Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis (NCT03047135), a na phase 2 study. The primary outcome is PSA50 Response Rate to Olaparib for Patients With High-risk Biochemically-recurrent Prostate Cancer.

2. Clinical Question

The clinical question concerns a biomarker response in an earlier disease setting than the metastatic castration-resistant prostate cancer discussed in the registry’s background. That background describes preliminary findings from another olaparib trial: 11 / 49 evaluable patients had a PSA response, and ten of 11 responders had mutations in DNA repair genes. Those figures explain the rationale recorded for examining olaparib and biomarker relationships in this study; they are not results from the present trial.

Because this is a single-group study, its primary question is descriptive: what PSA50 response was observed among participants assessed under the study definition? It cannot, on its own, estimate how the outcome would have differed under a concurrent alternative treatment or no study treatment. The registry record does not report the primary response count or response rate, so the trial’s answer to that question cannot be determined from the posted results.

3. Trial Design

This is a phase II, single-group study of olaparib in men with high-risk biochemically recurrent prostate cancer following radical prostatectomy. The registry lists an enrollment of 51 and identifies olaparib as the intervention. The recorded regimen is 300 mg by mouth twice daily on a continuous schedule. The description specifies two 150 mg tablets per dose, approximately 12 hours apart, taken with water.

The study is not randomized: allocation is listed as not applicable, and the design is single-group. Masking is listed as none. Accordingly, there is no concurrent control group for a like-for-like comparison, and the study does not provide a randomized treatment contrast. Any description of outcomes must therefore be read as an account of what was recorded in the olaparib group, not as evidence of a causal difference from another treatment.

The registry lists a start date of 2017-03-01 and a primary completion date of 2023-05-24. Its current status is active, not recruiting. The primary outcome timeframe is recorded as 6 years 2 months. This timeframe should not be mistaken for a reported response duration or a measured follow-up result; the record does not supply the primary outcome count or a participant-level follow-up summary.

The primary outcome is the count of participants with a confirmed PSA50 response. Secondary outcomes include treatment-related adverse events assessed by CTCAE v4.0, PSA progression-free survival, PSA doubling from baseline, and duration of undetectable PSA. The registry record lists five outcome measures, but does not report results for those secondary outcomes in the registry record for this analysis. It also does not report eligibility details beyond the population description, the analysis population, or the statistical plan.

The stated enrollment describes the registry entry, not necessarily the number who received treatment, completed follow-up, or contributed to every outcome. Those counts are not reported in the registry record. This distinction matters because endpoint denominators may differ from enrollment when participants are not assessed or do not have evaluable measurements.

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

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as PSA50 Response Rate to Olaparib for Patients With High-risk Biochemically-recurrent Prostate Cancer, measured over 6 years 2 months.

The primary endpoint is the number of participants with a PSA50 response. The registry defines response as at least a 50% decline in prostate-specific antigen (PSA) from the baseline value, confirmed by a second measurement at least 4 weeks apart. Thus, it is a binary outcome at the participant level: each participant either meets the stated response definition or does not, based on the recorded measurements and confirmation requirement.

A threshold-based response endpoint can make a biomarker change easier to interpret than a collection of individual PSA measurements. Requiring a confirmatory measurement also distinguishes a sustained qualifying change from a single measurement that meets the threshold. These are general features of response definitions; the registry does not report how measurements were scheduled, how borderline or missing measurements were handled, or how the response count was analyzed.

The endpoint is a biomarker outcome, not a direct measure of symptoms, quality of life, or survival. A PSA response should therefore be interpreted within the specific definition and disease setting, rather than treated as a complete account of clinical benefit. The primary outcome timeframe is listed as 6 years 2 months, but the record does not clarify the precise assessment window or provide the observed response count. The primary result is not reported in the registry record, so neither the response frequency nor its precision can be assessed from the available results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a count of participants meeting a binary response definition. In general, a binary endpoint classifies each participant according to whether an event or response occurred. For this study, the event is a confirmed PSA50 response: PSA must decline from baseline by at least 50%, and a second measurement must confirm the decline at least 4 weeks apart. The registry record does not report the resulting count or the number assessed.

What does a response count tell a reader?

A count records how many participants meet the definition, while a denominator records how many participants were assessed under that definition. Both are needed to understand the observed frequency. The enrollment figure is not automatically the denominator for an outcome: participants might not have an assessment, might not meet the confirmation rule, or might not be included in a particular analysis. Which of these occurred, and how the primary analysis handled them, is not reported in the registry record. It would therefore be inappropriate to derive a response percentage from enrollment.

In general, an estimate based on a finite group is subject to sampling uncertainty. A confidence interval expresses a range of values compatible with the data under a specified statistical method and assumptions; it does not guarantee that the true value lies in the interval. A wider interval indicates less precision, while a narrower one indicates greater precision. No primary response estimate or confidence interval is reported in this record, so the precision of the primary outcome cannot be evaluated.

Why does the single-group design matter?

