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 Preoperative Window of Endocrine Therapy Provides Information to Increase Compliance (NCT01614210), a na phase 2 study. The primary outcome is Change in Ki67 Expression in Tumors.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01614210 |
| Phase | Phase 2 |
| Condition | Newly Diagnosed Hormone Positive Clinical Stage 1 or 2 Breast Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 52 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Utah |
| Results posted | Yes |
2. Clinical Question
Population
People with newly diagnosed hormone-positive clinical stage 1 or 2 breast cancer. The record lists 52 enrolled participants; some were not evaluable for the primary endpoint for reasons described in the registry record.
Intervention
Tamoxifen in a preoperative window. The registry summary describes a total of 21 doses before and after surgery, while the primary endpoint focuses on change in Ki67 after 7 days of pre-surgical Tamoxifen.
Comparator
There was no separate comparison group. The trial is listed as a single-group study, with allocation recorded as not applicable and no masking.
Primary question
Does tumor Ki67 expression change after 7 days of pre-surgical Tamoxifen? The stated objective was to demonstrate a significant change. The registry record does not report the numerical estimate, confidence interval, or test result needed to judge the observed change.
The clinical question is about a short treatment window and a tumor measure, not a randomized comparison of Tamoxifen against another treatment or against no treatment. The study also lists questions about FACT-ES symptom scores, long-term endocrine therapy adherence, and the relationship between changes in Ki67 and symptoms. Those are secondary outcomes and should be distinguished from the primary endpoint.
Because there is only one study group, the central statistical evidence would concern change within the participants with evaluable measurements. A change over time in one group does not by itself establish what would have happened over the same period without the intervention. The registry record does not report a numerical primary result, so the size and precision of any observed change cannot be assessed from this record.
3. Trial Design
The registry describes a completed Phase 2, single-group study sponsored by the University of Utah. Enrollment was 52. The study started in 2012-08, and primary completion was recorded as 2016-11. Allocation is listed as not applicable, masking as none, and the model as single group. The record therefore does not describe a randomized allocation or a blinded assessment.
All enrolled participants are described as belonging to one group. The listed interventions are Tamoxifen and breast cancer surgery. The brief summary describes a total of 21 Tamoxifen doses before and after surgery, while the primary outcome description specifies a 7-day pre-surgical treatment window. The record does not provide a more detailed dosing schedule in the trial details summarized for this analysis.
The primary outcome is change in Ki67 expression in tumors, expressed as percentage change in Ki67, with a mean and 95% confidence interval specified as the outcome summary. The stated timeframe is 7 days. The record gives a primary objective of demonstrating a significant change after pre-surgical Tamoxifen, but it does not report the numerical mean change, confidence interval, or significance test result.
The listed secondary outcomes concern change in FACT-ES symptom scores, the number of participants with long-term endocrine therapy adherence, and correlation between changes in Ki67 and symptoms. Five outcome measures and one analysis are recorded. Details of the individual analysis procedures, including covariate adjustment or the handling of repeated measurements, are not reported in the registry record.
The single-group design can describe the observed course in participants, but it does not provide a concurrent control group for separating intervention-related change from other influences. The absence of masking also means the design does not include a masked assessment as recorded by the registry. These features are relevant to interpretation and do not, by themselves, show whether an observed change occurred.
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 | Tamoxifen Pre and Post Breast Surgery |
|---|---|
| STARTED | 52 |
| COMPLETED | 52 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: 3 were not evaluable due to rescheduling of surgery; 1 not evaluable due to pharmacy error. 2 patients had no invasive tumor on Ki-67 slides from pretreatment biopsy, and 2 patients had no invasive tumor on post-treatment surgery and were not evaluable.
