PGL4001 Versus GnRH-agonist in Uterine Myomas: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PGL4001 Versus GnRH-agonist in Uterine Myomas (NCT00740831), a randomized phase 3 study. The primary outcome is Percentage of Subjects With Reduction of Uterine Bleeding at Week 13 Visit Defined as Pictorial Blood-loss Assessment Chart (PBAC) Score < 75 at End-of-treatment Visit (Week 13 Visit).

2. Clinical Question

This is a comparison of a prespecified categorical response at the end of the treatment period. It does not describe the entire pattern of bleeding during treatment, nor does it directly measure blood loss in millilitres. The PBAC is a patient-recorded estimate based on menstrual products used and the degree of staining, with points also assigned for clots or flooding. A lower score is consistent with less recorded bleeding, but the trial’s primary response classification is specifically the threshold of less than 75 at the endpoint visit.

The registry also includes a secondary outcome concerning change in the total volume of the three largest myomas from baseline to Week 13. That outcome addresses a different aspect of the condition from the primary bleeding-response endpoint. Its presence does not change the primary question, which is whether participants met the stated PBAC response definition after treatment with one of the three regimens.

3. Trial Design

This was a phase III, randomized, parallel-group, double-blind, double-dummy, active-comparator-controlled, multicenter study. The registry lists an enrollment of 301 and describes the study as completed. The recorded start was 2008-08, and primary completion was 2010-01. The stated treatment period was 3 months, with the primary endpoint assessed at the Week 13 visit.

The three groups were PGL4001 5 mg, PGL4001 10 mg, and GnRH-agonist treatment with leuprorelin 3.75 mg. The PGL4001 groups received oral tablets plus a matching leuprorelin placebo injection; the active-comparator group received leuprorelin injection plus matching oral placebo. This double-dummy arrangement allowed the groups to follow similar oral and injection procedures while receiving different active drugs.

Random allocation and masking are features of the trial design, but the allocation sequence, concealment procedures, and details of how masking was maintained are not reported in the registry record. The registry’s primary outcome analysis population is per protocol. It does not report the original sample-size justification, the planned allocation ratio, or the full analysis plan, so these should not be inferred from the posted outcome counts.

The primary endpoint is binary: participants either met the PBAC threshold at the endpoint visit or did not. The registry reports percentages for each group and also lists comparisons. The group counts used for the primary per-protocol results differ from the enrollment and from the safety populations. Those figures refer to different reported analyses and should not be treated as interchangeable measures of who was randomized, who was assessed, or who contributed safety information.

The posted secondary outcome concerns myoma volume change. It uses a continuous measure and has its own reported analysis. The registry record does not give enough information to reconstruct all analytic decisions for either endpoint. In particular, the precise statistical methods behind the sponsor’s primary comparisons are not stated in the record.

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

Analysis population for the primary outcome, as defined in the registry: Per protocol

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 Percentage of Subjects With Reduction of Uterine Bleeding at Week 13 Visit Defined as Pictorial Blood-loss Assessment Chart (PBAC) Score < 75 at End-of-treatment Visit (Week 13 Visit), measured over 3 months.

The primary endpoint is the percentage of participants whose PBAC score was < 75 at the Week 13 visit. The registry describes the endpoint as reduction of uterine bleeding and states that the Week 13 score was calculated from the last 28 days of treatment. Participants recorded daily use of tampons and towels, how heavily each item was soiled, and the presence of small or large clots or flooding. These observations contribute to a score intended to estimate menstrual blood loss.

PBAC is used as a structured, patient-reported way to capture bleeding over time rather than relying only on a single recollection at the clinic visit. The registry describes a scale on which 0 represents amenorrhea and higher scores indicate more bleeding. It also defines menorrhagia as a PBAC score > 100 during one menstrual period, approximating blood loss of > 80 mL. Those background thresholds explain the scale but are not the trial’s primary response threshold: the primary outcome uses a score below 75 at the endpoint visit.

