This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for AS900672-Enriched in Ovulation Induction (NCT00553514), a randomized phase 2 study. The primary outcome is Percentage of Participants With Ovulation.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00553514 |
| Phase | Phase 2 |
| Condition | Ovulation Induction |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 71 |
| Arms in the primary outcome | 5 |
| Lead sponsor | Merck KGaA, Darmstadt, Germany |
| Results posted | Yes |
2. Clinical Question
Population
Oligo-anovulatory infertile women undergoing ovulation induction. The primary outcome was analyzed in the Per Protocol population: randomized participants without a medically relevant protocol deviation who were evaluable for the measure.
Intervention
AS900672-Enriched at 10, 20, 30, or 40 micrograms. The study description identifies this as an investigational long-acting follicle stimulating hormone.
Comparator
Follitropin alfa at 75 international units, identified in the trial record with the marketed name GONAL-f. Recombinant human chorionic gonadotropin was also listed as an intervention.
Primary question
What percentage of participants in each treatment group met the trial definition of ovulation? The comparison was intended to evaluate the investigational doses against the active comparator during an ovulation-induction cycle.
The registry record describes a Phase II, randomized, active-comparator, parallel-group dose-finding trial. Its central statistical question is about outcome frequency across dose groups, rather than a comparison of time until an event or change in a continuous measurement. Ovulation was assessed using a progesterone response, with clinical pregnancy also accepted as evidence when a positive progesterone response was absent.
The posted primary outcome values range from 33.3% to 53.8% across the five groups. These are observed group percentages from small analyzed samples, not precise estimates of what would occur in a larger population. The unadjusted pairwise intervals for the primary comparisons are broad and include no difference. The registry record does not report a prespecified dose-response model or an adjusted analysis that would establish a trend across the four investigational doses.
The clinical question therefore needs to be read as a comparison of observed outcomes and their uncertainty, not as a definitive ranking of treatments. The trial was terminated, and its record does not state why. The registry record also does not report a formal statistical analysis plan, a rationale for the planned sample size, or an interpretation of the findings by the sponsor.
3. Trial Design
This was a Phase II, multicentre, randomized, assessor-blinded, active-comparator, parallel-group dose-finding study. The record lists 71 participants enrolled and identifies the trial status as terminated. The listed study dates are 2007-12 for the start and 2009-03 for primary completion. The registry record does not report the reason for termination.
Five treatment groups are represented in the primary outcome results: AS900672-Enriched at 10, 20, 30, and 40 micrograms, and follitropin alfa at 75 international units. The brief summary describes comparison of four investigational doses with follitropin alfa, with ovulation rate as the focus. Recombinant human chorionic gonadotropin is also listed among the interventions. The registry record does not give further details about its use in each treatment group.
Random allocation is recorded, but the method used to generate the allocation sequence and the approach to allocation concealment are not reported in the registry record. Masking is listed as single, and the official title specifies assessor-blinding. The identity of any other masked parties is not reported. The parallel-group structure means that each participant was assigned to a treatment group rather than crossing between treatments, but further protocol details are not reported.
The primary outcome population was the Per Protocol population, defined in the record as randomized participants without a medically relevant protocol deviation. The outcome-specific participant count is the number evaluable for that measure. These analysis counts differ by outcome and are not the same as the total enrollment figure. The record does not report the reasons participants were excluded from the primary analysis or the handling of missing outcome data.
The trial also posted secondary outcomes concerning clinical pregnancy, stimulation duration, supplemental follitropin alfa treatment, and follicle counts. Results for only some of those outcomes are described in detail in the posted record. A protocol, sample-size justification, interim-analysis plan, stopping criteria, and full statistical analysis plan 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.
