A Study to Assess the Efficacy and Safety of Ganirelix (Orgalutran®) Treatment in Chinese Women Undergoing Controlled Ovarian Stimulation for in Vitro Fertilization (IVF) or Intra Cytoplasmatic Sperm Injection (ICSI) (Study 38651)(P05703): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Assess the Efficacy and Safety of Ganirelix (Orgalutran®) Treatment in Chinese Women Undergoing Controlled Ovarian Stimulation for in Vitro Fertilization (IVF) or Intra Cytoplasmatic Sperm Injection (ICSI) (Study 38651)(P05703) (NCT00725491), a randomized phase 3 study. The primary outcome is The Amount of International Units (IU) of Recombinant Follicle Stimulating Hormone (recFSH) Needed in a Controlled Ovarian Stimulation (COS) Cycle up to the First Day the Human Chorionic Gonadotropin (hCG) Criterion is Met..

2. Clinical Question

3. Trial Design

This was a Phase III, randomized, multi-center, open-label study with a parallel-group design. It compared ganirelix with triptorelin in Chinese women undergoing controlled ovarian stimulation for IVF or ICSI. The registry reports enrollment of 259 participants. The study is listed as completed, with a start date of 2007-05 and primary completion in 2008-12.

The official title identifies triptorelin, using a long protocol, as the reference treatment. The listed treatment arms are Ganirelix and Triptorelin. Because the study was open-label, participants and study personnel were not masked to assignment according to the registry’s masking designation. The record does not report the number of centers, details of random sequence generation, allocation concealment, or whether any safeguards were used to limit influence of treatment knowledge on outcome assessment.

The primary outcome was continuous: the amount of recFSH needed up to the first day the hCG criterion was met. The reported endpoint timeframe was completion of ovarian stimulation, maximally after 18 days of recFSH administration. The primary analysis population included participants in the intent-to-treat group who received hCG and for whom data were available. The registry reports 109.0 participants in the ganirelix outcome group and 114.0 in the triptorelin outcome group.

The registry describes the study purpose as assessing safety and tolerability as well as the efficiency of a recFSH-plus-ganirelix stimulation protocol. Its posted primary result is a comparison of mean recFSH use. It does not report a sample-size justification or the original assumptions used to plan enrollment, nor does it describe other design features such as interim monitoring.

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:

Analysis population for the primary outcome, as defined in the registry: The number of participants for this analysis included only those participants in the intent-to-treat (ITT) group who received hCG and for whom data was available.

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 Amount of International Units (IU) of Recombinant Follicle Stimulating Hormone (recFSH) Needed in a Controlled Ovarian Stimulation (COS) Cycle up to the First Day the Human Chorionic Gonadotropin (hCG) Criterion is Met., measured over At completion of ovarian stimulation; maximally after 18 days of recFSH administration..

The primary endpoint measures the amount of recombinant follicle stimulating hormone (recFSH), in international units (IU), used during a controlled ovarian stimulation cycle up to the first day the hCG criterion was met. The criterion was the observation of 3 follicles >= 17 mm. The registry defines the timeframe as completion of ovarian stimulation, maximally after 18 days of recFSH administration.

This is a continuous measure, summarized as a mean and standard deviation for each treatment group. It describes medication use during ovarian stimulation, rather than a pregnancy outcome. Comparing mean amounts can indicate whether the groups differed in average recFSH use under the study protocols. The recorded means were 1272.0 IU for ganirelix and 1416.0 IU for triptorelin.

The measure is used as an operational indicator of stimulation requirements: it records how much recFSH was administered before the specified follicle criterion was reached. It does not, by itself, establish how participants felt, whether embryos implanted, or whether pregnancy or live birth occurred. Those outcomes are not included among the posted outcomes in this record. The endpoint also depends on the timing and assessment of the follicle criterion, and the record does not provide additional detail about assessment procedures.

The analysis population was limited to participants in the intent-to-treat group who received hCG and had data available. Consequently, the reported means describe that analyzed group, not necessarily every participant enrolled or randomized. Details on unavailable endpoint data and their handling are not reported in the registry record.

7. Results Posted in the Registry

• Triptorelin: mean 1,416 versus 1,272 on control; difference 143.60 (95% CI 61.44 to 225.76), standardized effect d = 0.46; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

What does comparing means tell us?

