Preoperative Olaparib Endometrial Carcinoma Study (POLEN): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Preoperative Olaparib Endometrial Carcinoma Study (POLEN) (NCT02506816), a registered phase not stated study. The primary outcome is Expression of Cell Cycle-related Proteins.

2. Clinical Question

POLEN asked whether short exposure to olaparib was associated with changes in cell cycle-related proteins measured in endometrial tumor tissue. The study focused on biological effects in tumor samples, rather than testing clinical efficacy or safety as primary objectives.

The study is described as exploratory, with a biological primary endpoint. Its purpose was to identify biomarker changes associated with short exposure that might be potential predictors of activity. A potential predictor is not itself evidence of clinical benefit: it requires further evaluation, and this record does not report such validation.

3. Trial Design

POLEN is described as a preoperative, multicenter, pharmacokinetic-pharmacodynamic study of single-agent olaparib in patients with early-stage endometrial carcinoma. The registry status is COMPLETED. The record lists a start of 2016-02 and primary completion of 2018-07, with enrollment of 36 participants.

The intervention was olaparib, with drug exposure lasting 28 (+/- 5) days before the planned tissue assessment. The primary endpoint compares tumor biomarker expression at baseline and Day 28 (+/- 5). The study description emphasizes paired biological assessment within participants, but the registry record does not report the precise statistical method used to analyze those measurements.

The registry record does not describe a randomized comparison or identify a control intervention. Allocation is not stated, and a note associated with the record cautions that the arms are not a like-for-like control comparison. The available description therefore does not support interpreting the study as a randomized estimate of olaparib relative to another treatment or to no treatment.

The primary objective was biomarker-focused. The record explicitly characterizes clinical efficacy and safety as not being primary objectives. Secondary outcomes include protein expression of biomarkers related to PARP inhibition, plasma levels of olaparib, and the number of participants with olaparib-associated toxicities. Four outcome measures and two analyses are indicated, but further details about the analyses are not reported in the registry record.

The study was exploratory and used a short preoperative exposure. That design can support examination of biological measurements after exposure, but it does not by itself establish whether a biomarker change predicts later clinical outcomes. The registry record does not report the protocol’s sample-size justification, interim analyses, or a full statistical analysis plan.

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: Out of 49 patients initially considered for study eligibility, 9 did not sign the ICF and 4 did not meet eligibility criteria (screen failures). Out of 36 patients who were treated and included in the overall analysis and safety, 5 were excluded from the primary and secondary analysis because of no valid samples for biomarker characterization.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis was performed in the complete population of analysis (N = 36) and in the population of biomarkers (N = 31).

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: A total of 36 patients were treated and included in the overall population and safety analyses.

6. Primary Endpoint

The registry lists the primary outcome as Expression of Cell Cycle-related Proteins, measured over Baseline and Day 28 (+/- 5).

The primary endpoint is the expression of cell cycle-related proteins in endometrial tumor tissue, measured as an H-score at baseline and Day 28 (+/- 5). The named proteins are cyclin D1, Ki67, and active caspase-3. The registry describes the outcome as a change from baseline after 28 (+/- 5) days of olaparib-based therapy and specifies a mean with standard deviation as the summary format.

The H-score combines staining intensity and the proportion of tumor cells at each intensity: 1x(%light staining) + 2x(%moderate staining) + 3x(%strong staining). The stated score range is 0 to 300. The record describes 0 as absence of staining and 300 as maximum staining. It also links lower staining to lower tumor proliferation and better outcome, and maximum staining to higher tumor proliferation and worse outcome. These are the registry’s descriptions of the scale; they do not establish that a measured change predicts a clinical outcome in this study.

Biomarker measurements are used in this design to look for biological changes during a short exposure. They can help characterize a possible pharmacodynamic effect, but a change in a laboratory or tissue measure is not equivalent to proof of clinical efficacy. Numerical H-scores, changes, and variability estimates are not reported in the registry record, so the magnitude and precision of any observed biomarker changes cannot be assessed from it.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it is a score on a scale, summarized by a mean and standard deviation. The registry record describes measurements at baseline and Day 28 (+/- 5), with change from baseline as the endpoint. It does not report the numerical measurements or the exact statistical procedure used to analyze them.

What does a mean change describe?

General statistical explanation: a within-person change compares a participant’s measurement at follow-up with that participant’s baseline measurement. A mean change then averages these individual changes across the analysis population. This is different from comparing two unrelated groups, because the two measurements come from the same participant. The registry description identifies change from baseline but does not report how individual values were paired, how a participant without both measurements was handled, or whether any adjustment was made.

A mean can be useful for describing the average direction and size of change, but it may not represent every participant’s experience. The standard deviation describes the spread of values around the mean, not the precision of the mean itself. Large variation among participant measurements can make a group average less representative of any one participant. No numerical means or standard deviations for the primary outcome are reported in the registry record.

How should the H-score be understood?