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 | Tamoxifen Pre and Post Breast Surgery |
|---|---|---|
| Participants analysed | 52 | |
| Age, Continuous | years | 58.5 (38 to 79) |
| Sex: Female, Male: Female | Participants | 52 |
| Sex: Female, Male: Male | Participants | 0 |
| Region of Enrollment: United States | Participants | 52 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Ki67 Expression in Tumors, measured over 7 days.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage change in Ki67 |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in Ki67 expression in tumors over a 7-day pre-surgical Tamoxifen window. Ki67 is a measure of cell proliferation: in general, a change in the proportion of tumor cells expressing Ki67 can be used as a biological indicator of change in proliferative activity. In an early treatment-window study, a tissue measure can provide evidence about whether the tumor marker changes during exposure to the intervention.
The registry specifies the outcome as percentage change in Ki67 and identifies the summary measure as a mean with a 95% confidence interval. A mean describes the average change among the observations included in the analysis. A confidence interval conveys uncertainty around an estimate; it does not describe the range of individual participant responses. Its width depends on both the variability in the measured changes and the amount of evaluable information.
The registry's objective is to demonstrate a significant change, but the numerical estimate and confidence interval are not reported in the registry record. Consequently, the direction, magnitude, and precision of the primary endpoint cannot be assessed from the record. The endpoint is a tumor marker, not a direct measure of symptoms, long-term adherence, or clinical outcome. The secondary outcomes address some of those distinct questions, but their numerical results are also not reported in the registry record.
The record notes that some participants were not evaluable for Ki67. Such exclusions matter because the endpoint can only be estimated from participants with usable measurements under the analysis approach. The number and reasons listed in the record identify potential gaps in endpoint availability, but the record does not give enough detail to determine how those missing measurements were handled in the analysis.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the intended primary analysis as a mean change in tumor Ki67 expression, accompanied by a 95% confidence interval. However, the record does not report the numerical mean change, its confidence interval, or a p-value. It therefore does not permit an assessment of the observed direction, size, or statistical precision of the primary result. The stated aim of demonstrating a significant change is an objective, not evidence that the objective was met.
The single-group design is important when interpreting any within-participant change. In general, measuring participants before and after an intervention can describe change over time, but without a concurrent comparator it cannot isolate the intervention as the sole explanation for that change. Changes may coincide with the treatment window for other reasons. This is a design limitation, not a claim that any particular alternative explanation occurred in this study.
The registry lists 52 enrolled participants, while the primary endpoint description identifies participants who were not evaluable. Three were not evaluable because surgery was rescheduled, and one was not evaluable because of a pharmacy error. Two participants had no invasive tumor on Ki67 slides from the pretreatment biopsy, and two had no invasive tumor on post-treatment surgery. These are reasons relevant to availability of the primary endpoint. The record does not report the final number included in the primary analysis or the method used to address unavailable measurements.
A mean and its confidence interval are useful together: the mean estimates the average change, while the interval indicates the uncertainty around that estimate under the statistical model used. Neither can be interpreted in this case because their numerical values are not reported in the registry record. The interval also would not show how widely individual participants' changes varied unless participant-level distributions or other variability measures were reported.
The registry records one analysis and five outcome measures, but does not describe the testing sequence, any adjustment for multiple comparisons, or whether the reported primary analysis followed a prespecified plan. Thus, the possibility of multiple outcome assessments should be kept in mind without assuming that any particular multiplicity procedure was used. The statistical plan, including the model details and analysis population, is not reported in the registry record.
The trial record also includes a sample-size planning illustration based on the observed effect and hypothetical two-arm assumptions. It is not a statement of observed power and does not replace the missing estimate and uncertainty for the actual single-group primary endpoint. Planning values depend on their assumptions and describe a hypothetical design; they are not additional evidence about the trial result.
In short, the available registry entries support a description of the design, endpoint, and known evaluability issues, but not a numerical conclusion about the primary result. Neither statistical significance nor the clinical importance of a change can be inferred from the stated objective alone. The registered secondary questions likewise cannot be judged without their numerical results and analysis details.
9. Statistical Methods Explained
What does the mean represent?
For a continuous endpoint such as percentage change in Ki67, a mean is an average across the observations included in the analysis. It gives a concise estimate of the group’s average change, but it does not imply that every participant changed by that amount. Participants may have changes of different sizes or directions. Describing that spread requires information beyond the mean, such as a measure of variability or a distribution of individual observations.
