Prospective Study on Embolization of Intracranial Aneurysms With Pipeline™ Embolization Device: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Prospective Study on Embolization of Intracranial Aneurysms With Pipeline™ Embolization Device (NCT02186561), a na na study. The primary outcome is The Percentage of Participants With the Occurrence of Major Stroke in the Territory Supplied by the Treated Artery or Neurological Death at 12-Months Post Procedure.

2. Clinical Question

In plain terms, the study was designed to describe a safety outcome after device treatment, rather than to estimate the difference between two assigned treatments. Its primary endpoint combines a specified type of stroke with neurological death. That combination makes the endpoint a measure of serious neurological harm during the stated follow-up period; it is not itself a measure of aneurysm closure or overall clinical benefit.

The registry gives the endpoint population as participants enrolled and implanted with the investigational device. It also says missing 12-month evaluations without evidence of the endpoint were handled using multiple imputation. The registry does not report the primary endpoint’s observed percentage, its uncertainty interval, or the number of participants contributing observed endpoint assessments. Those omissions mean the stated clinical question can be identified, but its answer cannot be read from the posted primary result information.

Because the study has no randomized or other listed control group, its results cannot directly establish how the observed outcome compares with another treatment or with no treatment. The design can describe events among the participants studied, subject to the registry’s endpoint and missing-data approach. The record’s stated purpose was to assess safety and effectiveness, but the primary endpoint addresses safety. The effectiveness findings are not detailed in the available record information.

3. Trial Design

PREMIER is a prospective, single-group device study of the Pipeline Embolization Device. The registry lists 197 participants enrolled and identifies intracranial aneurysm as the condition. Its brief summary describes the intended population as people with unruptured, wide-neck intracranial aneurysms. The intervention listing includes the Pipeline Embolization Device and Pipeline Flex Embolization Device, while the arm description refers to treatment with the Pipeline Embolization Device.

The record lists allocation as not applicable and masking as none. In practical terms, this is not a randomized comparison in which participants are assigned to different treatment groups, and no masking is listed. A single-group study can describe outcomes observed after treatment, but it cannot isolate a treatment effect by comparing the treated participants with a concurrent randomized control group. Differences from other studies or populations would not, by themselves, resolve that limitation.

The study is listed as completed. Its recorded start date is 2014-07-24, and its primary completion date is 2016-11-18. The phase is listed as not applicable. The sponsor is Medtronic Neurovascular Clinical Affairs. These registry entries characterize the study record; they do not provide the full protocol or explain the reasoning behind design choices.

The primary endpoint timeframe is up to 12 months after the procedure. The registry also lists secondary outcomes concerning major stroke or neurological death at 30 days, delayed intracerebral hemorrhage after 30 days, and successful deployment of the investigational device. In total, the record identifies five outcome measures, but it does not report analyses in the information. The primary endpoint population is described as participants enrolled and implanted with the device, rather than simply everyone enrolled. The number actually implanted is not reported in the registry record.

No comparator arm is listed, so the study’s central statistical task is descriptive estimation of outcomes in a treated group. The registry record does not state a sample-size justification, detailed analysis plan, interim-analysis plan, or how the study’s design was selected. Those details should not be inferred from the enrollment figure or the single-group structure.

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.

Enrollment

Reasons for not completing this period:

Subjects Implanted With Device

30-Day Post Index Procedure Visit

Reasons for not completing this period:

180- Day Post Index Procedure Visit

Analysis population for the primary outcome, as defined in the registry: Participants enrolled and implanted with the Investigational Device (ITT)

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Intent to Treat Population was defined as all enrolled participants in whom deployment of the Investigational device was attempted.

6. Primary Endpoint

The registry lists the primary outcome as The Percentage of Participants With the Occurrence of Major Stroke in the Territory Supplied by the Treated Artery or Neurological Death at 12-Months Post Procedure, measured over Up to 12 Months Post Procedure.

The primary endpoint is the percentage of participants with major stroke in the territory posted by the treated artery or neurological death by 12 months after the procedure. The registry defines the stroke component as a stroke resulting in focal neurological deficit for 24 hours or more, an increase in the NIH Stroke Scale of at least 4, and an imaging correlate. The endpoint therefore combines clinical signs, a specified change on a neurological scale, and imaging evidence for the stroke component. Neurological death is included as an alternative event in the composite.

