Comparative Effectiveness of Pregnancy Failure Management Regimens: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparative Effectiveness of Pregnancy Failure Management Regimens (NCT02012491), a randomized phase 3 study. The primary outcome is Gestational Sac Expulsion With One Treatment Dose on Day 3 (Visit 2) and no Need for Additional Medical or Surgical Intervention Within 30 Days of Treatment..

2. Clinical Question

This framing separates the treatment regimens, the measured outcome, and the follow-up condition attached to that outcome. The endpoint is not simply whether expulsion occurred by the Day 3 visit: it also incorporates whether additional intervention was needed during the stated follow-up period. A participant therefore contributes to the primary outcome only if the registry's combined criteria are met. The posted results compare the number meeting that definition in each arm. They do not, by themselves, describe the timing of events within the follow-up window or explain individual reasons for additional intervention.

3. Trial Design

The registry identifies this as a phase 3, randomized, double-masked, parallel-group trial sponsored by the University of Pennsylvania. The listed enrollment is 300. The study status is completed; the record lists a start date of 2014-01 and primary completion on 2017-05-15. The registry's study purpose was to compare combination treatment with single-dose misoprostol for management of early pregnancy failure.

Participants were assigned to one of two treatment regimens. The misoprostol arm received 800 micrograms of vaginal misoprostol alone. The combination arm received 200 milligrams of oral mifepristone, followed 24 hours later by 800 micrograms of vaginal misoprostol. The registry describes misoprostol alone as standard of care. Both drugs are listed as drug interventions.

Randomized allocation supports a comparison between assigned groups, while double masking is intended to limit influences of awareness of treatment assignment. The record does not describe how the random sequence was generated, how allocation was concealed, who was masked, or how masking was maintained. It also does not report the actual allocation ratio or give further operational details about sites and enrollment procedures. Those details should not be inferred from the design labels.

The primary outcome is reported as a count of participants in each arm, with arm sizes of 149.0 for misoprostol and 148.0 for misoprostol plus mifepristone. The safety record uses at-risk counts of 151 and 149, respectively. The registry does not explain the different denominators across the outcome and safety records. The posted results should therefore be interpreted using the denominators attached to each specific outcome rather than assuming a single analysis population.

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 Sac Expulsion With One Treatment Dose on Day 3 (Visit 2) and no Need for Additional Medical or Surgical Intervention Within 30 Days of Treatment., measured over Day 3 (visit 2) and up to 30 days following visit (to ensure surgical measures were not done.

The primary endpoint counts participants who had gestational sac expulsion with one treatment dose at Day 3 (Visit 2) and did not need additional medical or surgical intervention within 30 days of treatment. It combines an observed outcome at the Day 3 visit with a condition about subsequent intervention. This makes the endpoint a binary measure: each participant either meets the complete definition or does not.

For this kind of outcome, a count gives the number meeting the definition, while the number of participants in the arm provides the denominator for understanding how common the outcome was in that group. The registry reports 100.0 participants meeting the endpoint among 149.0 in the misoprostol arm, and 124.0 among 148.0 in the combination arm. The reported comparison expresses the difference between the groups in the probability of meeting the endpoint.

The endpoint is useful for comparing the regimens on a clinically interpretable combined outcome rather than on expulsion alone. Its definition also means that a participant who had expulsion but needed additional intervention within the stated follow-up would not meet the complete endpoint. The registry record does not provide further detail on how every component was assessed or adjudicated.

7. Results Posted in the Registry

• Misoprostol Plus Mifepristone: 83.8% (124/148) versus 67.1% (100/149) on control; risk difference 16.7 percentage points (95% CI 7.1 to 26.3), risk ratio 1.25 (1.09–1.43); unadjusted two-proportion z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary because it records whether each participant met the combined endpoint definition. For a binary outcome, the count of participants with the event can be related to the number assessed in each arm to estimate an event probability. The registry reports both counts and arm-specific proportions, then gives several measures comparing those probabilities. These measures answer related but not identical questions.

What does the risk difference describe?

The risk difference is the estimated event probability in one arm minus the event probability in the comparator arm. In this record, the comparison is misoprostol plus mifepristone versus misoprostol, and the risk difference is 0.167. A positive value means the estimated probability of meeting the endpoint was higher in the combination arm. Unlike a relative measure, a risk difference stays on the absolute probability scale. It is therefore directly tied to the observed event frequency in the two groups.