The record specifies a mean as the primary summary, but does not report its numerical value. It also does not state whether the analysis used a particular transformation, adjustment, or model. The endpoint is described as change, but the precise calculation used to derive each participant’s percentage change is not reported in the registry record. That detail can matter when interpreting the scale and average of a change measure.
How should a confidence interval be read?
A confidence interval expresses uncertainty in an estimate under the assumptions of the analysis. General statistical interpretation treats an interval as more informative than a point estimate alone because it conveys a range of values compatible with the data and method. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. The interval is not a range expected to contain most individual participant values.
The specified interval is 95%, but its bounds are not reported in the registry record. Without those bounds, the precision of the mean change cannot be assessed. Nor can the interval be compared with any clinically meaningful threshold: no such threshold is reported in the registry record. The confidence level alone does not tell whether a result is statistically significant or whether a change is clinically important.
What does significance testing establish?
In general, a significance test evaluates how compatible the observed data are with a specified null hypothesis under the assumed statistical model. A small p-value can indicate that the data would be relatively unusual under that null model. It does not measure the probability that the null hypothesis is true, the size or importance of an effect, or the probability that the finding will recur.
The objective states that the study sought to demonstrate a significant change in Ki67. The actual test result and p-value are not reported in the registry record. The stated objective must not be mistaken for a reported test outcome. Also, even a statistically significant within-group change would not, by itself, provide a randomized estimate of the difference between Tamoxifen and a control condition, since the trial is single group.
Why does evaluability matter?
The primary endpoint requires interpretable Ki67 information. The registry reports several reasons why participants were not evaluable: rescheduling of surgery, a pharmacy error, and absence of invasive tumor in specified tissue specimens. When endpoint information is unavailable, the analysis population may differ from all enrolled participants. In general, missingness can affect both precision and the estimated result, particularly if the reasons for missing data are related to participants’ characteristics or outcomes.
The record identifies the stated reasons, but does not report the analysis population, the number included in the endpoint analysis, or a method for handling missing measurements. It is therefore not possible to determine whether the analysis used only complete measurements, applied an imputation procedure, or used another approach. No such method should be assumed.
Why does over-dispersion matter?
For count outcomes, over-dispersion means that the observed variability exceeds what a simple statistical model assumes. In general, if this extra variability is ignored, uncertainty can be understated and statistical evidence can appear more precise than it is. This concept is relevant to some count-data analyses, but the registered primary endpoint is continuous and is summarized as a mean. The registry record does not say that an over-dispersed count model was used for the primary endpoint, and the concept should not be applied to it without evidence.
How should the planning illustration be understood?
The record describes a planning illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the target effect is a specified fraction of the observed effect, and that sample sizes for non-time-to-event outcomes are expressed as participants per arm. These are hypothetical planning assumptions, not the design of this single-group study. In particular, the equal-allocation, two-arm assumption does not describe the trial’s enrolled structure.
A sample-size illustration asks how many participants a hypothetical study might require under stated assumptions. It is not a measure of the probability that this completed trial detected an effect. That probability is often called power, and a retrospective value derived from an observed estimate is not a substitute for the estimate, confidence interval, and analysis actually reported. Numerical planning results are not reported in the registry record described for this analysis. The record also does not report the trial’s own sample-size justification.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists five outcome measures and one analysis, including the primary Ki67 endpoint and secondary questions about FACT-ES symptom scores, long-term endocrine therapy adherence, and the correlation between Ki67 and symptoms. Multiple outcomes can create multiple opportunities to observe apparently notable results. In general, a prespecified primary endpoint helps distinguish the main study question from secondary or exploratory questions. The registry identifies a primary outcome but does not report whether any adjustment for multiple testing was planned or applied.
The analysis sequence, hypotheses for the secondary outcomes, and whether those analyses were prespecified are not reported in the registry record. It would therefore be inappropriate to assume either that multiplicity was adjusted for or that it was ignored. Results from secondary measures, if available elsewhere, would need to be read in light of their role and the analysis plan; their numerical findings are not reported in the registry record.
