Low-dose Gonal-f® in Ovulation Induction: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Low-dose Gonal-f® in Ovulation Induction (NCT01871532), a randomized phase 4 study. The primary outcome is Percentage of Cycles With Monofollicular Development.

2. Clinical Question

The study asked whether two dose-tailoring approaches using Gonal-f® could be compared on monofollicular development during ovulation induction. The registry describes a prospective, multicentre, open-label, randomized, parallel-group study in women with chronic anovulation who had previously failed to conceive with clomifene treatment. It identifies the population as WHO Type 2 anovulatory subjects.

The question is about a cycle-level follicular development outcome, not a direct comparison of pregnancy or live birth. The registry lists several secondary outcomes, including ovulatory cycles, clinical pregnancy, and multifollicular development, but it does not report their results. Because the primary endpoint was not assessed, the posted record cannot answer whether one protocol produced a different monofollicular development rate from the other.

3. Trial Design

This was a Phase IV, randomized, parallel-group, interventional study with two arms. It was described as prospective, multicentre, comparative, and open-label. Open-label means participants and study personnel were not masked to assigned treatment; the registry lists masking as none. The study compared two Gonal-f® dose protocols rather than Gonal-f® with an untreated or placebo group.

The low-dose protocol began with daily subcutaneous Gonal-f® at 50 IU for Week 1. For subjects with minimal response, the dose was gradually increased by 12.5 IU for two weeks, followed by a final increase of 25 IU, up to a maximum dose of 100 IU, until Week 4. The standard low-dose protocol also began with 50 IU daily for Week 1 and then increased by 12.5 IU for two weeks, up to a maximum dose of 125 IU, until Week 4 for subjects with minimal response. The registry descriptions continue with text about what happened after adequate follicular development, but those descriptions are incomplete in the registry record. Further details of the treatment procedures are not reported in the registry record.

The registry reports enrollment of 24 participants and a status of terminated. The study was terminated early because of a delay in providing additional study drug following a batch recall. The primary completion date is recorded as 2014-03, and the start date as 2013-07. The primary outcome timeframe was baseline up to 4 weeks, but the registry states that the outcome was not assessed because of early termination.

Random assignment is intended, in general, to reduce systematic differences between treatment groups at the time of assignment. It does not guarantee that groups will be alike in every characteristic, especially when the number of participants is limited. The record does not report the randomization sequence method, allocation concealment procedure, or further design details. It also does not report a protocol-level 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: Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall.

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.

Population: Intent-to-Treat (ITT) included all subjects randomized and that had received at least 1 Gonal-f injection and had number of follicles measured at any point.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Cycles With Monofollicular Development, measured over Baseline up to 4 weeks.

The primary endpoint was the percentage of cycles with monofollicular development, assessed from baseline up to 4 weeks. The registry defines a qualifying cycle as one with only one follicle greater than or equal to 17 mm and no other follicles greater than or equal to 14 mm following up to 4 weeks of Gonal-f® treatment. This definition distinguishes development of a single follicle meeting the stated size threshold from cycles with additional follicles meeting the second threshold.

In general, follicular development measures can describe the ovarian response to ovulation induction. A monofollicular outcome focuses on development meeting a specific single-follicle definition, while the registry's secondary outcomes separately include bifollicular and multifollicular development. The endpoint is expressed as a percentage of cycles, rather than as a continuous measurement of follicle size or as a participant-level pregnancy outcome. That distinction matters when interpreting the unit of analysis: a cycle-level percentage describes the share of cycles that meet the definition, not necessarily the share of participants.

