval is also broad compared with the point estimate, so the observed mean difference should be treated as uncertain rather than as a precise measure of the contrast between arms.

General explanation: a confidence interval reflects sampling uncertainty under the statistical method used. A narrower interval generally indicates greater precision, while a wider interval leaves more plausible values compatible with the data. The interval does not account automatically for every possible source of bias, such as missing observations, limitations in the scale description, or selective reporting. The registry record does not report a clinically important difference threshold, so the interval cannot be judged against a stated threshold for practical importance.

The secondary patient-rated pain comparison also has an interval spanning zero, from -3.92 to 23.92 mm. Its point estimate and uncertainty should be considered on its own scale and rating source. Neither interval establishes equivalence: a conclusion of equivalence would require a prespecified margin and an analysis designed to assess it, neither of which is reported in the registry record.

The small outcome-specific counts and the spread of scores contribute to uncertainty, but no additional precision calculation is needed to interpret the posted intervals. The central message is that the estimates are not sufficiently narrow to support a confident claim about the direction or size of an average difference.

12. 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 events. They are illustrations based on the observed effect, not the trial's original design assumptions. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The planning effect is the stated fraction of the observed effect. The registry record does not report the original sample-size justification or the trial's own design assumptions.

For planning at 100% of the observed primary effect, the illustration gives 253 participants per arm for 80% power and 339 participants per arm for 90% power. For planning at 75% of the observed effect, the figures are 449 participants per arm for 80% power and 602 participants per arm for 90% power. For planning at 50% of the observed effect, the figures are 1,011 participants per arm for 80% power and 1,353 participants per arm for 90% power. The corresponding secondary-outcome illustrations use the observed secondary effect and are 70 and 93 participants per arm for 100% of that effect, 124 and 165 for 75%, and 277 and 371 for 50%, for the 80% and 90% power targets respectively.

In plain terms, 80% power is a planning target describing the chance of detecting the assumed effect under the stated assumptions if that effect is real; 90% uses a higher detection target. Smaller assumed effects require more participants, which is why the planning figures increase as the fraction of the observed effect decreases. These figures are not observed power and do not show what the completed trial achieved. They are planning illustrations only, and results based on an observed effect can be optimistic or unstable, particularly when the estimate is imprecise.

13. 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 = -5.000; pooled standard deviation σ = 20.055.
2. n = 2 × (1.96 + 0.842)² × 20.055² / -5.000² = 252.6, rounded up to 253 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 <- -5                      # observed difference in means
sigma <- 20.0552267803713                     # 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(613366)
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 = 253 (80% power), 339 (90% power)
 75% of observed effect: n per arm = 449 (80% power), 602 (90% power)
 50% of observed effect: n per arm = 1,011 (80% power), 1,353 (90% power)
power.t.test: 253.5 
Simulated power at n = 253 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.

14. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity plan. This matters because the trial has a primary outcome and a secondary outcome, and examining multiple endpoints can increase the possibility of apparently notable results even when no true differences exist. General explanation: statistical approaches to multiplicity can control the overall false-positive risk, or a prespecified hierarchy can define which findings are confirmatory and which are exploratory. Without a reported approach, the unadjusted secondary result should be interpreted cautiously. The registry record does not say whether any correction or hierarchy was specified outside the posted record.

The primary outcome population is labelled intent to treat. The registry record does not provide a detailed definition of that population, participant flow, reasons for absent outcome values, or the method used to handle missing data. The primary outcome summaries include 17 participants in the active arm and 18 in the placebo arm, while enrollment is recorded as 40. Those figures alone do not explain which participants were randomized, which contributed an outcome, or why any observations were unavailable. No missing-data assumptions or sensitivity analyses are reported in the registry record.

General explanation: missing outcome data can affect a comparison if the likelihood of having an observed measurement is related to treatment assignment or to the outcome itself. An intent-to-treat label does not by itself establish how missing values were handled or guarantee that all randomized participants contributed to the estimate. The record's lack of detail makes it difficult to assess the impact of missingness.

The registry reports no analyses in its analysis count and no reported secondary analyses. It does not report whether an interim analysis was conducted, how the primary analysis was prespecified, whether covariates were considered, or whether any deviations from an analysis plan occurred. These omissions limit assessment of prespecification and analysis transparency; they do not establish that such procedures were or were not used.

15. 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 adverse-event record reports zero serious adverse events in the misoprostol arm among 17 at risk and zero in the placebo arm among 18 at risk. It also reports zero other adverse events in the misoprostol arm among 17 at risk and zero in the placebo arm among 18 at risk. These are the posted counts and denominators for the adverse-event categories in the registry.

Zero reported events in these groups means no events were recorded for those categories in the posted results; it does not establish that an event is impossible or exclude uncommon harms. General explanation: safety estimates are limited by the amount of observation and by how events were defined, collected, and reported. The registry record does not give further details about adverse-event definitions, follow-up duration for safety, or the process used to solicit or assess events.

