PARTNER II Trial: S3iCAP: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PARTNER II Trial: S3iCAP (NCT02687035), a na na study. The primary outcome is Death.

2. Clinical Question

In plain terms, the registry describes a continued-access program for people with severe aortic stenosis and intermediate surgical risk who received TAVR with the SAPIEN S3 valve. The central outcome question is whether participants died within the stated 30-day timeframe. The record names death as the primary outcome and defines its measure as a participant count.

This is a descriptive question in a single-group setting, not a randomized comparison of the valve with another treatment. The record therefore does not support estimating a relative treatment effect against a concurrent control group. It also does not establish what would have happened to these participants under a different treatment or without the procedure. The registry’s primary-outcome result is not reported in the registry record, so the primary question cannot be answered from the posted primary outcome data.

The record also names adverse outcomes, including vascular complications, dissections, bleeding events, and other outcomes. These provide additional safety context, but they do not substitute for the primary outcome or create a controlled comparison. Any interpretation should keep the study population, single-group design, and distinction between the primary endpoint and safety listings in view.

3. Trial Design

This completed study is titled the PARTNER II Trial: S3iCAP. Its official title describes a continued-access program for the SAPIEN 3 device in intermediate-risk participants. The record states that access followed completion of enrollment in the PARTNER II SAPIEN 3 intermediate-risk trial. The study condition is aortic stenosis, and its brief summary specifies severe aortic stenosis and intermediate surgical risk.

The registry describes the design as single-group. The treatment group is TAVR with the SAPIEN S3 valve; there is no separate control group in the record. Allocation is listed as NA, masking as none, and phase as NA. The planned enrollment is listed as 1822. The record gives a start of 2015-01, a primary completion of 2017-10, and a status of completed. These entries describe the registry record and do not supply further details about recruitment, follow-up procedures, or conduct.

The primary outcome is death, measured as the number of participants, with a timeframe of 30 days. The record lists 14 outcome measures and names secondary outcomes that include annular dissection, aortic dissection, major access vascular site complication, unplanned vascular surgery or intervention, retroperitoneal bleeds, gastrointestinal bleed, genitourinary bleed, and bleeding at the access site. The record does not report the results for those outcomes in the registry record for this analysis.

The registry lists Edwards Lifesciences as sponsor. Details of the protocol, eligibility criteria beyond the population description, follow-up schedule, sample-size justification, interim analyses, and analysis plan are not reported in the registry record. Because the design is single-group, outcome counts describe the treated group; they do not establish a treatment contrast with a concurrent control.

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: Participants that did not receive an Edwards device were not followed in the trial.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

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

Population: 1814 subjects received the SAPIEN 3 valve

6. Primary Endpoint

The registry lists the primary outcome as Death, measured over 30 days.

The primary endpoint is death measured as a count of participants, with a timeframe of 30 days. It is a binary participant-level outcome in the sense that each participant either experienced the event within the specified interval or did not; the registry’s stated measure is the number of participants with the event. The result for this primary endpoint is not reported in the registry record.

In general, mortality is used in clinical research because it is a clearly defined event and is directly meaningful as an outcome. A participant count can describe how often the event occurred in a study group. By itself, however, a count does not show how the outcome compares with another treatment, and it does not explain why an event occurred. Interpretation also depends on the defined timeframe and the number of participants with outcome information. The registry gives the 30-day timeframe, but the primary endpoint result and its analysis details are not reported in the registry record.

The adverse-event listing includes a death count, but the record does not identify that count as the primary endpoint result or attach the primary endpoint’s 30-day timeframe to it. It should therefore be treated as a separate safety entry rather than assumed to be the primary endpoint result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is recorded? The primary endpoint is a participant count for death within 30 days. This is a binary outcome at the participant level: the event is either recorded for a participant during the stated interval or it is not. The count is a summary of occurrences, rather than a measurement on a continuous scale. The primary result itself is not reported in the registry record, so no endpoint estimate or uncertainty measure can be interpreted from that entry.

What can a single-group design estimate? In general, a single-group study can describe the outcomes observed among participants who received the intervention. Such a description may be useful for characterizing the enrolled group and the events recorded during follow-up. It cannot, on its own, estimate what the same participants’ outcomes would have been under an alternative treatment. That unobserved alternative is the counterfactual needed for a causal treatment comparison. The registry labels this study SINGLE GROUP, lists allocation as NA, and cautions that its arms are not a like-for-like control comparison.

What do event counts mean? A count tells how many participants were recorded with an event, provided that the relevant population and observation period are clear. Counts need a denominator and follow-up context to be interpreted as a frequency in the study group. The serious adverse-event entry reports 1814 participants at risk and 818 affected. The other adverse-event entry reports 1814 at risk and 0 affected. The entry also reports 87 deaths. The record does not establish that this death count corresponds to the primary endpoint’s 30-day result. Keeping distinct outcome entries separate prevents an apparent match in terminology from being mistaken for a match in definition or follow-up.

