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 The Effect of Simvastatin on Breast Cancer Cell Growth in Women With Stage I-II Breast Cancer (NCT03454529), a na phase 2 study. The primary outcome is Change in Ki-67 Expression Assessed in Tumor Tissue by Immunohistochemistry.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03454529 |
| Phase | Phase 2 |
| Condition | Invasive Breast Carcinoma, Stage I Breast Cancer AJCC v7, Stage IA Breast Cancer AJCC v7 |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 24 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Michael Simon |
| Results posted | Yes |
2. Clinical Question
Population
Women with stage I–II breast cancer were the population of interest. The registry lists invasive breast carcinoma and several stage I and stage II categories among the conditions. Enrollment was 24. The primary-outcome description notes that one patient did not have both pre-treatment and post-treatment measurements.
Intervention
The intervention was simvastatin, taken by mouth daily for 2–4 weeks, unless disease progression or unacceptable toxicity occurred. Laboratory biomarker analysis was also listed as an intervention type, but the registry does not give additional procedural details.
Comparator
This was a single-group study, with no concurrent control group listed. The intended contrast for the primary outcome was each participant’s tumor Ki-67 measurement before treatment versus after treatment. That within-participant contrast is not the same as a comparison with an untreated or placebo group.
Primary question
The primary question was whether the percentage of tumor cells expressing Ki-67 changed from baseline to follow-up, with follow-up assessed up to 4 weeks after treatment began. The registry describes assessment by immunohistochemistry and says the pre-treatment and post-treatment difference was to be reported with a 95% confidence interval. The numerical result is not reported in the registry record.
The study’s stated purpose was to identify molecular and genetic mechanisms by which statins may influence breast cancer cell proliferation. Its brief description proposes that simvastatin might affect tumor-cell growth by blocking enzymes involved in cell growth and might influence cell aggressiveness. Those statements describe the study’s rationale, not a result established by the posted outcome data.
Because there was no listed control group, the primary question concerns change over time among participants receiving simvastatin. A before-and-after change can describe what happened during the study period, but by itself cannot distinguish a treatment-related change from other influences, including time, measurement variability, or changes in care. The record does not report a randomized comparison or a separate control arm.
3. Trial Design
This was a phase II, single-group study with an enrollment of 24. The registry lists allocation as not applicable and masking as none. It was marked completed. The listed study start was 2018-03-09, and primary completion was 2021-10-06. The sponsor was Michael Simon.
Participants in the treatment group received simvastatin by mouth daily for 2–4 weeks, in the absence of disease progression or unacceptable toxicity. The registry also lists laboratory biomarker analysis. It does not report further details about the laboratory procedures, treatment adherence, dose, or the timing of individual participants’ assessments beyond the primary outcome’s baseline-to-up-to-4-weeks timeframe.
The primary endpoint was defined as change in Ki-67 expression assessed in tumor tissue by immunohistochemistry. The measurement was the percentage of cells expressing Ki-67, and the registry describes a pre-treatment versus post-treatment difference with a 95% confidence interval. One patient did not have both pre-treatment and post-treatment measurements. The registry record does not provide the numerical estimate, interval limits, or a detailed account of how the outcome analysis handled that missing pair of measurements.
A single-group design can characterize within-group measurements over time, but it does not provide a concurrent comparison that would help separate treatment-associated change from other changes that occur during the same period. The registry’s allocation and masking fields, together with the single-group model, indicate that the study was not a blinded randomized comparison. The record does not report a protocol-based sample-size justification, a planned interim analysis, or a detailed statistical analysis plan.
The registry lists seven outcome measures and no analyses. The other outcome definitions and their numerical findings are not reported in the registry record. As a result, the available record gives the study’s general design and primary measurement but not a complete account of the trial’s outcome analyses.
