Dysregulation of FSH in Obesity: Functional and Statistical Analysis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dysregulation of FSH in Obesity: Functional and Statistical Analysis (NCT02478775), a non-randomized na study. The primary outcome is Difference Between Peak Inhibin B.

2. Clinical Question

The study concerns hormonal responses in the context of obesity and fertility. Its stated primary measure focuses on peak inhibin B after repeated recombinant FSH dosing under antagonist blockade. The endpoint definition uses a within-participant contrast between the two study days, rather than a direct randomized comparison between treatment groups. The record also lists peak inhibin B per subject and peak E2 per subject as secondary outcomes. It does not report the values for these outcomes, nor does it provide results that would establish whether the response differed by weight group. The clinical question is therefore identifiable from the protocol description, but its answer cannot be read from the posted results because primary and secondary outcome findings are not reported in the registry record.

3. Trial Design

This completed study, NCT02478775, is titled “Dysregulation of FSH in Obesity: Functional and Statistical Analysis.” The sponsor is the University of Colorado, Denver. The registry lists a start date of 2015-07, primary completion of 2021-06-30, an enrollment of 99, and phase as NA. Obesity and fertility are the listed conditions.

The registry describes the allocation as non-randomized, masking as none, and model as single group. It lists frequent blood sampling arms using Degarelix or Cetrorelix blockade before repeated recombinant FSH dosing. The Degarelix arm description says it was terminated due to adverse events and that the study continued with the Cetrorelix product. The Cetrorelix arms are identified separately for normal-weight and obese participants. The record does not describe a randomized treatment allocation or a blinded comparison.

For the primary endpoint, the record explicitly excludes the Degarelix arm because no data was collected from those participants. It describes the endpoint as the maximum hormone value during Day 1 subtracted from the maximum during Day 2. The timing is described as every 10 minutes over 2 10-hour frequent blood sampling sessions. The intervention descriptions concern repeated bolus dosing of recombinant FSH following antagonist blockade over a 2-day period.

The registry lists three outcome measures and two secondary outcomes by name, but does not report primary or secondary outcome values. It also lists no analysis entries. The record does not report a detailed statistical analysis plan, a sample-size justification, or how the planned enrollment relates to the endpoint analysis. The stated enrollment is not a substitute for an endpoint-specific analysis population, particularly because the primary endpoint population excludes the Degarelix arm.

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: Some participants were excluded after signing the consent.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The Degarelix arm is excluded because no data was collected from those participants. The Degarelix arm was terminated due to adverse events and was replaced with the Cetrorelix arm.

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 Difference Between Peak Inhibin B, measured over Every 10 minutes over 2 10-hour frequent blood sampling sessions..

The primary endpoint, “Difference Between Peak Inhibin B,” is a continuous measure expressed in picograms/mL. For each participant, it is defined as the maximum hormone value during Day 1 of the study subtracted from the maximum during Day 2. Measurements were scheduled every 10 minutes over 2 10-hour frequent blood sampling sessions. The measure therefore captures a contrast between peak values across the two study days under the study’s dosing and blockade protocol.

Peak measures can be used to describe the maximum observed response during a defined sampling period. In this study, comparing the two daily peaks gives a within-participant summary rather than a comparison of randomized treatment assignments. The endpoint’s interpretation depends on the sampling schedule and on how a peak is identified from repeated measurements. The registry provides the endpoint definition, but does not report the resulting peak values, their distribution, or the estimated Day 1-to-Day 2 difference.

The record specifies a mean as the parameter and standard deviation as the dispersion measure. In general, a mean describes the average value in the analyzed group, while a standard deviation describes the spread of individual values around that average. Those summaries can help convey both the typical endpoint level and its variability, but they do not by themselves establish a difference between groups or quantify uncertainty in an estimated contrast. No endpoint estimate, standard deviation, confidence interval, or p-value is reported in the registry record. The listed secondary outcomes are peak inhibin B per subject and peak E2 per subject; their results are also not reported.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods descriptions in the registry are limited. They identify a continuous primary outcome, its mean as the summary parameter, its standard deviation as the dispersion measure, and the repeated sampling schedule. They do not identify a statistical test, model, covariate adjustment, or method for handling incomplete hormone series. The explanations below distinguish general statistical concepts from methods reported for this study.

What does a mean and standard deviation describe?

In general, the mean is an average across the analyzed observations. The standard deviation describes how dispersed individual observations are around that average. For a continuous endpoint such as a hormone concentration, these summaries can describe a central level and variability. A standard deviation is not the same as a standard error: the standard deviation describes variation among observations, whereas a standard error describes uncertainty in an estimated summary under a statistical model. The registry names mean and standard deviation for the primary measure, but does not post their values or identify whether they refer to participant-level endpoint differences, daily peaks, or another summary in the results.

Why does the paired endpoint definition matter?

The endpoint is defined for each participant as the maximum during Day 1 subtracted from the maximum during Day 2. In general, a paired comparison uses information from both measurements on the same participant and can account for the fact that repeated observations from one person may be related. This is distinct from treating the two days as if they came from unrelated participants. The record’s endpoint definition is consistent with a within-participant contrast, but it does not state which inferential method, if any, was used to summarize or test that contrast. No uncertainty estimate for the contrast is reported.