In a single-group study, outcome summaries describe participants who received the intervention, but there is no concurrent randomized group to establish what would have happened under a different condition. Random allocation helps balance measured and unmeasured factors on average across groups; without it, an observed before-and-after change can have explanations other than the intervention. This is a general limitation of uncontrolled comparisons. It does not mean the observed data are uninformative, but it restricts conclusions to descriptive interpretation and makes causal attribution more uncertain.

The registry lists no masking. In general, masking can reduce the influence of expectations on assessment or reporting, although its relevance depends on the outcome and procedures. PSA is a laboratory measure, but the record does not describe measurement procedures, laboratory masking, or adjudication. No assumptions about these procedures should be made from the masking field alone.

How should planning calculations be read?

Sample-size calculations are planning tools that relate a target effect, variability assumptions, allocation, and a chosen error rate to an illustrative number of participants or events. The record’s stated assumptions describe an illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect framed as a fraction of an observed effect. Such calculations are not observed power: they do not measure the probability that this completed study detected an effect, and they are not trial results.

Those assumptions describe a hypothetical two-arm planning comparison, whereas the registered study is single-group and has no like-for-like control arm. They should not be read as the study’s own design justification or as a description of its actual analysis. The record does not report a sample-size justification, the effect assumed in the original design, or an analysis plan. Any planning illustration based on an observed effect is especially dependent on the estimate used and should not be substituted for a prespecified design rationale.

What does over-dispersion mean in general?

Over-dispersion occurs when observed variability is greater than a statistical model expects. For event counts, this can make standard errors too small if the model assumes less variability than the data contain, leading to confidence intervals that are too narrow and tests that appear more decisive than warranted. Appropriate methods depend on the outcome and data structure. The registry record does not state that over-dispersion was assessed or that a count model was used; the primary endpoint is described as a count of participants with a binary response, and no analysis details are reported.

For time-to-event outcomes, general methods account for when events occur and for participants whose event time is not observed during follow-up. Such analyses often rely on assumptions about censoring and event hazards. The registry lists PSA progression-free survival as a secondary outcome, but does not report event counts, censoring information, an analysis method, or results. No time-to-event conclusion can be drawn from the outcome name alone.

Finally, the registry lists five outcome measures and zero analysis records. A listed outcome indicates that it was designated for assessment in the registry; it does not by itself establish that results were posted, that every participant contributed data, or that a particular model was used. Methods for missing observations, multiplicity, subgroup analyses, and analysis populations are not reported in the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Olaparib 300 mg BID")
n      <- c(51)
events <- c(13)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Olaparib 300 mg BID  51  13  25.5  14.3  39.6  15.5  38.9  15.6  38.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures: the primary PSA50 response and secondary outcomes covering treatment-related adverse events assessed by CTCAE v4.0, PSA progression-free survival, PSA doubling from baseline, and duration of undetectable PSA. Considering multiple outcomes can raise the chance of at least one apparently unusual result when each is tested separately. General approaches include prespecifying a primary outcome, adjusting for multiple tests, or treating secondary findings as exploratory. The registry record does not report a multiplicity strategy or the statistical tests used.

The record lists zero analysis records. It does not give the primary endpoint result, secondary outcome estimates, confidence intervals, or p-values. No claims about statistical significance or the consistency of outcomes can therefore be made from the posted results. The registry record also does not state whether the listed secondary outcomes were analyzed, or how any analyses were prioritized.

Missing-data handling is not reported in the registry record. The primary endpoint requires a baseline value and a confirmatory measurement; the record does not explain how a missing baseline, absent confirmation, treatment discontinuation, or incomplete follow-up affected classification. These details can change both the outcome denominator and the interpretation of a response estimate. The enrollment figure should not be assumed to be the primary analysis population.

There is no reported definition of an intention-to-treat, treated, or evaluable population. Nor does the record state whether exclusions were made after enrollment or how participants with unavailable assessments were handled. Without these details, selection into the analyzed group and the potential effect of missing outcomes cannot be assessed. These are reporting limitations, not evidence that any particular data problem occurred.

12. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anemia (2.0%), cerebrovascular accident (2.0%).

The registry’s adverse-event information lists the olaparib group with 2 serious adverse events among 51 at risk, 35 other adverse events among 51 at risk, and 0 deaths. The listed serious-event terms are anemia and cerebrovascular accident, each reported as 2.0%. These are registry counts and percentages, not estimates calculated from the primary endpoint.

The serious and other adverse-event figures are separate categories in the record. They should not be added together, treated as mutually exclusive, or interpreted as a count of unique participants; the record does not explain overlap or provide event-level detail. The figures also do not convey when events occurred, how long participants were observed, or whether a participant experienced repeated events.

The secondary outcome is described as treatment-related adverse events assessed by CTCAE v4.0, but the adverse-event summary alone does not establish attribution for each listed event. A serious adverse event is not interchangeable with an event judged related to treatment. The registry record does not provide individual causality assessments, severity grades for these terms, exposure duration, or comparative safety data. With a single-group design and no concurrent comparator, these counts describe reported events in the olaparib group rather than a comparative risk.

