A Dose-response Trial Using rFSH FE 999049 in Women Undergoing IVF/ICSI Treatment: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Dose-response Trial Using rFSH FE 999049 in Women Undergoing IVF/ICSI Treatment (NCT01426386), a randomized phase 2 study. The primary outcome is Number of Oocytes Retrieved.

2. Clinical Question

The endpoint was assessed on the day of oocyte retrieval, up to Day 18 after stimulation began. The trial is described as randomised, controlled, assessor-blind, parallel-group, multinational and multicentre. The registry does not report the details of the randomisation procedure or which trial personnel were masked. The observed results describe the participants included in the analysis; they do not, on their own, establish what would happen in a different population or treatment setting.

3. Trial Design

This was a completed phase 2 randomized, controlled, parallel-group trial of FE 999049 in women undergoing IVF/ICSI treatment. The official title describes it as assessor-blind, multinational and multicentre. The record identifies the masking as single, but does not report which individuals were masked or how masking was maintained. It lists Ferring Pharmaceuticals as the sponsor.

The registry records an enrollment of 265 participants. The primary endpoint analysis included the modified intention-to-treat population, described as all randomised and exposed subjects and equivalent to the Full Analysis Set. The group sizes in the primary outcome results range from 42 to 47 participants. The record does not provide a detailed flow of participants through screening, randomisation, treatment and analysis, so reasons for any differences between enrollment and the analyzed group counts are not reported in the registry record.

Five groups received FE 999049 at doses from 5.2 µg through 12.1 µg. The sixth group received GONAL-F 11 µg. The posted primary comparisons use the 5.2 µg FE 999049 group as the reference, while the sponsor-reported ANCOVA dose-response analysis includes the FE 999049 dose groups. The record does not describe the rationale for selecting the doses, the allocation ratio, or the original sample-size calculation.

The primary outcome was the number of oocytes retrieved. Secondary outcomes listed in the record include follicle measures, endocrine profile, total IMP dose, fertilised oocytes, blastocyst measures, clinical pregnancy with fetal heart beat, and adverse events. The record gives numerical results for some secondary measures, but numerical results for the other listed outcomes are not reported in the registry 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.

Before assignment: In total 334 subjects were screened. Of these, 69 were screening failures and 265 were randomised. All randomised subjects were exposed to investigational medicinal product (IMP).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified Intention-to-treat (mITT) population (all randomised and exposed subjects). This is equivalent to the Full Analysis Set (FAS)

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Oocytes Retrieved, measured over Day of oocyte retrieval (up to Day 18 after start of stimulation).

The primary endpoint is the number of oocytes retrieved, measured on the day of retrieval, up to Day 18 after stimulation began. It is a count of oocytes, but the registry summarizes it as a continuous measure using a mean and standard deviation. The mean describes the group’s average number retrieved; the standard deviation describes how much individual observations varied around that average.

This endpoint is relevant to a dose-response trial because it records an outcome of ovarian stimulation and allows the group averages across FE 999049 doses to be compared. The registry reports both group means and an ANCOVA analysis of the slope of the dose-response curve. It also gives comparisons of each higher FE 999049 dose and the GONAL-F group against the FE 999049 5.2 µg reference group.

The endpoint is not a complete account of the treatment experience or of later reproductive outcomes. It does not, by itself, describe fertilisation, embryo development, pregnancy or adverse events. Those topics appear among the registry’s secondary outcomes, but results for each are not all reported. The number of oocytes retrieved should therefore be interpreted as a specific stimulation outcome, rather than as a substitute for the other outcomes listed in the record.

7. Results Posted in the Registry

• FE 999049 6.9 µg: mean 7.90 versus 5.20 on control; difference 2.70 (95% CI 0.71 to 4.69), standardized effect d = 0.56; z-test p = 0.008.
• FE 999049 8.6 µg: mean 9.20 versus 5.20 on control; difference 4.00 (95% CI 2.31 to 5.69), standardized effect d = 1.00; z-test p = <0.001.
• FE 999049 10.3 µg: mean 10.50 versus 5.20 on control; difference 5.30 (95% CI 3.00 to 7.60), standardized effect d = 0.96; z-test p = <0.001.
• FE 999049 12.1 µg: mean 12.20 versus 5.20 on control; difference 7.00 (95% CI 5.04 to 8.96), standardized effect d = 1.44; z-test p = <0.001.

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.