Deaths are not reported in the registry record. The absence of a posted death count should not be interpreted as a confirmed zero. The adverse-event figures should therefore be read narrowly as the reported category counts, with the limitations of the record's safety detail in mind.

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

The posted primary result is an estimate of the difference between mean provider ratings in the misoprostol and placebo arms at the time of insertion. It describes the participants contributing to the reported outcome summaries and the stated measurement. It does not establish a causal mechanism, an objective procedural benefit, or a difference in outcomes beyond the recorded rating. The scale description's pain anchors and the primary outcome's ease-of-insertion title are not fully aligned in the registry record, which adds uncertainty about how score direction should be understood.

The estimate is imprecise: its confidence interval spans zero and includes values on both sides of the point estimate. That does not prove that the arms are equivalent, nor does it prove that a difference exists. The registry record does not report an equivalence margin or a threshold for clinical importance, so neither equivalence nor practical importance can be determined from the posted comparison alone.

The secondary endpoint reflects patient-rated pain, a separate subjective experience. Its result should not be collapsed into the provider-rated primary outcome. Both comparisons leave uncertainty, and the registry record does not report a multiplicity strategy that would support treating the secondary result as confirmatory.

These findings do not provide medical advice and should not be generalized automatically to other populations, settings, or procedures. The record describes women who have never delivered a baby, but does not report detailed eligibility criteria or participant characteristics. The small outcome-specific groups, absent information about missing data, and limited analysis documentation constrain interpretation. The appropriate conclusion is statistical and descriptive: the registry reports group summaries and uncertain comparisons, while several details needed to judge precision, measurement, and analysis are not reported in the registry record.

17. Why This Trial Matters Statistically

This trial illustrates why a point estimate and its uncertainty should be read together. The primary comparison has a numerical estimate, but the confidence interval spans zero and a wide range of possible differences. A reader who focuses only on the direction of the estimate could overstate what the evidence establishes; a reader who focuses only on the p-value could mistake lack of statistical evidence for proof of no difference.

It also shows the importance of defining a subjective endpoint clearly. The primary outcome is titled as provider-rated ease, while the instrument description uses pain anchors. Since interpretation depends on what the scale asks and how its ends are labelled, that ambiguity matters for the meaning of a lower or higher score. The separate patient-rated pain endpoint underscores that different observers can assess different aspects of the same procedure.

The registry record also demonstrates how reporting details shape statistical interpretation. The intent-to-treat label is useful, but without participant flow and missing-data methods it does not fully describe how the posted estimates were obtained. Likewise, randomization and masking are design strengths in principle, but the record does not detail their implementation. Finally, the absence of a reported multiplicity plan makes secondary comparisons less suitable for strong confirmatory claims.

These are broadly relevant statistical issues for clinical researchers: distinguish estimates from certainty, distinguish outcome constructs, and treat missing analysis details as limits on interpretation rather than invitations to speculate.

18. 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 specific to this trial are apparent in the registry record. First, the primary outcome is described as provider-rated ease, but its instrument description uses anchors for pain. The record does not clarify whether that wording accurately reflects the scale used for provider ratings. This makes score direction and construct interpretation less straightforward than the endpoint title alone suggests.

Second, the study summary describes women who have never delivered a baby, but detailed eligibility criteria and participant characteristics are not reported in the registry record. This limits assessment of which clinical settings or participant groups the findings may represent. The relationship of the listed magnesium oxide intervention to the misoprostol and placebo arms is also not explained.

Third, the outcome-specific counts are smaller than the enrollment figure, and the record does not describe participant flow, missing outcome data, or how missing values were handled. The registry labels the primary population intent to treat, but this label does not resolve those reporting gaps. The record also does not report the original sample-size justification, the statistical analysis plan, or an explanation of why the analysis count is zero despite posted summary comparisons.

Finally, no multiplicity plan is reported, and the secondary analyses are not listed as reported analyses. These omissions make confirmatory interpretation of secondary findings difficult. The posted estimates and intervals remain useful descriptions, but the missing measurement and analysis details constrain how confidently they can be interpreted.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Misoprostol With Intrauterine Device Insertion — NCT00613366.
• Registry record last updated 2013-03-15; status last verified 2013-02.
• Results first posted 2013-03-15.
• 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.

22. Record Summary

NCT00613366 is a completed randomized, quadruple-masked, parallel-group study sponsored by Oregon Health and Science University. It examined cervical preparation with misoprostol versus placebo before intrauterine device insertion. The registry lists enrollment of 40, with a primary provider-rated ease outcome and a secondary patient-rated pain outcome, both measured using a 100mm visual analog scale at insertion.

The posted primary comparison is a mean difference of -5.0 mm, with a 95% confidence interval from -18.25 to 8.255 mm and an unadjusted p-value of 0.46. The confidence interval spans zero, leaving substantial uncertainty about the average difference. Important details about the scale description, missing data, multiplicity, and original design assumptions are not reported in the registry record.