How should frequent sampling be understood?

The registry describes measurements every 10 minutes over 2 10-hour sessions. Repeated observations can show the pattern of a hormone response over time, while a peak summary compresses those observations to a maximum value for each day. As a general statistical consideration, a maximum is sensitive to the set of times observed and to measurement variability: more opportunities to observe a high value can affect the maximum. The record does not describe a method for smoothing the measurements, defining a peak beyond the stated maximum, or analyzing the full repeated-measures profile. It also does not report plots or numerical time-course results in the registry record.

What can a confidence interval or p-value add?

In general, a confidence interval presents a range of values compatible with the observed data and the assumptions of the analysis. Its width conveys precision: a wider interval indicates less precision than a narrower interval, all else equal. A p-value summarizes how unusual the observed data would be under a specified null hypothesis and model. It is not the probability that the null hypothesis is true, and it does not convey the magnitude or practical importance of an effect. The registry does not report a confidence interval or p-value for the primary endpoint, and it lists no analysis entries. It is therefore not possible to interpret inferential evidence for the endpoint from this record.

What do the planning assumptions mean?

The record describes a sample-size planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, such illustrations give a total number of events; for other outcomes, they give participants per arm. These are planning assumptions, not observed trial results and not observed power. The registry record does not report the numerical planning outputs, the observed effect used as their basis, or a trial-specific sample-size justification.

As a general principle, planning calculations depend on assumptions about the target effect, variability, statistical test, allocation, and desired operating characteristics. If an illustration is based on an effect observed in a study, it describes a hypothetical future design under those assumptions; it does not establish the probability that the completed study detected an effect. Because the primary endpoint results and their variability are not posted, the illustration cannot be independently interpreted from the registry record. No sample-size number should be inferred from the enrollment listing alone.

What does over-dispersion mean in general?

For count outcomes, over-dispersion means the observed variability exceeds what a simple model assumes. A model that does not account for excess variability may understate uncertainty. This concept is general and does not describe the primary endpoint here, which is continuous. The registry does not report a count-outcome analysis or a model for over-dispersion. For continuous repeated hormone measures, appropriate analysis choices would depend on the question, the distribution of measurements, and how within-participant dependence is handled; those choices are not specified in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Experimental: Frequent Blood Sampling, Cetrorelix:", "Experimental: Frequent Blood Sampling, Cetrorelix:")
n   <- c(27, 27)
m   <- c(100.8, 38.8)
sp  <- c(73.7, 37.9)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Experimental: Frequent Blood Sampling, Cetrorelix:  27  100.800  73.700  71.645  129.955
CARM  Experimental: Frequent Blood Sampling, Cetrorelix:  27  38.800  37.900  23.807  53.793

11. Multiplicity, Missing Data and Analysis Populations

The record lists three outcome measures, names peak inhibin B per subject and peak E2 per subject as secondary outcomes, and identifies “Difference Between Peak Inhibin B” as the primary endpoint. It does not report the complete outcome results, analysis entries, or a multiplicity strategy. The registry record does not say whether statistical tests were planned for each outcome, whether a hierarchy was used, or whether any adjustment for multiple testing was intended. In general, testing several outcomes can increase the chance of at least one apparently unusual result, so a prespecified strategy can help readers interpret a collection of tests. No such strategy is reported.

The primary endpoint population excludes the Degarelix arm because no data was collected from those participants. The registry says the arm was terminated due to adverse events and the study continued with Cetrorelix. The record does not explain whether data were unavailable by design, whether any other endpoint observations were missing, or how missing measurements within the sampling sessions would be handled. It also does not report participant flow for the Cetrorelix arms or endpoint-specific denominators.

The registry identifies an enrollment of 99, but does not provide the number included in each outcome analysis. Enrollment should not be assumed to equal the number with complete endpoint data. No imputation method, complete-case rule, or sensitivity analysis is reported in the registry record. The analysis population definitions beyond the explicit exclusion of the Degarelix arm are not reported in the registry record. These gaps limit assessment of whether missing observations could affect the endpoint summaries or comparisons.

12. 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 non-serious adverse event terms

The registry lists serious adverse events as zero in each of the three safety groups. The Degarelix group lists 6 participants at risk and 0 affected; the Cetrorelix normal-weight group lists 27 at risk and 0 affected; the Cetrorelix obese group lists 27 at risk and 0 affected. Deaths are listed as 0 in each group.

For other adverse events, the Degarelix group lists 6 participants at risk and 5 affected. The Cetrorelix normal-weight group lists 27 at risk and 0 affected, and the Cetrorelix obese group lists 27 at risk and 0 affected. The registry does not list any top serious adverse event terms.

These are descriptive counts in the safety record. They do not establish that a treatment caused or prevented an event, and the groups should not be treated as randomized comparisons. The Degarelix arm description separately states that it was terminated due to adverse events; the posted safety counts do not specify which events led to that decision. The safety population counts also do not provide the missing hormone endpoint results for the Degarelix arm.