Number and Size of Follicles During Stimulation

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • FE 999049 6.9 µg: mean 23.00 versus 19.20 on control; difference 3.80 (95% CI 0.07 to 7.53), standardized effect d = 0.42; z-test p = 0.046.
  • FE 999049 8.6 µg: mean 25.00 versus 19.20 on control; difference 5.80 (95% CI 2.35 to 9.25), standardized effect d = 0.71; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for FE 999049 6.9 µg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for FE 999049 8.6 µg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Endocrine Profile

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • FE 999049 6.9 µg: mean 5,221 versus 3,642 on control; difference 1,579 (95% CI 247.66 to 2,911), standardized effect d = 0.50; z-test p = 0.020.
  • FE 999049 8.6 µg: mean 5,690 versus 3,642 on control; difference 2,048 (95% CI 566.95 to 3,528), standardized effect d = 0.58; z-test p = 0.007.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for FE 999049 6.9 µg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for FE 999049 8.6 µg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Total IMP Dose

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • FE 999049 6.9 µg: mean 61.90 versus 50.00 on control; difference 11.90 (95% CI 6.58 to 17.22), standardized effect d = 0.93; z-test p = <0.001.
  • FE 999049 8.6 µg: mean 71.90 versus 50.00 on control; difference 21.90 (95% CI 16.45 to 27.35), standardized effect d = 1.69; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for FE 999049 6.9 µg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for FE 999049 8.6 µg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The numerical secondary results address related aspects of ovarian stimulation, including follicle measures, endocrine profile and total IMP dose. Across these outcomes, the group summaries generally show a pattern associated with increasing FE 999049 dose. The registry also reports dose-response slope analyses for follicle measures and endocrine profile. These secondary outcomes are biologically and statistically related to the primary stimulation endpoint, but they measure different features and should not be treated as interchangeable with the number of oocytes retrieved.

The secondary outcomes can add context to the primary finding by describing other responses during stimulation. They cannot, by themselves, confirm or replace the primary endpoint result. The record lists additional outcomes concerning fertilised oocytes, blastocysts, clinical pregnancy with fetal heart beat, and adverse events, but their numerical outcome results are not reported in the registry record. Consequently, the full pattern across all prespecified or collected outcomes cannot be assessed from the posted results.

Unadjusted secondary comparisons carry less weight than a prespecified primary analysis because many outcomes and contrasts can create opportunities for apparently notable results to arise by chance. Whether multiplicity was planned or controlled is not reported in the registry record. Secondary estimates are therefore best viewed as descriptive or supportive evidence, with attention to their uncertainty and to whether the result was part of a prespecified analysis. The record does not provide enough detail to determine how the secondary tests were prioritized or interpreted within the original statistical plan.

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

• Number and Size of Follicles During Stimulation
• Endocrine Profile
• Total IMP Dose
• Number of Fertilised Oocytes
• Number and Quality of Blastocysts on Day 5
• Clinical Pregnancy With Fetal Heart Beat Rate
• Frequency and Intensity of Adverse Events

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is a continuous summary of a count: the mean number of oocytes retrieved in each group. A mean gives the arithmetic center of the observed values, while the standard deviation describes dispersion around that center. It is not a confidence interval for the group mean and does not indicate how certain the estimated mean difference is. The group sizes and the observed variation both contribute to the precision of a comparison.

The posted recalculated comparisons are unadjusted differences in means between each listed group and FE 999049 5.2 µg. A mean difference is expressed in the original outcome units, so these estimates describe the difference in average oocytes retrieved. A positive difference in these results means the group mean is higher than the reference-group mean. The estimate should be considered together with its confidence interval: the interval conveys uncertainty around the estimated difference, while the point estimate alone does not.

The comparison calculations use the posted group means, standard deviations and group sizes. These recalculations are unadjusted, summary-statistic analyses and are not a substitute for the sponsor’s reported ANCOVA. The registry does not report an adjustment set for the recalculated comparisons, and none is applied in interpreting them. The comparison p-values are unadjusted; no multiplicity adjustment is reported for this set of comparisons.

What does the ANCOVA result describe?

The registry reports an ANCOVA analysis for the slope of the dose-response curve across the FE 999049 groups. ANCOVA is a general statistical approach for relating an outcome to a group or exposure while accounting for specified covariates. The registry identifies the method and the slope parameter, but the covariates, model specification, dose coding and other implementation details are not reported in the registry record. Those details should not be inferred from the label ANCOVA alone.