The registry also provides the arm-specific proportions: 0.671 for misoprostol and 0.838 for the combination regimen. These describe the fraction meeting the endpoint in each arm. They are not adjusted for other participant characteristics in the posted comparison. Whether an adjusted analysis was planned or performed is not reported in the registry record.

How do relative risk and odds ratio differ?

The relative risk compares the event probability in the combination arm with the probability in the misoprostol arm. The reported relative risk is 1.248, with a confidence interval from 1.093 to 1.426. The odds ratio compares event odds rather than probabilities; its reported value is 2.532, with a confidence interval from 1.454 to 4.409. Odds and probabilities are related but are not interchangeable, so the odds ratio can look different in magnitude from the relative risk, particularly when an outcome is not rare. The risk difference, relative risk, and odds ratio all describe the same binary comparison on different scales.

These measures do not describe why participants did or did not meet the endpoint. They also do not separately quantify the components of the combined endpoint. The record does not report the number of participants with expulsion considered apart from subsequent intervention, so no component-specific comparison can be inferred.

What does the confidence interval contribute?

A confidence interval gives a range of values compatible with the observed data under the statistical method and its assumptions. For the risk difference, the reported interval runs from 0.071 to 0.263. It communicates uncertainty around the estimated contrast rather than replacing the estimate. Intervals that are narrower indicate greater precision on the stated scale; wider intervals indicate that a broader range of effects remains compatible with the data. The interval does not account for possible biases or limitations that are not represented in the calculation.

The registry's unadjusted p-value is <0.001. In general, a p-value is calculated under a null model and summarizes how unusual data at least as discrepant as those observed would be if that model and the analysis assumptions held. It is not a measure of the probability that treatment has no effect, and it does not indicate the clinical importance of a result. The reported p-value is unadjusted; whether any multiplicity adjustment was planned or used is not reported in the registry record.

What is not described about the analysis?

The registry lists no analysis records. It does not report the statistical test used for the primary comparison, an analysis population such as intention-to-treat or per-protocol, covariate adjustment, missing-data methods, or an interim-analysis plan. Those details cannot be reconstructed from the point estimates and summary statistics alone. The reported comparison can be interpreted as the posted unadjusted contrast, but it should not be attributed to a specific unreported modeling procedure.

General statistical practice distinguishes the assigned treatment from the treatment actually received, and the analysis population can affect how a randomized comparison is interpreted. The record does not state how protocol deviations or participants with incomplete endpoint information were handled. It also does not provide the study's original sample-size justification. Those omissions limit assessment of how the posted analysis relates to the trial protocol, without changing the numerical estimates recorded for the primary endpoint.

10. Confidence Intervals and Precision

The risk-difference estimate is 0.167, and its 95% confidence interval extends from 0.071 to 0.263. This interval gives a range of plausible values for the underlying absolute difference under the statistical method used. In this comparison, the entire interval is above zero. The estimate is therefore not just a single point; the interval indicates that the data are compatible with a range of positive differences, with uncertainty remaining about the exact size.

Precision is distinct from whether an estimate is important to patients or clinicians. A narrow interval would indicate that the estimate is more tightly determined on its scale; a broad interval would leave more uncertainty about its magnitude. No threshold for a clinically important difference is reported in the registry record, so the confidence interval alone cannot determine whether every value within it would be meaningful in practice.

The relative risk interval, from 1.093 to 1.426, and the odds-ratio interval, from 1.454 to 4.409, provide uncertainty on their respective relative scales. The endpoints of these intervals should not be compared directly with the risk-difference interval because each measure has a different interpretation. All three estimates use the same underlying arm comparison but express it differently.

Confidence intervals capture sampling uncertainty under their calculation assumptions. They do not automatically account for unreported design features, missing data, outcome measurement issues, or selective reporting. The registry record does not provide enough information to evaluate all such sources of uncertainty. The counts and intervals should therefore be read as the precision of the posted comparison, not as a complete measure of every limitation affecting interpretation.

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 sample-size figures are planning illustrations based on fractions of the observed risk-difference effect, not the trial's original design targets. They assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. For this binary comparison, the figures are participants per arm, not total events. The trial's own original sample-size assumptions and justification are not reported in the registry record.

For planning at 100% of the observed effect, the illustration gives 104 participants per arm for 80% power and 138 participants per arm for 90% power. At 75% of the observed effect, it gives 196 participants per arm for 80% power and 261 participants per arm for 90% power. At 50% of the observed effect, it gives 462 participants per arm for 80% power and 618 participants per arm for 90% power.

