Olaparib in Adults With Recurrent/Metastatic Ewing's Sarcoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Olaparib in Adults With Recurrent/Metastatic Ewing's Sarcoma (NCT01583543), a na phase 2 study. The primary outcome is Objective Response Rate of Olaparib.

2. Clinical Question

The registry record describes a Phase II study of olaparib in adults with recurrent or metastatic Ewing's sarcoma following failure of prior chemotherapy. Its primary question is whether participants had an objective response, defined as a complete or partial response according to RECIST 1.1. The record identifies the primary outcome as the number of participants with an objective response over a timeframe of 2 years.

This setup can describe outcomes among participants receiving the study intervention, but it does not directly compare those outcomes with a concurrent control group. Consequently, the record as posted cannot establish how the observed response experience would differ from an alternative treatment or from outcomes without the intervention. The registry entry also does not report a response estimate, uncertainty interval, or inferential test for the primary endpoint. The clinical question is therefore identifiable from the outcome definition, while its numerical answer is not available in the registry record.

3. Trial Design

This is a Phase II, single-group study sponsored by Massachusetts General Hospital. The registry lists an enrollment of 12 and marks the study as completed. The intervention is olaparib, with the arm description specifying 400mg PO BID continuously. The study title and brief description place the population as adults with recurrent or metastatic Ewing's sarcoma following failure of prior chemotherapy.

The allocation is listed as not applicable, and masking is listed as none. Those details are consistent with the single-group model recorded for the study: the record does not describe random assignment or a blinded comparison. There is no separate control arm against which to make a like-for-like treatment comparison. Any observed outcomes would therefore be outcomes in the enrolled group, rather than an estimate of a randomized contrast between olaparib and another intervention.

The primary outcome is the number of participants with an objective response, with response defined as complete response or partial response under RECIST 1.1 and a timeframe of 2 years. Progression-free survival and overall survival are named as secondary outcomes, along with the number of participants experiencing a grade 3 or 4 clinically significant and related adverse event. The registry lists four outcome measures overall, but the posted details do not provide the observed primary response count or the analysis results for these outcomes.

The registry lists a study start of 2012-05 and primary completion of 2014-01. These administrative dates and the completed status describe the study record, but they do not supply outcome results. The statistical analysis plan, protocol-level sample-size justification, analysis populations, and details about interim analyses are not reported in the registry record. The enrollment figure alone does not establish how many participants contributed evaluable data to any particular outcome.

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

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 Objective Response Rate of Olaparib, measured over 2 years.

The primary endpoint is titled “Objective Response Rate of Olaparib,” while its stated measure is the number of participants with an objective response. The registry defines objective response as complete response plus partial response, determined using RECIST 1.1. A complete response means disappearance of all target lesions. A partial response is defined as at least a 30% decrease in the sum of the longest diameter of target lesions. The stated timeframe is 2 years.

Response endpoints are used to record whether tumor measurements meet prespecified criteria for shrinkage or disappearance. Combining complete and partial responses gives a binary outcome for each participant: a participant either meets the stated response definition or does not. The registry’s description, however, specifies a count of participants, not the denominator or a calculated response proportion. Although the endpoint title uses the term “rate,” the posted measure is a count. The observed count and any derived rate are not reported in the registry record.

That distinction matters when reading the endpoint. A count needs a defined analysis population and a known number of participants with assessable response data to be interpreted as a proportion. The total enrollment is 12, but the record does not say whether all enrolled participants were included in the primary endpoint analysis. It also does not report how missing or unevaluable response assessments were handled. The response criteria explain what qualifies as an event; they do not, by themselves, reveal how many events occurred or how precise an estimate would be.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a binary endpoint represent?

In general, a binary endpoint classifies each participant according to whether a defined event occurred. For this study, the event is an objective response: a complete response or partial response under RECIST 1.1. A participant whose assessment meets either response category contributes to the event count; the endpoint description does not say how participants with missing or unevaluable assessments are classified. The registry identifies the measure as a count of participants rather than reporting a rate or a model-based effect estimate.

Binary outcomes can be summarized with a count and, when the denominator is specified, a proportion. A proportion gives the fraction of an analysis population meeting the endpoint. Its interpretation depends on knowing which participants are included in the denominator, how endpoint assessments were made, and how unavailable observations were handled. For this study, the record reports enrollment of 12 but does not report the primary outcome count, the analysis denominator, or the missing-data approach. A response proportion therefore cannot be reconstructed from the registry entry.

What do the response criteria contribute?

RECIST 1.1 provides the response definitions stated in the registry. Complete response requires disappearance of all target lesions. Partial response requires at least a 30% decrease in the sum of the longest diameter of target lesions. The primary endpoint combines these categories. Standardized definitions help make the endpoint more explicit than an informal judgment of improvement, but a definition alone is not an outcome result. The registry does not report the assessments, the response count, or any adjudication procedure beyond identifying RECIST 1.1.

How should uncertainty be understood?