The record states that this outcome was not assessed because the study was terminated early after a delay in providing additional study drug following a batch recall. It therefore contains no observed primary endpoint percentage or arm-to-arm estimate. The registry record does not report endpoint results, uncertainty intervals, or an inferential test for this outcome. The endpoint's clinical relevance does not substitute for an observed comparison; without the measurements, the posted record cannot establish how either protocol performed on the defined outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

In general, randomization assigns participants to treatment groups by chance. Its purpose is to make systematic differences between groups less likely at the start of a study, including differences that investigators may not have measured. Randomization does not ensure identical groups, and it does not correct problems that arise after assignment, such as incomplete outcome collection or differences in follow-up. The registry identifies this study as randomized but does not report how the random sequence was generated or how assignments were concealed before enrollment.

The parallel-group structure means that participants were assigned to one of the two Gonal-f® protocols rather than crossing from one protocol to the other as part of the design described in the record. The record also labels the study open-label and lists masking as none. In general, lack of masking can affect participant or investigator behavior and may influence outcome assessment, particularly when assessment involves judgment. It does not establish that such influence occurred in this study. The registry does not report additional procedures used to standardize or independently assess outcomes.

What does the primary endpoint measure?

The endpoint is a percentage of cycles meeting the registry's monofollicular development definition during baseline up to 4 weeks. The definition requires one follicle at least 17 mm and no other follicles at least 14 mm after up to 4 weeks of treatment. A percentage requires a numerator, the cycles meeting the definition, and a denominator, the cycles considered for assessment. Neither the outcome percentages nor those underlying counts are reported. The registry states that the outcome was not assessed because the study ended early after a delay in providing additional study drug following a batch recall.

In general, a cycle-level endpoint and a participant-level endpoint answer different questions. One participant may contribute more than one cycle, depending on the protocol and study conduct. The record does not state the number of cycles per participant or give an analysis approach accounting for any repeated cycles. It would therefore be inappropriate to assume that every participant contributed exactly one cycle or that the cycle outcomes were statistically independent.

How should estimates and uncertainty be understood?

In general, an estimate summarizes the observed data, while a confidence interval describes the range of values compatible with the data under the assumptions of the statistical method. A narrower interval indicates greater precision than a wider interval, although an interval does not resolve possible bias, missing outcomes, or limitations of the design. A significance test addresses compatibility with a specified null hypothesis under its assumptions; it does not measure the size or clinical importance of an effect. No primary outcome estimate, confidence interval, or statistical test is reported in the registry record, so these interpretive tools cannot be applied to the primary comparison.

The registry describes planning illustrations using a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation, with the effect to detect stated as a fraction of the observed effect. These are described as planning illustrations and not as the study's own design. The record does not provide the original sample-size justification. In general, planning calculations depend on an assumed effect and variability; they do not show the probability that a completed study found a true effect, and they are not a substitute for the observed estimate and its uncertainty. Since the primary outcome was not assessed, there is no posted primary effect estimate to interpret as an observed result.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variability is greater than a statistical model expects. For count or proportion outcomes, unaccounted extra variability can make standard errors too small and confidence intervals too narrow, giving an overly confident impression. Methods that allow for over-dispersion can produce more appropriate uncertainty estimates when the model's assumptions otherwise understate variability. This is a general statistical consideration, not a reported analysis feature of this study. The registry does not report a model, a dispersion assessment, or an adjustment for clustering or repeated cycles.

What analysis choices are not documented?

The registry record does not report the statistical analysis plan, the primary comparison method, covariate adjustment, the handling of protocol deviations, or the definition of an analysis population. It also does not report interim analyses or stopping rules. Because the trial ended early for a drug-supply delay following a batch recall, readers should distinguish that stated operational reason from a statistical stopping decision; the registry does not identify the termination as being based on interim efficacy or safety analyses. The analysis details needed to assess the impact of early termination are not reported in the registry record.

The registry gives no primary results and records 0 analyses. That limits statistical interpretation more fundamentally than a choice between alternative models: there is no posted primary outcome dataset or estimate to which a model could be applied. Any general description of statistical methods must therefore remain separate from claims about what this trial found.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures, including the primary percentage of cycles with monofollicular development and secondary outcomes concerning bifollicular and multifollicular development, ovulatory cycles, hCG administration, clinical pregnancy, multiple pregnancy, fetuses, and miscarriages after confirmation of clinical pregnancy. The number of analyses recorded is 0, and no outcome results are posted. The registry record does not report a multiplicity plan, such as a hierarchy among outcomes or an adjustment for multiple statistical tests.