Turning the endpoint into a yes-or-no response makes the group percentages straightforward to compare, but it discards information about the exact score among participants on either side of the threshold. A participant just below the threshold and one with a much lower score both count as meeting the response definition. Conversely, a score just above the threshold and a substantially higher score both count as not meeting it. The primary result therefore describes the frequency of the specified response, not the average change in PBAC score or the full distribution of bleeding measurements.

7. Results Posted in the Registry

• B (PGL4001 10mg): 97.9% (93/95) versus 90.3% (84/93) on control; risk difference 7.6 percentage points (95% CI 0.9 to 14.2), risk ratio 1.08 (1.01–1.17); unadjusted two-proportion z-test p = 0.027.
• C (GnRH-agonist): 89.1% (82/92) versus 90.3% (84/93) on control; risk difference -1.2 percentage points (95% CI -9.9 to 7.6), risk ratio 0.99 (0.90–1.09); unadjusted two-proportion z-test p = 0.789.

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.

Change in the Total Volume of the Three Largest Myomas From Baseline to Week 13

• 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 errors.
• Result:
  • B (PGL4001 10mg): mean -0.22 versus -0.18 on control; difference -0.04 (95% CI -0.14 to 0.06), standardized effect d = -0.12; z-test p = 0.427.
  • C (GnRH-agonist): mean -0.27 versus -0.18 on control; difference -0.09 (95% CI -0.19 to 0.01), standardized effect d = -0.25; z-test p = 0.089.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between B (PGL4001 10mg) and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between C (GnRH-agonist) and the control. The interval gives the range of effects that remain compatible with the data.

The registry posts one secondary outcome: change in the total volume of the three largest myomas from baseline to Week 13. It is a continuous outcome, unlike the primary binary PBAC response. The sponsor-reported analyses use ANCOVA and compare final values; unadjusted recalculations are also listed. These results concern change in myoma volume and should be understood as a separate endpoint rather than as another measure of the primary bleeding response.

Across the secondary comparisons, the posted estimates do not form a uniformly precise pattern. The comparison of PGL4001 10 mg with PGL4001 5 mg has an unadjusted mean difference of -0.041, a confidence interval from -0.142 to 0.060, and p = 0.427. The comparison of GnRH-agonist with PGL4001 5 mg has an unadjusted mean difference of -0.089, a confidence interval from -0.192 to 0.014, and p = 0.089. Both intervals include zero. The sponsor’s reported ANCOVA results use a different analysis specification, so the recalculated estimates should not be substituted for those results.

The secondary outcome provides context about myoma volume but does not confirm or negate the primary PBAC response result. The endpoints measure different features, use different scales, and are analyzed with different methods. A pattern in one does not automatically establish a corresponding pattern in the other.

General explanation: when several outcomes or comparisons are examined, the chance of at least one apparently notable result can increase if each is assessed without accounting for the full set. The registry record does not report whether multiplicity adjustments were planned or applied. The secondary findings are therefore best treated as supportive or exploratory evidence, with less inferential weight than a clearly prespecified primary analysis, especially when the adjustment strategy and analysis plan are unavailable. The data do not support combining the secondary outcome with the primary endpoint into a single conclusion.

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

• Change in the Total Volume of the Three Largest Myomas From Baseline to Week 13

9. Statistical Interpretation

10. Statistical Methods Explained

For a binary endpoint, each participant is classified according to whether the event occurred. In this trial, the event is meeting the PBAC response definition at Week 13. The percentage for a group is the share of participants in that analysis population who met the definition. General explanation: a percentage communicates how common the recorded response was in that group, while a comparison quantifies how far the group results differ under a chosen scale.

The recalculated primary comparisons use a risk difference. This is the difference between the two response proportions, expressed in the underlying proportion scale. A value above zero means the first group in the stated contrast has a higher observed response proportion; a value below zero means it has a lower one. The direction depends on which group is subtracted from which, so the comparison labels matter. These recalculations are simple, unadjusted comparisons of the posted summary statistics. They are not adjusted for baseline characteristics or other potential predictors.

