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 Pilot Study of Denosumab in BRCA1/2 Mutation Carriers Scheduled for Risk-Reducing Salpingo-Oophorectomy (NCT03382574), a randomized early/phase 1 study. The primary outcome is Ki67 Proliferation Index Fallopian Tube Fimbrial Epithelial Cells.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03382574 |
| Phase | EARLY/Phase 1 |
| Condition | Ovarian Carcinoma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 2 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Cancer Institute (NCI) |
| Results posted | Yes |
2. Clinical Question
Population
BRCA1/2 mutation carriers scheduled for risk-reducing salpingo-oophorectomy were the intended population. The record does not report further eligibility criteria. Although the enrollment field records 2, the registry states that no participants were randomized and no data were collected.
Intervention
The planned experimental arm paired denosumab with risk-reducing salpingo-oophorectomy. Denosumab was to be given by subcutaneous injection every 4 weeks for 1-2 doses, beginning within 3 days of the menstrual cycle. Surgery was planned 14-28 days after the last dose.
Comparator
The control arm was risk-reducing salpingo-oophorectomy without study treatment beforehand. Participants in this arm were to receive no treatment for 2-8 weeks and then undergo surgery.
Primary question
The planned primary comparison concerned Ki67 expression in fallopian tube fimbrial epithelial cells between the two arms. Ki67 was to be assessed by immunohistochemistry and scored as the percentage of positive cells. Because no participants were randomized, the record reports no measurements with which to answer that question.
3. Trial Design
The registry describes a randomized, parallel-arm, open-label early phase I pilot study. One arm was assigned denosumab before risk-reducing salpingo-oophorectomy; the other was assigned surgery without preceding study treatment. The design therefore planned a comparison of tissue and other biomarker measurements in two groups, rather than a reported clinical-outcome comparison.
The denosumab schedule was to begin within 3 days of the menstrual cycle, with subcutaneous doses every 4 weeks for 1-2 doses. In that arm, surgery was planned 14-28 days after the last dose. In the comparison arm, no treatment was planned for 2-8 weeks before surgery. These are descriptions of the planned procedures, not evidence that they were carried out.
The record lists enrollment as 2 but also states that no participants were randomized and no data were collected. The trial status is terminated. The registry record does not report why the study was terminated, whether any screening or other study activities occurred, or whether the recorded enrollment represents participants who entered any particular stage of the study. The dates recorded for study start and primary completion are 2019-03-14 and 2021-10-22, respectively; they do not establish that the planned comparison was conducted.
The primary endpoint was a tissue biomarker, with secondary outcomes covering other tissue-based measures, gene-expression profiling, serum biomarkers, serial serum C-terminal telopeptide levels, and toxicity. The record describes no outcome analyses. It also does not report the randomization procedure, allocation concealment, or any statistical analysis plan beyond noting that a two-sample t-test would be considered for the primary comparison.
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: 2 participants consented at Tel Aviv Sourasky Medical Center, no participants randomized nor received trial intervention (Participant 1 was deemed ineligible due to elevated FSH level and Participant 2 did not start intervention due to COVID-19 lockdown restrictions).
Overall Study
| Stage | Arm I (Denosumab, Risk-reducing Salpingo-oophorectomy)/Arm II (Risk-reducing Salpingo-oophorectomy) |
|---|---|
| STARTED | 0 |
| COMPLETED | 0 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: No participants were randomized, therefore no data collected.
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: 2 participants consented at Tel Aviv Sourasky Medical Center, no participants randomized nor received trial intervention combined arms due to the participants were not randomized.
| Characteristic | Unit | Arm I (Denosumab, Risk-reducing Salpingo-oophorectomy)/ Arm II (Risk-reducing Salpingo-oophorectomy) |
|---|---|---|
| Participants analysed | 0 | |
| Age, Categorical: <=18 years | — | |
| Age, Categorical: Between 18 and 65 years | — | |
| Age, Categorical: >=65 years | — | |
| Sex: Female, Male: Female | — | |
| Sex: Female, Male: Male | — | |
| Region of Enrollment: Israel | participants | — |
6. Primary Endpoint
The registry lists the primary outcome as Ki67 Proliferation Index Fallopian Tube Fimbrial Epithelial Cells, measured over Up to 12 months.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was Ki67 proliferation index in fallopian tube fimbrial epithelial cells. The registry describes assessment by immunohistochemistry, with quantitative expression scored as the percentage of positive cells. A pathologist was to score the samples while blinded to treatment assignment. The stated timeframe was up to 12 months.