In general, a point estimate describes the result observed in a study, while a confidence interval describes the uncertainty around that estimate under a specified statistical method. A narrower interval generally indicates greater precision for the quantity being estimated; a wider interval indicates greater uncertainty. The width also depends on the amount of usable information and on the endpoint’s variability. These are general statistical principles, not reported findings for this study. The registry does not post a response estimate, confidence interval, or method for calculating one.

A p-value, in general, measures how compatible the observed data are with a specified null hypothesis under a chosen model. It is not a measure of the size or clinical importance of an effect, and it does not replace an estimate with an uncertainty interval. No p-value or primary-outcome hypothesis test is reported in the registry record. The absence of a reported test means no conclusion about statistical significance can be drawn from this entry.

What does a single-group design permit?

In general, a single-group study can describe outcomes within the group receiving an intervention. Without a concurrent comparison group, the study does not directly estimate the contrast between that intervention and an alternative. Changes or events observed in participants may be due to multiple influences, and the design cannot isolate the intervention’s contribution through randomized comparison. This is a design limitation, not a claim about what the results would show if reported.

The registry identifies this study as single-group, with allocation not applicable and no masking. It does not describe random assignment. Consequently, the primary endpoint, if reported, would be interpreted as a response experience in the enrolled group. The entry does not provide the comparator data needed for a randomized treatment-effect estimate. A historical or external comparison is not specified in the registry record and should not be assumed.

What do sample-size illustrations mean?

In general, a sample-size calculation estimates how much information a planned study might need under stated assumptions. It is not an observed result and does not show whether a completed study found an effect. The registry’s planning description states a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it also describes planning for stated fractions of an observed effect. For time-to-event calculations, the description refers to total events, while other calculations are expressed as participants per arm.

Those are planning assumptions, not a description of this trial’s actual single-group design. The posted record does not report the protocol’s sample-size justification, the assumptions used by the investigators when designing the study, or an inferential analysis plan. Planning illustrations based on a reported effect do not establish observed power. They should not be interpreted as showing that the study was adequately powered or that its result was statistically conclusive. The record’s enrollment of 12 is a study characteristic, not by itself a measure of statistical power or precision.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variation is greater than a statistical model assumes. If a model assumes less variability than is present, uncertainty estimates can be too small and tests can appear more conclusive than warranted. Model choice and its assumptions therefore matter for outcomes such as counts or rates. The registry identifies the primary measure as a participant count and does not report an over-dispersion assessment or model. No claim about over-dispersion or a count-model analysis can be made for this study.

More broadly, a statistical method is interpretable only alongside its target estimand, assumptions, analysis population, and missing-data handling. These details are not reported in the registry record for the primary outcome. The posted entry identifies the endpoint and its criteria, but not the analysis that would connect observed assessments to an estimate and its uncertainty.

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")
n      <- c(12)
events <- c(0)
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  12  0  0.0  0.0  26.5  0.0  24.2  0.2  24.7

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when investigators evaluate several outcomes or conduct multiple statistical tests. In general, examining more outcomes can increase the chance of at least one apparently unusual finding if no adjustment or prespecified testing strategy is used. Whether adjustment is appropriate depends on the scientific questions and the analysis plan. The registry lists a primary outcome and secondary outcomes of progression-free survival, overall survival, and a grade 3 or 4 clinically significant and related adverse-event measure. The analysis strategy for these outcomes, including any multiplicity procedure or hierarchy, is not reported in the registry record.

The entry identifies four outcome measures overall, but it does not provide the complete statistical analysis plan or results for those measures. It lists zero analyses. Therefore, the registry does not establish which analyses were conducted, whether the primary outcome was tested against a particular null value, or how any secondary analyses would be interpreted alongside the primary outcome. No multiplicity-adjusted or unadjusted inferential result is reported.

Missing-data handling is also not reported. The record does not state how participants without an evaluable response assessment were treated, whether participants who discontinued treatment remained in the endpoint analysis, or how incomplete follow-up affected survival outcomes. These choices can change the population represented by an endpoint estimate. Enrollment of 12 does not establish that 12 participants contributed data to every outcome.

The analysis populations are not reported in the registry record. It is therefore not possible to determine whether the endpoint was intended to use all enrolled participants, participants who received treatment, or another defined group. The protocol and statistical analysis plan are not reported, so details should not be inferred from the outcome labels alone.

12. Safety Results

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

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: death (16.7%), hemoptysis (8.3%).

The registry’s safety summary lists 12 participants at risk in the olaparib group. It records 2 participants affected by serious adverse events and 11 participants affected by other adverse events. These are separate registry summary categories; the record does not provide enough detail to infer overlap between them or to determine how many individual events occurred. The serious-event terms listed include Death at 16.7% and hemoptysis at 8.3%.

These figures describe what the adverse-event summary records, not a comparison against another group. Because the study is single-group, there is no randomized control group in this record for estimating a difference in event frequency. The percentages attached to the listed terms should be read as registry-reported figures; they do not by themselves establish causality. The registry summary does not establish that each listed event was caused by olaparib.

The secondary outcome description refers to participants experiencing a grade 3 or 4 clinically significant and related adverse event. The summary figures do not, by themselves, show which events met that specific outcome definition. The number of deaths as a separate participant outcome, and details of timing or relationship to treatment, are not reported in the registry record. The death term listed among serious events should not be treated as a complete account of mortality without those details.