A confidence interval gives a range of effect estimates compatible with the observed data under the calculation’s assumptions and its confidence procedure. General explanation: it is not a range containing a fixed proportion of individual participant outcomes, and it is not the probability that the true effect lies inside that specific interval. For the PGL4001 10 mg versus PGL4001 5 mg recalculation, the risk-difference interval is 0.009 to 0.142. For GnRH-agonist versus PGL4001 5 mg, it is -0.099 to 0.076. The first interval is on one side of zero; the second covers zero as well as values on either side. This difference in interval placement is more informative than treating a p-value as a simple yes-or-no verdict.

A p-value measures how discordant the observed result is with a specified null model, conditional on the method and assumptions used. It is not the probability that the null hypothesis is true, nor a measure of clinical importance. The recalculated p-values are unadjusted: 0.027 for PGL4001 10 mg versus PGL4001 5 mg and 0.789 for GnRH-agonist versus PGL4001 5 mg. The registry does not report the calculation method behind the sponsor’s tests or whether the trial’s planned analyses adjusted for multiple comparisons.

The sponsor’s primary results are classified in the registry as non-inferiority or equivalence analyses and report differences in proportions with 97.5% confidence bounds. General explanation: a non-inferiority analysis asks whether the data rule out an unacceptable loss relative to a comparator, using a prespecified margin. An equivalence analysis usually asks whether the plausible difference lies within prespecified bounds in both directions. These are not the same question as whether an ordinary confidence interval excludes zero. In this record, the margins and the upper confidence bounds for the sponsor’s primary comparisons are not reported. Consequently, the sponsor’s intended decision rule cannot be reconstructed from the listed values alone.

The primary outcome is identified as per protocol. General explanation: a per-protocol analysis focuses on participants who met the protocol’s specified requirements for analysis, whereas an intention-to-treat analysis generally retains participants in their randomized groups. These populations answer related but not identical questions, and exclusions or deviations can affect the estimates. The registry record does not report the criteria used to define the per-protocol population, the number excluded, or whether an intention-to-treat analysis was also performed.

For a continuous outcome, such as change in myoma volume, the comparison is expressed as a mean difference rather than a difference in response proportions. The registry gives standard errors for the arm means. General explanation: a standard error describes uncertainty in an estimated mean, not the spread of individual participant values. The secondary recalculations are also unadjusted. Their reported intervals and p-values should be interpreted as estimates from the posted summary statistics, not as replacements for the sponsor’s analysis.

Over-dispersion is a general concern when count or binary data vary more than a model assumes. If a model understates that variability, standard errors may be too small and confidence intervals too narrow. The posted primary recalculations are simple comparisons of proportions rather than a reported regression model, and the registry does not describe an over-dispersion assessment. It is therefore not possible to say whether such a diagnostic or any other model check was part of the sponsor’s analysis.

Randomization is intended to make treatment groups comparable on average, but it does not guarantee balance in every realized trial. Masking can reduce some forms of measurement and treatment expectation bias. The double-blind, double-dummy design is relevant because the active treatments were delivered by different routes. However, the registry record does not describe the specific randomization procedure, masking assessment, or safeguards against unmasking.

These distinctions explain why the recalculations are useful as a transparent reading of the posted summary values but should be kept separate from the sponsor’s primary analyses. The registry identifies the outcome definition and populations, but does not supply enough detail to reproduce the sponsor’s complete inferential procedure or to resolve every analytic choice.

11. Confidence Intervals and Precision

The primary response estimates are high in all three reported groups, but the precision of a comparison depends on the range of values compatible with the data, not just on the point estimates. For the unadjusted recalculation comparing PGL4001 10 mg with PGL4001 5 mg, the risk difference is 0.076 and its confidence interval is 0.009 to 0.142. The interval lies above zero, while still allowing a range of effect sizes rather than identifying one exact difference.

For GnRH-agonist versus PGL4001 5 mg, the recalculated risk difference is -0.012 and the confidence interval is -0.099 to 0.076. This interval is compatible with a modest difference in either direction as well as with no difference. The p-value of 0.789 is consistent with that uncertainty; it is not evidence that the groups are identical. The interval’s breadth is important when considering what the trial can rule out.