For a continuous endpoint, a comparison of group means estimates the difference in average values between treatment groups. Here, the posted means are 1272.0 IU for ganirelix and 1416.0 IU for triptorelin. The reported mean difference is 143.6 IU, with the comparison oriented as triptorelin minus ganirelix. The estimate is expressed in the outcome’s natural unit, international units, so its scale can be interpreted directly as recFSH use.

A mean difference is not a statement about every participant. Participants within each group can have values that vary around the group mean, as reflected by the standard deviations of 265.8 IU and 355.6 IU. The group summaries do not describe the full shape of those distributions or show whether individual values overlap. A group-level mean comparison answers a question about average use, not whether all participants had a similar response.

What does the p-value mean?

The sponsor’s registry-reported analysis uses the Cochran-Whitehead method and gives p < 0.001. In general, a p-value describes how compatible the observed data are with a specified null hypothesis, under the assumptions of the analysis. A small p-value is evidence against that null hypothesis, but it does not quantify the size or clinical importance of the difference. It also does not show the probability that the null hypothesis is true.

The record does not report the parameter tested by the Cochran-Whitehead analysis or additional methodological detail about its implementation. The p-value should therefore be reported as the sponsor’s result without attributing unreported details to the test. The separate unadjusted p-value is also <0.001. Since the record does not flag a discrepancy, the posted result and the unadjusted recalculation are not identified as conflicting; the sponsor’s analysis remains the primary registry-reported analysis.

Why is a confidence interval useful?

A confidence interval gives a range of estimates compatible with the data and the method used to construct it. The recalculated unadjusted interval for the mean difference is 61.44 to 225.8 IU. In general, a narrower interval indicates greater precision, while a wider interval indicates more uncertainty about the size of the effect. An interval is not a range containing a fixed proportion of individual participants’ observations, and it does not include all uncertainty about trial design, measurement, or missing data.

The interval is for the unadjusted difference derived from posted summary statistics. It is not reported as the sponsor’s confidence interval. The registry lists a 95% confidence level for the reported analysis, but its lower and upper confidence limits are not reported in the registry record. The distinction matters because different analyses can produce different estimates or uncertainty measures, and the sponsor’s own analysis is the relevant reported test.

What does over-dispersion mean in general?

In general, over-dispersion means that the observed variability is greater than expected under a model’s assumptions. When a model underestimates variability, standard errors can be too small and confidence intervals too narrow, making statistical evidence appear stronger than it should. The posted primary endpoint is continuous and is summarized with standard deviations; the registry does not report an over-dispersion assessment or indicate that an over-dispersion model was used. This concept is therefore general context, not a claim about a diagnosed problem in this trial.

For continuous outcomes, it is important that the analysis and its uncertainty estimate are appropriate for the outcome distribution and study design. The registry identifies the sponsor’s method as Cochran-Whitehead but does not give enough detail to evaluate all model assumptions. It also does not report diagnostics, adjustments, or a complete statistical analysis plan. The recalculation uses unadjusted summary statistics and should not be treated as a replacement for an adequately documented prespecified analysis.

How do randomization and open-label conduct affect interpretation?

Random assignment is intended to create groups that are comparable on average with respect to both measured and unmeasured characteristics. It supports a causal comparison when allocation, follow-up, outcome measurement, and analysis are appropriately conducted. The registry reports randomized allocation, but details of sequence generation and concealment are not reported in the registry record.

Open-label conduct means treatment assignment was not masked. For an endpoint based on the amount of medication administered before a follicle criterion is reached, knowledge of assignment could potentially influence management or assessment. This is a general concern with unmasked studies, not evidence that bias occurred in this trial. The record does not report procedures designed to address this concern or details of outcome assessment.

Finally, the primary analysis was limited to participants who received hCG and had data available. General statistical interpretation should distinguish the randomized population from the subset used for the outcome estimate. The registry does not report the extent or reasons for exclusion from this endpoint analysis, nor the missing-data method. These omissions limit assessment of possible bias even when the reported test is statistically significant.

10. Confidence Intervals and Precision

The recalculated unadjusted mean difference is 143.6 IU, with a confidence interval from 61.44 to 225.8 IU. The comparison is oriented as triptorelin minus ganirelix, so the positive estimate corresponds to the higher observed mean in the triptorelin group. The interval gives a range of values compatible with the posted summary data under the recalculation’s assumptions. It does not describe the spread of individual recFSH amounts.