How should uncertainty be considered? In general, a confidence interval describes uncertainty around an estimate under the assumptions of the analysis. A narrow interval indicates greater statistical precision than a wide interval, but neither width nor statistical precision alone establishes clinical importance. Statistical tests and p-values address compatibility between observed data and a specified null model; they do not measure the probability that a treatment works. No primary endpoint estimate, confidence interval, or p-value is reported in the registry record. Without these, the primary endpoint’s statistical precision cannot be described from the posted entry.

What does over-dispersion mean? In general, over-dispersion occurs when variation in event data exceeds what a chosen statistical model expects. It can make model-based uncertainty too small if the extra variation is ignored. Its relevance depends on the outcome and model used. The primary endpoint is listed as a participant count, but the record does not report a statistical model, dispersion estimate, or analysis that would establish whether over-dispersion was assessed. It would be inappropriate to infer such a modeling choice from the endpoint type alone.

How should planning calculations be read? The record describes sample-size illustrations as planning calculations based on the observed effect, not as the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. The record specifies that time-to-event illustrations use total events, while other illustrations use participants per arm. These assumptions describe hypothetical planning comparisons and do not change the actual study’s single-group design. Any resulting sample sizes are planning illustrations, not observed power, and do not show that the trial had a particular probability of detecting an effect. The primary outcome result and its inferential analysis are not reported in the registry record, so a planning illustration should not be treated as a substitute for an observed endpoint estimate.

What is not available about the analysis? The registry lists zero analyses. A statistical analysis plan, model specification, adjustment strategy, handling of repeated observations, and methods for estimating uncertainty are not reported in the registry record. General statistical principles can explain how such choices affect inference, but they cannot identify which methods were used in this study. Accordingly, interpretation should stay with the design and outcomes explicitly described in the record and avoid attributing unreported analysis methods to the investigators.

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("SAPIEN 3")
n      <- c(1814)
events <- c(12)
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  SAPIEN 3  1814  12  0.7  0.3  1.2  0.4  1.2  0.4  1.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 14 outcome measures and zero analyses. The primary outcome is death within 30 days; the listed secondary outcomes include several forms of dissection, vascular complications, unplanned intervention, and bleeding. The registry record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a plan distinguishing confirmatory from exploratory analyses.

In general, multiplicity arises when researchers test or estimate several outcomes. When many hypotheses are examined, the chance of at least one apparently notable finding can increase unless the analysis plan accounts for the number and relationship of tests. This general issue does not establish that any particular adjustment was needed or used in this trial. The registry’s outcome list alone does not reveal which outcomes were analyzed, how they were prioritized, or whether any results were intended as confirmatory.

Missing-data methods and analysis populations are also not reported in the registry record. The record does not specify how participants with incomplete follow-up were handled, how outcome status was established, or whether all enrolled participants were included in each analysis. The enrollment figure is 1822, while the serious adverse-event entry lists 1814 at risk. The record does not explain this difference, so no reason for it should be inferred. In general, incomplete outcome information can affect both estimates and their precision, and the way it is handled should be described to assess that risk.

These omissions limit statistical interpretation. They do not establish that an issue occurred, but they mean the registry information does not permit evaluation of the multiplicity strategy, missingness, or analysis-population definitions.

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 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: non-valve related readmission (19.5%), conduction/native pacer disturbance requiring pacemaker (12.1%), unplanned vascular surgery or intervention (2.9%), ischemic stroke (2.7%), major bleeding event (1.8%).

The serious adverse-event entry identifies the SAPIEN 3 group and reports 1814 participants at risk and 818 participants affected. It lists Non-valve Related Readmission at 19.5%, Conduction/native pacer disturbance requiring pacemaker at 12.1%, Unplanned Vascular Surgery or Intervention at 2.9%, Ischemic Stroke at 2.7%, Major Bleeding Event at 1.8%, and Unplanned Other Cardiac Surgery or Intervention at 1.6%. The registry also lists 87 deaths in this safety entry. These figures should be read as the entries recorded, not as proof of a treatment effect.

The record does not state in the summarized safety information the observation window for these serious-event terms or the denominator used for their percentage labels. It also does not establish that the safety-entry death count is the primary endpoint count for death within 30 days. The serious adverse-event count and the individual event terms are not interchangeable: a participant may experience more than one event, and the registry entry does not explain whether categories overlap.

In general, adverse-event summaries describe events observed and reported during a study; they do not by themselves show that the device caused each event. Without a control group and fuller event definitions and follow-up details, comparative safety conclusions cannot be drawn from these entries alone.