General explanation: a confidence interval conveys both the direction and precision of an estimate. Narrower intervals indicate greater precision under the same method; wider intervals leave more uncertainty about the effect. Precision is affected by the number of observations contributing to the analysis and by variability in the outcome. The primary per-protocol group counts are 93.0, 95.0, and 92.0, respectively, but these are not the safety population counts and do not describe the full randomized enrollment.

The sponsor’s primary comparisons are reported with 97.5% confidence bounds, with lower limits of -9.3 and 0.4; the corresponding upper limits are not reported in the registry record. Without the upper bounds and the non-inferiority margin, the precision and decision criteria of those sponsor analyses cannot be fully evaluated. Confidence intervals should therefore be read alongside the population, contrast direction, outcome definition, and analysis method, rather than as standalone proof of a treatment conclusion.

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 illustrations based on the observed effect, not the original trial’s documented design calculation. The registry record does not report the original sample-size assumptions. The illustrations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect.

For these comparisons, the figures are participants per arm, not total participants across a trial. In general, the 80% power column gives the estimated per-arm size under which a study would have an 80% chance of detecting the specified effect under the stated assumptions, if that effect were the true effect. The 90% power column uses a higher chance of detection and therefore requires a larger planned group size under the same assumptions. These are planning quantities, not outcomes observed in this trial.

The rows describe planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. For the primary comparison of PGL4001 10 mg with PGL4001 5 mg, planning for 100% of the observed effect gives 151 participants per arm for 80% power and 202 for 90% power. Planning for 75% gives 309 and 413, respectively; planning for 50% gives 785 and 1,051. For GnRH-agonist versus PGL4001 5 mg, the corresponding values are 10,181 and 13,629; 17,867 and 23,918; and 39,676 and 53,114.

The large changes across rows reflect a general statistical principle: smaller effects are harder to distinguish from random variation, so detecting them with the same planned power generally requires more participants. These calculations are not observed power and should not be used to characterize the power achieved by the completed trial. They also do not establish that any particular effect is clinically important.

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

Worked calculation for this trial

1. Control proportion p₀ = 0.903; treatment proportion p₁ = 0.979; average p̄ = 0.941.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.3330 = 0.6527.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.3287 = 0.2766.
4. n = (0.6527 + 0.2766)² / (0.0757)² = 150.6, rounded up to 151 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 <- 0.903225806451613                          # control proportion
p1 <- 0.978947368421053                          # 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(740831)
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 = 151 (80% power), 202 (90% power)
 75% of observed effect: n per arm = 309 (80% power), 413 (90% power)
 50% of observed effect: n per arm = 785 (80% power), 1,051 (90% power)
power.prop.test: 150.6 
Simulated power at n = 151 per arm: 0.831 (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.

14. Analyses Reported by the Sponsor

The registry lists sponsor-reported primary analyses as differences in proportions, classified as non-inferiority or equivalence analyses. For PGL4001 5 mg versus GnRH-agonist, the reported difference is 1.2, with a lower 97.5% confidence bound of -9.3. For PGL4001 10 mg versus GnRH-agonist, the reported difference is 8.8, with a lower 97.5% confidence bound of 0.4. The upper confidence bounds and the non-inferiority or equivalence margin are not reported in the registry record.

The unadjusted recalculations use PGL4001 5 mg as the reference group, and therefore do not reproduce both sponsor comparisons. The sponsor’s 5 mg comparison is listed as PGL4001 5 mg versus GnRH-agonist, whereas the recalculation is expressed in the opposite direction. The sponsor’s 10 mg comparison is against GnRH-agonist, while the recalculation for 10 mg is against PGL4001 5 mg. The values answer different contrast questions and should not be directly equated.

The sponsor’s method is not reported in the registry record for the primary outcome. The posted recalculations are simple unadjusted comparisons based on summary statistics; they are not a reconstruction of the sponsor’s non-inferiority or equivalence procedure. The registry record does not document a discrepancy between the posted result and the recalculation. The sponsor’s stated analysis should be distinguished from, rather than replaced by, the unadjusted estimates, and its decision rule cannot be independently checked without the missing margin and confidence-bound information.