For the primary endpoint, the record identifies several sources of non-evaluability: three participants because surgery was rescheduled, one because of a pharmacy error, two with no invasive tumor on pretreatment biopsy slides, and two with no invasive tumor on post-treatment surgery. The record does not explain how these cases were treated in the analysis, give the final analysis population, or state whether missing values were imputed. It also does not define an intention-to-treat, per-protocol, or other analysis population.
These omissions limit evaluation of potential bias and precision. The listed reasons show why some outcome measurements were unavailable, but do not establish whether the missingness was related to the unobserved Ki67 changes. The statistical analysis plan and detailed missing-data strategy 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 |
|---|---|---|---|
| Tamoxifen Pre and Post Breast Surgery | 1 | 52 | 1.9% |
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 |
|---|---|
| Tamoxifen Pre and Post Breast Surgery | 42 of 52 |
Most frequent serious adverse event terms
| Event term | Organ system | Tamoxifen Pre and Post Breast Surgery |
|---|---|---|
| Thromboembolic Event | Vascular disorders | 1 of 52 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Tamoxifen Pre and Post Breast Surgery |
|---|---|---|
| hot flashes | Vascular disorders | 19 of 52 |
| Nausea | Gastrointestinal disorders | 11 of 52 |
| fatigue | General disorders | 5 of 52 |
| headache | Nervous system disorders | 5 of 52 |
| insomnia | Psychiatric disorders | 5 of 52 |
| cough | Respiratory, thoracic and mediastinal disorders | 4 of 52 |
| Blurred Vision | Eye disorders | 3 of 52 |
| Bloating | Gastrointestinal disorders | 3 of 52 |
| Constipation | Gastrointestinal disorders | 3 of 52 |
| Diarrhea | Gastrointestinal disorders | 3 of 52 |
Serious events with the highest arm-level rate: thromboembolic event (1.9%).
The registry lists 52 participants at risk for serious adverse events and 1 affected, with a thromboembolic event shown among the top serious terms at 1.9%. It also lists 52 participants at risk for other adverse events and 42 affected. These are registry counts for the study group; they do not provide a comparison with an untreated or alternative-treatment group.
In general, an adverse event is an event recorded during a study and does not, by itself, establish that the intervention caused it. A serious adverse event is a classification of seriousness, not a measure of how likely an event is to be caused by treatment. The registry figures therefore describe reported events in the study, not a causal effect of Tamoxifen.
The record does not provide further details about event timing, duration, severity beyond the serious classification, or individual participants’ clinical circumstances. It also does not report a comparative safety analysis. The listed counts should be interpreted as descriptive registry data rather than as proof of a treatment-related risk or absence of risk.
12. What the Result Does, and Does Not, Mean
The study addresses a focused biological question: whether tumor Ki67 expression changes during a 7-day pre-surgical Tamoxifen window. Its single-group structure and named endpoint make the question clear. However, the registry record does not report the numerical primary result, so it does not establish the direction or magnitude of the observed mean change, its precision, or the result of a significance test.
The registry’s description of an aim to demonstrate significant change is not a result. Without the mean estimate and 95% confidence interval, readers cannot determine whether the observed change was small or large, whether it was estimated precisely, or whether the data were compatible with a range of effects. The record also supplies no clinical threshold for deciding what magnitude of Ki67 change would be important.
Even if a numerical within-group change were available, the design would still limit causal interpretation. There is no separate comparator group, and the registry lists no masking. A pre/post change can describe what happened in the observed group over the study period, but it does not provide the same evidence as a randomized comparison. This distinction is especially important when moving from a biomarker result to claims about clinical outcomes.
The primary endpoint is a tumor measure, while the secondary outcomes concern symptoms, long-term adherence, and an association between symptom and Ki67 changes. These questions are related but not interchangeable. A biomarker change would not alone establish a change in symptoms, adherence, or longer-term clinical outcomes. The numerical results for the secondary outcomes are not reported in the registry record.
The registry does report safety counts, including one serious adverse event and other adverse events in the study group. Those counts are descriptive and do not establish causation or comparative risk. Taken together, the record allows a cautious account of the study design and its reported event counts, but the missing outcome estimates prevent a statistical judgment about the primary efficacy question.