In general, a composite endpoint combines more than one event type into a single outcome. This can summarize a clinically important family of events, but the combined result does not show how much each component contributed. Here, without component-level primary results, a reported composite percentage would not by itself tell a reader how many participants had stroke or how many had neurological death. Those component counts are not reported in the registry record.

A safety endpoint of this kind is used to describe serious neurological events during a defined follow-up period. The time boundary matters: this primary measure concerns outcomes through 12 months, whereas the registry separately lists a 30-day outcome and other secondary outcomes. Results for one timeframe should not be treated as results for another. The primary endpoint’s observed percentage and precision are not reported in the registry record, so its magnitude cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In general, a single-group study describes outcomes among participants who receive the study intervention. For a binary endpoint such as whether a participant experienced an event, the basic descriptive target is the proportion with the event in the defined analysis population over the stated timeframe. That proportion depends on the endpoint definition, who is included, how follow-up is handled, and how missing outcomes are treated.

PREMIER is listed as a single-group study, with allocation not applicable and no masking. No control group is listed. Consequently, the design can describe the observed safety experience in the study group, but does not provide a randomized between-group contrast. In general, a randomized contrast helps distinguish outcomes associated with assigned treatments from other differences between groups. That kind of contrast is not available. The registry record does not report an alternative comparator analysis.

How should the primary endpoint be understood?

The endpoint is a binary composite: a participant either meets the defined event criteria or does not, within the 12-month timeframe. The composite includes major stroke in the territory posted by the treated artery or neurological death. The stroke definition requires focal neurological deficit lasting 24 hours or more, an increase in the NIH Stroke Scale of at least 4, and an imaging correlate. These criteria specify what counts for the primary safety measure; they do not report how many participants met it.

In general, composite endpoints can make a set of related outcomes easier to summarize as one measure. Their interpretation depends on the component definitions and the relative contribution of each component. A single composite percentage cannot, on its own, show the separate frequency of stroke and neurological death. The registry does not provide component-specific primary results.

What does an estimate’s uncertainty convey?

In general, a confidence interval presents uncertainty around an estimate under a particular statistical method and set of assumptions. It is not a guarantee that the true value lies within the interval, and it is not a measure of clinical importance. For an event proportion, the interval helps readers judge how much statistical uncertainty remains around the reported proportion. An estimate without an interval gives less information about precision.

The primary endpoint estimate and confidence interval are not reported in the registry record. No p-value or primary inferential comparison is reported in the information. Since there is no listed control group, readers should not expect a treatment-versus-control estimate from this design unless one is separately reported; no such comparison is reported.

How does the registry describe missing outcomes?

The registry states that missing data for participants who did not complete the 12-month post-procedure evaluation, without evidence of major stroke in the treated artery territory or neurological death, were imputed using multiple imputation. In general, multiple imputation is a method for representing uncertainty about missing values by creating multiple plausible completed datasets under a specified model, analyzing each, and combining the results. It can preserve uncertainty due to missingness better than treating a single guessed value as known.

That general description does not identify which variables were used in the imputation model, how many imputations were made, what assumptions were used, or whether sensitivity analyses were conducted. Those details are not reported in the registry record. The missing outcome count and the primary result after imputation are also not reported. Therefore, readers can identify the stated approach but cannot independently assess its implementation or the effect of missingness on the estimate.

Why are the adverse-event timepoints separate?

The registry lists CEC-adjudicated adverse-event summaries through 1-year, 2-year, and 3-year follow-up. In general, safety summaries grouped by follow-up time describe what has been recorded within a particular observation window. They should be interpreted in their stated categories and timeframes. A longer follow-up summary does not automatically represent a new, independent group of participants or a separate risk estimate. The record does not specify in the information whether participants or events can recur across timepoint summaries, so figures should not be added or treated as independent observations.

The record reports participants at risk and affected counts for serious and other adverse events, as well as deaths. These are descriptive safety data, not a substitute for the primary endpoint analysis. The serious-event terms and percentages offer additional detail, but the record information does not establish that those terms are mutually exclusive or that they account for all events. It is safest to read each listed category on its own terms.

What analysis details remain unknown?