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 | Treatment (Simvastatin) |
|---|---|
| STARTED | 24 |
| COMPLETED | 17 |
| NOT COMPLETED | 7 |
Reasons for not completing this period:
| Reason | Treatment (Simvastatin) |
|---|---|
| Did not receive treatment | 6 |
| Received < 80% doses | 1 |
Analysis population for the primary outcome, as defined in the registry: one patient did not have pre and post measures
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: All evaluable patients, including those recevied \>80% doses
| Characteristic | Unit | Treatment (Simvastatin) |
|---|---|---|
| Participants analysed | 17 | |
| Age, Continuous | years | 63 (48 to 73) |
| Sex: Female, Male: Female | Participants | 17 |
| Sex: Female, Male: Male | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 2 |
| Race (NIH/OMB): White | Participants | 9 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 6 |
| Region of Enrollment: United States | participants | 17 |
| Estrogen Receptor Status: Positive | Participants | 15 |
| Estrogen Receptor Status: Negative | Participants | 2 |
| Progesterone Receptor Status: Positive | Participants | 11 |
| Progesterone Receptor Status: Negative | Participants | 6 |
| HER2 Status: Positive | Participants | 0 |
| HER2 Status: Negative | Participants | 12 |
| HER2 Status: Unknown | Participants | 5 |
| Tumor Stage: Stage 0: limited to the inside of the milk duct; is non-invasive; does not invade nearby tissues. | Participants | 6 |
| Tumor Stage: Stage I: Invasive; Primary Tumor < 20mm; No lymph nodes affected; No metastasis. | Participants | 11 |
| Tumor Stage: Stage II: Primary Tumor 20-50 mm; 0-<4 lymph nodes in the same side of the breast; No metastasis | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Ki-67 Expression Assessed in Tumor Tissue by Immunohistochemistry, measured over Baseline up to 4 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of cells expressing Ki67 |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change in the percentage of tumor cells expressing Ki-67, measured in tumor tissue by immunohistochemistry. The registry specifies measurements from baseline up to 4 weeks and describes a difference between the pre-treatment and post-treatment percentages. One participant did not have both measurements. The numerical change and its 95% confidence interval are not reported in the registry record.
Ki-67 is a marker used to assess cell proliferation: it identifies cells that are in active phases of the cell cycle. In general, a tissue-based measure of Ki-67 can be used to study whether cell-proliferation markers change over a defined period. A percentage expresses the fraction of assessed cells that meet the marker’s positivity criteria; it is not a direct count of all tumor cells and does not, by itself, establish what caused a change.
For a before-and-after endpoint, the relevant contrast is the change in the same participants’ measurements across the specified time period. This can make each participant’s baseline value a reference for their later value. However, without a concurrent control group, a change cannot be attributed uniquely to the intervention. The registry record does not provide the laboratory scoring details, the method for summarizing participant-level changes, or the actual estimate and interval needed to assess the observed size and precision of any change.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a primary outcome and the intended time comparison, but does not report the numerical outcome. There is no posted mean change in Ki-67 percentage, no confidence-interval limits, and no reported test statistic or p-value. Consequently, the direction, magnitude, and statistical precision of the primary result cannot be assessed from the registry record. The absence of a posted result should not be interpreted as evidence that the endpoint did or did not change.
The study enrolled 24 participants, while the primary-outcome description says one participant lacked pre-treatment and post-treatment measurements. The registry does not state the number included in the endpoint analysis or explain how the missing measurements were handled. It is therefore not possible to determine from the record whether the primary estimate used only participants with both measurements, used another approach, or was not calculated for posting.
The single-group design is important when interpreting any before-and-after estimate. In general, a within-participant change can show that measurements differed over time among those observed, but without a concurrent control group it cannot isolate the intervention’s contribution from other explanations. The registry lists no randomized allocation and no masking. These design features limit causal interpretation independently of the size or statistical significance of a change.
The enrollment count is a description of the study, not a measure of how informative the primary outcome is. Precision depends on the observed variation and the analysis, as well as the number of usable outcome pairs. Those outcome details are not reported in the registry record. A confidence interval would ordinarily communicate the range of values reasonably compatible with the data under the analysis assumptions; because its limits are not posted, the degree of precision cannot be judged.
The registry states that seven outcome measures were listed, but numerical results for them are not reported in the registry record. It lists no analyses. The record also does not report a multiplicity strategy or a detailed analysis plan. Without those details, it is not possible to establish how the outcomes were prioritized analytically, how missing values were handled across outcomes, or whether any reported result would account for multiple statistical tests.