In general, a confidence interval combines an estimated effect with its statistical uncertainty. Its width conveys precision: a narrower interval would indicate a more precise estimate under the same method, while a wider interval would leave greater uncertainty about the effect’s size. The interval is entirely on the positive side of zero, consistent with the reported unadjusted p-value of <0.001. This does not establish clinical importance, because that depends on context and outcomes beyond the statistical interval.

The interval is an unadjusted recalculation, not a confidence interval reported for the sponsor’s Cochran-Whitehead analysis. The registry gives a 95% confidence level for the sponsor-reported analysis, but its confidence limits are not reported in the registry record. The recalculated interval should therefore be interpreted as a summary-statistic-based estimate, while the sponsor’s own reported test remains the registry analysis.

Precision also has limits beyond the interval itself. It does not account for possible bias from open-label conduct, uncertainty about missing endpoint data, or incomplete reporting of analysis procedures. Nor does it describe how results might vary in other populations. The analyzed group included 109.0 ganirelix participants and 114.0 triptorelin participants, selected according to the registry’s stated outcome population. The interval’s statistical precision does not remove uncertainty arising from these design and reporting limitations.

11. Planning a Similar Trial: Sample Size

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

The planning figures are participants per arm for this continuous endpoint, not total events. The planning illustration uses two-sided significance level 0.05, equal allocation between the two arms, and a normal approximation. Its target effect is expressed as a fraction of the observed effect: the listed scenarios use 100%, 75%, and 50% of the observed effect. These are planning illustrations based on the observed result, not the trial’s original design justification; the trial’s own design assumptions are not reported in the registry record.

The 80% power column gives the estimated participants per arm for a design with 80% power to detect the specified effect under those assumptions. The 90% power column gives the corresponding estimate for 90% power. Power is a design probability calculated under a set of assumptions; it is not a probability that the trial’s conclusion is correct. Smaller effects need more participants to detect under the same planning assumptions.

For 100% of the observed effect, the illustration lists 76 participants per arm for 80% power and 102 for 90% power. For 75% of the observed effect, it lists 135 participants per arm for 80% power and 180 for 90% power. For 50% of the observed effect, it lists 303 participants per arm for 80% power and 405 for 90% power. These values are planning estimates, not observed trial enrollment targets. This is not observed power.

The trial enrolled 259 participants, while the endpoint analysis included 109.0 in the ganirelix group and 114.0 in the triptorelin group. Comparing those observed analysis counts with planning illustrations does not establish whether the original design was adequately powered, because the original assumptions and sample-size justification are not reported in the registry record.

12. How the Sample Size Is Derived

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

Formula

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

Worked calculation for this trial

1. Observed difference Δ = 143.600; pooled standard deviation σ = 314.931.
2. n = 2 × (1.96 + 0.842)² × 314.931² / 143.600² = 75.5, rounded up to 76 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 <- 143.6                      # observed difference in means
sigma <- 314.931327715219                     # 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(725491)
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 = 76 (80% power), 102 (90% power)
 75% of observed effect: n per arm = 135 (80% power), 180 (90% power)
 50% of observed effect: n per arm = 303 (80% power), 405 (90% power)
power.t.test: 76.5 
Simulated power at n = 76 per arm: 0.799 (20000 replicates)

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

13. Analyses Reported by the Sponsor

The registry reports a sponsor analysis using the Cochran-Whitehead method, with p < 0.001. It does not report the analysis’s effect estimate or confidence limits. The posted group summaries also support a simple unadjusted recalculation: the mean difference is 143.6 IU, with an unadjusted confidence interval from 61.44 to 225.8 IU and an unadjusted p-value of <0.001.

The recalculation is based on the posted group means and standard deviations. It is not a reconstruction of every feature of the sponsor’s analysis, and its confidence interval should not be attributed to the sponsor. Because the registry does not flag a discrepancy, there is no reported conflict between the two p-values. The sponsor’s own analysis remains the primary registry-reported result, while the recalculation provides a transparent, unadjusted comparison based on the available summary statistics.