15. Multiplicity, Missing Data and Analysis Populations

The primary outcome is identified as per protocol, but the registry record does not report the full analysis populations, the criteria for inclusion in the per-protocol set, or how participants with missing Week 13 PBAC data were handled. It also does not report whether the sponsor conducted an intention-to-treat analysis, used an alternative missing-data method, or carried out sensitivity analyses. These omissions matter because the estimated response percentage depends on which participants contribute and how unavailable endpoint measurements are treated.

The registry lists multiple treatment comparisons and a secondary endpoint. It does not report whether a hierarchy of tests was specified, whether the primary comparisons were adjusted for multiplicity, or how the secondary analyses were treated in the testing plan. The unadjusted recalculated p-values should therefore not be interpreted as if they account for all comparisons. The registry record also does not report interim analyses or stopping rules.

For the sponsor’s primary results, the method is not reported. Although the results are labeled as non-inferiority or equivalence analyses, the margin and upper confidence bounds are not reported in the registry record. Without those details, the stated analysis cannot be fully reproduced or checked against its intended decision rule. The registry also does not report the original sample-size justification, so the planning illustrations based on observed effects should not be mistaken for the trial’s design rationale.

General explanation: missing outcome data can affect both the estimated response rate and the uncertainty around a group comparison. The direction of any bias cannot be determined merely from the fact that data are missing; it depends on why measurements are unavailable and on the analysis assumptions. Similarly, multiple testing does not automatically invalidate a result, but the planned strategy helps readers judge how much weight to place on a nominal finding. Here, the relevant details are not reported in the registry record, so claims about missing-data handling, multiplicity control, interim monitoring, or protocol-specific analysis decisions would be speculative.

16. 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 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: headache (1.0%), thyroid cancer (1.0%), sarcoma (1.0%), post procedural complication (1.0%), operative hemorrhage (1.0%).

The registry reports serious adverse events affecting 5 of 97 participants in the PGL4001 5 mg group, 4 of 103 in the PGL4001 10 mg group, and 4 of 101 in the GnRH-agonist group. These are counts within the safety populations listed for each group. They should be read separately from the per-protocol primary outcome populations, because the analysis populations and denominators differ.

The registry also lists serious-event terms, each with a reported frequency of 1.0%: headache, thyroid cancer, sarcoma, post procedural complication, operative hemorrhage, and uterine hemorrhage. The record excerpt does not assign these listed terms to specific treatment groups, so group attribution should not be inferred. A listed adverse event does not, by itself, establish that the study treatment caused it.

Deaths are not reported in the registry record. The serious-event counts alone do not describe event timing, severity details, recurrence, or causal assessment. They are a limited summary of safety events and should not be treated as a complete comparative safety evaluation.

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

The posted primary results describe the proportion of per-protocol participants who met the registry’s PBAC response definition at Week 13. The recorded percentages are 90.3% for PGL4001 5 mg, 97.9% for PGL4001 10 mg, and 89.1% for GnRH-agonist treatment. They indicate that the response threshold was met by a high proportion of participants in each reported group. They do not describe every participant’s bleeding experience or the magnitude of change for those who met the threshold.

The unadjusted recalculation finds a positive risk-difference estimate for PGL4001 10 mg versus PGL4001 5 mg, with an interval above zero, while the recalculated contrast of GnRH-agonist versus PGL4001 5 mg has an interval spanning zero. These are comparisons of posted summary statistics, not adjusted analyses. The sponsor’s primary analyses address comparisons with GnRH-agonist and are classified as non-inferiority or equivalence analyses. Because the registry omits the margin and some confidence-bound information, the sponsor’s decision rule cannot be independently evaluated from the posted details alone.

These results do not establish that one treatment is clinically preferable, that the treatments are identical, or that a response will occur for an individual. They are limited to the trial population, treatment period, endpoint definition, and analysis population reported. A threshold-based PBAC response is not the same as a direct measurement of blood loss or a complete assessment of symptoms, function, or longer-term outcomes.

The registry reports a secondary myoma-volume outcome, but that outcome addresses a different measure and has its own uncertainty. The available record does not report full details about missing data, multiplicity, the original sample-size assumptions, or all analysis methods. Safety summaries are also limited to the reported event counts and terms. A balanced reading therefore considers the response percentages alongside their confidence intervals, the specific contrasts, the sponsor’s distinct analyses, and the information that is not reported.