Overall Study
| Stage | AS900672-Enriched 10 Mcg | AS900672-Enriched 20 Mcg | AS900672-Enriched 30 Mcg | AS900672-Enriched 40 Mcg | Follitropin Alfa 75 IU |
|---|---|---|---|---|---|
| STARTED | 14 | 14 | 15 | 13 | 15 |
| COMPLETED | 6 | 6 | 9 | 6 | 8 |
| NOT COMPLETED | 8 | 8 | 6 | 7 | 7 |
Reasons for not completing this period:
| Reason | AS900672-Enriched 10 Mcg | AS900672-Enriched 20 Mcg | AS900672-Enriched 30 Mcg | AS900672-Enriched 40 Mcg | Follitropin Alfa 75 IU |
|---|---|---|---|---|---|
| Protocol deviation | 0 | 0 | 0 | 1 | 0 |
| Lack of ovarian response | 4 | 5 | 5 | 5 | 6 |
| Ovarian hyperstimulation syndrome risk | 3 | 0 | 1 | 0 | 0 |
| Risk of multiple pregnancy | 0 | 2 | 0 | 1 | 0 |
| Other | 1 | 1 | 0 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Per Protocol (PP) population included all the randomized participants who were without a medically relevant protocol deviation. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.
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.
| Characteristic | Unit | AS900672-Enriched 10 Mcg | AS900672-Enriched 20 Mcg | AS900672-Enriched 30 Mcg | AS900672-Enriched 40 Mcg | Follitropin Alfa 75 IU | Total |
|---|---|---|---|---|---|---|---|
| Participants analysed | 14 | 14 | 15 | 13 | 15 | 71 | |
| Age, Continuous | years | 29.5 (23 to 36) | 31.5 (23 to 36) | 28.0 (26 to 35) | 30.0 (23 to 36) | 30.0 (23 to 34) | 30 (23 to 36) |
| Sex: Female, Male: Female | Participants | 14 | 14 | 15 | 13 | 15 | 71 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Ovulation, measured over Mid-luteal phase progesterone assessed 5-10 days or clinical pregnancy 35-42 days after recombinant human chorionic gonadotropin (r-hCG) administration day (end of stimulation cycle [approximately 14 days]).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants with ovulation. The registry defines ovulation as a mid-luteal phase progesterone level of at least 30 nanomoles per liter, also stated as 10 nanograms per milliliter. If a positive progesterone response was absent, clinical pregnancy was also considered evidence of ovulation. The assessment was scheduled in the mid-luteal phase or at the clinical-pregnancy assessment, with timing described relative to recombinant human chorionic gonadotropin administration and the end of the stimulation cycle.
This endpoint expresses a binary outcome as a percentage: each evaluable participant either meets the definition or does not. In general, a binary endpoint can be useful when the clinical question is whether a specified event occurred, because its interpretation is tied to the proportion of participants experiencing that event. Here, the registry’s definition combines a laboratory criterion with a pregnancy-based criterion for participants without a positive progesterone response.
The endpoint is intended to capture whether ovulation occurred during the treatment cycle, rather than how long stimulation lasted or how much supplemental treatment was used. Those additional measures address different aspects of the treatment course and are secondary outcomes. The primary endpoint’s definition and timing are reported, but the registry record does not describe the laboratory assay, procedures for adjudicating borderline results, or whether outcome assessment was centrally reviewed.
Because the primary analysis is Per Protocol, the percentages describe participants who were evaluable and met the specified population criteria, rather than every randomized participant. The posted record does not provide enough detail to determine how an analysis including all randomized participants would compare.
7. Results Posted in the Registry
- AS900672-Enriched 20 Mcg: 46.2% (6/13) versus 46.2% (6/13) on control; risk difference 0.0 percentage points (95% CI -38.3 to 38.3), risk ratio 1.00 (0.44–2.29); unadjusted two-proportion z-test p = 1.000.
- AS900672-Enriched 30 Mcg: 38.5% (5/13) versus 46.2% (6/13) on control; risk difference -7.7 percentage points (95% CI -45.6 to 30.2), risk ratio 0.83 (0.34–2.06); unadjusted two-proportion z-test p = 0.691.
- AS900672-Enriched 40 Mcg: 33.3% (4/12) versus 46.2% (6/13) on control; risk difference -12.8 percentage points (95% CI -50.8 to 25.2), risk ratio 0.72 (0.27–1.95); unadjusted two-proportion z-test p = 0.513.
- Follitropin Alfa 75 IU: 53.8% (7/13) versus 46.2% (6/13) on control; risk difference 7.7 percentage points (95% CI -30.6 to 46.0), risk ratio 1.17 (0.54–2.53); unadjusted two-proportion z-test p = 0.695.