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

The registry record establishes that a Phase II, single-group study enrolled 12 adults with recurrent or metastatic Ewing's sarcoma following failure of prior chemotherapy and evaluated olaparib. It defines the primary outcome as the count of participants with complete or partial response under RECIST 1.1 over 2 years. Those details identify the study question and the way a response was intended to be classified.

The record does not report the observed primary response count, an estimated response rate, or an uncertainty interval. It also lists zero analyses. As a result, the posted record does not support a numerical conclusion about how many participants responded or how precise an estimate would be. The absence of a posted result should not be read as a finding of no response; the result is simply not reported in the registry record.

The design also sets limits on what an outcome could show. There is no concurrent comparator or random assignment described, so an outcome in the olaparib group would not, by itself, provide a randomized comparison with another treatment. It would describe the enrolled group rather than establish a comparative treatment effect. No treatment recommendation follows from the registry information.

The safety summary reports participants affected by serious and other adverse events and gives selected serious-event terms. These descriptive data do not establish that the events were caused by the intervention, nor do they replace the specifically defined secondary adverse-event outcome. Further details about event ascertainment, attribution, timing, and analysis are not reported in the registry record.

Overall, the record supplies design and endpoint definitions but not the primary efficacy result or inferential analysis. Readers can identify what the study set out to measure, but should distinguish that objective from an observed finding. The distinction is especially important when a registry entry has an outcome title but no posted result for that outcome.

14. Why This Trial Matters Statistically

This study illustrates a basic distinction in clinical-trial reporting: an endpoint definition is not the same as an endpoint result. The registry specifies a response criterion based on RECIST 1.1 and states a 2-year timeframe, but it does not report the primary response count. Statistical interpretation depends on the observed data and the analysis used, not solely on the label attached to an outcome.

The study is also a useful example of how design determines the scope of inference. A single-group study can report what happened among participants in that group, but it lacks a randomized comparator for estimating a contrast between interventions. Recognizing that boundary is essential when reading any future or external account of the study; a within-group outcome should not automatically be read as a comparative treatment effect.

Enrollment of 12 makes the analysis population and uncertainty especially important to identify, but the registry does not state how many participants contributed evaluable data to the primary endpoint. Without that denominator and a reported estimate, precision cannot be assessed. The record also does not give the statistical plan, missing-data approach, multiplicity strategy, or protocol sample-size justification. Those details are not optional embellishments when interpreting estimates; they help clarify what was measured and how robustly.

The posted safety summary adds descriptive information, but it does not resolve the missing efficacy result or establish event causation. Taken together, the registry entry shows why readers should separate study purpose, design, outcome definitions, observed results, and inferential conclusions. Each answers a different statistical question, and only some of them are reported in this record.

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 main limitation for statistical interpretation is that the registry record does not report the primary endpoint result. Although the endpoint is defined as a count of participants with objective response, neither that count nor an estimated rate is posted. No confidence interval, p-value, or analysis is reported, and the registry lists zero analyses. This prevents assessment of the magnitude and precision of the primary outcome.

The study is single-group and has no randomized comparator recorded. Thus, even if a within-group outcome were available, it would not supply a randomized estimate of the difference between olaparib and another approach. The registry also does not identify an external comparator or a prespecified benchmark, so neither should be assumed.

Enrollment is listed as 12, but the number of participants included in the primary endpoint analysis is not reported. The record does not explain missing assessments, discontinuation, follow-up completeness, or the analysis population. These omissions make it impossible to determine whether the enrolled group and the endpoint denominator were the same.

The outcome definition gives RECIST 1.1 response criteria, but the record does not report assessment details or how response data were handled in analysis. It also does not provide the statistical analysis plan, protocol sample-size justification, interim-analysis details, or multiplicity strategy. The adverse-event summary provides selected counts and terms, but does not clarify attribution or give the details needed to equate those summaries with the specifically described grade 3 or 4 related-event outcome.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Olaparib in Adults With Recurrent/Metastatic Ewing's Sarcoma — NCT01583543.
• Registry record last updated 2017-05-19; status last verified 2017-04.
• Results first posted 2017-05-19.
• 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

NCT01583543 is a completed Phase II, single-group study sponsored by Massachusetts General Hospital. The registry lists enrollment of 12 and describes olaparib at 400mg PO BID continuously for adults with recurrent or metastatic Ewing's sarcoma following failure of prior chemotherapy. Allocation is not applicable and masking is none.

The primary outcome is the number of participants with complete or partial response under RECIST 1.1, with a timeframe of 2 years. Progression-free survival, overall survival, and a grade 3 or 4 clinically significant and related adverse-event outcome are listed as secondary outcomes. The primary response result and analysis are not reported in the registry record, which lists zero analyses.

The adverse-event summary lists 12 at risk, 2 affected by serious events, and 11 affected by other events. Serious-event terms include Death at 16.7% and hemoptysis at 8.3%. The registry record does not report the primary statistical analysis plan, analysis populations, or missing-data methods.