In general, examining several outcomes can increase the chance of at least one apparently unusual result if each is tested separately without accounting for the number of tests. Prespecified priorities or appropriate adjustments can help clarify which findings are confirmatory and which are exploratory. Since the record contains no reported analyses, there are no posted tests to evaluate for multiplicity, and no adjustment should be inferred.

The record states that the primary outcome was not assessed because of early termination following a delay in providing additional study drug after a batch recall. This is different from reporting a measured outcome with some missing participant values. The record does not describe participant-level missingness, exclusions, or imputation. It also does not identify an intention-to-treat, per-protocol, or other analysis population. These analysis-population definitions and missing-data procedures are not reported in the registry record.

In general, missing outcome information can affect both precision and the interpretation of a comparison, especially if the availability of measurements differs between groups or is related to participant outcomes. The record does not provide enough detail to assess such patterns. No assumptions about how unobserved outcomes were handled can be made from the posted information.

11. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: abortion spontaneous (8.3%).

The registry safety records list 12 participants at risk in each arm. In the Low Dose Gonal-f group, 0 participants are listed with a serious adverse event and 2 with other adverse events. In the Standard Low Dose Gonal-f group, 1 participant is listed with a serious adverse event and 3 with other adverse events. These are participant counts in the adverse-event record; they are not the primary efficacy outcome and do not establish a comparative treatment effect.

The registry lists Abortion spontaneous as a top serious adverse event term, with 8.3%. That term-level entry is reported without enough accompanying detail to assign it to a specific arm or to understand its full context. The death counts are not reported in the registry record. The adverse-event summary does not provide event timing, severity beyond the serious-versus-other categories, relatedness assessment, or detailed descriptions of the other adverse events. Those details are not reported in the registry record.

In general, adverse-event counts describe events recorded during the specified safety collection, but interpretation depends on the definitions, follow-up period, exposure, and completeness of reporting. The record's at-risk counts should not be treated as the denominator for the primary endpoint. The early termination was attributed to delayed provision of additional study drug following a batch recall; the registry does not state that the study was terminated because of the adverse-event counts.

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

The registry record establishes that a randomized, open-label, parallel-group study was planned and conducted to compare two Gonal-f® dose-tailoring protocols in women with chronic WHO Type 2 anovulation who had previously failed to conceive with clomifene. It identifies monofollicular development as the primary outcome and defines the follicle-size criteria used to classify a cycle. It also records enrollment of 24 participants and describes the reason for early termination.

What the record does not establish is how often monofollicular development occurred in either arm, or whether the protocols differed on that outcome. The primary endpoint was not assessed, and no primary estimate, confidence interval, or statistical test is reported. Secondary outcome results are also not reported. Therefore, the posted information does not establish a benefit, lack of benefit, or equivalence between the protocols. The absence of a result should not be read as a finding of no difference.

The safety entries provide limited descriptive counts: 0 serious adverse events and 2 other adverse events in the Low Dose Gonal-f group, compared with 1 serious adverse event and 3 other adverse events in the Standard Low Dose Gonal-f group. These counts are not a complete safety profile, and the registry's serious-event term entry does not provide enough context to attribute that term to an arm. Death counts and several details needed for a fuller safety interpretation are not reported in the registry record.

In general, a randomized design can support a comparative estimate when outcomes are collected and analyzed appropriately. It cannot compensate for an unmeasured primary outcome, and the design label alone does not demonstrate that the results would be precise. The reported enrollment and termination explain why the record is limited, but they do not reveal what the unobserved outcome values would have been. Accordingly, the sound conclusion is descriptive: the registry records the study question, design, early termination, and limited safety counts, but it does not contain the primary efficacy result.