In general, Ki67 is used as a marker of cellular proliferation: its measurement can describe the proportion of cells in a tissue sample expressing the marker. A percentage-based measure provides a quantitative way to compare marker expression across groups. In this planned study, the endpoint was intended to describe a tissue-level biological measure, not directly to establish a clinical outcome.
The registry says a two-sample t-test would be considered to evaluate the difference between arms. That is a proposed analysis, not a reported result. The record states that no participants were randomized and no data were collected, so it contains no Ki67 values, group estimates, difference estimate, confidence interval, or test result. It is therefore not possible to characterize the observed level or between-arm distribution of Ki67 from this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical fact is that the planned randomized comparison did not yield reported outcome data. The record states that no participants were randomized and no data were collected. Consequently, there is no observed primary endpoint estimate to interpret, and no evidence in the record about the direction, size, or precision of a difference between the planned arms.
The enrollment field records 2, but that entry does not alter the record's explicit statement that no participants were randomized and that no data were collected. It should not be read as a completed randomized comparison or as a basis for calculating group-level outcomes. The record reports zero analyses. It contains no primary endpoint values, group summaries, treatment-effect estimate, confidence interval, or p-value.
The registry identifies a two-sample t-test as a method that would be considered for comparing Ki67 expression. Naming a test does not mean the test was performed. Without observations in each arm, the planned test cannot produce a result. Nor can precision be assessed: a confidence interval requires an estimate based on observed data, and no such estimate is reported.
The adverse-event entries show zero participants at risk and zero events in each listed group. Because the record also says no participants were randomized and no data were collected, those entries do not establish that denosumab or surgery caused no adverse effects. They describe a registry record with no reported participant exposure or collected outcome data, rather than reassuring safety observations from a treated group.
The registry lists a set of secondary biomarker and toxicity outcomes, but it provides no outcome analyses for them. Their inclusion indicates what the study intended to assess, not what was measured or found. There are no reported results from which to compare tissue markers, serum markers, gene-expression profiles, or adverse effects between groups.
Any planning illustration based on an observed effect must be treated cautiously in this record. No observed effect is available because no participants were randomized and no outcomes were collected. A sample-size illustration is not an observed finding or observed power, and without a documented effect estimate it cannot describe what this trial detected. The registry record does not report a sample-size justification for the original study.
Overall, the posted information describes the intended design and outcome measures, but not a statistical comparison. It cannot support conclusions about the primary biomarker endpoint, treatment effects, or safety. The reason for termination and the circumstances behind the absence of randomized participants are not reported in the registry record.
9. Statistical Methods Explained
The study was planned as a randomized parallel-group comparison. In general, random allocation is used to make treatment assignment less dependent on participant characteristics and to support a comparison between groups. A parallel design assigns participants to one study arm rather than having each participant receive both study conditions. The record labels the study randomized and parallel, but it does not describe the randomization sequence or allocation concealment. More importantly for interpreting results, it states that no participants were randomized.
What would the planned t-test compare?
The primary outcome description says that Ki67 expression would be quantified as the percentage of positive cells and that a two-sample t-test would be considered to evaluate the difference between arms. In general, a two-sample t-test compares the means of a quantitative outcome from two independent groups. It uses the observed group means and variability to assess how compatible the estimated difference is with a null hypothesis of no mean difference. The registry does not report an estimate or test statistic because it reports no collected data.
A t-test relies on assumptions that need consideration in an actual analysis. Observations should be independent within and between groups. The distribution of the outcome, or the sampling distribution of the mean, should be suitable for the test. A conventional pooled t-test also assumes equal variances between groups; a version that does not require equal variances is another general option. The record does not say which version would have been used, how assumptions would have been assessed, or whether any alternative analysis was planned.