The H-score combines the percentage of tumor cells showing light, moderate, and strong staining, assigning weights of 1, 2, and 3 to those staining categories. The formula is 1x(%light staining) + 2x(%moderate staining) + 3x(%strong staining), and the stated range is 0 to 300. Thus, the measure combines staining intensity and the proportion of cells in each category into one score. It is not a direct count of tumor cells or a clinical outcome.

As a general measurement principle, a composite score condenses information and can be easier to compare than separate staining categories. It also means that different patterns of staining may contribute to the same overall score. The record does not report the underlying staining distributions or numerical H-scores, so it is not possible to inspect how the composite values arose.

What do uncertainty measures add?

General statistical explanation: a confidence interval communicates uncertainty around an estimate under a particular analysis method. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. The interval is not a guarantee that the true value lies within its limits. No confidence intervals for the primary endpoint are reported in the registry record.

A p-value, when reported, addresses how compatible the observed data are with a specified null model and its assumptions. It does not measure the size or clinical importance of a change. The registry record does not report a p-value or identify a hypothesis test for the primary endpoint. Without an estimate and uncertainty measure, neither statistical evidence nor precision can be judged from the endpoint description alone.

Why does the comparison structure matter?

General statistical explanation: a controlled comparison can help separate change associated with an intervention from change that might arise over time or through other factors. In a before-and-after study without a like-for-like control, the observed change is not automatically attributable to the intervention. The registry record does not describe a randomized control comparison; allocation is not stated, and its accompanying note says the arms are not a like-for-like control comparison.

The sample-size assumptions described for planning use equal allocation between two arms, a two-sided significance level of 0.05, and a normal approximation. They specify detecting a stated fraction of the observed effect. These assumptions define a planning illustration, not a reported design feature or a substitute for results. The registry record does not report its sample-size justification, and planning counts are not observed power.

Why can over-dispersion matter?

General statistical explanation: over-dispersion occurs when observed variability is greater than a statistical model expects. If a model assumes less variation than the data actually contain, standard errors can be too small and uncertainty can be understated. The H-score endpoint is summarized as a mean and standard deviation, but the registry record does not identify a model for the primary analysis or report evidence about over-dispersion. This concept is therefore relevant as a general modeling consideration, not as a reported feature of POLEN’s analysis.

The registry indicates four outcome measures and two analyses, but does not specify the precise analytic methods, handling of repeated measurements, adjustment for covariates, or approach to multiple testing. Those details are necessary for a fuller assessment of how the numerical results were produced; they are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record indicates four outcome measures and two analyses. It names the primary outcome and lists secondary outcomes concerning protein expression of biomarkers related to PARP-inhibition, plasma levels of olaparib, and participants with olaparib-associated toxicities. It does not report how the two analyses relate to the outcomes or whether any multiplicity adjustment was planned or used.

General statistical explanation: when several outcomes or tests are examined, the chance of obtaining at least one apparently notable result can increase. Statistical approaches can account for multiple testing, or an analysis can designate a primary outcome and treat other findings as exploratory. The registry record identifies a biological primary endpoint and describes the study as exploratory, but a specific multiplicity strategy is not reported. No inference about adjustment should be made from the count of outcomes or analyses alone.

The primary outcome description identifies a complete population of analysis of N = 36 and a population of biomarkers of N = 31. The record does not explain why these analysis populations differ, whether the difference reflects missing measurements, or how missing values were addressed. It also does not state whether participants needed baseline and follow-up samples to enter the biomarker population.

General statistical explanation: missing outcome data can affect the estimate if the availability of a measurement is related to the value that would have been observed. Analyses may use different assumptions or methods to address missingness, and interpretation depends on what was planned and what was observed. The registry record does not report a missing-data method, reasons for unavailable data, or sensitivity analyses. The difference in population counts alone is not enough to determine the amount, cause, or likely impact of missing data.

Details about the statistical analysis plan, interim analyses, and sample-size justification are not reported in the registry record. As a result, the planned hierarchy of analyses and the handling of incomplete observations cannot be reconstructed from the available description.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: post-surgical wound infection (2.8%).

The safety summary lists 36 participants at risk for serious adverse events and one participant affected. It lists 36 participants at risk in the other adverse-event category and 15 participants affected. The record reports zero deaths. These figures are counts of participants, not estimates from a controlled comparison.

Post-surgical wound infection is listed among the top serious adverse-event terms at 2.8%. The registry record does not give a separate event count for this term in the information, so the percentage should not be converted into a count. The term identifies an event recorded in the serious-event listing; it does not establish that olaparib caused the event.

General statistical explanation: an adverse-event count describes what was recorded in the study population. Without a like-for-like control group, it cannot quantify how much the event rate differs from what would have occurred under another treatment or no treatment. Counts also do not convey timing, duration, severity beyond the serious classification, or the relationship of an event to the intervention unless those details are reported.

The registry description says clinical efficacy and safety were not primary objectives. The safety figures should therefore be read as a descriptive summary, not as a comparative safety analysis or a complete basis for causal conclusions.

