Study to Assess the Safety and Effectiveness of the Penumbra System: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Assess the Safety and Effectiveness of the Penumbra System (NCT00334061), a non-randomized phase 2 study. The primary outcome is Percentage of Participants With Revascularization of the Occluded Target Vessel.

2. Clinical Question

3. Trial Design

This was a Phase 2, prospective, single-arm, multi-center clinical evaluation of the Penumbra System. The registry classifies its allocation as non-randomized and its model as single group; masking is listed as none. Enrollment was 125. The study is marked completed. The recorded start is 2006-06 and primary completion is 2007-06.

A single-group design can describe outcomes among participants who received an intervention, but it does not create a contemporaneous control group. It therefore cannot by itself separate outcomes associated with treatment from the course of the condition, other care, participant selection, or differences in how outcomes were assessed. Random assignment and masking, which can help limit certain biases in comparative trials, were not features of this trial according to the registry record.

The primary endpoint was revascularization of the occluded target vessel at 3-Month Post-Procedure, defined with a TIMI score of 2 or 3. The primary population is identified as intention to treat. The registry also lists secondary outcomes concerning NIHSS improvement or mRS status at discharge or 30 days, mRS status at 90 days, all-cause mortality, and symptomatic hemorrhage. Their observed results and analysis details are not reported in the registry record.

The brief summary states that the clinical evaluation was intended to assess safety and effectiveness in patients with acute ischemic stroke secondary to intracranial large-vessel occlusive disease. The registry record does not report the recruitment process, detailed inclusion and exclusion criteria, study locations, treatment procedures, follow-up completeness, or reasons for any exclusions after enrollment. The stated enrollment should therefore not be assumed to describe the number with complete outcome data.

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

Analysis population for the primary outcome, as defined in the registry: Intention to Treat

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 Percentage of Participants With Revascularization of the Occluded Target Vessel, measured over 3-Month Post-Procedure.

The primary endpoint is the percentage of participants with revascularization of the occluded target vessel at 3-Month Post-Procedure. The registry defines revascularization as a Thrombolysis in Myocardial Infarction (TIMI) score of 2 or 3 after use of the Penumbra System. It explains that TIMI scores describe blood flow at the treated vessel, with 0 designating no flow and 3 designating normal flow. Thus, the specified endpoint treats scores of 2 or 3 as meeting the revascularization definition.

A binary percentage endpoint classifies each assessed participant as either meeting or not meeting a prespecified outcome definition, then expresses the frequency of that outcome in the assessed population. This kind of measure can communicate how often the target-vessel flow criterion was reached in a single-group study. It does not, by itself, indicate how much an outcome differs from what would have happened without the intervention.

The endpoint’s clinical meaning depends on the timing, measurement process, and availability of follow-up assessments. The registry identifies the timing and score threshold, but does not report further details about adjudication, measurement procedures, or missing endpoint data. Although the endpoint definition is present, the observed percentage and an uncertainty estimate are not reported in the registry record. Its magnitude and precision therefore cannot be evaluated from the registry information described in the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group estimate describe?

As a general statistical concept, a single-group percentage describes the frequency of an outcome among the participants included in that analysis. For this trial, the intended primary measure is the percentage meeting the defined revascularization criterion. Such a measure can be informative about the observed experience of the enrolled group, provided the outcome data and analysis population are adequately described. It does not estimate a treatment contrast because the design has no concurrent comparison group.

A comparison is needed to distinguish an outcome under an intervention from the outcome that might have occurred under an alternative. In a non-randomized, single-group study, the latter is not observed in a comparable group. Historical expectations or external data, if used, would require their own supporting details; none are reported in the registry record. The record therefore cannot support a randomized treatment-effect interpretation.

What does the outcome definition contribute?

A prespecified endpoint definition makes clear which observations count as an event. Here, the registry defines revascularization as a TIMI score of 2 or 3 after use of the Penumbra System, and explains that the score describes blood flow at the treated vessel. A threshold turns a graded score into a binary outcome for the percentage measure. This can make a result easier to interpret as the share meeting a defined criterion, although it also means that observations on either side of the threshold are categorized differently.

Interpretation also depends on how the score was obtained and whether assessment was consistent. The registry record does not report details about assessor training, blinding of outcome assessors, central review, or adjudication. Masking for the study is listed as none, but that alone does not establish how each endpoint was assessed. Those measurement details are not reported in the registry record.

How should uncertainty be understood?

General explanation: a point estimate is an estimate from the observed data, while a confidence interval expresses uncertainty around that estimate under specified statistical assumptions. For a binary percentage, uncertainty is influenced by the number of participants with usable outcome information and the observed distribution of outcomes. A reported percentage without its denominator can be difficult to interpret, and an estimate without an interval does not show its precision.

