Understanding Outcomes With the EMBLEM™ S-ICD in Primary Prevention Patients With Low Ejection Fraction: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Understanding Outcomes With the EMBLEM™ S-ICD in Primary Prevention Patients With Low Ejection Fraction (NCT02433379), a na na study. The primary outcome is Percentage of Patients Who Did Not Experience an Inappropriate Shock From Their EMBLEM S-ICD.

2. Clinical Question

The endpoint is framed as an 18-month inappropriate-shock-free rate, with the timeframe also described as 0 to 540 days. This is a single-group question about the proportion of participants meeting an outcome, not a randomized estimate of the difference between two treatments. The registry record names the endpoint and its confidence-interval format but does not report the observed percentage or confidence limits. Consequently, the degree to which the posted result was above, below, or near the performance goal cannot be assessed from the registry record.

3. Trial Design

This completed study, NCT02433379, evaluated the EMBLEM S-ICD System in a single group of patients receiving the device for primary prevention. The registry lists 1173 participants as the enrollment figure. Its design is identified as single group, with allocation recorded as NA and masking recorded as NONE. The study was sponsored by Boston Scientific Corporation. The listed start date is 2015-06-09, and the primary completion date is 2019-12-06.

The study description says the device was to be programmed with rate-zone cutoffs at 200 bpm and 250 bpm, intended to mimic programming settings in MADIT RIT. The arm description likewise states that subjects were implanted with an EMBLEM S-ICD with rate zones set at 200 bpm and 250 bpm per protocol. The brief description says the inappropriate-shock incidence would be compared with the incidence observed in MADIT RIT. That is not a concurrent randomized comparison: the registry lists one study group and does not report an analysis comparing the groups or cohorts.

The registry identifies four outcome measures and lists secondary outcomes concerning system- or procedure-related complications from 0 to 30 days and freedom from all-cause shock. It does not report the results for these outcomes in the record. The primary endpoint analysis population is described as implanted subjects, excluding one participant who was co-enrolled in another study that may have affected the analysis. Four participants for whom implantation was attempted but who did not receive a device were also excluded. The record does not provide further detail on follow-up completeness, analysis procedures, or the reason for the enrollment figure differing from the described implanted analysis population.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All implanted subjects were included in the analysis except for one participant who was co-enrolled in another study that may have affected the results of this analysis. There were 4 subjects who were attempted to be implanted but did not receive a device and therefore not included in the analysis. The endpoint was analyzes using intent to treat analysis.

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: UNTOUCHED Study subjects who were implanted or attempted for implant are included in the Baseline Demographics.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Patients Who Did Not Experience an Inappropriate Shock From Their EMBLEM S-ICD, measured over 18 months.

The primary endpoint is the percentage of participants who did not experience an inappropriate shock from the EMBLEM S-ICD. The stated timeframe is 18 months, also expressed as 0 to 540 days. The endpoint description calls this the inappropriate-shock-free rate and says it is compared with a performance goal of 91.6%.

This type of endpoint summarizes how often a specified event did not occur in the defined participant group during the stated observation period. In general, a proportion is easier to interpret when its denominator, event definition, observation period, and handling of incomplete follow-up are clear. The registry record gives the endpoint label and timeframe, but does not report the observed percentage, the confidence limits, or further operational details defining an inappropriate shock for this analysis.

The endpoint is clinically relevant to the study question because the study description focuses on inappropriate shocks from the implanted device. It should not be read as a measure of all device outcomes: the registry separately lists all-cause shock and system- or procedure-related complications as secondary outcomes. Nor does a single-group proportion by itself estimate a causal difference from another device or treatment. The posted primary endpoint result is not reported in the registry record, so the stated performance goal cannot be evaluated against an observed value.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a binary percentage endpoint: participants are classified according to whether they experienced an inappropriate shock, and the primary outcome is the percentage who did not. In general, this kind of endpoint is a proportion. Its interpretation depends on the event definition, the population used as the denominator, and the observation period. For this study, the stated period is 18 months, also given as 0 to 540 days. Further detail on the event definition and follow-up procedures is not reported in the registry record.

What does the confidence interval describe?

The registry specifies a 95% confidence interval for the primary endpoint, but it does not report the interval itself or the point estimate. In general, a confidence interval expresses uncertainty in an estimate arising from sampling variability under a statistical method’s assumptions. A narrower interval indicates greater precision than a wider interval, while an interval that spans a broad range indicates less precision. Neither the width nor the location of this study’s interval can be assessed without the posted estimate and limits. A confidence interval is not a probability statement about the fixed true value after the data have been observed.

How should a performance goal be understood?

The endpoint description states that the inappropriate-shock-free rate is compared with a performance goal of 91.6%. A performance goal is a benchmark against which an observed single-group result may be considered. In general, interpretation depends on the prespecified question and inferential procedure, including how uncertainty is handled. The registry record does not report the observed rate, confidence limits, p-value, or details of a statistical test against the goal. It therefore does not establish whether the result was above, below, or statistically distinguishable from the benchmark.