The reported slope is a model-based summary of the dose-response relationship, with a confidence interval and p-value. It should be distinguished from the individual mean differences, which contrast particular arms with the 5.2 µg arm. A slope summarizes the pattern across dose groups according to the fitted model; it does not state that every adjacent dose pair has an equal difference or that the response follows a particular shape beyond what the model assumes. The full shape assumptions are not reported in the registry record.

How should p-values be read?

A p-value describes how surprising data at least as incompatible with a specified null hypothesis would be if that hypothesis and the statistical model were correct. It is not the probability that the null hypothesis is true, and it is not a measure of the probability that a result will repeat. The p-values for the pairwise comparisons are explicitly unadjusted. The sponsor-reported ANCOVA p-value is reported separately for the slope analysis. The registry does not report whether any other planned tests were conducted or how the number of analyses informed interpretation.

Several aspects of the analysis plan are not reported in the registry record, including the original sample-size justification, the planned handling of missing observations, and whether any interim analyses were conducted. The analysis population is described as modified intention-to-treat, including all randomised and exposed subjects, and equivalent to the Full Analysis Set. This is a useful definition, but details on exclusions, missing endpoint values and any imputation methods are not reported in the registry record.

General statistical context: dose-response analyses can be informative when the scientific question concerns how an outcome changes across assigned dose levels. However, the interpretation depends on how dose is represented in the model and on the model’s assumptions. Random allocation supports comparisons between assigned groups, but does not resolve uncertainty about incomplete data, multiplicity or external applicability. The posted means, estimated differences, confidence intervals and reported ANCOVA result should therefore be read together, with attention to which statistical question each estimate addresses.

11. Confidence Intervals and Precision

A confidence interval expresses uncertainty around an estimated quantity under the analysis used. For a mean difference, it gives a range of values compatible with the data and assumptions; it does not describe the range of individual participants’ outcomes. The width of an interval reflects precision: a narrower interval indicates less statistical uncertainty than a wider one, all else being equal. An interval is not a guarantee that the true value lies within it.

For the primary comparisons, the intervals are reported as recalculated unadjusted 95% confidence intervals. For the 6.9 µg group, the mean difference is 2.7 oocytes, with an interval from 0.708 to 4.692. For 8.6 µg, the estimate is 4.0, with an interval from 2.314 to 5.686. For 10.3 µg, it is 5.3, with an interval from 3.003 to 7.597. For 12.1 µg, it is 7.0, with an interval from 5.04 to 8.96. The GONAL-F comparison is 5.2, with an interval from 3.353 to 7.047.

Each of those intervals is above zero, in keeping with the positive estimated mean differences. Their widths also show that the estimates are not exact; the data remain compatible with a range of difference sizes. The intervals do not account for multiplicity across the several comparisons, because the recalculations are unadjusted. The registry-reported ANCOVA slope has its own 95% confidence interval, from 5.69 to 10.18, which pertains to the dose-response parameter rather than to a pairwise mean difference.

Group standard deviations and sample sizes also help explain precision. Greater variation and smaller analyzed groups generally make estimates less precise. The observed standard deviations differ across arms, and the primary group sizes range from 42 to 47. Confidence intervals should be interpreted with the analysis population and the unreported missing-data details in mind.

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 sample-size figures are planning illustrations based on the observed effect in a comparison, not the original trial’s sample-size calculation. For continuous outcomes, the figures are participants per arm; they are not total event counts. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. The original design assumptions for this trial are not reported in the registry record.

The 80% power column gives the planned participants per arm for an illustration with an 80% probability of detecting the chosen effect under those assumptions, if that effect and the model assumptions were correct. The 90% power column uses a higher probability of detection under the same general planning framework. For example, for the comparison of 6.9 µg with 5.2 µg, planning for 100% of the observed effect gives 51 participants per arm for 80% power and 68 participants per arm for 90% power. Planning for 75% of the observed effect gives 90 and 120 participants per arm, respectively; planning for 50% gives 201 and 269.

The pattern illustrates that smaller effects need more participants to detect: a smaller target signal is harder to distinguish from random variation. The same principle explains why the planned group sizes increase as the selected fraction of the observed effect gets smaller. The figures are sensitive to the observed effect and variability used as their basis, so they should not be treated as a design recommendation or as evidence about the trial’s operating characteristics. This is not observed power; it is a planning illustration under stated assumptions.