Planning illustrations based on an observed effect are not the same as observed power, and the registry explicitly distinguishes its planning assumptions from the trial’s own design. In general, such illustrations describe hypothetical sample sizes under stated assumptions; they do not replace the actual estimate and uncertainty from the trial. The numerical primary result remains necessary to interpret what the participants’ measurements showed.
9. Statistical Methods Explained
The primary endpoint is a continuous measurement: the percentage of tumor cells expressing Ki-67. The registry says the outcome is summarized as a mean and describes a 95% confidence interval for the pre-treatment versus post-treatment difference. The record does not give the estimate, confidence-interval limits, or detailed calculation method.
What does a mean change describe?
General statistical explanation: A mean summarizes the average value in a group of measurements. For a before-and-after endpoint, analysts can first define a change for each participant and then summarize those changes. That average change describes the group’s central tendency, but it does not show whether every participant changed in the same direction or by a similar amount. A mean may also be influenced by unusually large or small individual changes.
The registry’s endpoint description refers to differences in the percentage of positive cells before and after treatment. It does not report the precise sign convention used for the difference, whether any transformation was applied, or the statistical test or model. Those details should not be inferred. The actual mean difference is not reported in the registry record.
What does a 95% confidence interval communicate?
General statistical explanation: A confidence interval is an uncertainty interval around an estimate, calculated using a specified statistical procedure. A narrower interval indicates greater precision under that procedure; a wider interval indicates less precision. A 95% confidence interval is not a statement that there is a 95% probability that a particular fixed parameter lies within the interval. Rather, the 95% level describes the long-run performance of the method across repeated applications under its assumptions.
For this endpoint, the interval would help readers assess which mean changes are reasonably compatible with the observed data and the analysis method. An interval’s interpretation depends on how the data were collected and analyzed. Because the registry does not report the interval limits, no conclusion about precision or the range of compatible changes can be drawn from the posted record.
Why does the single-group structure matter?
General statistical explanation: Repeated measurements on the same participant are related rather than independent. An analysis of within-participant change should account for that pairing. A single-group before-and-after design can estimate a change over time among participants with the required measurements, but it does not itself estimate what would have happened over the same period without the intervention. A concurrent control group can help address that counterfactual question, although its quality depends on the design and analysis.
The registry identifies a single-group model and no masking. It does not report the exact statistical procedure used for the repeated measurements. It would therefore be inappropriate to assign a particular paired test, regression model, or covariance structure to the analysis. The record also does not report whether the analysis adjusted for any participant characteristics or other factors.
What is over-dispersion, and is it relevant?
General statistical explanation: Over-dispersion occurs when the observed variability in data is greater than a statistical model assumes. If a model underestimates variability, its standard errors can be too small and its confidence intervals too narrow. The outcome in this study is a percentage derived from cell assessments, but the registry record does not describe the statistical model or report a dispersion assessment. There is not enough information to determine whether over-dispersion was considered or whether it was relevant to the analysis used.
What can the posted design information support?
The record supports a description of the study as phase II, single-group, and unmasked, with 24 enrolled participants and simvastatin given daily for 2–4 weeks. It also supports the description of the primary tissue marker, measurement scale, and baseline-to-follow-up timeframe. It does not support a reconstruction of the statistical analysis, since the analysis method and numerical outcome are not reported in the registry record.
The record’s planning assumptions describe illustrations using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the detectable effect expressed as a stated fraction of the observed effect. Those are planning assumptions, not a description of this single-group trial’s treatment allocation. The record says the illustrations are not the trial’s own design. Such sample-size illustrations are not observed power and should not be read as evidence about the trial’s actual result or precision.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists seven outcome measures, but does not report their numerical results or a multiplicity adjustment. It also lists no analyses. The record does not state whether a hierarchy of outcomes was planned, whether any outcomes were exploratory, or how statistical testing across multiple outcomes was intended to be interpreted. These points are not reported in the registry record.
