An Observational Study of Follitropin Alpha Biosimilar: the Real-world Data: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Observational Study of Follitropin Alpha Biosimilar: the Real-world Data (NCT04854707), a registered phase not stated study. The primary outcome is Number of Oocytes Retrieved.

2. Clinical Question

The study asked how many oocytes were retrieved among participants undergoing ovarian stimulation that included follitropin alpha biosimilar therapy. It also listed mature oocytes, fertilized oocytes and total biosimilar dose as secondary outcomes. The study was observational, and the registry record does not describe a randomized allocation or a like-for-like control comparison.

The registry record describes the study aim as investigating efficacy in routine practice, but it does not report the numerical primary outcome results. The clinical question can therefore be identified, while the size and precision of the observed oocyte counts cannot be assessed from the registry record.

3. Trial Design

This was an observational study, titled “An Observational Study of Follitropin Alpha Biosimilar: the Real-world Data,” sponsored by IVFarma LLC. It is listed as completed, with enrollment of 5484. The study started on 2020-01-12, and primary completion is recorded as 2020-12-20. These registry entries describe the study record; they do not establish how participants entered each protocol group.

The overall protocols included monotherapy using follitropin alpha biosimilar and mixed protocols combining recombinant with urinary-derived gonadotropins. Both types could include GnRH antagonists or agonists. A separate description divides monotherapy into protocols using GnRH antagonists and protocols using GnRH agonists. The combined monotherapy group for outcome reporting includes those two subgroups. The mixed protocol definition specifies that biosimilar use lasted at least 5 days during ovarian stimulation.

The record lists Follitropin Alfa and Follicle Stimulating Hormone/Luteinizing Hormone among the interventions. The intervention listing includes repeated entries, but the record does not explain the relationship between those entries and the protocol groups. The listed protocol descriptions give more detail about treatment combinations, but do not specify how clinicians selected among them or whether other participant characteristics influenced treatment choice.

Because this is not a randomized comparison and allocation is not stated, the protocol groups should not be read as interchangeable arms of a controlled experiment. The groups may differ in treatment combinations and could also differ in characteristics not described in the record. The registry record does not report a comparator designed to isolate the effect of biosimilar therapy from the other components of ovarian stimulation.

The primary outcome was the mean number of oocytes retrieved. Secondary outcomes were the number of mature oocytes, number of fertilized oocytes and total dose of follitropin alpha biosimilar. The record lists 5 outcome measures and 9 analyses, but does not report the detailed analysis plan, statistical model, adjustment strategy or sample-size justification.

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: Arm "Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH" is combined group for primary and secondary outcome measures and consist of patients from "Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH" and "Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH".

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 Number of Oocytes Retrieved, measured over From date of start of ovarian stimulation with follitropin alpha up to 15 days.

The primary endpoint was the total number of oocytes retrieved at ovum pick-up, summarized as a mean with a standard deviation. The record defines the observation window as from the start of ovarian stimulation with follitropin alpha up to 15 days. It describes retrieval as occurring on the day of ovum pick-up and no more than 37 hours from introduction of the ovulation inducer, either HCG or a GnRH agonist.

Oocyte count is a direct measure of the ovarian response observed at retrieval. In a study of ovarian stimulation protocols, it provides a count-based outcome that can be summarized across participants and protocol groups. The mean describes the average count, while the standard deviation describes how spread out individual counts are around that average. Neither statistic alone describes every participant’s response, and a mean should not be taken to imply that outcomes were similar for all participants.

The endpoint is also conditional on reaching retrieval. The registry record states that some participants did not complete ovarian stimulation and had no oocytes retrieved because of lack of efficacy of therapy; those participants were excluded from the analysed populations reported for the primary outcome. Thus, the reported analysis populations do not represent all enrolled participants in the same way as an analysis that retained everyone from the start of treatment.

The registry record does not report the primary endpoint means or standard deviations. It therefore does not permit assessment of the observed average count, variation within groups, or differences between protocol groups. Mature and fertilized oocytes are listed as secondary outcomes, but their results are also not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a continuous summary of a count: the number of oocytes retrieved for each participant, summarized as a mean and standard deviation. A mean is the arithmetic average of the observed values. A standard deviation describes the spread of those values around the mean. Together, they give a compact description of the group, but they do not show the full distribution or how many participants had particular counts.

What would a confidence interval add?