The endpoint is expressed as a percentage, so its possible values are bounded. In general, bounded measures may have distributions that are asymmetric or concentrated near their limits, depending on the observed data. That does not establish a problem with the proposed test in this study: there are no endpoint observations with which to assess the distribution, and the registry does not report a transformation or another model. Any choice among methods would require the actual data and a prespecified or otherwise justified analysis approach.
What does blinding contribute?
The trial is listed as having no masking, while the primary outcome description says the pathologist scoring Ki67 would be blinded to treatment assignment. These statements concern different parts of the process. Open-label describes the overall study masking classification; blinded pathology scoring was specifically planned for the endpoint assessment. In general, keeping an outcome assessor unaware of assignment can reduce the chance that knowledge of group status influences measurement or scoring. It does not create data where none were collected, and it does not establish that the planned scoring procedure occurred.
What can be said about precision?
A confidence interval is a range calculated from observed data and an analysis model. In general, it communicates the uncertainty around an estimated quantity; a narrower interval indicates greater statistical precision under the model. No interval is reported for Ki67, and none can be inferred from the study design alone. Likewise, no p-value can be interpreted without an observed comparison and its test results.
The registry describes sample-size assumptions for planning illustrations: a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect expressed as a stated fraction of an observed effect. Such illustrations are planning calculations, not results from the trial and not observed power. Since this record reports no randomized participants or outcome data, it supplies no observed effect on which to base a meaningful interpretation of such an illustration. The record does not report the trial's own sample-size justification.
What analysis was actually reported?
The record reports zero analyses. This is consistent with its statement that no participants were randomized and no data were collected. There are no reported statistical methods applied to observed endpoint data, no adjusted or unadjusted estimates, and no subgroup comparisons. The two-sample t-test appears as a method under consideration in the endpoint description, not as a completed analysis. The statistical plan, including any covariate adjustment, handling of unusual observations, or decision rules, is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists primary and secondary outcomes, but it does not report a multiplicity strategy. In general, when multiple outcomes or comparisons are tested, the chance of at least one apparently unusual result can increase if each test is treated as an independent opportunity for a finding. A prespecified hierarchy, adjustment method, or clear designation of confirmatory and exploratory analyses can help readers understand how multiple testing was handled. None is described in the registry record.
The record lists secondary outcomes involving Ki67 in ovarian surface epithelium and endometrium; other tissue-based biomarkers; gene-expression profiling; serum biomarkers, including progesterone, estradiol, and denosumab drug levels; serial serum C-terminal telopeptide levels; and toxicity. These are planned outcome areas, not reported analyses. The record does not specify which comparisons would be primary within each secondary outcome, whether outcomes would be analyzed jointly or separately, or how multiplicity would be addressed.
Missing-data handling is also not reported. In general, an analysis plan may specify how to handle missing measurements, incomplete follow-up, or participants who do not have an evaluable specimen. Here, the registry states that no participants were randomized and no data were collected, so there are no reported endpoint observations for which an imputation or other missing-data method could be applied. The record does not describe a planned approach to missing measurements if they had occurred.
The analysis population is not reported beyond the explicit statement that no participants were randomized. The record does not define an intention-to-treat population, a per-protocol population, or a population for safety analyses. With no randomized participants and no collected data, the posted results do not provide an analyzed population or outcome estimates.
11. What the Result Does, and Does Not, Mean
This record describes a planned pilot study of denosumab before risk-reducing salpingo-oophorectomy, compared with surgery without preceding study treatment, in BRCA1/2 mutation carriers. It identifies a primary tissue biomarker and several secondary biomarker and toxicity outcomes. Those details show what the trial was designed to investigate; they are not evidence that the planned assessments took place.
The record states that no participants were randomized and no data were collected. Accordingly, there is no reported comparison of Ki67 expression between arms, no estimate of a treatment-associated difference, and no measure of statistical precision. No conclusion about the primary endpoint can be drawn from the posted results. There are also no reported analyses of the listed secondary outcomes.