18. Why This Trial Matters Statistically

This trial illustrates why a group percentage alone is not enough to interpret a clinical-trial result. The primary outcome is a binary response based on a stated PBAC threshold, and the posted percentages are high across all groups. Yet the interpretation changes depending on which groups are compared and whether attention is given to the uncertainty around the difference. A risk difference and its confidence interval make the direction and range of a contrast more explicit than a comparison of percentages alone.

The record also distinguishes a simple unadjusted recalculation from the sponsor’s non-inferiority or equivalence analyses. Those analyses compare different groups and have incomplete reporting of the decision criteria. Keeping the contrasts separate prevents a recalculated result from being mistaken for a reproduction of the sponsor’s analysis. It also shows why a non-inferiority label cannot be independently evaluated without its margin and full confidence bounds.

The trial highlights the role of analysis populations. The primary endpoint is per protocol, while safety results use different group counts. These figures describe different sets of observations and answer different questions. A reader should not assume that enrollment, outcome, and safety denominators are interchangeable.

Finally, the sample-size illustrations show how planning requirements depend on the effect one seeks to detect: smaller assumed effects require more participants under the stated assumptions. Such illustrations are not observed power and do not explain the original trial design. Together, these points make the record useful for understanding the distinction between observed outcome rates, comparative estimates, uncertainty, and the limits imposed by incomplete reporting.

19. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The registry record does not report the full protocol, the original sample-size justification, or the statistical analysis plan. Details of randomization, allocation concealment, masking assessment, and the criteria for the per-protocol population are also not reported. These omissions limit assessment of how closely the posted analysis follows the intended design.

Missing-data handling is not reported. The record does not state how participants without a Week 13 PBAC result were treated, whether sensitivity analyses were performed, or whether an intention-to-treat analysis was available. Since the primary outcome is reported for a per-protocol population, the absence of population-flow and exclusion details limits interpretation of how broadly the results represent randomized participants.

The registry does not report multiplicity procedures, interim analyses, or stopping rules. The primary sponsor analysis is labeled non-inferiority or equivalence, but its margin and upper confidence bounds are not reported. The recalculated comparisons are unadjusted and use PGL4001 5 mg as the reference; they do not reproduce the sponsor’s comparisons of each PGL4001 dose with GnRH-agonist treatment. These are specific limits on interpreting the apparent differences, not evidence that the analyses were conducted improperly.

The PBAC endpoint is a threshold-based patient-recorded estimate, and the primary response classification does not retain the full score distribution. The posted secondary measure covers myoma volume and is not a substitute for the primary bleeding outcome. Safety reporting is limited to the stated serious adverse event counts and listed terms; deaths are not reported in the registry record. These limitations leave important questions about analysis details, outcome completeness, and safety characterization unresolved.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: PGL4001 Versus GnRH-agonist in Uterine Myomas — NCT00740831.
• Registry record last updated 2012-12-17; status last verified 2012-12.
• Results first posted 2012-11-16.
• 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.

23. Record Summary

The registry describes a completed phase III, randomized, parallel-group, double-blind, double-dummy, active-comparator-controlled, multicenter study of PGL4001 versus GnRH-agonist treatment for pre-operative treatment of symptomatic uterine myomas. The three groups received PGL4001 5 mg, PGL4001 10 mg, or leuprorelin 3.75 mg with matching placebo components. Enrollment was 301, and the recorded treatment period was 3 months.

The primary outcome was the percentage of per-protocol participants with a PBAC score < 75 at Week 13, based on the last 28 days of treatment. The registry reports response percentages of 90.3%, 97.9%, and 89.1% across the respective groups. Unadjusted recalculations and sponsor-reported non-inferiority or equivalence analyses use different comparison structures, and key sponsor-analysis details are not reported.

A secondary outcome assessed change in total volume of the three largest myomas. The record also reports serious adverse event counts by safety group. Important details about missing data, multiplicity, analysis populations, the sponsor’s decision margin, and the original sample-size rationale are not reported in the registry record.