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

The record establishes that this was a completed, single-group continued-access study of the SAPIEN S3 valve for TAVR among intermediate-risk patients with severe aortic stenosis. It identifies death within 30 days as the primary endpoint and gives a planned enrollment of 1822. It also records serious adverse-event data for the SAPIEN 3 group, including 1814 participants at risk, 818 participants affected, and 87 deaths in the adverse-event entry. Several serious adverse-event terms are listed with percentages.

Those observations do not answer the primary endpoint question, because the primary outcome result is not reported in the registry record. The death count in the adverse-event entry cannot be assumed to be the primary endpoint result: the record does not attach the 30-day timeframe to that safety count. The listed event-term percentages also lack a stated denominator and observation window in the summarized record, which constrains interpretation of their frequency.

In general, data from a single treated group can describe recorded outcomes among participants who received the intervention. They do not provide a randomized comparison, and they cannot show what would have happened to the same people under a different treatment. The study therefore does not establish a comparative effect on death or other outcomes from the registry information. The record itself cautions that the arms are not a like-for-like control comparison.

The absence of a reported statistical analysis, uncertainty estimates, missing-data approach, and analysis-population definitions further limits evaluation of precision and robustness. These absences do not demonstrate that the study was poorly conducted; they mark what cannot be determined from the registry record. The sound interpretation is descriptive and bounded by the recorded design, outcome definitions, and available safety entries.

14. Why This Trial Matters Statistically

This study illustrates an important distinction in clinical-trial interpretation: a large enrollment count does not turn a single-group study into a controlled comparison. The registry lists planned enrollment of 1822, but the study design is single-group, with TAVR using the SAPIEN S3 valve. Its observed outcomes can describe the treated group, while a causal comparison with an alternative requires a suitable comparator and an analysis addressing differences between groups.

The record also illustrates why endpoint labels and result entries must be matched carefully. Death is the primary endpoint with a 30-day timeframe, but its primary result is not reported in the registry record. A death count appears separately in the adverse-event entry. Without a stated link between that count and the primary endpoint definition and interval, treating the safety entry as the primary result would go beyond the record.

Safety summaries also need denominators, follow-up periods, and event definitions to support interpretation. The registry gives counts at risk and affected for serious adverse events and lists several event terms with percentages, but the summarized record does not specify the denominator or observation window for those percentages. That makes it important to separate the literal registry entries from broader claims about event rates or comparative safety.

Finally, the record lists outcomes but no analyses. This highlights the difference between registering outcome measures and reporting an analysis of them. Statistical interpretation depends not only on outcome names and counts, but also on definitions, populations, follow-up, missing-data handling, and uncertainty estimates. The absence of those details in the registry record limits what can be concluded without changing the descriptive information that is 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 principal limitation for interpretation is the single-group design. There is no concurrent comparator described, so the record cannot support a like-for-like treatment comparison. The registry explicitly cautions against treating the arms as a control comparison. Outcomes in this group therefore cannot isolate the effect of the valve from other factors that may influence observed events.

The primary endpoint result is not reported in the registry record. Although death is defined as the number of participants within 30 days, the separate safety entry’s 87 deaths are not explicitly linked to that endpoint or timeframe. The primary outcome’s estimate and precision therefore cannot be recovered from the record information summarized for this analysis.

The safety listing is also limited in detail. It gives 1814 participants at risk and 818 affected by serious adverse events, and lists event terms with percentages, but the summarized record does not state the observation window or percentage denominator. It does not explain whether participants could appear in more than one event category. The 0 affected for other adverse events is a recorded entry and should not be expanded into a broader claim beyond that entry.

Other limitations arise from unreported methods. The registry does not report a statistical analysis plan, interim analyses, sample-size justification, multiplicity approach, missing-data methods, analysis populations, or primary endpoint uncertainty estimates. These details are needed to evaluate how outcomes were analyzed and how robust the estimates are. Their absence from the registry record does not show that the methods were not planned or used; it means they cannot be assessed from the record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: PARTNER II Trial: S3iCAP — NCT02687035.
• Registry record last updated 2021-04-08; status last verified 2020-12.
• Results first posted 2021-04-08.
• 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 PARTNER II Trial: S3iCAP is a completed, single-group continued-access study of the SAPIEN S3 valve for TAVR in intermediate-risk patients with severe aortic stenosis. Planned enrollment is 1822. The primary endpoint is the participant count for death within 30 days, but its result is not reported in the registry record.

The adverse-event entry lists 1814 participants at risk and 818 affected by serious adverse events, along with 87 deaths and several serious event terms reported with percentages. The record does not establish that the safety-entry death count is the primary endpoint result. No analyses are listed. Because there is no like-for-like control group, the registry information supports descriptive interpretation of the treated group, not a randomized comparative treatment effect.