What does the single-group design allow?

The study is identified as a single group, and allocation is listed as NA. There is no concurrent randomized control arm in the registry description. A single-group estimate can describe outcomes among the included participants, but it cannot by itself separate the effect of the device from other influences on the observed outcome. The study description mentions comparison with the incidence observed in MADIT RIT, but the registry record does not report a comparative analysis. In general, comparisons across separate studies require attention to differences in populations, definitions, follow-up, and outcome measurement. Details needed to assess such comparability are not reported in the registry record.

Why do the analysis population and denominator matter?

The primary endpoint description says the analysis included all implanted subjects except for one person co-enrolled in another study that may have affected the analysis. It also says four people whose implantation was attempted but who did not receive a device were not included. The registry lists enrollment as 1173 but does not state the final denominator used for the primary endpoint. In general, an outcome percentage is interpretable only with a clear denominator and a clear account of how participants with missing or incomplete follow-up were handled. Those follow-up details are not reported in the registry record.

The registry identifies four outcome measures and lists secondary outcomes involving complications and all-cause shock. It lists zero analyses. No statistical analysis plan, method for handling multiple outcomes, or approach to missing observations is reported in the registry record. These omissions matter because analytic choices can affect the estimate and the strength of any inferential claim. No interim analyses, sample-size justification, or prespecified hypothesis-testing procedure is reported in the registry record.

General statistical context is useful but does not fill these reporting gaps. For a proportion, uncertainty is affected by the amount of information available and by the method used to form the interval. If participant observation varies or follow-up is incomplete, a simple percentage may not fully represent time under observation; the record does not say whether a time-to-event method was used. The endpoint is described as a percentage, and no further estimator is specified.

The sample-size material is described as a planning illustration based on a fraction of the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated illustration is not the trial’s own design justification. The registry record does not report a sample-size justification. Such planning calculations are not observed power and do not establish that the study had a particular probability of detecting an effect. They are conditional illustrations based on their stated assumptions. Since the primary outcome estimate is not reported in the registry record, the illustration should not be treated as evidence about the observed result.

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("S-ICD")
n      <- c(1111)
events <- c(1065)
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  S-ICD  1111  1065  95.9  94.5  97.0  94.5  96.9  94.5  96.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures, including the primary inappropriate-shock-free endpoint and secondary outcomes concerning system- or procedure-related complications and freedom from all-cause shock. It lists zero analyses. The record does not report a statistical analysis plan, a hierarchy for testing outcomes, or a procedure for controlling multiplicity. Without those details, it is not possible to determine whether or how the possibility of chance findings across multiple outcomes was addressed. The results for the secondary outcomes are also not reported in the registry record.

The analysis population for the primary endpoint is described as implanted subjects, excluding one co-enrolled participant whose participation in another study may have affected the analysis. Four attempted implantations that did not result in a device were also excluded. The registry does not report a final analyzed denominator, the number of participants with complete follow-up, or the handling of missing outcome data. It does not state whether participants with partial follow-up were included in a particular way, or how any censoring was treated.

These details affect interpretation because the estimated percentage depends on which participants contribute to the numerator and denominator and how incomplete observation is handled. In general, missing-data assumptions can influence both an estimate and its uncertainty. No specific missing-data method should be inferred from the endpoint description alone. Similarly, the record does not report interim analyses or a sample-size justification. The absence of those details in the registry record does not establish what procedures may have been used outside the record; it means they cannot be evaluated from the registered information.

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: multiple heart failure symptoms (8.2%), dyspnea - heart failure (2.8%), heart failure symptoms - unspecified (2.4%), chest pain - heart failure (2.2%), gastrointestinal (2.2%).

The registry lists one adverse-event group, labeled S-ICD, with 1116 participants at risk for serious adverse events and 1116 at risk for other adverse events. It reports 354 under serious adverse events, 155 under other adverse events, and 57 deaths. These are the counts recorded for the group; the registry information does not provide enough detail to infer whether categories overlap or to establish a causal relationship with the device.

The listed serious-event terms include “Multiple heart failure symptoms” at 8.2%, “Dyspnea - Heart failure” at 2.8%, “Heart failure symptoms - Unspecified” at 2.4%, “Chest pain - Heart failure” at 2.2%, “Gastrointestinal” at 2.2%, and “Pulmonary” at 1.9%. These are registry-listed terms and percentages. The record does not give further information about how these terms were grouped, the time period for adverse-event collection, or the denominator used for each displayed percentage.

In general, adverse-event counts describe events recorded during a study and do not, on their own, establish that the study intervention caused them. The at-risk counts, event definitions, observation time, severity classifications, and possible overlap among categories are important context. The listed deaths are not, by themselves, evidence about cause. The adverse-event information should therefore be read as descriptive reporting, not as a causal comparison or a complete assessment of risk relative to another group.