13. Why This Trial Matters Statistically

This study illustrates a central distinction in clinical-trial interpretation: a well-defined research question is not the same as an answer to that question. The registry specifies a randomized comparison and gives an operational definition for monofollicular development. Yet the primary outcome was not assessed, so the record offers no direct evidence about the comparative endpoint. Statistical interpretation must begin with whether the outcome was observed, before considering which model, test, or interval might be appropriate.

The early termination is also important to distinguish from statistical stopping. The registry attributes termination to a delay in providing additional study drug following a batch recall. It does not report an interim efficacy analysis or a statistical stopping rule. This distinction matters because the reason a trial ends affects how readers understand the missing results; an operational interruption should not be recast as a finding about treatment effects.

The record also demonstrates why analysis populations, outcome denominators, and missing-data procedures matter. Enrollment of 24 and safety counts for 12 participants in each arm do not disclose how many outcome cycles were measured, whether follow-up was complete, or which participants entered an efficacy analysis. The absence of those details cannot be repaired by deriving percentages from unrelated safety counts.

Finally, the registry lists a range of secondary outcomes, but no analysis entries or outcome results. In general, multiple outcomes require clarity about priorities and multiplicity, while early termination can make an intended comparison incomplete. Neither an assumed sample-size calculation nor a design label can replace observed estimates and their uncertainty. The statistical significance of this record lies in what it makes explicit: a precise endpoint definition and a randomized design are useful, but the missing primary outcome sharply limits what can be concluded.

14. 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 principal limitation is that the primary endpoint was not assessed. The registry attributes this to early termination after a delay in providing additional study drug following a batch recall. Without endpoint observations, there is no reported comparison of monofollicular development and no estimate of its precision. The registry also contains no results for the listed secondary outcomes.

Enrollment was 24, and the record does not report the number of cycles assessed or the endpoint denominator in either arm. Because the primary outcome is defined per cycle, the absence of cycle counts and any account of repeated cycles prevents assessment of how the outcome data would have been structured. The record does not identify an analysis population or explain how participants with incomplete treatment or follow-up would have been handled.

The study was open-label, with no masking reported. In general, this can be relevant to participant behavior, treatment decisions, and outcome assessment, though the registry does not establish that any such bias occurred. Details of random sequence generation and allocation concealment are also not reported in the registry record. Treatment descriptions are incomplete after the text about adequate follicular development, so the full protocol cannot be reconstructed from the registry description.

The statistical analysis plan, sample-size justification, interim analyses, stopping rules, multiplicity procedures, model specifications, and missing-data methods are not reported in the registry record. The safety information is limited to the posted event counts and one serious-event term with a percentage; the record does not give enough context to assign that term to an arm or assess the full safety experience. These limitations mean that the available information is useful for describing the intended comparison and the reason for termination, but not for estimating comparative efficacy or drawing a comprehensive safety conclusion.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Low-dose Gonal-f® in Ovulation Induction — NCT01871532.
• Registry record last updated 2016-08-11; status last verified 2016-06.
• Results first posted 2016-08-11.
• 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.

18. Record Summary

NCT01871532 records a Phase IV, randomized, open-label, parallel-group study of two Gonal-f® dose-tailoring protocols for ovulation induction. The intended population was women with chronic WHO Type 2 anovulation who had previously failed to conceive with clomifene. The study enrolled 24 participants.

The primary outcome was the percentage of cycles with monofollicular development from baseline up to 4 weeks, defined using follicle-size thresholds. The registry states that this outcome was not assessed because the study was terminated early after a delay in providing additional study drug following a batch recall. No primary or secondary outcome results are reported. Safety records list 0 serious and 2 other adverse events in the Low Dose Gonal-f group, and 1 serious and 3 other adverse events in the Standard Low Dose Gonal-f group. The registry does not provide enough detail for a complete safety interpretation. Overall, the record describes the design and reason for termination but does not provide an efficacy comparison.