Efficacy and Safety of Olaparib in Pretreated Patients With Measurable Colorectal Cancer, Stratified by Microsatellite Instability (MSI) Status: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Olaparib in Pretreated Patients With Measurable Colorectal Cancer, Stratified by Microsatellite Instability (MSI) Status (NCT00912743), a na phase 2 study. The primary outcome is Tumour Response.

2. Clinical Question

3. Trial Design

The registry describes a Phase II, open-label, multicenter trial of olaparib alone in previously treated patients with measurable stage IV colorectal cancer. Its title states that MSI status was used for stratification. The study model is recorded as single-group; allocation is NA, and masking is none. The registry lists 33 enrolled participants and marks the study completed. The recorded start is 2009-05, and primary completion is 2012-03.

The treatment question was not tested through randomized assignment to olaparib or a control treatment. MSI-H and Non-MSI-H are status-defined groups, not randomized treatment arms. The arm description names an MSI-H arm, while the adverse-event information gives figures for both MSI-H and Non-MSI-H groups. Those labels should not be interpreted as evidence of a controlled comparison. Differences between groups, if described elsewhere, could reflect differences in the patients or their disease status as well as other factors; the registry record does not provide a design that separates such influences.

The primary outcome was tumor response, defined as the number of patients who had a complete or partial response at least once during the assessment period. Assessments were specified from baseline, defined as up to 28 days before the first study drug dose, and then every 2 cycles (8 weeks) until objective disease progression, with assessment described up to 35 months. The full analysis set is described as all treated patients. Progression-free survival and overall survival are listed as secondary outcomes.

The registry record does not report a detailed protocol, the statistical analysis plan, or the rationale for the enrollment target. It also does not report results for the primary endpoint or secondary outcomes. The fact that the study is marked completed does not by itself supply those missing estimates or explain how the planned analyses were conducted.

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: Subjects with stage IV, measurable disseminated CRC incurable by surgery, with tumour progression following standard combination front-line or second-line chemotherapy, relapsed or recurrent disease within 6 months completing adjuvant or neoadjuvant chemotherapy and met all inclusion/exlusion criteria.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set - all treated patients

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 Tumour Response, measured over From baseline, i.e. up to 28 days before first study drug dose, and then every 2 cycles (8 weeks) up to objective disease progression by RECIST, assessed up to 35 months.

The primary endpoint is tumor response, expressed as the percentage of participants. The registry defines a response as a complete or partial response occurring at least once during the assessment period, according to RECIST version 1.1. The listed population is the full analysis set, defined as all treated patients. The stated precision measure is a 95% confidence interval.

A response endpoint captures whether a participant met the specified tumor-response criteria during follow-up. It is different from an endpoint that measures how long disease control lasts: a participant can meet response criteria at some assessment without that endpoint alone describing the duration of response. Progression-free survival and overall survival are separately listed as secondary outcomes, but their results are not reported in the registry record.

In general, a percentage gives the frequency of participants meeting the endpoint within the analyzed population, while a confidence interval conveys the statistical uncertainty around that estimate. A confidence interval is not a guarantee that the true value lies within its bounds; it describes a range of values compatible with the data under the analysis assumptions. Here, the registry record names the response measure and the intended confidence interval, but does not report either the observed percentage or the interval limits. Therefore, the endpoint definition can be explained, but the observed response level and its precision cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation starts with the design. This registry describes an open-label, single-group Phase II study, with allocation recorded as NA and masking as none. In general, a single-group study estimates outcomes in the participants who received the study intervention; it does not create a randomized counterfactual group for estimating what would have happened under another treatment. A response proportion from such a study can be described as an observed outcome, but it should not be treated as a randomized estimate of a treatment difference.

What does the response percentage represent?

The primary outcome is the percentage of participants with a complete or partial response at least once during the assessment period, according to RECIST version 1.1. The listed analysis population is the full analysis set, defined as all treated patients. In general, a percentage for a binary outcome is calculated from the number of participants meeting the outcome and the number included in the analysis. The registry record does not report the response count, the response percentage, or the interval limits. Those quantities therefore cannot be interpreted from this record.

The endpoint is based on whether a response occurred at least once, rather than on the duration of response. In general, repeated assessments can identify whether a participant ever meets the response criteria during follow-up, while a time-to-event outcome accounts for the time until a defined event. The assessment schedule is described as baseline, up to 28 days before the first study drug dose, then every 2 cycles (8 weeks) until objective disease progression, with assessment up to 35 months. The registry does not report how assessments that were missed, delayed, or unevaluable were handled.

What does a 95% confidence interval communicate?

In general, a confidence interval expresses uncertainty in an estimate under the assumptions of the statistical method used. A narrower interval indicates greater precision than a wider interval, while the interval's location indicates the values compatible with the observed data under that method. A confidence interval does not account automatically for every source of bias, and it does not make a nonrandomized study equivalent to a randomized comparison. Although the registry names a 95% confidence interval as the dispersion measure for the response endpoint, it does not post the interval or state the calculation method.

How should the MSI groups be understood?