The registry information does not report a sample-size justification, a detailed statistical analysis plan, an interim-analysis plan, or the full set of analysis methods. It lists five outcome measures and zero analyses in the available record information. The endpoint population is defined as enrolled and implanted participants, but the number implanted is not stated. These gaps limit assessment of analysis choices and completeness. General statistical principles can explain why such details matter, but they cannot fill in what the registry record does not say.

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("PREMIER")
n      <- c(141)
events <- c(3)
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  PREMIER  141  3  2.1  0.4  6.1  0.7  6.1  0.8  6.0

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies five outcome measures, including the primary endpoint and secondary outcomes concerning a 30-day stroke or neurological death measure, delayed intracerebral hemorrhage after 30 days, and successful device deployment. It lists zero analyses in the record information. The multiplicity strategy, if any, is not reported in the registry record. In general, testing several outcomes can increase the chance of at least one apparently unusual result when each is assessed separately. A prespecified hierarchy or adjustment can address some of that concern, but no such plan should be assumed.

The primary endpoint description does identify a missing-data procedure. Participants who did not complete the 12-month evaluation and had no evidence of the specified event were handled using multiple imputation. In general, imputation methods rely on assumptions about how missingness relates to observed information and the unobserved outcome. The registry record does not report the imputation model, variables used, number of imputations, or sensitivity analyses. It also does not report the number of missing outcomes or the resulting primary estimate.

The endpoint population is participants enrolled and implanted with the investigational device, described as ITT. The number implanted is not reported in the registry record, so it is not possible to reconcile that population with the enrollment total from the information. The analysis population used for each secondary outcome is also not detailed in this summary. The registry record does not report a fuller analysis-population definition, a protocol deviation approach, or how other incomplete follow-up was handled.

These omissions do not establish that a particular method was or was not used beyond what is explicitly described. They limit how fully a reader can evaluate the risk of missing-data bias, the handling of multiple outcomes, and the relationship between enrollment and analyzed participants.

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: aneurysm repair (6.4%), headache (4.3%), cerebral haemorrhage (2.8%), coronary artery disease (2.1%), gastrointestinal haemorrhage (2.1%).

The registry lists CEC-adjudicated adverse events through 1-year, 2-year, and 3-year follow-up. For each period, it reports 141 participants at risk for the serious and other adverse-event summaries. The serious-event affected counts are 39 through 1-year, 49 through 2-year, and 60 through 3-year; the other-event affected counts are 107, 112, and 112, respectively. The listed death counts are 1, 1, and 2 across those timepoints.

These figures are descriptive summaries for the categories and timeframes shown. In general, counts across follow-up summaries should not be added unless the record establishes that they are distinct, non-overlapping observations. The registry information does not specify enough to treat these timepoint counts as independent or to infer how events were distributed across participants. The counts also do not provide a direct comparison with another group.

The record lists serious-event terms including aneurysm repair at 6.4%, headache at 4.3%, cerebral haemorrhage at 2.8%, coronary artery disease at 2.1%, gastrointestinal haemorrhage at 2.1%, and chest pain at 2.1%. These terms and percentages add detail to the safety summary, but they do not replace the primary endpoint result. The denominator and specific calculation basis for each term are not described in the information, so the percentages should be read as posted rather than reinterpreted. The serious adverse-event figures are not the primary endpoint’s event percentage.

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

The study record establishes what investigators set out to assess: safety and effectiveness of the Pipeline device for unruptured, wide-neck intracranial aneurysms. It also gives a precise primary safety endpoint and states that participants with missing 12-month evaluations in specified circumstances were handled using multiple imputation. Those details let readers understand the intended outcome and some of the planned data handling.

What the record information does not provide is the numerical primary endpoint result. The percentage of participants meeting the 12-month composite, its uncertainty interval, and component-specific results are not reported in the registry record. Without them, this page cannot describe the observed frequency or precision of the primary safety outcome. The absence of a posted result is not evidence that events did or did not occur at a particular rate.

The study design also limits what could be inferred even if a group-level percentage were available. Because the record describes one group and no randomized comparator, an outcome rate would describe the studied participants, not a treatment difference relative to another group. In general, outcome rates in a single group can be affected by participant characteristics, clinical context, outcome ascertainment, and follow-up. The design alone cannot separate these influences from effects associated with treatment.