The record does not report the primary result, its denominator, a confidence interval, or the statistical method used to calculate it. Enrollment is listed as 125, but enrollment is not necessarily equivalent to the number included in a particular outcome analysis. The primary population is described as intention to treat; the record does not provide further definitions of that population or explain how participants with missing measurements were handled.

Why does the design matter for inference?

Randomization is a general method for making treatment groups comparable, on average, with respect to measured and unmeasured baseline characteristics. This study was non-randomized and had a single group, so that protection against confounding through random assignment is absent. The design can describe what was recorded after treatment, but it cannot establish that an outcome rate differs from the rate under an alternative strategy.

Masking is another general design feature that can reduce the influence of expectations on treatment delivery or outcome assessment. Masking is listed as none. The record does not report whether outcome assessors were otherwise separated from treatment decisions or whether any objective review procedure was used. It would be inappropriate to infer either a particular bias or its absence from the masking entry alone.

What can be learned from the reported safety information?

General explanation: adverse-event percentages describe event reporting within a specified group and period; they do not establish causation. Interpretation depends on definitions, surveillance, duration, and whether participants could experience more than one event. A serious adverse event is not interchangeable with a primary efficacy outcome, and event-term percentages may not represent mutually exclusive categories.

The record reports serious adverse events affecting 65 participants among 125 at risk and lists several serious-event terms with percentages. It does not report the event ascertainment procedures, participant follow-up for safety, or whether terms overlap. Deaths are not numerically reported in the adverse-event information. The secondary outcome of all-cause mortality is listed, but its result is not reported in the registry record.

What analysis plan is available?

The registry record lists no analyses. It does not report the statistical model or calculation method for the primary endpoint, any prespecified hypothesis test, confidence-interval method, covariate adjustment, interim analysis, or protocol-based sample-size justification. These details should not be inferred from the study phase or design label. In general, analysis choices affect how estimates and uncertainty are calculated; without a reported plan, those choices cannot be assessed.

The registry record also does not report a multiplicity strategy for the primary and secondary outcomes. Multiple outcome assessments can raise the chance of a false-positive finding when formal tests are conducted without adjustment. That general concern does not imply that such tests were performed: no analysis results are listed. A robust statistical interpretation would require the protocol or analysis plan and the actual endpoint results, neither of which is 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("Penumbra System")
n      <- c(125)
events <- c(102)
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  Penumbra System  125  102  81.6  73.7  88.0  73.9  87.4  73.9  87.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary revascularization endpoint and secondary outcomes covering NIHSS improvement or mRS status at discharge or 30 days, mRS status at 90 days, all-cause mortality, and symptomatic hemorrhage. When a study evaluates multiple outcomes, general statistical practice distinguishes the primary question from additional questions and considers whether formal testing across outcomes needs a multiplicity strategy. Without such a strategy, interpreting isolated p-values across many tests can overstate the strength of evidence. The registry record does not report a multiplicity plan, and it lists no analyses.

Outcome definitions are not outcome results. The registry record does not report results for the primary endpoint or the listed secondary outcomes, nor does it give confidence intervals or test statistics. The absence of these results prevents an assessment of the direction, magnitude, or precision of the outcomes. The record does not report whether any interim analyses were planned or conducted.

The primary analysis population is identified as intention to treat. The registry record does not explain how that population was operationalized, whether all enrolled participants were included in the primary endpoint analysis, or how missing measurements were handled. It also does not report how many participants had endpoint data at the specified follow-up time. Missing outcome information can affect the interpretation of a percentage, especially if the availability of measurements is related to participants’ outcomes.

The registry record does not report imputation methods, sensitivity analyses, reasons for missingness, or a complete analysis-population flow. It is therefore not possible to assess the impact of missing data or to determine whether reported analyses followed a prespecified plan. These omissions should be treated as unreported information, not as evidence that missing data or multiplicity were absent.

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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cerebral edema (11.2%), intracerebral hemorrhage (8.0%), respiratory dysfunction/failure (8.0%), worsening symptoms of qualifying stroke (7.2%), infection (5.6%).

The registry reports 65 participants affected by serious adverse events among 125 at risk in the Penumbra System group. It also lists selected serious adverse-event terms with percentages: Cerebral Edema, 11.2%; Intracerebral Hemorrhage, 8.0%; Respiratory Dysfunction/Failure, 8.0%; Worsening Symptoms of Qualifying Stroke, 7.2%; Infection, 5.6%; and Other Pulmonary Complications, 5.6%.

These figures are descriptive reports for the study group. The registry record does not report a control group or a comparative analysis, so the listed frequencies cannot establish whether the device caused an event or changed its risk. The percentages for terms should not be assumed to add to the percentage of participants with any serious event: the record does not state whether categories overlap or how events were counted. It also does not report detailed safety follow-up, event adjudication, or the period used for each serious-event term.

All-cause mortality and symptomatic hemorrhage are listed as secondary outcomes, but their results are not reported in the registry record. The deaths entry in the serious-event information has no numerical value. These omissions mean the listed serious-event figures do not provide a complete account of all safety outcomes.