In plain language, the 80% power column gives the estimated participants per arm under the stated assumptions for a design intended to detect the specified effect with 80% power. The 90% power column gives the corresponding planning estimate for 90% power. Higher target power generally requires a larger planned sample under otherwise matching assumptions. The illustrations also show that smaller effects need more participants to detect: as the assumed fraction of the observed effect decreases, the stated per-arm requirements increase.

A sample-size curve conveys this relationship across effect assumptions rather than reporting an observed result from the trial. These figures are planning illustrations, not observed power. They cannot establish what the trial was originally designed to detect, because its original design assumptions are not reported.

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 = 0.671; treatment proportion p₁ = 0.838; average p̄ = 0.754.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6087 = 1.1930.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5971 = 0.5026.
4. n = (1.1930 + 0.5026)² / (0.1667)² = 103.5, rounded up to 104 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 <- 0.671140939597315                          # control proportion
p1 <- 0.837837837837838                          # 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(2012491)
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 = 104 (80% power), 138 (90% power)
 75% of observed effect: n per arm = 196 (80% power), 261 (90% power)
 50% of observed effect: n per arm = 462 (80% power), 618 (90% power)
power.prop.test: 103.5 
Simulated power at n = 104 per arm: 0.812 (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 six outcome measures and two posted secondary outcomes: frequency of serious adverse events between study arms and adverse events reported by participants. It also lists the primary endpoint of gestational sac expulsion with one treatment dose on Day 3 and no additional medical or surgical intervention within 30 days. The record does not describe a prespecified hierarchy among outcomes or explain how the primary and secondary outcomes were handled as a family of statistical tests.

Multiplicity arises when several outcomes, time points, groups, or analyses are examined. In general, making multiple statistical comparisons can increase the chance that at least one result appears statistically notable by chance. Methods such as prespecifying a primary endpoint or adjusting inference can address this concern, but the registry record does not report whether multiplicity procedures were planned or applied. The primary comparison has an unadjusted p-value of <0.001; it should not be described as multiplicity-adjusted.

The registry reports zero analysis records. It does not report the statistical methods used for the primary outcome or the secondary outcomes, nor does it provide results for statistical comparisons of the posted secondary safety outcomes. The absence of an analysis record does not establish that no analysis was conducted; it means the analysis details are not reported in the registry record.

Missing-data handling and analysis populations are also not reported. The record does not state whether the primary comparison included all randomized participants, participants with available endpoint information, or another defined group. It does not describe how incomplete outcome information, withdrawals, protocol deviations, or treatment non-adherence were handled. It also does not report an interim-analysis plan or stopping rules. These are important details for judging the analysis, but they cannot be inferred from the posted event counts, confidence interval, or p-value.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: bleeding resulting in blood transfusion (2.0%), pelvic infection (1.3%).

The serious-adverse-event record gives separate at-risk counts for the two arms. In the misoprostol arm, 151 participants were at risk and 3 were affected by serious adverse events. In the misoprostol-plus-mifepristone arm, 149 were at risk and 5 were affected. Deaths are listed as 0 in each arm. These figures are counts, not comparative effect estimates, and the record does not provide a confidence interval or statistical test for the difference.

The registry lists bleeding resulting in blood transfusion at 2.0% and pelvic infection at 1.3% among the top serious-event terms. The record does not identify those terms by treatment arm in the posted summary, so they should not be assigned to either group. Counts for other adverse events are 115 of 151 at risk in the misoprostol arm and 118 of 149 in the combination arm. These are separate from the serious-event counts.

The at-risk denominators for safety differ from the primary-outcome arm sizes, and the registry does not explain why. The safety counts are descriptive; they do not by themselves establish that the regimens have equivalent or different safety profiles. The registry record does not provide further detail on event severity, timing, attribution, or a formal comparative safety analysis.

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

The posted primary result describes a higher observed proportion meeting the combined endpoint in the misoprostol-plus-mifepristone arm than in the misoprostol-alone arm. The estimated risk difference is 0.167, with a 95% confidence interval from 0.071 to 0.263. The relative risk and odds ratio also have estimates above 1, with their reported confidence intervals above 1. Together, these statistics describe the direction and uncertainty of the comparison for this trial's primary endpoint.