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

The record describes an exploratory, preoperative study of short-duration olaparib exposure, designed to assess biological changes in tumor samples from patients with early-stage endometrial carcinoma. Its primary endpoint concerns H-scores for cyclin D1, Ki67, and active caspase-3 measured at baseline and Day 28 (+/- 5). The stated analysis populations are N = 36 and N = 31.

The registry record does not report numerical results for those biomarker measurements. It therefore does not establish whether the scores changed, the direction or magnitude of any change, how variable the measurements were, or how precisely a change was estimated. No statistical significance or clinical importance can be inferred from the endpoint description alone.

The study’s stated purpose was to identify biomarker changes associated with short exposure as potential predictors of activity. A potential predictor is a research hypothesis, not a validated clinical predictor. Establishing predictive value would require evidence connecting biomarker measurements to relevant outcomes and showing that the relationship holds in appropriate analyses. Such validation is not reported in the registry record.

The record also does not describe a randomized, like-for-like control comparison. A change between baseline and follow-up, if reported, would not by itself show that olaparib caused the change. Time-related changes and other influences would remain possible explanations without a suitable comparison.

The safety summary reports one participant with a serious adverse event, 15 participants in the other adverse-event category, and zero deaths among the listed groups of 36 at risk; post-surgical wound infection is listed at 2.8%. These are descriptive figures, not comparative estimates. Overall, the registry information supports understanding the study’s biological aim and measurement plan, but not a conclusion about clinical efficacy, a causal treatment effect, or validated biomarker prediction.

13. Why This Trial Matters Statistically

This trial is statistically notable for asking a focused biological question in a preoperative setting. Measuring tumor tissue before and after a short exposure can make within-participant biomarker change the central object of interest. That differs from a trial designed primarily to compare clinical outcomes between treatment groups.

The distinction between a biological endpoint and a clinical endpoint matters. A tissue score can help investigate whether a treatment is associated with a measurable biological response, but a biomarker finding does not automatically translate into a patient-centered benefit. The registry explicitly describes the primary objective as exploratory and says clinical efficacy and safety are not primary objectives.

The study also illustrates why the comparison structure is essential to interpretation. The registry does not establish a randomized, like-for-like control comparison, and allocation is not stated. A before-and-after measurement can describe change over the study period, but attributing that change to an intervention requires assumptions that a controlled comparison can help assess.

Population definitions matter as well. The record reports a complete population of analysis of N = 36 and a biomarker population of N = 31. Without an explanation for the distinction or details of missing-data handling, readers cannot determine why the endpoint population differs or how that difference may affect interpretation.

Finally, this record shows the value of separating design information from numerical findings. It identifies the measure, time points, and intended summaries, yet numerical primary endpoint results are not reported. A clear outcome definition is useful, but it cannot substitute for estimates and measures of uncertainty when judging what the data show.

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 registry description is limited for evaluating the primary biomarker result because it does not report numerical H-scores, changes from baseline, standard deviations, confidence intervals, or test results. The magnitude, direction, and precision of the endpoint cannot be assessed.

The study is described as exploratory, with clinical efficacy and safety not identified as primary objectives. Biomarker measurements can address biological questions, but the record does not report evidence that these markers predict clinical outcomes or that changes in them correspond to patient benefit.

No randomized, like-for-like comparator is described. Allocation is not stated, and a note in the registry record cautions that the arms are not a like-for-like control comparison. This limits causal interpretation of any within-study change.

The record reports a complete analysis population of N = 36 and a biomarker population of N = 31, but does not explain the difference or report a missing-data approach. It is therefore not possible to assess whether missing measurements could have influenced the biomarker findings.

The study enrolled 36 participants and used short exposure of 28 (+/- 5) days. Those features define the scope of the record; the registry does not provide information to assess precision beyond the absent estimates, or to determine how well findings would extend beyond the described population and setting. Details of the statistical analysis plan, sample-size justification, interim analyses, and multiplicity handling are not reported in the registry record. The safety summary is descriptive and does not provide a controlled comparison.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Preoperative Olaparib Endometrial Carcinoma Study (POLEN) — NCT02506816.
• Registry record last updated 2020-11-30; status last verified 2019-11.
• Results first posted 2019-11-15.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

POLEN (NCT02506816) is a completed, multicenter, preoperative study of olaparib in early-stage endometrial carcinoma. The registry lists MedSIR as sponsor, enrollment of 36, a start of 2016-02, and primary completion of 2018-07. Exposure was 28 (+/- 5) days.

The primary endpoint was change from baseline in H-scores for cyclin D1, Ki67, and active caspase-3, measured at baseline and Day 28 (+/- 5). The record describes a complete analysis population of N = 36 and a biomarker population of N = 31, but does not report numerical primary endpoint results.

Secondary outcomes include protein expression of biomarkers related to PARP-inhibition, plasma levels of olaparib, and participants with olaparib-associated toxicities. The safety summary lists one serious adverse event among 36 at risk, 15 participants in the other adverse-event category among 36 at risk, zero deaths, and post-surgical wound infection at 2.8%. The study is described as exploratory, and clinical efficacy and safety were not primary objectives.