The posted adverse-event summaries provide additional observations over 1-year, 2-year, and 3-year periods. They include affected counts, deaths, and selected serious-event terms. These figures are useful for understanding what safety categories the registry reports, but they should not be conflated with the primary endpoint, and they do not create a controlled comparison.

Accordingly, the defensible reading is narrow: the registry describes a completed, prospective, single-group device study, specifies its primary safety measure, and posts selected adverse-event summaries. The available information does not support a numerical conclusion about the primary endpoint or a comparative conclusion about treatment. Assessment of the primary outcome would require a reported estimate and its analysis details; comparative assessment would require suitable comparative evidence.

14. Why This Trial Matters Statistically

This study illustrates an important distinction in clinical-trial reporting: defining an outcome and reporting its result are separate steps. The registry gives a detailed primary endpoint, including the clinical, scale-based, and imaging criteria for the stroke component. It also identifies the follow-up timeframe and an approach to missing evaluations. These details make the question interpretable, but without the endpoint estimate they do not answer it.

The design is statistically important as well. A prospective single-group study can collect outcomes in a defined cohort and describe the resulting safety experience. It does not offer the same inferential structure as a randomized comparison. Readers must distinguish a within-group description from evidence about a difference between treatments. That distinction applies even when a registry states that a study aims to assess safety and effectiveness.

The record also shows why analysis population and missing data matter. Enrollment is listed as 197, while the primary endpoint population is described as enrolled and implanted participants. Those are not necessarily interchangeable descriptions, and the number implanted is not reported. The stated use of multiple imputation signals that incomplete endpoint follow-up was anticipated or occurred, but the missing-data details and result are not available in the information. Without those details, the path from enrollment to analysis cannot be fully reviewed.

Finally, the safety summaries use several follow-up timepoints and categories. Reading each category within its stated timeframe, rather than combining counts or treating them as a comparator, helps prevent overinterpretation. Overall, PREMIER is a useful example of how a record can disclose design and endpoint definitions while leaving key inferential quantities unavailable. Statistical interpretation depends not only on what was measured, but also on what results and analysis details are reported.

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 consequential limitation for interpreting the posted primary outcome is that its numerical result is not reported in the registry record. The percentage, uncertainty interval, and component-specific counts are unavailable. This prevents direct assessment of the event frequency and precision, irrespective of how clearly the endpoint is defined.

The single-group design provides no listed concurrent comparator. It can describe outcomes in the study group, but cannot directly estimate a between-group difference. No allocation to comparison arms is listed, and masking is listed as none. The registry record does not report whether any external comparison was planned or conducted.

The enrollment total is 197, but the primary population is described as enrolled and implanted participants. The number implanted and the number included in the endpoint analysis are not reported in the registry information. The record states that multiple imputation was used for some missing 12-month evaluations, but does not report the missingness count, model details, assumptions, or sensitivity analyses. These gaps prevent an independent review of how incomplete outcome data may affect the result.

The registry lists five outcome measures but does not report analyses in the available information. The multiplicity approach, sample-size justification, interim-analysis plan, and full statistical analysis plan are not reported in the registry record. The adverse-event summaries provide selected counts and terms, but their definitions and overlap across timepoints are not fully. These limitations concern the available record information; they should not be taken as proof that a method or analysis was absent from the study itself.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Prospective Study on Embolization of Intracranial Aneurysms With Pipeline™ Embolization Device — NCT02186561.
• Registry record last updated 2019-12-27; status last verified 2019-12.
• Results first posted 2019-05-21.
• 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

PREMIER (NCT02186561) is a completed, prospective, single-group study of the Pipeline Embolization Device in intracranial aneurysm. The record lists 197 participants enrolled, no masking, and no allocation to a comparator group. The primary endpoint is the percentage of enrolled and implanted participants with major stroke in the territory posted by the treated artery or neurological death through 12 months after the procedure.

The registry defines the stroke component and describes multiple imputation for specified missing 12-month evaluations. It also posts CEC-adjudicated adverse-event summaries through 1-year, 2-year, and 3-year follow-up. The primary endpoint estimate and its uncertainty are not reported in the registry record. The record information therefore supports description of the study design and outcome definitions, but not a numerical interpretation of the primary result or a comparison of treatment effects.