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

The registry record establishes that this completed single-group study asked about the proportion of implanted participants who remained free from inappropriate EMBLEM S-ICD shocks over 18 months. It also gives a performance goal of 91.6% and describes an intended comparison with incidence observed in MADIT RIT. These details define the question and its benchmark; they do not reveal the study’s primary result.

The observed inappropriate-shock-free percentage and its 95% confidence interval are not reported in the registry record. As a result, the available information cannot establish whether the observed value met the performance goal or how precisely it was estimated. The record also does not report a p-value or the result of a comparison with MADIT RIT. A completed study status does not supply these missing statistical results.

Even with an observed percentage, a single-group study would primarily describe outcomes in its analyzed population. It would not, on its own, provide a randomized estimate of the effect of choosing this device over another strategy. The historical comparison mentioned in the study description would require careful interpretation, and a comparative result is not reported in the registry record. The available information also does not permit conclusions about the causes of adverse events or deaths.

In general, an endpoint estimate and its uncertainty answer different questions: the estimate describes the observed outcome, while its interval communicates uncertainty around that estimate under the analysis method. Both are needed to judge magnitude and precision. Here, the endpoint definition and confidence-interval format are recorded, but neither the estimate nor its interval is available. The sound interpretation is therefore limited to the study’s design, population description, endpoint, benchmark, and recorded safety counts, without a claim that the device did or did not achieve a particular clinical result.

14. Why This Trial Matters Statistically

This study illustrates an important distinction between describing an outcome and estimating a comparative effect. Its primary endpoint is a participant percentage in a single group, with a stated benchmark of 91.6%. That structure can address whether the observed group-level proportion is compatible with a performance goal, if the estimate, uncertainty, and analysis are reported. It does not provide the same evidence as a randomized comparison with a concurrent control group.

The record also shows why endpoint reporting needs more than a label. The 18-month timeframe and the population exclusions are stated, but the observed proportion, confidence interval, final analysis denominator, and missing-follow-up procedures are not reported in the registry record. Without the estimate and interval, neither the outcome level nor its precision can be assessed. Without details on the analyzed population and follow-up, readers cannot fully evaluate how the percentage was constructed.

The study description’s intended comparison with MADIT RIT adds a further statistical issue: comparisons across studies do not automatically isolate a treatment effect. In general, valid interpretation depends on whether outcome definitions, participant characteristics, follow-up, and measurement are sufficiently comparable. The registry record does not provide a comparative analysis or the details needed to assess that comparison.

Finally, the record lists adverse-event counts and selected event-term percentages, but descriptive safety reporting is not equivalent to a causal comparison. Clear denominators, time periods, event definitions, and attribution methods are essential for interpreting such figures. This study therefore provides a useful case for separating the research question, the design’s inferential limits, and the information needed to assess the posted results.

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 central limitation for interpreting the primary endpoint is that the observed inappropriate-shock-free percentage and its 95% confidence interval are not reported in the registry record. The performance goal is stated as 91.6%, but without the estimate and its uncertainty, the result cannot be evaluated against that goal. The registry also does not report a p-value or other inferential result for the benchmark comparison.

The study is single group, with no concurrent randomized control arm. Although the brief description says the incidence would be compared with that observed in MADIT RIT, a comparative estimate is not reported. The registry does not provide details sufficient to assess how comparable the separate study populations or outcome ascertainment were. The listed enrollment is 1173, while the primary endpoint description gives exclusions but does not state the final analysis denominator.

Additional limitations arise from reporting gaps. The registry record does not describe the primary endpoint’s detailed event definition, how incomplete follow-up or missing outcomes were handled, or how the confidence interval was calculated. It lists four outcome measures and zero analyses, but does not report a statistical analysis plan or multiplicity procedure. Sample-size justification and interim-analysis details are not reported in the registry record.

The safety information is also limited in the registry description: the adverse-event time period, event attribution, category overlap, and denominators for the listed term percentages are not stated. These gaps do not prove that relevant procedures or details were absent from the study; they limit what can be assessed from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Understanding Outcomes With the EMBLEM™ S-ICD in Primary Prevention Patients With Low Ejection Fraction — NCT02433379.
• Registry record last updated 2025-03-24; status last verified 2025-03.
• Results first posted 2021-01-08.
• 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

NCT02433379 is a completed, single-group study sponsored by Boston Scientific Corporation. The registry lists enrollment of 1173, a start date of 2015-06-09, and a primary completion date of 2019-12-06. It assessed the EMBLEM S-ICD System in primary-prevention patients with low ejection fraction, with rate zones described as 200 bpm and 250 bpm.

The primary endpoint was the percentage of participants without an inappropriate shock over 18 months, compared with a stated performance goal of 91.6%. The analysis description excludes one co-enrolled participant and four attempted implantations that did not result in a device. The observed endpoint result, confidence interval, and comparative analysis are not reported in the registry record. Listed safety information includes 354 serious adverse events, 155 other adverse events, and 57 deaths among a group with 1116 at risk.