The study title describes stratification by MSI status, and adverse-event information is separated into MSI-H and Non-MSI-H groups. Stratification is a way to organize participants by a characteristic; it does not itself randomize treatment or make groups exchangeable. In general, comparisons between status-defined groups can be affected by differences in patient characteristics, disease features, follow-up, or other factors. The registry says allocation is NA and the study model is single-group, so the MSI labels should not be treated as randomized treatment arms or as a concurrent control comparison.

What can be said about the statistical plan?

The registry record does not report the detailed statistical analysis plan, the method used to calculate the response interval, planned subgroup analyses, or the handling of incomplete outcome data. It lists 0 analyses in the posted results record. That listing does not establish whether analyses were conducted outside the registry; it means no analyses are recorded there. In general, an analysis plan helps clarify how outcomes, analysis populations, missing observations, and multiple endpoints are handled before results are interpreted.

Planning illustrations based on an observed effect are not the same as observed results or observed power. In general, a sample-size calculation estimates the number of participants needed under explicit assumptions, whereas observed power calculated from an observed result does not add information beyond the estimate and its uncertainty. The planning assumptions described for the illustrations include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. These are planning assumptions, not evidence that this single-group study used that design. The registry record does not report the trial's own sample-size justification, and the illustrations should not be mistaken for observed power or for the trial's actual design.

For binary outcomes, general statistical methods commonly distinguish the estimated event frequency from the uncertainty around that frequency. For time-to-event outcomes such as progression-free survival and overall survival, methods generally account for follow-up time and censoring, which occurs when the event time is not observed during available follow-up. The registry lists those outcomes but provides no definitions, estimates, confidence intervals, or analysis details for them. No assumptions about censoring, event definitions, or analysis methods can therefore be attributed to this trial from 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("MSI-H", "Non-MSI-H")
n      <- c(13, 20)
events <- c(0, 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  MSI-H  13  0  0.0  0.0  24.7  0.0  22.8  0.2  23.2
ARM  Non-MSI-H  20  0  0.0  0.0  16.8  0.0  16.1  0.1  16.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists tumor response as the primary outcome and progression-free survival and overall survival as secondary outcomes. It also reports three outcome measures, but does not provide the detailed analysis plan or explain how the listed outcomes were organized into statistical tests. A multiplicity strategy—such as a prespecified hierarchy, adjustment, or other control of the overall chance of false-positive findings—is not reported in the registry record. It is not possible to determine from the record whether or how multiplicity was addressed.

The registry does not report the primary response estimate, its 95% confidence interval, or results for the secondary outcomes. It also does not report the statistical methods used for these endpoints. As a result, readers cannot assess the estimates, their precision, or whether all planned outcome analyses are represented in the posted record. The record lists 0 analyses; this is a description of the registry posting, not proof that no analyses took place.

The primary analysis population is described as the full analysis set, defined as all treated patients. The registry does not state how participants with missing or unevaluable response assessments were handled, whether all treated participants contributed to the endpoint denominator, or how withdrawals and incomplete follow-up affected secondary outcomes. Missing-data procedures and sensitivity analyses are not reported in the registry record. In general, missing outcome information can affect both the estimate and its uncertainty, particularly when the likelihood of missingness is related to participant condition or outcome. No particular missing-data mechanism or method should be assumed for this study.

These omissions matter because endpoint definitions alone do not establish how the data were analyzed. A complete interpretation would require the estimates, uncertainty intervals, analysis populations, and methods for handling incomplete data and multiple outcomes. Those details are not reported in the registry record.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: small intestinal obstruction (15.4%), hydronephrosis (15.4%), anaemia (7.7%), nodal rhythm (7.7%), abdominal pain (7.7%).

The registry lists serious adverse-event figures separately for MSI-H and Non-MSI-H participants. In the MSI-H group, 13 participants are listed as at risk and 6 as affected by serious adverse events. In the Non-MSI-H group, 20 are listed as at risk and 3 as affected. These are group-specific counts as recorded; they should not be read as a randomized comparison because MSI status defined the groups and the study was not a randomized controlled trial.

The record also lists other adverse events: 12 affected among 13 at risk in the MSI-H group, and 20 affected among 20 at risk in the Non-MSI-H group. The registry provides no additional detail about event timing, duration, recurrence, severity grading beyond the serious-event category, or whether events were considered related to olaparib. The number of deaths is not reported in the adverse-event entries.

The listed serious-event terms include Small intestinal obstruction and Hydronephrosis, each reported as 15.4%, and Anaemia, Nodal rhythm, Abdominal pain, and Ascites, each reported as 7.7%. The registry does not specify in this record how these term percentages were calculated or assign each term to a particular MSI group. These terms and percentages should therefore be read as registry-listed safety information, not as estimates of comparative risk or proof of causation.

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

The registry record supports a description of the trial's question and design: a Phase II, open-label, single-group study of olaparib alone in previously treated patients with measurable stage IV colorectal cancer, with MSI status used to define groups. It also gives the primary response definition and some serious and other adverse-event counts. These details help clarify what the study set out to evaluate and what safety information was posted.