General statistical explanation: When several outcomes or hypotheses are tested, the chance of at least one apparently notable finding can increase if each test is interpreted separately. A multiplicity plan may address this by defining a primary outcome, ordering tests, or adjusting the interpretation of multiple comparisons. The appropriate approach depends on the study’s objectives and prespecified analysis plan. No such plan is described in the registry record, so no particular approach can be attributed to this study.
The primary-outcome description notes that one patient did not have pre-treatment and post-treatment measurements. The record does not say why those measurements were absent, whether the participant had one measurement but not the other, or how the absence affected the endpoint analysis. The analysis population is not reported in the registry record, nor are the numbers with usable measurements for each outcome.
General statistical explanation: Missing outcome data can affect both the amount of information available and the interpretation of an estimate. Complete-case analysis, imputation, and model-based approaches make different assumptions; none can be presumed without an analysis description. The number of participants enrolled alone does not establish how many contributed to a particular analysis. The registry record does not report which missing-data method, if any, was used.
The record does not report whether outcomes were analyzed according to an intention-to-treat principle, in a per-protocol population, or through another defined analysis set. It also does not describe protocol deviations or the handling of participants who stopped treatment early. These details are necessary for a fuller assessment of the analysis population and are not reported in the registry record.
11. 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 |
|---|---|---|---|
| Treatment (Simvastatin) | 0 | 17 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment (Simvastatin) | 0 of 17 |
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 |
|---|---|
| Treatment (Simvastatin) | 2 of 17 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment (Simvastatin) |
|---|---|---|
| Musculoskeletal and connective tissue disorder - Other, specify | Musculoskeletal and connective tissue disorders | 1 of 17 |
| Bladder infection | Infections and infestations | 1 of 17 |
The registry lists one treatment group with 17 participants at risk for serious adverse events and zero affected by serious adverse events. It also lists 17 at risk for other adverse events and two affected. Deaths are listed as zero. The registry does not provide serious adverse-event terms; the top serious terms list is empty. The identities and descriptions of the two other adverse events are not reported in the registry record.
These figures describe the counts posted for the group and should be read in their stated categories. “At risk” is the registry’s denominator for the relevant adverse-event category; it is not the same as the total enrollment of 24. The record does not explain why the at-risk denominator is 17 or give additional exposure details. It would be inappropriate to infer the reasons for that denominator.
General statistical explanation: A count of affected participants is a descriptive safety summary, not a comparison of risks between treatments. With no control group listed, these figures do not estimate a relative difference against another treatment or no treatment. They also do not establish whether an event was caused by the study treatment. The registry record does not report event timing, severity grades for the other events, or detailed causal assessments.
12. What the Result Does, and Does Not, Mean
This trial record describes a phase II investigation of simvastatin and tumor-tissue Ki-67 in women with early-stage breast cancer. The intended primary measure was a change in the percentage of Ki-67-positive cells between baseline and follow-up up to 4 weeks. The record identifies the study question and design, but the primary numerical result is not reported in the registry record.
Accordingly, the posted information does not establish the direction or size of the mean change, how precisely it was estimated, or whether the analysis met any statistical threshold. It also does not establish that Ki-67 changed, that it did not change, or that any change was caused by simvastatin. Those conclusions require outcome estimates and an analysis that are not included in the registry record.
The single-group, unmasked design is relevant to what the study could establish. In general, before-and-after measurements can describe change among participants over time, but cannot by themselves separate a treatment effect from other factors that could influence the measurement. No randomized comparator is listed. Even if a numerical change were available, this design would require careful interpretation and would not provide a like-for-like control comparison.
The brief description presents a biological rationale involving cell proliferation and tumor-cell growth. A biomarker outcome can contribute information about a biological process, but it is not automatically equivalent to a clinical outcome. The registry record does not report a clinical outcome result that would allow the Ki-67 measure to be connected to a patient-level benefit or harm.
The adverse-event summary lists zero participants affected by serious adverse events among 17 at risk, two affected by other adverse events among 17 at risk, and zero deaths. These counts are descriptive, and no comparison group is available for interpreting relative safety. The record does not identify the two other events or provide fuller event details.