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

The record supports a clear description of the intended primary measure: a participant-level difference between the maximum inhibin B value during Day 1 and the maximum during Day 2, after repeated recombinant FSH dosing under antagonist blockade. It also documents the sampling schedule and the change from a Degarelix protocol to Cetrorelix. Those details clarify what investigators set out to measure and which arm was excluded from the primary endpoint population.

The record does not report the primary endpoint estimate, the distribution of participant-level values, a confidence interval, or a p-value. It therefore does not show the size or direction of the Day 1-to-Day 2 peak difference, how precisely it was estimated, or whether the data provide evidence against a statistical null hypothesis. The secondary outcome results are not reported either. No conclusion about the observed hormonal response can be drawn from the posted outcome information.

Nor does the registry record provide a reported analysis comparing obese and normal-weight participants. The Cetrorelix groups are labeled by weight category, but allocation is non-randomized. Any unadjusted difference between such groups, if one were reported elsewhere, would not by itself establish that weight category caused that difference. The record does not provide a model or adjustment strategy for such a comparison.

These limitations concern interpretation of the registry record, not whether the study question is scientifically relevant. The study’s protocol description links obesity and fertility to hormonal response and includes repeated measures intended to characterize a peak. The available record gives design and safety information, but not the numerical outcome evidence needed to evaluate the primary endpoint. Statistical planning illustrations, even if based on an observed effect, are not substitutes for observed results and do not establish observed power.

14. Why This Trial Matters Statistically

This study raises statistical issues that are common in clinical research using repeated biomarker measurements. A frequent sampling schedule can capture changes over time, while a peak-based endpoint offers a compact summary. The choice of summary affects what is being estimated: a maximum highlights the highest recorded value, whereas a full time-course analysis would retain information about timing and shape. The registry defines the peak contrast but does not describe a full repeated-measures analysis.

The within-participant Day 1-to-Day 2 definition also makes the analysis population central. The Degarelix arm was terminated due to adverse events and excluded from the primary endpoint because no data was collected from those participants. That change in protocol history should be kept distinct from the endpoint comparison itself. The study cannot be read as a randomized Degarelix-versus-Cetrorelix trial, and the registry describes non-randomized allocation.

The record is also useful as an example of the difference between study registration details and outcome evidence. It lists an enrollment of 99 and provides a detailed endpoint definition, but does not report endpoint estimates or analyses. Design information can identify the question and some potential sources of bias; it cannot reveal the size or precision of an unreported result. Likewise, safety counts and planning assumptions answer different questions from the primary biomarker analysis.

For statistical interpretation, clear reporting of analysis populations, missing measurements, outcome summaries, and uncertainty would be important. Those details are not reported in the registry record. As a result, the study’s methods can be described at the level of the registered protocol, but the primary statistical findings cannot be evaluated from this record.

15. 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.

A key limitation is that primary and secondary outcome results are not reported in the registry record. The primary endpoint is defined, but there is no estimate, standard deviation, confidence interval, or p-value to assess the size and precision of the response. The record lists three outcome measures but provides only two secondary outcome names and no result values for them.

The record classifies allocation as non-randomized and masking as none. It also classifies the model as single group while listing Cetrorelix arms for normal-weight and obese participants. This information does not support interpreting the weight categories as randomized treatment groups. The registry record does not report a formal comparison strategy or adjusted analysis to address potential group differences.

The Degarelix arm was terminated due to adverse events, was replaced by Cetrorelix, and is excluded from the primary endpoint population because no data was collected from those participants. The record does not provide further detail on the circumstances of the termination or identify the events associated with it. Although safety counts are listed, they do not resolve the absence of hormone endpoint data from that arm.

The registry does not report endpoint-specific denominators for the Cetrorelix groups, the amount or pattern of missing data, or methods for handling missing hormone measurements. It does not report a detailed statistical analysis plan, multiplicity handling, or a trial-specific sample-size justification. The enrollment listing alone cannot establish how many participants contributed to each endpoint. These reporting gaps restrict assessment of precision, potential bias, and the robustness of any result.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Dysregulation of FSH in Obesity: Functional and Statistical Analysis — NCT02478775.
• Registry record last updated 2024-06-05; status last verified 2024-05.
• Results first posted 2022-04-07.
• 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.

19. Record Summary

NCT02478775 is a completed, non-randomized, unmasked study listed as single group, with enrollment of 99 and phase NA. It investigates hormone response in the context of obesity and fertility using frequent blood sampling after recombinant FSH dosing under GnRH-antagonist blockade. The Degarelix arm was terminated due to adverse events and replaced by Cetrorelix.

The primary endpoint is the difference between peak inhibin B on Day 1 and Day 2, with measurements scheduled every 10 minutes over 2 10-hour sessions. The Degarelix arm is excluded from that endpoint population because no data was collected from those participants. The record lists peak inhibin B per subject and peak E2 per subject as secondary outcomes, but reports no outcome results and no analysis entries.

Safety listings report no serious adverse events or deaths in the listed groups; other adverse event counts are 5 in the Degarelix group and 0 in each Cetrorelix group. These counts are descriptive and do not provide the missing primary endpoint analysis.