The record does not report the primary response percentage or its 95% confidence interval. It therefore does not permit an estimate of how often participants met the response definition or how precise that estimate was. The same limitation applies to the listed secondary outcomes, progression-free survival and overall survival, for which outcome estimates are not reported in the registry record. A study being marked completed does not substitute for those results.

Even if a response estimate were available, this design would describe outcomes among treated participants rather than provide a randomized comparison with another intervention. MSI-H and Non-MSI-H are status-defined groups, not treatment and control groups. A difference between such groups would not, by itself, establish that MSI status caused the difference or that treatment effects differ by status. The record does not report a controlled comparison that would support such an interpretation.

The safety counts indicate how many participants were recorded as affected within the listed groups, and the term percentages identify reported serious-event categories. They do not establish that olaparib caused the events, nor do they provide a comparative estimate against another treatment. The registry record does not report the additional detail needed to evaluate attribution, timing, or completeness of event ascertainment.

Accordingly, this record can be used to understand the study structure, endpoint, and the limits of the posted safety information. It cannot support a numerical conclusion about the primary efficacy outcome, its precision, or comparative treatment effects. No statement that treatment works or does not work follows from the information reported in this registry record.

14. Why This Trial Matters Statistically

This study is statistically notable because its clinical question is organized around MSI status while its registry design is recorded as single-group and nonrandomized. That distinction is important: grouping participants by a tumor characteristic is not the same as assigning them to treatment conditions. It affects what comparisons can be made and how cautiously any apparent difference between groups should be interpreted.

The primary endpoint is a binary response measure: participants either meet the complete-or-partial-response definition at least once during the assessment period or they do not. Such an endpoint can provide a clear description of observed response frequency, but a complete interpretation also requires the estimate, its uncertainty, and the analysis population. The registry record names a 95% confidence interval and defines the full analysis set as all treated patients, yet it does not report the response estimate or interval. This makes the gap between a clearly stated endpoint and an interpretable result especially visible.

The assessment schedule also underscores the difference between response and time-to-event outcomes. Response is assessed repeatedly from baseline through follow-up, while progression-free survival and overall survival are listed separately as secondary outcomes. Each outcome answers a different statistical question and needs its own definition and analysis. The registry record does not provide the secondary outcome estimates or methods.

Finally, the safety entries show why counts need context. Group-specific numbers and listed event terms are useful descriptive information, but they are not causal comparisons and cannot substitute for a control group. The record leaves important analysis details unreported, including missing-data handling and multiplicity. These limitations do not erase the descriptive value of the study; they define the boundaries of the conclusions that can be drawn from its registry 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 most direct limitation is that the registry record does not report the primary tumor-response result. Although the endpoint definition and intended 95% confidence interval are stated, neither the response percentage nor the confidence interval limits are available. The listed secondary outcomes, progression-free survival and overall survival, also have no reported estimates. The statistical analysis methods for these outcomes are not reported in the registry record.

The study is described as open-label and single-group, with allocation recorded as NA and masking as none. There is no randomized control group in the registry description. The MSI-H and Non-MSI-H categories are patient-status groups, not randomized assignments, so they cannot serve as a like-for-like control comparison. This limits causal and comparative interpretations of any outcomes reported by group.

Enrollment was 33, and the adverse-event entries are divided between groups with 13 and 20 participants at risk. The record does not give further information about how participants were selected into the groups or whether the groups were comparable on other characteristics. The serious-event terms are listed with percentages, but the record does not specify in this entry how those percentages were calculated or which group they describe. Death counts are not reported in the adverse-event entries.

The registry record does not report the protocol details or sample-size justification, the missing-data approach, or the handling of incomplete or unevaluable response assessments. It does not report whether planned analyses differed from the posted record, and lists 0 analyses. Multiplicity methods and the detailed statistical plan are not reported in the registry record. These gaps prevent a full assessment of how the planned outcomes were analyzed and how robust the results might be.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy and Safety of Olaparib in Pretreated Patients With Measurable Colorectal Cancer, Stratified by Microsatellite Instability (MSI) Status — NCT00912743.
• Registry record last updated 2016-11-09; status last verified 2016-09.
• Results first posted 2016-11-09.
• 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 identifies NCT00912743 as a completed Phase II, open-label, multicenter study of olaparib alone in previously treated patients with measurable stage IV colorectal cancer. The study enrolled 33 participants and was stratified by MSI status. Its start is recorded as 2009-05 and primary completion as 2012-03. The study model is listed as single-group, with allocation NA and no masking.

The primary endpoint was the percentage of participants with a complete or partial tumor response at least once during assessment, according to RECIST version 1.1, in the full analysis set of all treated patients. A 95% confidence interval is specified, but the response estimate and interval are not reported in the registry record. Progression-free survival and overall survival are listed as secondary outcomes, without reported results.

Adverse-event information is listed for MSI-H and Non-MSI-H groups, including serious-event counts and selected terms. The record does not report the detailed analysis plan, missing-data methods, or multiplicity handling. Its posted information therefore describes the study design and endpoints more fully than it describes the efficacy results.