The adverse-event entries have zero counts, but the record reports zero participants at risk in both listed groups and no collected data. These entries do not demonstrate an absence of adverse effects under exposure. They cannot be used to characterize the safety of denosumab or the surgical procedure in this study.
The study is marked terminated, but the reason for termination is not reported in the registry record. The record also does not explain the difference between the enrollment entry and the statement that no participants were randomized. Neither the status nor the enrollment field supplies an outcome result or an explanation for the absence of data.
In general, a pilot study can be designed to examine feasibility, measurement procedures, or preliminary biological signals, but the record does not report results that would allow those aims to be evaluated. The described endpoint and proposed statistical test should therefore be read as planned methods. They do not establish a biological effect, a clinical effect, or evidence for or against treatment benefit.
12. Why This Trial Matters Statistically
This trial is statistically notable because the registry distinguishes a planned randomized comparison from an observed comparison: the design and endpoints are described, yet no participants were randomized and no data were collected. That distinction is essential. A detailed protocol description does not itself generate an effect estimate, and a proposed test does not constitute an analysis.
The primary endpoint also illustrates the difference between a biological measurement and a clinical outcome. Ki67 percentage in fallopian tube fimbrial epithelial cells was selected as a tissue measure of proliferation. In general, such markers can be useful for studying biological processes, but interpreting them requires observed measurements and a clear account of how they relate to the questions of interest. This record offers no values or analysis with which to assess that endpoint.
The record also makes the limits of safety counts visible. Zero events alongside zero participants at risk are not equivalent to observing no events among exposed participants. Denominators and exposure matter when interpreting event counts, and the record contains no randomized study population from which to estimate event frequency.
Finally, the termination status without a reported reason limits what readers can infer about study conduct. Statistical interpretation must stay within the documented information: the planned comparison can be described, but its effects, precision, safety findings, and operational outcome cannot be reconstructed from the record.
13. 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 main limitation is the absence of randomized participants and collected outcome data. This prevents estimation of the primary endpoint and leaves the planned treatment comparison unanswered in the registry record. The enrollment field records 2, but the record explicitly states that no participants were randomized; it does not clarify the enrollment entry's relationship to study participation or explain the absence of randomization.
The record marks the study terminated but does not report the reason. It does not describe whether recruitment began, what led to termination, or whether any planned procedures were undertaken. These gaps prevent readers from distinguishing among possible operational explanations, and none should be inferred.
Important design and analysis details are not reported. The record does not describe eligibility criteria beyond the intended population, randomization procedures, allocation concealment, a full statistical analysis plan, the version of the proposed t-test, or methods for missing data and multiplicity. The endpoint description says a two-sample t-test would be considered, but no analysis is reported.
The adverse-event counts are zero, with zero participants at risk in both groups. In the context of no randomized participants and no collected data, these entries cannot characterize safety during exposure. More generally, this record contains no reported outcome estimates or uncertainty measures, so neither biological effects nor clinical outcomes can be assessed.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: Pilot Study of Denosumab in BRCA1/2 Mutation Carriers Scheduled for Risk-Reducing Salpingo-Oophorectomy — NCT03382574.
- Registry record last updated 2022-06-14; status last verified 2022-05.
- Results first posted 2022-06-14.
- 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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17. Record Summary
NCT03382574 is listed as a randomized, open-label, parallel early phase I pilot study of denosumab before risk-reducing salpingo-oophorectomy in BRCA1/2 mutation carriers. The planned comparator was surgery without preceding study treatment. The primary outcome was Ki67 proliferation index in fallopian tube fimbrial epithelial cells, assessed by immunohistochemistry as the percentage of positive cells. A two-sample t-test was to be considered.
The record lists enrollment as 2 and status as terminated, while stating that no participants were randomized and no data were collected. No outcome analyses are reported. The reason for termination is not reported in the registry record, and the posted results do not provide estimates for the primary endpoint or the listed secondary outcomes.