Risk difference: AS900672-Enriched 20 Mcg
95% CI: -38.3 to 38.3 percentage points
Recalculated from the posted summary statistics
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.
| Secondary outcome | Type | Effect measure | Estimate (95% CI) | Planning size, 80% power |
|---|---|---|---|---|
| Percentage of Participants With Clinical Pregnancy | Binary Endpoint | Risk difference | -23.1 pts (-46.0 to -0.2) | n/a |
| Duration of Ovarian Stimulation | Continuous Endpoint | Mean difference | 1.80 (-1.62 to 5.22) | 97 per arm |
| Duration of Supplemental Follitropin Alfa Treatment | Continuous Endpoint | Mean difference | 0.00 (-1.17 to 1.17) | n/a |
Percentage of Participants With Clinical Pregnancy
- Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
- Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
- Result:
- AS900672-Enriched 20 Mcg: 0.0% (0/13) versus 23.1% (3/13) on control; risk difference -23.1 percentage points (95% CI -46.0 to -0.2); unadjusted two-proportion z-test p = 0.066.
- AS900672-Enriched 30 Mcg: 7.7% (1/13) versus 23.1% (3/13) on control; risk difference -15.4 percentage points (95% CI -42.5 to 11.7), risk ratio 0.33 (0.04–2.80); unadjusted two-proportion z-test p = 0.277.
- Interpretation:
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AS900672-Enriched 20 Mcg and the control. The interval gives the range of effects that remain compatible with the data.
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AS900672-Enriched 30 Mcg and the control. The interval gives the range of effects that remain compatible with the data.
Duration of Ovarian 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:
- AS900672-Enriched 20 Mcg: mean 11.80 versus 10.00 on control; difference 1.80 (95% CI -1.62 to 5.22), standardized effect d = 0.40; z-test p = 0.303.
- AS900672-Enriched 30 Mcg: mean 14.00 versus 10.00 on control; difference 4.00 (95% CI 1.02 to 6.98), standardized effect d = 1.03; z-test p = 0.009.
- Interpretation:
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AS900672-Enriched 20 Mcg and the control. The interval gives the range of effects that remain compatible with the data.
- The 95% confidence interval excludes no difference, so the mean is statistically higher for AS900672-Enriched 30 Mcg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
Duration of Supplemental Follitropin Alfa Treatment
- 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:
- AS900672-Enriched 20 Mcg: mean 6.60 versus 6.60 on control; difference 0.00 (95% CI -1.17 to 1.17), standardized effect d = 0.00; z-test p = 1.000.
- AS900672-Enriched 30 Mcg: mean 7.70 versus 6.60 on control; difference 1.10 (95% CI -0.09 to 2.29), standardized effect d = 0.75; z-test p = 0.070.
- Interpretation:
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AS900672-Enriched 20 Mcg and the control. The interval gives the range of effects that remain compatible with the data.
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AS900672-Enriched 30 Mcg and the control. The interval gives the range of effects that remain compatible with the data.
The secondary outcomes cover several distinct parts of the treatment course: clinical pregnancy, duration of ovarian stimulation, duration and cumulative dose of supplemental follitropin alfa, and follicle counts in specified size categories. These outcomes are related to ovulation induction but are not interchangeable with the primary endpoint. They can provide complementary descriptions of pregnancy and treatment burden, while the primary outcome asks whether the registry definition of ovulation was met.
Across the posted secondary results, estimates vary by outcome and treatment group rather than forming a uniform pattern that mirrors the primary percentages. The record therefore does not support a single broad conclusion from the secondary outcomes. Some outcomes have small group counts, and not every outcome has a full set of posted pairwise comparisons. Five secondary outcomes are listed, but detailed numerical results are posted for only some of them.
Unadjusted secondary results carry less weight because multiple endpoints and treatment comparisons create more opportunities for apparently notable findings to arise by chance. The registry record does not report a multiplicity strategy that would control this issue. In addition, secondary measures may be based on different evaluable subsets and assessment windows. Their results should therefore be read as supporting descriptions, not as independent confirmation of the primary result.
As a general statistical point, a coherent pattern across outcomes can sometimes strengthen interpretation when it is anticipated and assessed using a prespecified plan. The record does not report such a plan for integrating these endpoints. Nor does it report a model linking pregnancy, duration, supplemental treatment, follicle counts, and the primary ovulation outcome. The secondary results are informative about what was measured, but they do not resolve the imprecision of the primary comparisons or establish a dose-response relationship.