13. How the Sample Size Is Derived

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

Formula

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

Worked calculation for this trial

1. Observed difference Δ = 2.700; pooled standard deviation σ = 4.824.
2. n = 2 × (1.96 + 0.842)² × 4.824² / 2.700² = 50.1, rounded up to 51 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 <- 2.7                      # observed difference in means
sigma <- 4.82411832846779                     # 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(1426386)
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 = 51 (80% power), 68 (90% power)
 75% of observed effect: n per arm = 90 (80% power), 120 (90% power)
 50% of observed effect: n per arm = 201 (80% power), 269 (90% power)
power.t.test: 51.1 
Simulated power at n = 51 per arm: 0.806 (20000 replicates)

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

14. Analyses Reported by the Sponsor

The registry reports the sponsor’s ANCOVA analysis of the dose-response slope for the primary outcome. The estimated slope is 7.9, with a 95% confidence interval from 5.69 to 10.18 and p < 0.001. This is the reported model-based analysis across the FE 999049 dose groups.

The recalculated pairwise results are unadjusted differences in means derived from the posted group summary statistics. They answer a narrower question: how the mean in each specified arm compares with the mean in the 5.2 µg reference arm. These estimates are not a reconstruction of the ANCOVA model, and they should not be interpreted as if they used the same estimand or adjustment structure.

The registry’s reported slope analysis and the recalculated comparisons are complementary rather than competing results. The record does not report enough ANCOVA implementation detail to reproduce the sponsor’s model, including its covariates and complete specification. The posted results do not identify a discrepancy between the reported and recalculated results. The sponsor’s reported analysis remains the appropriate description of the analysis it conducted, while the unadjusted recalculations provide a transparent summary-statistic view of selected arm contrasts.

15. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is clearly identified as the number of oocytes retrieved, and the registry reports an ANCOVA analysis of the dose-response slope. It also includes recalculated pairwise comparisons against the lowest FE 999049 dose. Those pairwise p-values are unadjusted. The registry does not report a multiplicity adjustment for those comparisons or explain how the primary slope test and pairwise contrasts were prioritized in the planned analysis.

Multiplicity matters because testing several contrasts or outcomes increases the chance of observing a small p-value even when there is no underlying difference. This does not mean that any particular result is false; it means that a p-value from one unadjusted comparison should be interpreted in the context of the full set of tests. The record includes multiple secondary outcomes, but a complete statistical testing hierarchy or multiplicity strategy is not reported in the registry record. The number of analyses recorded does not establish that every possible comparison or outcome was tested.

The primary analysis population is defined as all randomised and exposed subjects, equivalent to the Full Analysis Set. The registry does not report the number of participants with missing primary endpoint data, the reasons for missingness, or how missing values were handled. It also does not report whether any interim analyses took place. These omissions prevent a complete assessment of how missing data or repeated looks at the accumulating data might affect inference.

The registry record does not report the trial’s original statistical analysis plan or sample-size justification. It therefore cannot establish which analyses were planned before results were known, how deviations were handled, or what assumptions guided the original design. The posted results remain interpretable as reported, but the absent information limits assessment of the complete confirmatory framework.

16. 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 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 (2.3%).

The adverse-event summary reports serious adverse events among participants at risk in each group. There were no serious adverse events recorded for the 5.2 µg, 6.9 µg, 8.6 µg or 12.1 µg FE 999049 groups, or for the GONAL-F group. One participant in the FE 999049 10.3 µg group was recorded as affected by a serious adverse event. The registry reports no deaths in any group.

Ectopic pregnancy is listed among the leading serious adverse-event terms at 2.3%. The record does not assign that term to a particular treatment group in the posted summary, so it should not be attributed to an arm. The serious-event counts are small, and a lack of recorded events in a group does not demonstrate that an event cannot occur. Conversely, a count alone does not establish a treatment-related cause.

The registry also reports counts of participants affected by other, non-serious adverse events, but those counts do not provide a detailed account of event types, severity, timing or relatedness. The adverse-event summary is descriptive; it does not establish comparative safety or permit conclusions about uncommon harms. More complete event definitions and follow-up details are not reported in the registry record.

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

The posted primary results show increasing group means for the number of oocytes retrieved across the studied FE 999049 dose groups. The sponsor-reported ANCOVA analysis also reports a positive dose-response slope, with a confidence interval that does not include zero and p < 0.001. The recalculated unadjusted pairwise comparisons show positive differences between the higher-dose groups and the 5.2 µg reference group. These findings describe the analyzed trial participants and the recorded endpoint.