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

The registry record documents an evaluation of the Penumbra System in patients with acute ischemic stroke secondary to intracranial large-vessel occlusive disease. It identifies a primary outcome focused on revascularization of the occluded target vessel and specifies a TIMI threshold and assessment time. It also reports selected serious adverse-event information. These details clarify what the study set out to measure and what safety information is present in the record.

The record does not report the observed primary outcome percentage. It therefore does not establish the frequency of revascularization under the study’s definition. Nor does it report a confidence interval or other measure of uncertainty for that endpoint. A trial’s completed status and its enrollment count cannot substitute for an outcome estimate or show how precisely it was measured.

The study’s non-randomized, single-group design also places limits on causal interpretation. Even if an outcome percentage were available, it would describe the observed study group rather than a contrast against a concurrent control. The design does not show what would have happened to comparable participants under another treatment or without the device. Differences in participant characteristics, disease course, other care, and outcome assessment cannot be resolved by a single-group percentage alone.

Similarly, the serious adverse-event figures describe reported events among participants at risk; they are not comparative estimates of harms attributable to the device. The registry does not report results for the listed secondary outcomes or detailed methods for safety monitoring. It is not possible to infer missing outcome values from the endpoint definitions or event-term list.

Accordingly, the record supports a description of the study question, design, primary endpoint definition, and selected safety reports. It does not support a conclusion about the magnitude or precision of the primary outcome, comparative effectiveness, or causal safety effects. Those questions require results and analytic details that are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between defining an outcome and reporting an outcome result. The registry gives a specific primary endpoint: a percentage meeting a TIMI-based revascularization definition at 3-Month Post-Procedure. A clear threshold helps make the intended measurement interpretable, but without the observed percentage and its uncertainty, readers cannot assess the result itself.

The design also illustrates the limits of single-group evidence. A single-group percentage can describe outcomes among participants who received the intervention, but there is no concurrent comparator to anchor a treatment contrast. This is particularly important when a study’s stated purpose includes assessing effectiveness: the design and available record determine what can be inferred, not the purpose statement alone.

Safety reporting raises related questions about denominators, overlap, follow-up, and event definitions. The record gives serious-event information, yet does not describe enough of the ascertainment and analysis process to interpret the term-specific percentages as a complete safety profile. A descriptive event frequency and a causal estimate answer different statistical questions.

Finally, the record lists several secondary outcomes but no analyses or outcome results. This makes it impossible to assess how outcomes were prioritized, whether missing data affected estimates, or how multiple statistical tests were handled. The trial is therefore a useful reminder that registry design information, outcome definitions, and numerical results are separate components of evidence. Each is needed for a complete statistical appraisal.

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.

Several trial-specific limitations follow directly from the registry information. The study is non-randomized, single-group, and unmasked, with no concurrent control. Its primary endpoint may describe the treated cohort, but the design cannot provide a randomized comparison or isolate a treatment effect. The registry record does not report whether any external comparator was used in interpretation.

The primary result is not reported in the registry record. There is no stated primary-endpoint percentage, denominator, confidence interval, or analysis result. Although the primary population is identified as intention to treat and enrollment is listed as 125, the record does not explain endpoint completeness or give the number analyzed for the primary outcome. The enrolled count should not be treated as proof that every participant contributed a measured endpoint.

The registry record also does not report detailed eligibility criteria, participant characteristics, outcome-assessment procedures, or missing-data methods. These omissions restrict assessment of generalizability, measurement reliability, and potential bias. The listed secondary outcomes have no reported results, and no multiplicity plan or statistical analysis details are given. The safety information lacks detailed ascertainment and follow-up methods, and the deaths entry has no numerical value.

These are limitations of what is reported in the registry record; they do not establish that additional information was not collected or analyzed. They do mean that the record alone is insufficient for a full assessment of efficacy, precision, missingness, or comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Assess the Safety and Effectiveness of the Penumbra System — NCT00334061.
• Registry record last updated 2019-09-18; status last verified 2019-09.
• Results first posted 2009-01-12.
• 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

NCT00334061 is a completed Phase 2, prospective, single-arm, multi-center evaluation of the Penumbra System. The registry lists non-randomized allocation, no masking, enrollment of 125, a recorded start of 2006-06, and primary completion in 2007-06. The study concerned acute ischemic stroke secondary to intracranial large-vessel occlusive disease.

The primary endpoint was the percentage of participants with revascularization of the occluded target vessel at 3-Month Post-Procedure, with revascularization defined as a TIMI score of 2 or 3. The primary population is identified as intention to treat. The observed primary result, its uncertainty, the secondary-outcome results, and the statistical analyses are not reported in the registry record.

The serious adverse-event information reports 65 affected among 125 at risk and lists selected event terms with percentages. The design and reporting permit descriptive context, but not a controlled estimate of treatment effect or a complete assessment of outcome precision.