13. Why This Trial Matters Statistically
This trial illustrates how a short preoperative window can be used to ask a focused question about change in a tumor marker. In general, treatment-window studies can generate information about biological responses over a defined period, while their design and endpoint determine what conclusions can reasonably follow. Here, the stated primary timeframe is 7 days, and the endpoint is change in Ki67 expression.
It also shows why a clearly stated endpoint is not enough to evaluate evidence. The registry identifies the measure, summary type, and confidence level, but does not report the numerical mean change or interval. Without those estimates, readers cannot judge effect size or precision. A stated goal of statistical significance cannot stand in for the actual result.
The single-group design highlights the distinction between describing change and estimating a comparative effect. A within-group observation can be informative about what was recorded among participants, but without a control group it cannot distinguish intervention-associated change from changes that might have occurred for other reasons. This is a general design principle, not a claim about what happened in this study.
The record’s account of non-evaluable primary measurements also demonstrates why analysis populations and missing-data methods matter. Reasons for unavailable tissue measurements are listed, yet the final analysis population and handling of missing values are not reported. Those details would help readers assess how much information contributed to the estimate and whether exclusions could affect interpretation.
Finally, the planning illustration is based on hypothetical two-arm assumptions, whereas the actual study is single group. Keeping planning assumptions separate from the completed study’s design prevents sample-size illustrations from being misread as observed power or evidence of an outcome. The record therefore offers a useful setting for distinguishing design, estimation, missingness, and interpretation.
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 main limitation for interpreting the primary outcome is that the numerical result is not reported in the registry record. The mean percentage change in Ki67, its 95% confidence interval, and any significance-test result are unavailable. This prevents assessment of the endpoint’s direction, magnitude, and precision, regardless of the study’s stated objective.
The single-group design has no concurrent control group, and the registry records no masking. Consequently, the design does not support a randomized between-group comparison. The record does not describe any other design feature that could provide such a comparison.
Primary endpoint evaluability is another concern. The registry identifies participants who could not be evaluated because of rescheduled surgery, a pharmacy error, or absence of invasive tumor in the specified tissue specimens. It does not state the number included in the primary analysis, the analysis population definition, or the approach to missing measurements. The effect of these unavailable measurements on the estimate cannot be assessed.
Although the record specifies a mean and 95% confidence interval, detailed analysis procedures are not reported. The precise calculation of percentage change, any adjustment, and the assumptions used to obtain the interval are not stated. The registry also does not report a sample-size justification for the single-group design or a detailed statistical analysis plan.
There are five outcome measures, but the record does not describe any multiplicity strategy or the analysis sequence. Numerical results for the secondary outcomes are not reported in the registry record. Safety information is descriptive and lacks a comparative group, so it cannot establish relative risk or causation. These limitations constrain interpretation of efficacy, safety, and the relationship among the listed outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Preoperative Window of Endocrine Therapy Provides Information to Increase Compliance — NCT01614210.
- Registry record last updated 2018-08-01; status last verified 2018-07.
- Results first posted 2017-12-13.
- 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
This completed Phase 2 study enrolled 52 participants with newly diagnosed hormone-positive clinical stage 1 or 2 breast cancer. It is recorded as single group, with no masking and allocation not applicable. The listed interventions were Tamoxifen and breast cancer surgery. The registry summary describes 21 doses before and after surgery.
The primary outcome was change in tumor Ki67 expression, expressed as percentage change and specified as a mean with a 95% confidence interval over 7 days. The registry record does not report the numerical primary estimate, confidence interval, or test result. It lists secondary outcomes for FACT-ES symptom scores, long-term endocrine therapy adherence, and correlation between Ki67 and symptom changes.
The record identifies reasons for primary endpoint non-evaluability and lists serious and other adverse-event counts. It does not report the final primary analysis population, missing-data method, or detailed statistical plan. Its planning illustration uses hypothetical two-arm assumptions and should not be mistaken for the single-group study design or for observed power.