In general, a confidence interval expresses uncertainty around an estimated quantity. For a group mean, it can indicate a range of values compatible with the data and the method used to construct the interval. For a difference between means, it can show both the estimated contrast and its precision. A narrow interval is generally more precise than a wide interval, while an interval that includes no difference would not, on its own, establish that groups are equivalent. No confidence interval for the primary outcome is reported in the registry record, so precision cannot be assessed from the posted results.

Why does the observational design matter?

In general, random allocation helps balance both measured and unmeasured participant characteristics between treatment groups. In an observational study, treatment choice is not assigned at random unless the record says otherwise. Here, allocation is not stated, and the record describes different protocol combinations rather than a like-for-like control. Group comparisons can therefore reflect differences in protocol components or participant characteristics, as well as any contribution from the biosimilar. The registry record does not report an adjusted analysis that would address such differences.

How should a count outcome be considered?

Oocyte retrieval is a count outcome, so individual values are whole-number counts and may have a skewed distribution. In general, counts can show over-dispersion: the variability may be greater than expected under a simple model that assumes a particular relationship between the mean and variance. Over-dispersion matters because a statistical model that understates variation can produce uncertainty estimates that are too small. The registry record reports a mean and standard deviation for the endpoint but does not report the statistical model, distributional assumptions, or diagnostic checks used in analysis. It is therefore not possible to determine from the record whether over-dispersion was assessed or how it was handled.

What does the analysis population represent?

The endpoint analysis excluded participants whose ovarian stimulation was not completed and who had no oocytes retrieved because of lack of efficacy. In general, an analysis limited to participants with an observed retrieval outcome describes that selected group, rather than all participants who began a treatment strategy. Such exclusions can affect interpretation if the excluded participants differ systematically from those who proceeded to retrieval. The record gives exclusion and analysed counts for the protocol groups, but does not report additional missing-data methods or sensitivity analyses.

What can be said about statistical significance?

A p-value, in general, measures how incompatible the observed data are with a specified null hypothesis under a statistical model. It does not measure the probability that a treatment is effective, nor does it convey the size or practical importance of a difference. The registry record does not report p-values for the primary endpoint, and it does not state which hypotheses or comparisons were tested. Statistical significance therefore cannot be assessed from the posted results.

What does the planning illustration describe?

In general, sample-size planning asks how many participants would be needed to detect a chosen effect under stated assumptions. The planning illustration associated with this study uses a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation; its target effect is expressed as a fraction of an observed effect. For continuous outcomes, the illustration is expressed as participants per arm for a stated power level. These calculations are planning illustrations, not observed power, and do not establish that the study had a particular probability of detecting an effect. The registry record does not report its own sample-size justification. Numerical planning results are not reported in the registry record.

The assumptions describe a generic two-arm calculation, whereas the study itself is observational and includes several protocol descriptions. A planning calculation cannot correct for confounding, make protocol groups comparable, or replace a clearly specified analysis. The registry record does not report whether such planning assumptions guided the study.

Why are multiple outcomes and analyses relevant?

The record lists 5 outcome measures and 9 analyses. In general, testing multiple outcomes or comparisons creates multiple opportunities to observe apparently noteworthy results by chance. Multiplicity methods can control or describe that issue, but the suitable approach depends on the planned hypotheses and analysis strategy. The registry record does not report a multiplicity adjustment, a hierarchy of outcomes, or which analyses were primary versus exploratory beyond the stated primary endpoint. The number of listed measures and analyses alone does not establish how multiplicity was addressed.

Because numerical endpoint results and a detailed statistical analysis plan are not reported in the registry record, the available information supports description of the intended summaries and study structure, but not independent verification of effect estimates, uncertainty, model fit or statistical conclusions.

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("Mixed Protocols: Recombinant and Urinary-derived G", "Monoprotocols: Follitropin Alpha Biosimilar Only a", "Monoprotocols: Follitropin Alpha Biosimilar Only a", "Monoprotocols: Follitropin Alpha Biosimilar Only a", "The Overall Protocols")
n   <- c(2547, 2770, 2124, 646, 5317)
m   <- c(8.6, 10.3, 10.5, 9.6, 9.5)
sp  <- c(6.8, 7.4, 7.5, 7, 7.2)
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  Mixed Protocols: Recombinant and Urinary-derived G  2547  8.600  6.800  8.336  8.864
CARM  Monoprotocols: Follitropin Alpha Biosimilar Only a  2770  10.300  7.400  10.024  10.576
CARM  Monoprotocols: Follitropin Alpha Biosimilar Only a  2124  10.500  7.500  10.181  10.819
CARM  Monoprotocols: Follitropin Alpha Biosimilar Only a  646  9.600  7.000  9.059  10.141
CARM  The Overall Protocols  5317  9.500  7.200  9.306  9.694