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

This record describes a study designed to assess confirmed PSA50 response during olaparib treatment in men with high-risk biochemically recurrent prostate cancer following radical prostatectomy. It also identifies secondary safety and PSA-related outcomes. The primary endpoint definition is specific: a decline of at least 50% from baseline, confirmed by a second measurement at least 4 weeks apart. However, the primary response count and denominator are not reported in the registry record.

Because the primary result is absent, the record does not show how often the defined response occurred or how precisely it was estimated. Missing reporting is not equivalent to no responses, and it does not establish that the endpoint was not assessed. It means that the endpoint result cannot be interpreted from the registry information available.

Even if a response estimate were available, a single-group study would not establish how outcomes compare with another treatment or with no study treatment. The design has no concurrent control arm, and the record lists no masking. It is therefore important to distinguish a descriptive outcome among participants in the study from a causal treatment effect. The registry does not report an analysis plan, missing-data methods, or an analysis population that would further clarify the result.

The adverse-event counts offer limited descriptive safety information, but they do not provide event timing, exposure-adjusted rates, participant-level overlap, or a controlled comparison. The registry’s background findings from metastatic castration-resistant prostate cancer provide context for the study rationale, not evidence of the current trial’s outcome. The current record cannot establish whether olaparib changed PSA outcomes relative to an alternative, nor can it support conclusions about survival or quality of life, which are not identified as reported results.

14. Why This Trial Matters Statistically

Statistically, the study highlights the difference between defining an outcome and reporting its result. The registry gives a clear threshold-based primary endpoint and a confirmation requirement, but does not report the corresponding response count, denominator, or uncertainty. A well-defined endpoint helps readers understand what would count as a response; without the result and its analysis population, it cannot answer how frequently that response occurred.

The single-group structure is also central to interpretation. It permits descriptive assessment of outcomes in the olaparib group, while leaving no randomized comparator for estimating a treatment contrast. The registry’s background notes earlier olaparib findings in metastatic castration-resistant prostate cancer, but the present study concerns a different disease setting after radical prostatectomy. Keeping those populations and results separate is necessary to avoid treating rationale as evidence from this trial.

The registry also lists safety and PSA-related secondary outcomes, making transparent reporting of denominators, missingness, analysis methods, and multiplicity important. These details help readers distinguish a planned outcome from a posted result and understand the precision and limitations of any estimate. In this record, those analysis details are not reported.

The statistical importance of the record is therefore not a claim about efficacy. It is the way design and reporting define the conclusions that can be supported: a single-group study can describe observed outcomes, but the primary numerical outcome and its uncertainty are not available in the registry record. The listed adverse-event counts provide only a partial descriptive view and cannot substitute for comparative evidence.

15. 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 principal limitation for interpreting the primary endpoint is that the registry record does not report its result. There is no response count, denominator, response estimate, or confidence interval. The enrollment of 51 does not establish how many participants had an evaluable baseline and confirmatory PSA measurement, and the endpoint analysis population is not reported.

The single-group design has no concurrent control group, so it cannot estimate a randomized comparison. Allocation is listed as not applicable and masking as none. The record does not report methods for reducing bias in assessment, handling missing PSA measurements, or accounting for changes in follow-up. These gaps limit the ability to evaluate how participants entered the analysis and how robust an outcome estimate might be.

The registry lists secondary outcomes but provides no outcome results or analysis records. It does not report how multiple outcomes were handled, whether any subgroup analyses were planned, or whether the analysis methods were prespecified. The stated sample-size assumptions describe a planning illustration and do not establish the study’s original sample-size justification or actual statistical power.

Safety reporting is also aggregate. The record does not describe event timing, repeated events, individual overlap between categories, exposure duration, or detailed causal assessments. The listed serious-event terms do not provide a controlled comparison or a complete account of tolerability. Finally, the registry status is active, not recruiting; the record does not establish whether all follow-up or analyses are complete. These are limitations of what can be interpreted from the registry record, not proof that relevant data were never collected.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis — NCT03047135.
• Registry record last updated 2026-10-30; status last verified 2026-10.
• Results first posted 2024-07-03.
• 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.

19. Record Summary

The registry describes a phase II, single-group study of olaparib 300 mg twice daily in men with high-risk biochemically recurrent prostate cancer following radical prostatectomy. Enrollment is listed as 51. The study started on 2017-03-01, has a primary completion date of 2023-05-24, and is listed as active, not recruiting.

The primary endpoint is the count of participants with a confirmed PSA50 response, defined as at least a 50% decline from baseline confirmed at least 4 weeks apart. The primary result, denominator, and analysis methods are not reported in the registry record. Secondary outcomes include adverse events and PSA-related measures, but their results are not reported in the information available.

The adverse-event summary lists 2 serious events among 51 at risk, 35 other events among 51 at risk, and 0 deaths. Anemia and cerebrovascular accident are each listed among serious events at 2.0%. The single-group design permits descriptive interpretation only; the record provides no concurrent comparison for estimating a treatment contrast.