Overall, the registry supports a description of the study’s purpose, population, intervention, design, primary endpoint, and limited posted safety counts. It does not contain enough outcome or analysis information to determine what the primary biomarker measurements showed or to draw causal conclusions.
13. Why This Trial Matters Statistically
This study is statistically notable because its primary question is framed as a within-participant change in a continuous biomarker, while the design has a single group and no listed control. That distinction matters: a change over time and a treatment effect relative to an alternative are different quantities. The registry’s design permits the former to be studied, but does not provide a randomized contrast for the latter.
The endpoint is also a tissue-based percentage, and the registry specifies that the intended summary is a mean difference with a 95% confidence interval. Such reporting would let readers consider both the estimated average change and its uncertainty. However, the numerical estimate and interval are not reported in the registry record. This makes it impossible to assess the magnitude and precision of the primary result from the posted information.
Missing measurements are another important statistical detail. The endpoint description notes that one patient did not have both measurements, yet the analysis population and missing-data method are not reported. In general, even a small amount of missingness can matter if the reason measurements are missing is related to participants’ outcomes. The record does not give enough information to evaluate that possibility or determine how the analysis addressed it.
The record lists seven outcome measures and no analyses. Without posted outcome estimates or a stated multiplicity approach, readers cannot assess the full pattern of outcomes or how multiple statistical questions were handled. This is distinct from the design limitation: statistical procedures can address some issues around multiple testing, but cannot create a concurrent control group where none was included.
The case illustrates why a clear endpoint definition is not a substitute for complete results reporting. The registry identifies the marker, assessment method, timeframe, and intended uncertainty summary. The missing estimates, methods, and analysis-population details prevent readers from evaluating what was observed and how robustly it was estimated.
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 central limitation of the available record is that the primary outcome’s numerical result is not reported in the registry record. No mean change, confidence-interval limits, or outcome test result is posted. Therefore, neither the observed direction nor the precision of the primary endpoint can be assessed.
The single-group design has no listed concurrent control. Any before-and-after change would describe measurements over time in the treated group, but could not by itself distinguish treatment-associated change from other influences. The registry also lists masking as none. It does not report whether laboratory assessors were masked to measurement time or provide procedures for limiting measurement bias.
The primary-outcome description notes that one participant lacked both pre-treatment and post-treatment measures, but does not explain the reason or the handling of those data. The analysis population and usable sample size for the primary endpoint are not reported in the registry record. The record also does not report the statistical model, test, assumptions, or any adjustment for other variables.
Although seven outcomes are listed, their numerical findings and any strategy for interpreting multiple outcomes are not reported. No analyses are listed. The record does not provide details of the other outcome definitions, protocol deviations, treatment adherence, or the reasons participants may not have contributed to each measure.
The treatment description gives a daily oral schedule of 2–4 weeks, but does not report a dose. The laboratory biomarker analysis is listed without procedural detail. The adverse-event summary has limited descriptive information: the two participants affected by other adverse events are not described, and the record does not provide event timing or further assessments. These limits constrain interpretation of both the endpoint and the safety summary.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: The Effect of Simvastatin on Breast Cancer Cell Growth in Women With Stage I-II Breast Cancer — NCT03454529.
- Registry record last updated 2023-08-01; status last verified 2023-07.
- Results first posted 2023-08-01.
- 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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18. Record Summary
The registry describes a completed phase II, single-group study of simvastatin in women with early-stage breast cancer. Enrollment was 24. Participants in the treatment group received simvastatin by mouth daily for 2–4 weeks, subject to disease progression or unacceptable toxicity. The record lists no masking and no randomized comparison.
The primary endpoint was the change in the percentage of tumor cells expressing Ki-67, assessed by immunohistochemistry from baseline up to 4 weeks. The registry describes a mean difference with a 95% confidence interval and notes that one patient did not have both measurements. The numerical endpoint result, interval, analysis method, analysis population, and missing-data handling are not reported in the registry record.
The safety summary lists 17 participants at risk for serious adverse events, with zero affected; 17 at risk for other adverse events, with two affected; and zero deaths. The two other events are not described. The record lists seven outcomes and no analyses. Its posted information is sufficient to characterize the design and intended primary measure, but not to interpret the primary numerical result.