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 5 outcome measures and 9 analyses. It identifies the number of oocytes retrieved as the primary outcome and lists mature oocytes, fertilized oocytes and total dose of follitropin alpha biosimilar as secondary outcomes. It does not report a hierarchy for the analyses, a multiplicity adjustment, or the full set of comparisons planned. The consequences of testing multiple outcomes or groups therefore cannot be assessed from the record.

For the primary endpoint, the record states that participants who did not complete ovarian stimulation and had no oocytes retrieved because of lack of efficacy were not included in the analysed population. The mixed protocol population was 2625, with 78 described as having lack of efficacy and 2547 analysed. The combined monotherapy population was 2859, with 89 described as having lack of efficacy and 2770 analysed. Within monotherapy, the antagonist group was 2183, with 59 described as having lack of efficacy and 2124 analysed; the agonist group was 676, with 30 described as having lack of efficacy and 646 analysed.

These exclusions mean the primary outcome summaries concern the analysed participants who reached the relevant retrieval outcome, rather than all participants initially listed in those protocol populations. The registry record does not report whether there were other missing observations, how any such observations were handled, or whether sensitivity analyses were conducted. It also does not describe an intention-to-treat analysis or other analysis population definitions. The implications of missingness beyond the stated exclusions are not reported in the registry record.

Because the reported protocol groups include a combined monotherapy group and its antagonist and agonist components, they should not be treated as entirely separate, independent cohorts in every interpretation. The record does not report a detailed statistical plan explaining how overlap or multiple comparisons were handled.

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 record lists 5484 participants at risk for serious adverse events and 0 affected by a serious adverse event. For other adverse events, it lists 5484 at risk and 657 affected. No serious adverse-event terms are listed.

These are registry counts for the overall protocols. They describe the number of participants recorded as affected, not the total number of event episodes. The record does not report the definitions used for serious and other adverse events, how events were collected, the observation period for safety, or how causality was assessed. It also does not provide detailed descriptions of the 657 other adverse events.

The serious-event count of 0 means no serious adverse events are recorded in this registry entry. It does not establish that the risk of serious events is absent, and it does not show whether safety monitoring captured every event. Similarly, the other-event count does not by itself indicate severity, relationship to treatment or differences between protocol groups. No arm-specific safety results are reported in the registry record, so safety cannot be compared across the listed protocols using these figures alone.

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

The study is relevant as a record of real-world use of follitropin alpha biosimilar during ovarian stimulation across monotherapy and mixed protocols. It reports enrollment of 5484 and defines the primary endpoint as the mean number of oocytes retrieved. It also records exclusions from the endpoint analysis for lack of efficacy and gives analysed populations for the described protocol groups.

However, the registry record does not report numerical results for the primary outcome or secondary outcomes. It therefore does not show the observed number of oocytes retrieved, the variability among participants, or the size and precision of differences between protocol groups. Without those results, the direction or magnitude of any difference cannot be described. The record also does not provide inferential statistics such as confidence intervals or p-values for the primary endpoint.

The observational design limits causal interpretation. The treatment groups represent different combinations of gonadotropins and GnRH antagonists or agonists, and allocation is not stated. A comparison among those groups would not isolate the biosimilar’s contribution unless differences in treatment and participant characteristics were appropriately addressed. The registry record does not describe an adjusted analysis or a randomized control comparison.

The endpoint analysis excludes participants who did not complete stimulation and had no oocytes retrieved because of lack of efficacy. As a result, the analysed outcome summaries, if available, would describe the participants included in those analyses rather than everyone enrolled. This matters when interpreting an outcome focused on retrieval, because not reaching retrieval is part of the treatment experience but is not represented in the analysed endpoint population described by the record.

The safety counts report 0 serious adverse events and 657 other adverse events among 5484 participants at risk in each category. The record does not provide detailed event terms, methods of collection or causal attribution. These counts are informative as registry entries but do not establish complete safety characterization.