Secondary outcomes registered for this trial, for reference (only those above were recalculated):
- Percentage of Participants With Clinical Pregnancy
- Duration of Ovarian Stimulation
- Duration of Supplemental Follitropin Alfa Treatment
- Cumulative Dose of Supplemental Follitropin Alfa Administered
- Number of Follicles With Mean Diameter Less Than (<) 11 Millimeter (mm) and Greater Than or Equal to (>=) 11 mm
9. Statistical Interpretation
In the primary Per Protocol results, the observed ovulation percentages were 46.2% for AS900672-Enriched 10 micrograms, 46.2% for 20 micrograms, 38.5% for 30 micrograms, 33.3% for 40 micrograms, and 53.8% for follitropin alfa 75 international units. The analyzed group sizes were 13, 13, 13, 12, and 13, respectively. These small groups mean that each participant’s outcome has a substantial influence on the displayed percentage.
The posted unadjusted comparisons do not establish a clear difference in ovulation between an investigational dose and the active comparator. The risk-difference confidence intervals for these primary comparisons include zero, and the unadjusted p-values are 1.0 for 20 micrograms, 0.691 for 30 micrograms, 0.513 for 40 micrograms, and 0.695 for follitropin alfa relative to the designated 10-microgram group. These comparisons should not be treated as adjusted evidence or as a complete dose-response analysis: no multiplicity adjustment or formal dose-trend analysis is reported in the registry record.
The observed percentages do not increase with increasing investigational dose. That descriptive pattern alone does not demonstrate a true inverse relationship or rule out a dose-related effect; the estimates are imprecise and the groups are small. The record does not report a prespecified statistical model for assessing dose response.
The trial also posted outcomes related to clinical pregnancy and treatment duration. These measures add context but do not replace the primary outcome. They involve their own definitions, participant counts, and comparisons, and the record does not report a multiplicity plan for interpreting the collection of outcomes. Accordingly, isolated secondary p-values should be viewed as exploratory rather than as independent confirmation.
The trial’s terminated status is relevant to context, but the reason is not reported in the registry record. It should not be inferred from the outcome estimates. Nor do the results establish why termination occurred, whether it affected follow-up, or whether the observed estimates were the intended basis for a final decision. The posted results describe the measured outcomes in the analyzed groups; they do not by themselves establish comparative clinical benefit or lack of benefit.
10. Statistical Methods Explained
The primary outcome is binary, so the posted group summaries are percentages with ovulation. The primary comparisons use risk differences: the percentage in one group minus the percentage in the other, expressed on the probability scale. A risk difference of zero corresponds to equal observed proportions. The registry comparisons are unadjusted pairwise comparisons; no multiplicity-adjusted results are reported.
What does a confidence interval describe?
As a general statistical explanation, a confidence interval describes a range of values compatible with the observed data under the method used to construct it. It conveys uncertainty about an estimated contrast; it is not a range containing a fixed proportion of individual participants’ outcomes. Wider intervals indicate less precision. For the primary comparisons, the intervals are broad and include zero, so the posted data are compatible with both directions of difference as well as no difference. This is not proof that the groups are equivalent.
How should p-values be read?
As a general explanation, a p-value measures how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the test assumptions were true. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The posted p-values are unadjusted. Since several doses and outcomes are considered, the registry record’s lack of a reported multiplicity procedure limits how strongly isolated p-values can be interpreted.
How are the continuous outcomes summarized?
For duration of ovarian stimulation and duration of supplemental follitropin alfa treatment, the registry reports group means and standard deviations. A mean is a measure of the group’s central value; the standard deviation describes variation among participant measurements. Mean differences compare the reported group averages. As a general statistical point, a mean difference is most informative when interpreted alongside its uncertainty interval and the measurement scale. It does not show the distribution of individual observations, and a mean can conceal skewness or unusual values.
The posted mean-difference comparisons use unadjusted intervals and p-values. The record does not report a model adjusting for covariates, a distributional assessment, or a planned analysis of repeated measurements. The primary outcome is binary, so the continuous-outcome methods should not be read as a substitute for the primary risk-difference comparisons.
Why can small groups produce uncertain estimates?