The registry record does not give enough detail to determine all differences between the sponsor analysis and the recalculation, such as covariate adjustment or other analysis features. Those details are not reported in the registry record. The two analyses should therefore be described by their documented methods and outputs, without assuming that they estimate uncertainty in exactly the same way.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and one analysis, and it reports no posted secondary outcomes. However, this does not establish that the complete study protocol had no other outcomes, analyses, or planned comparisons. A multiplicity adjustment or strategy is not reported in the registry record. Multiplicity matters in general when several hypotheses are tested, because the chance of at least one false-positive result can increase as the number of tests grows. The available record is not sufficient to assess the full testing family or whether any adjustment was planned.

The primary analysis population is described as participants in the intent-to-treat group who received hCG and for whom data were available. This is more specific than an analysis of everyone randomized. The registry does not report the number of randomized participants who did not receive hCG, lacked outcome data, or were otherwise excluded from this endpoint analysis. Reasons for missing or unavailable data are also not reported in the registry record.

The method used to handle missing endpoint data is not reported in the registry record. It is therefore not possible to determine whether missingness was addressed by imputation, a complete-case approach, or another method. In general, conclusions can be affected when the availability of outcome data is related to treatment assignment or outcome values. The reported group comparison should be read as applying to the defined analyzed population, with uncertainty about how unavailable data may affect its generalizability.

The registry does not report a full statistical analysis plan, the timing of analysis decisions, interim analyses, or any prespecified handling of protocol deviations. These are not assumptions that can be filled in from the reported p-value. The record gives the sponsor’s test method and result, but not enough detail to independently evaluate every aspect of the analysis population, missing-data strategy, or multiplicity control.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: ectopic pregnancy (1.8%), ovarian hyperstimulation syndrome (1.7%), abortion spontaneous (0.9%).

For serious adverse events, the registry reports 112 participants at risk in the ganirelix group, of whom 4 were affected, and 120 at risk in the triptorelin group, of whom 2 were affected. For other adverse events, it reports 112 at risk and 13 affected in the ganirelix group, compared with 120 at risk and 13 affected in the triptorelin group. These are counts as reported; the record does not provide enough detail to assess event severity beyond the serious-event classification or to compare event rates with adjusted analyses.

The registry lists ectopic pregnancy at 1.8%, ovarian hyperstimulation syndrome at 1.7%, and abortion spontaneous at 0.9% among the top serious adverse event terms. Arm-specific counts for those terms and further definitions are not reported in the registry record. Deaths are not reported in the registry record; a missing death value should not be interpreted as a statement that no deaths occurred.

Adverse-event counts are descriptive and are not, by themselves, evidence that a treatment caused an event or that the groups differ statistically. The exposed populations and reporting period also matter. Detailed event narratives, severity grades, relatedness assessments, and comprehensive safety tables are not reported in the registry record. These figures should be read as the safety information posted for this study, not as a complete safety profile.

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

The primary result shows lower mean recFSH use in the ganirelix group than in the triptorelin group among participants included in the endpoint analysis: 1272.0 IU compared with 1416.0 IU. The posted mean difference, oriented as triptorelin minus ganirelix, is 143.6 IU. The sponsor-reported Cochran-Whitehead test gives p < 0.001, and the unadjusted recalculation also gives p < 0.001. The recalculated confidence interval is 61.44 to 225.8 IU.

These results describe an average difference in recFSH use up to the specified hCG criterion. They do not establish that the treatments differ in pregnancy, live birth, or other outcomes, which are not posted as outcomes in this record. They also do not show that the difference has a particular clinical importance. Statistical evidence against equal group means is not the same as evidence of a meaningful patient benefit.

The randomized design supports a comparative interpretation, but the study was open-label. The registry does not report details of allocation concealment, outcome assessment, missing-data handling, or the complete statistical plan. The primary endpoint population excluded participants without the required observed outcome or who did not receive hCG, according to the registry description. Those features matter when considering how far the result can be generalized beyond the analyzed participants.

Safety counts are also posted, including serious adverse events affecting 4 ganirelix participants and 2 triptorelin participants. The record does not provide enough information to interpret those counts as comparative risks or attribute individual events to treatment. The trial’s registry result should therefore be understood as evidence about the reported stimulation endpoint and posted safety observations, not as a complete assessment of all outcomes or the overall balance of benefits and harms.