In short, the record describes a study question, treatment protocols, endpoint definitions, selected analysis populations and overall adverse-event counts. It does not report the results needed to judge the size or precision of outcome differences, nor does its observational structure support a causal conclusion from protocol-group comparisons.

14. Why This Trial Matters Statistically

This study illustrates why registry design details and outcome results need to be read together. The record identifies a clinically relevant real-world question about oocyte retrieval under ovarian stimulation protocols that include follitropin alpha biosimilar. It also makes clear that treatment occurred in different combinations, including biosimilar monotherapy and mixed gonadotropin protocols, with GnRH antagonists or agonists. Those distinctions are important for statistical interpretation because they define what is being compared.

The analysis population is another key feature. The record excludes participants who did not complete stimulation and had no oocytes retrieved because of lack of efficacy. This makes the endpoint summary conditional on reaching retrieval. An analysis that excludes such participants answers a different question from one that includes everyone who entered a protocol. Reporting the group populations and exclusions allows readers to recognize that distinction, even though the registry record does not provide all details of missing-data handling.

The study also highlights the difference between describing an endpoint and reporting its estimate. A mean and standard deviation are appropriate descriptive quantities to identify for a continuous summary, but without the actual values, confidence intervals or comparisons, readers cannot evaluate the observed response or its precision. Registration information alone does not substitute for numerical outcome results.

Finally, the observational design is central. Without stated random allocation or a like-for-like control, differences among protocol groups may reflect treatment combinations or other participant differences. Statistical adjustment, if used, could help address measured differences, but its use is not reported in the registry record. The study is therefore valuable for understanding how a real-world question was framed and which populations were described, while the available record does not support a causal estimate or a quantitative conclusion about outcomes.

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.

The most important limitation for interpretation is that the registry record does not report numerical results for the primary or secondary outcomes. The stated primary endpoint is the number of oocytes retrieved, but group means, standard deviations and estimates of between-group differences are not reported. Confidence intervals, p-values and other measures of uncertainty are also not reported in the registry record. This prevents assessment of effect magnitude and precision.

The study is observational, allocation is not stated, and the registry description says the protocol groups are not a like-for-like control comparison. The groups differ in their treatment combinations, including monotherapy versus mixed protocols and use of GnRH antagonists or agonists. Participant characteristics and treatment-selection factors that might influence outcomes are not reported in the registry record. An adjusted statistical analysis is not described.

The primary analysis excludes participants whose stimulation was not completed and who had no oocytes retrieved because of lack of efficacy. The registry record gives counts for these exclusions, but does not report additional missing-data methods or sensitivity analyses. The analysed populations therefore should not be assumed to represent all enrolled participants for the endpoint.

The record lists 5 outcome measures and 9 analyses, but does not report the detailed statistical plan, how multiple outcomes or comparisons were handled, or which analyses beyond the primary endpoint were prespecified. It does not report a sample-size justification. The planning assumptions associated with an illustration do not substitute for a stated study design rationale, and numerical planning results are not reported in the registry record.

For safety, overall counts are listed, but event definitions, ascertainment methods, timing, detailed terms and causal attribution are not reported in the registry record. Arm-specific safety results are not reported. These limitations restrict both efficacy interpretation and the completeness of safety assessment.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: An Observational Study of Follitropin Alpha Biosimilar: the Real-world Data — NCT04854707.
• Registry record last updated 2021-10-22; status last verified 2021-09.
• Results first posted 2021-10-22.
• 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.

19. Record Summary

NCT04854707 is an observational study sponsored by IVFarma LLC, listed as completed with enrollment of 5484. The registry record gives a start date of 2020-01-12 and a primary completion date of 2020-12-20. The stated aim was to investigate follitropin alpha biosimilar therapy in a nonselected real-world population.

The primary outcome was the mean number of oocytes retrieved. Protocol descriptions include biosimilar monotherapy and mixed protocols with recombinant and urinary-derived gonadotropins, alongside GnRH antagonists or agonists. The record lists 5 outcome measures and 9 analyses and describes analysed populations after exclusions for lack of efficacy.

The registry record does not report numerical primary or secondary outcome results, confidence intervals, p-values, a detailed statistical plan or a sample-size justification. Overall safety entries list 0 serious adverse events and 657 other adverse events among 5484 participants at risk for each category. The observational design and lack of a stated like-for-like control comparison limit causal interpretation.