As a general statistical explanation, estimates based on few participants can change noticeably when one or a small number of outcomes differ. This is especially relevant for percentages, where the numerator is a count of participants meeting the definition and the denominator is the evaluable group. The primary groups contain 12 or 13 evaluable participants each. Their percentages are therefore descriptive estimates with limited precision, even when displayed to one decimal place.
What do the planning illustrations mean?
The registry record includes planning illustrations based on observed effects for selected comparisons. These are prospective sample-size illustrations, not observed power and not evidence that the trial was designed with those sample sizes. They use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the assumed effect is a stated fraction of the observed effect. The illustrations are expressed as participants per arm for 80% power and participants per arm for 90% power. They should be treated cautiously because an effect estimated from a small trial can be unstable, and planning from that estimate does not show that the observed trial had adequate power.
The record does not report the trial’s own sample-size assumptions or justification. It also does not report whether the design included interim analyses, how any stopping decision was made, or which analysis methods were prespecified. These omissions matter because they prevent a reader from distinguishing the original design choices from analyses that may have been added later.
What is not established by these methods?
Randomization supports comparisons between assigned groups, but it does not remove uncertainty from small samples or resolve incomplete outcome information. The Per Protocol analysis excludes randomized participants with medically relevant protocol deviations by definition. The registry record does not report a corresponding intention-to-treat primary analysis, imputation methods, sensitivity analyses, or detailed reasons for non-evaluability. Statistical interpretation is therefore limited to the populations and analyses actually described in the posted results.
11. Confidence Intervals and Precision
The primary percentages are based on small Per Protocol groups, with 12 or 13 evaluable participants in each arm. The observed values are consequently sensitive to a small number of participant outcomes. Reporting a percentage to one decimal place does not make the underlying estimate precise.
The posted primary risk-difference intervals are broad and include zero for each comparison. This means the data do not pin down the direction or magnitude of the difference with much precision. The intervals are compatible with potentially meaningful differences in either direction, as well as little or no difference. They should not be interpreted as evidence of equivalence: an equivalence conclusion would require a prespecified margin and an appropriate design and analysis, neither of which is reported in the registry record.
Confidence intervals are also relevant for the secondary continuous outcomes. For example, the stimulation-duration comparison between the 30-microgram group and the 10-microgram group has an interval that excludes zero, while other reported comparisons have intervals that include zero. This is an unadjusted secondary comparison in a trial with multiple treatment groups and outcomes; it does not establish a general effect across outcomes or doses. The registry record does not report multiplicity control.
As a general statistical point, interval width depends on the amount of information in the data and on the variability of the outcome. Small analyzed groups typically yield less precise estimates than larger groups, although the exact precision also depends on the observed data and analysis method. The registry record does not provide adjusted confidence intervals or a prespecified clinically important difference for the primary outcome. Thus, the observed estimates can be described, but the precision is insufficient to support a confident ranking of the treatments.
12. Multiplicity, Missing Data and Analysis Populations
The trial has several treatment groups, a primary outcome, and multiple secondary outcomes. Comparing several doses with a reference group creates multiple opportunities for apparently unusual results. The registry record does not report whether the sponsor planned a hierarchy of hypotheses, a family-wise error procedure, a false-discovery approach, or another method for handling multiplicity. The posted pairwise p-values are unadjusted and should be interpreted with that limitation in mind.
The registry record identifies the primary analysis population as Per Protocol: randomized participants without a medically relevant protocol deviation who were evaluable for the measure. This definition is important because excluding participants after randomization can affect how well the comparison preserves the protection offered by random allocation. The record does not report a parallel intention-to-treat analysis or explain how participants with protocol deviations were handled in other analyses.
Missing-data methods are not reported in the registry record. The record does not describe how missing progesterone results, unavailable pregnancy assessments, or other incomplete measurements were classified, nor whether imputation or sensitivity analyses were used. It is also not reported whether missingness differed between groups. Without those details, the observed percentages should be understood as results among the participants evaluable for the outcome, not as estimates adjusted for all randomized participants.
The record does not report a detailed analysis plan, interim analyses, stopping rules, or the reasons for termination. These omissions constrain interpretation of whether the analyses were prespecified, whether decisions during the trial affected the evidence, or whether incomplete follow-up could have influenced the posted results. They do not invalidate the reported observations, but they limit what can be concluded about the full trial process.
13. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| AS900672-Enriched 10 Mcg | 0 | 14 | 0.0% |
| AS900672-Enriched 20 Mcg | 0 | 14 | 0.0% |
| AS900672-Enriched 30 Mcg | 0 | 15 | 0.0% |
| AS900672-Enriched 40 Mcg | 0 | 13 | 0.0% |
| Follitropin Alfa 75 IU | 0 | 15 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| AS900672-Enriched 10 Mcg | 7 of 14 |
| AS900672-Enriched 20 Mcg | 3 of 14 |
| AS900672-Enriched 30 Mcg | 6 of 15 |
| AS900672-Enriched 40 Mcg | 4 of 13 |
| Follitropin Alfa 75 IU | 7 of 15 |
Most frequent non-serious adverse event terms
| Event term | Organ system | AS900672-Enriched 10 Mcg | AS900672-Enriched 20 Mcg | AS900672-Enriched 30 Mcg | AS900672-Enriched 40 Mcg | Follitropin Alfa 75 IU |
|---|---|---|---|---|---|---|
| Headache | Nervous system disorders | 2 of 14 | 1 of 14 | 3 of 15 | 3 of 13 | 2 of 15 |
| Abdominal pain | Gastrointestinal disorders | 1 of 14 | 1 of 14 | 0 of 15 | 1 of 13 | 2 of 15 |
| Abdominal distension | Gastrointestinal disorders | 1 of 14 | 1 of 14 | 0 of 15 | 1 of 13 | 0 of 15 |
| Nasopharyngitis | Infections and infestations | 0 of 14 | 1 of 14 | 0 of 15 | 1 of 13 | 1 of 15 |
| Dizziness | Nervous system disorders | 1 of 14 | 0 of 14 | 0 of 15 | 1 of 13 | 0 of 15 |
| Breast tenderness | Reproductive system and breast disorders | 0 of 14 | 1 of 14 | 1 of 15 | 0 of 13 | 0 of 15 |
| Adnexa uteri pain | Reproductive system and breast disorders | 1 of 14 | 0 of 14 | 1 of 15 | 0 of 13 | 0 of 15 |
| Vaginal pain | Reproductive system and breast disorders | 0 of 14 | 0 of 14 | 0 of 15 | 0 of 13 | 2 of 15 |
| Nausea | Gastrointestinal disorders | 1 of 14 | 1 of 14 | 0 of 15 | 0 of 13 | 0 of 15 |
| Fatigue | General disorders | 1 of 14 | 1 of 14 | 0 of 15 | 0 of 13 | 0 of 15 |
The registry reports zero serious adverse events in each of the five treatment groups. The numbers at risk for the serious-adverse-event summaries were 14, 14, 15, 13, and 15 across the listed groups. These safety denominators are not the same as the Per Protocol denominators for the primary outcome.
A zero count in a small group means that no serious adverse events were recorded among the participants included in that summary. It does not demonstrate that the true risk is zero or exclude uncommon events. The registry record lists no serious adverse-event terms. Death counts are not reported in the registry record, so no conclusion about deaths can be drawn from the displayed serious-event counts.
Other adverse events were recorded in each group, with counts ranging from 3 to 7 in the listed summaries. The record does not provide further detail in the adverse-event information, such as event types, severity, duration, or relationship to treatment. These figures alone do not support a comparative safety assessment. As a general statistical point, interpretation of safety counts depends on the number followed, time under observation, and consistent event definitions; those details are not fully reported in the registry record.
14. What the Result Does, and Does Not, Mean
The posted results describe ovulation percentages in small analyzed groups and show uncertainty around the comparisons. They do not establish that any investigational dose is superior, inferior, or equivalent to follitropin alfa on the primary outcome. The point estimates differ, but the primary comparison intervals are broad and include no difference. The data are also not sufficient to establish a dose-response pattern.
The findings should not be treated as a definitive estimate of outcomes in a broader population. The primary analysis uses the Per Protocol population, the group sizes are small, and the registry record does not report detailed missing-data methods or an intention-to-treat analysis. Differences in which participants were evaluable can matter when interpreting percentages across outcomes.