The endpoint has a specific definition: gestational sac expulsion with one treatment dose at Day 3, together with no need for additional medical or surgical intervention within 30 days of treatment. The result does not separately show expulsion without the follow-up condition, nor does it identify which component accounts for participants not meeting the full definition. It is not a result for every possible outcome of pregnancy failure management.

The result also does not establish the comparative safety of the treatments. The registry lists serious and other adverse-event counts, but does not report a statistical comparison or detailed safety analysis. Nor does the primary endpoint estimate address outcomes beyond the stated follow-up, or provide information on outcomes and populations not described in the record.

Statistical evidence from a randomized trial is specific to its enrolled participants, outcome definition, conduct, and analysis. The registry does not provide detailed participant characteristics, analysis populations, missing-data procedures, or a full statistical analysis plan. Those gaps limit how confidently the result can be extended beyond the posted comparison. The result should be understood as a comparison of the two assigned regimens on the specified primary endpoint, not as a general statement about all patients, settings, or outcomes.

16. Why This Trial Matters Statistically

This trial illustrates how an endpoint can incorporate more than an event at a single visit. Gestational sac expulsion at Day 3 is combined with the absence of additional medical or surgical intervention within 30 days. That definition determines what the reported counts mean and makes clear why the endpoint cannot be paraphrased as expulsion alone. Careful reading of outcome definitions is essential when comparing clinical-trial results.

The posted comparison also illustrates why absolute and relative measures should be read together. The risk difference of 0.167 describes an absolute contrast in endpoint probability. The relative risk of 1.248 and odds ratio of 2.532 express comparisons on relative scales. They are different statistical summaries of the same underlying event counts, not independent replications of the result. The confidence intervals show uncertainty on each scale, while the unadjusted p-value addresses compatibility with a no-difference model under its assumptions.

Finally, the record demonstrates the importance of distinguishing outcome results from the documentation needed to evaluate an analysis fully. The posted primary counts and estimates allow a reader to understand the main comparison, but they do not supply details about missing data, analysis populations, multiplicity, or the original design rationale. Safety data are present as counts but lack a reported comparative analysis. Interpreting the evidence requires attending both to the observed statistics and to what the registry does not report.

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 registry record reports aggregate counts rather than individual participant data. It does not provide detailed characteristics of the enrolled population, so the similarity of the trial population to other populations cannot be assessed from this record. It also does not report the analysis population, how missing endpoint information was handled, or whether deviations from assigned treatment affected inclusion in the primary comparison.

There is a difference between the primary outcome arm sizes, 149.0 and 148.0, and the safety at-risk counts, 151 and 149. The record does not explain the denominator difference. It is therefore important not to assume that the outcome and safety summaries use identical populations. The registry also does not report how endpoint components were determined or whether outcomes were independently adjudicated.

The analysis documentation is limited. No analysis records are listed, and the statistical test, covariate adjustment, multiplicity strategy, interim analyses, and missing-data procedures are not reported in the registry record. The original sample-size rationale and design assumptions are also not reported. The planning illustration based on the observed effect does not substitute for that original rationale.

Although the record lists secondary safety outcomes and event counts, it does not report formal comparative analyses for them. The serious-event terms are not assigned to a treatment arm in the summary. These limitations do not change the posted primary estimate, but they constrain assessment of its analysis context, broader applicability, and the safety comparison.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Comparative Effectiveness of Pregnancy Failure Management Regimens — NCT02012491.
• Registry record last updated 2019-07-18; status last verified 2019-07.
• Results first posted 2018-12-21.
• 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

NCT02012491 is a completed phase 3 randomized, double-masked, parallel-group trial sponsored by the University of Pennsylvania. The registry lists enrollment of 300, a start date of 2014-01, and primary completion on 2017-05-15. The trial compared 800 micrograms of vaginal misoprostol alone with 200 milligrams of oral mifepristone followed 24 hours later by 800 micrograms of vaginal misoprostol.

The primary outcome counted participants with gestational sac expulsion after one treatment dose at Day 3 and no additional medical or surgical intervention within 30 days. The registry reports 100.0 of 149.0 participants meeting the endpoint in the misoprostol arm and 124.0 of 148.0 in the combination arm. The risk difference is 0.167, with a 95% confidence interval from 0.071 to 0.263, and an unadjusted p-value of <0.001. Safety counts are also posted, but a comparative safety analysis and several statistical-plan details are not reported in the registry record.