17. Why This Trial Matters Statistically

This trial illustrates how a clinical study can report an outcome that is measurable and directly tied to treatment delivery, while leaving other clinically important outcomes unanswered in the registry record. The primary endpoint is the amount of recFSH used before the follicle-based hCG criterion was met. The mean comparison and its uncertainty describe that specific process measure, not the full experience or outcome of IVF or ICSI.

It also shows why statistical significance and clinical interpretation should be kept distinct. The sponsor-reported result is statistically significant at p < 0.001, and the unadjusted recalculation gives a difference of 143.6 IU. Those findings indicate evidence of a group difference in the measured endpoint, but the registry does not establish what that difference means for pregnancy outcomes or other patient-centered outcomes. Statistical tests answer a limited question about data compatibility under assumptions; they do not supply a clinical threshold of importance.

The record also makes analysis populations consequential. Although enrollment was 259, the endpoint analysis included participants in the intent-to-treat group who received hCG and had data available. Without details on unavailable outcomes or their handling, a reader cannot fully evaluate how selection into the analyzed population might affect the estimate.

Finally, the study provides a practical example of separating sponsor-reported inference from an unadjusted recalculation. The sponsor’s method and p-value are reported, while the recalculated interval offers a separate view of the effect’s precision. Both are useful when clearly labeled, but they are not interchangeable. Careful reporting of endpoints, populations, estimates, uncertainty, and missing-data methods helps readers understand exactly what a trial’s results do and do not answer.

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.

The registry record does not provide a full protocol or statistical analysis plan. It does not report the original sample-size justification, design assumptions, interim analyses, multiplicity strategy, or the timing of analysis decisions. Consequently, the planning illustrations based on the observed effect cannot establish what the trial was designed to detect.

The study was open-label. The registry does not report allocation concealment or detailed procedures for outcome assessment. Since the primary endpoint concerns medication use up to a follicle-based criterion, awareness of assigned treatment could be relevant to management or assessment in general, although the record does not establish that bias occurred.

The endpoint analysis was restricted to participants in the intent-to-treat group who received hCG and had available data. The registry does not report the number or reasons for participants without an endpoint result, nor the method used to handle missing data. This limits assessment of selection effects and the extent to which the endpoint results represent all randomized participants.

The sponsor’s analysis is identified as Cochran-Whitehead, but the record does not include an estimated effect or confidence interval for that analysis, and its implementation details are not reported. The recalculated unadjusted interval is based on the posted group summaries and should not be mistaken for the sponsor’s interval. Secondary outcomes are not posted, so the registry record does not provide a broader account of efficacy or patient-centered outcomes. Safety information is also limited: detailed event definitions, arm-specific information for the listed serious event terms, and deaths are not reported in the registry record.

These reporting gaps restrict independent assessment of the analysis and the broader clinical meaning of the findings. They do not negate the posted group summaries or test result, but they narrow the conclusions that can be drawn from them.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Study to Assess the Efficacy and Safety of Ganirelix (Orgalutran®) Treatment in Chinese Women Undergoing Controlled Ovarian Stimulation for in Vitro Fertilization (IVF) or Intra Cytoplasmatic Sperm Injection (ICSI) (Study 38651)(P05703) — NCT00725491.
• Registry record last updated 2022-02-03; status last verified 2022-02.
• Results first posted 2010-01-22.
• 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

NCT00725491 is a completed Phase III, randomized, multi-center, open-label, parallel-group study sponsored by Organon and Co. It compared ganirelix with triptorelin in Chinese women undergoing controlled ovarian stimulation for IVF or ICSI. Enrollment was 259; the study start was 2007-05 and primary completion was 2008-12.

The primary outcome was mean recFSH use up to the first day the hCG criterion was met, defined as 3 follicles >= 17 mm. Mean use was 1272.0 IU with ganirelix and 1416.0 IU with triptorelin. The sponsor-reported Cochran-Whitehead analysis gave p < 0.001. The unadjusted recalculated mean difference was 143.6 IU, with a confidence interval from 61.44 to 225.8 IU.

The outcome analysis included participants in the intent-to-treat group who received hCG and had data available. The record does not report the original sample-size justification, missing-data method, full statistical plan, or secondary outcomes. Serious adverse events affected 4 participants in the ganirelix group and 2 in the triptorelin group; the posted safety information is limited.