The secondary results describe additional endpoints, but they do not change the basic uncertainty in the primary comparison. Several outcomes and pairwise comparisons are involved, and no multiplicity strategy is reported. Any isolated secondary finding is therefore less conclusive than a single prespecified primary analysis would be under a clearly reported statistical plan.
The trial’s terminated status is a record fact, not an explanation of the results. The reason for termination is not reported in the registry record, so it should not be attributed to efficacy, safety, recruitment, or any other cause. The posted data also do not establish that the treatments work or do not work in clinical practice. They report outcomes observed in this trial and the precision of the available comparisons.
15. Why This Trial Matters Statistically
This trial illustrates why a dose-finding study can be statistically informative without delivering a definitive treatment ranking. Five groups allow observed outcomes to be compared across several doses and an active comparator, but the small analyzed groups leave substantial uncertainty around each percentage. A visually ordered series of point estimates would not by itself establish a dose trend, especially when the observed percentages do not rise steadily across the investigational doses.
The record also demonstrates the importance of distinguishing an outcome definition from an analysis population. Ovulation had a specified progesterone threshold and an additional pregnancy-based criterion, while the primary estimates came from evaluable participants meeting Per Protocol criteria. Both details shape what the percentages mean. Without fuller reporting of missing outcomes and protocol deviations, the analysis population cannot be connected completely to all randomized participants.
Another statistical lesson is that secondary findings require context. Multiple outcomes and dose comparisons can generate isolated results that look more compelling than the overall evidence warrants. When the registry record does not report multiplicity procedures or a full analysis plan, those results should remain exploratory in interpretation.
Finally, the planning illustrations emphasize that a sample-size calculation depends on an assumed effect. Illustrations based on the observed effect are not evidence of the trial’s original design or of observed power. When estimates come from small groups, they may be unstable inputs for planning future studies. The trial therefore offers a useful example of how effect estimates, uncertainty, analysis populations, and design transparency all contribute to responsible interpretation.
16. 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.
- Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.
The main trial-specific limitation is the small number of participants evaluable for the primary endpoint in each group. The registry reports 71 participants enrolled, while the primary outcome groups contain 12 or 13 participants each. The posted estimates are therefore imprecise, and the record does not explain all differences between enrollment and endpoint-specific analysis counts.
The primary outcome was analyzed in a Per Protocol population rather than a clearly reported all-randomized population. The registry record does not give the number or reasons for protocol deviations, the number with missing primary outcomes, or sensitivity analyses for missing data. This limits assessment of whether exclusions could have influenced the group comparisons.
The registry identifies the trial as terminated, but the reason is not reported. The record also does not report the original sample-size justification, detailed randomization or allocation-concealment procedures, a complete statistical analysis plan, interim analyses, or stopping criteria. Those gaps make it difficult to determine how the final analyses relate to the trial’s original plan.
Only some secondary outcomes have detailed results and pairwise comparisons in the record, and the multiplicity approach is not reported. Safety reporting is also limited: serious adverse-event counts are shown, but event terms are not listed and deaths are not reported. These constraints do not erase the observed results, but they narrow the conclusions that can be drawn from this trial alone.
17. Related Tutorials
18. Related Statistical Calculators
19. Sources
- ClinicalTrials.gov: AS900672-Enriched in Ovulation Induction — NCT00553514.
- Registry record last updated 2014-02-13; status last verified 2014-01.
- Results first posted 2013-07-25.
- 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.
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20. Record Summary
The registry describes a Phase II, randomized, assessor-blinded, parallel-group dose-finding trial of four AS900672-Enriched doses against follitropin alfa 75 international units in oligo-anovulatory infertile women undergoing ovulation induction. The record lists 71 participants enrolled, a start date of 2007-12, primary completion in 2009-03, and terminated status.
The primary endpoint was the percentage of participants with ovulation, defined using a mid-luteal progesterone threshold or, in its absence, clinical pregnancy as evidence. The primary results are based on small Per Protocol groups. Their unadjusted comparisons are imprecise, and the registry record does not report a formal dose-response analysis, multiplicity strategy, detailed missing-data methods, or the reason for termination.
Secondary outcomes address clinical pregnancy and treatment duration, among other measures. The posted results offer descriptive information but do not resolve the uncertainty in the primary comparisons. Serious adverse events were reported as zero in each group; deaths are not reported in the registry record.