They do not establish that the observed pattern will be identical in other populations, treatment settings or protocols. The registry record does not report the original sample-size rationale, the full analysis plan, detailed handling of missing outcome data, or multiplicity procedures. The group counts are modest and the standard deviations indicate variation between participants. Those features are important when judging how much precision and generalizability to assign to the findings.

The primary endpoint is not itself a pregnancy outcome or a complete measure of treatment success. The registry lists additional reproductive and safety outcomes, but numerical results for several of them are not reported in the registry record. The number of oocytes retrieved should therefore not be used as a proxy for those unreported outcomes.

The comparisons with GONAL-F are between the group summaries reported in this trial. They do not establish equivalence or superiority under a prespecified margin, because such a margin and a corresponding analysis are not reported in the registry record. Similarly, p-values do not establish clinical importance, and confidence intervals do not remove uncertainty. The results support a statistical description of the reported dose-response pattern, not a medical recommendation or a definitive account of all benefits and harms.

18. Why This Trial Matters Statistically

This trial is statistically informative because it studies several assigned doses rather than limiting the primary question to a single treatment-versus-control contrast. A range of doses allows investigators to assess whether group outcomes vary with dose and provides a basis for describing a dose-response relationship. The registry’s ANCOVA slope result and the arm-specific summaries address related but distinct statistical questions.

The example also illustrates why outcome summaries and inferential analyses should be read together. Group means describe the observed data, standard deviations show participant-to-participant variability, and confidence intervals express uncertainty in estimated differences or slopes. A p-value alone cannot communicate the magnitude or precision of an effect. The distinction between a model-based dose-response slope and unadjusted mean differences is particularly important: each estimate answers a different question and has different assumptions.

The registry also highlights limits in interpreting a collection of outcomes. Multiple secondary measures can provide useful context, but unadjusted tests across outcomes and contrasts require caution. Missing information about the original statistical plan, sample-size justification, multiplicity and missing-data handling restricts assessment of the complete analysis strategy. Those gaps do not erase the posted results; they define what can and cannot be concluded from the public record.

Finally, the planning illustrations demonstrate that sample-size requirements depend on the effect targeted and the assumed variability. They are not evidence of the trial’s original design rationale or of the probability that the observed results were detected. Keeping those planning calculations separate from observed trial evidence is central to sound interpretation.

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.

The registry record gives a concise account of the study but does not report several details needed to fully evaluate the analysis. The original sample-size calculation and its assumptions are not reported. Although planning illustrations can be derived from observed effects under stated assumptions, those calculations do not reveal the reasoning behind the actual enrollment target.

The ANCOVA result is reported as a dose-response slope, but the full model specification is not available in the registry record. The covariates, dose coding and other model details are not reported. Consequently, the sponsor’s result cannot be independently reconstructed from the record, and its precise interpretation depends on details that are unavailable.

The primary analysis population is defined, but participant flow and missing-data handling are not reported. The record does not provide a detailed account of missing endpoint observations, exclusions after randomisation, or imputation. This limits assessment of whether the analyzed participants represent the intended population and how incomplete outcomes may affect estimates.

The primary pairwise recalculations are unadjusted, and a multiplicity plan for the primary contrasts and secondary outcomes is not reported. The registry also does not report whether interim analyses occurred. Numerical results for several listed secondary outcomes are not available in the record, limiting evaluation of the full efficacy and safety profile. Finally, the record describes assessor blinding and single masking but does not specify who was masked or provide implementation details. These limitations affect the completeness of interpretation without changing the numerical results that are posted.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Dose-response Trial Using rFSH FE 999049 in Women Undergoing IVF/ICSI Treatment — NCT01426386.
• Registry record last updated 2020-11-17; status last verified 2018-08.
• Results first posted 2018-08-03.
• 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 2 randomized, controlled, assessor-blind, parallel-group trial of FE 999049 in women undergoing IVF/ICSI treatment. Enrollment was 265. Five FE 999049 doses were studied, alongside GONAL-F 11 µg.

The primary endpoint was the mean number of oocytes retrieved on the day of retrieval, up to Day 18 after stimulation began. Group means increased across the FE 999049 dose groups. The sponsor-reported ANCOVA analysis estimated a dose-response slope of 7.9, with a 95% confidence interval from 5.69 to 10.18 and p < 0.001. Recalculated pairwise comparisons are unadjusted and compare groups with FE 999049 5.2 µg.

The record lists related stimulation outcomes and reproductive outcomes, but numerical results for several listed outcomes are not reported in the registry record. The original sample-size justification, full analysis plan, multiplicity approach and missing-data procedures are also not reported.