Evaluation of Automatic Threshold Algorithms: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Automatic Threshold Algorithms (NCT02097290), a na na study. The primary outcome is Primary Safety Endpoint is to Evaluate the System-related Complication-free Rate.

2. Clinical Question

The registry also lists secondary efficacy endpoints concerning the percentage of commanded RVAT and LVAT tests that resulted in an appropriate outcome. Those endpoint descriptions indicate what the algorithms were being evaluated on, but the record does not report their results. The available information therefore describes the questions the study set out to address, rather than supplying estimates that answer them. It does not support a comparison with another device or care approach.

3. Trial Design

This was a completed, single-group device evaluation sponsored by Boston Scientific Corporation. The registry lists 216 participants enrolled, with the study starting in 2014-04 and primary completion in 2016-01. Its phase and allocation are recorded as NA, and masking is recorded as NONE. These entries do not describe a randomized controlled design; the registry explicitly identifies a single-group model.

Participants with an AUTOGEN CRT-D were included in the algorithm evaluation described in the arm entry. The study assessed the PaceSafe RVAT and LVAT features. The primary safety endpoint was defined at 3 months after implant, while the secondary endpoint descriptions concern commanded tests and their appropriateness. The record does not provide additional follow-up schedules for the secondary endpoints.

The enrolled population and the primary endpoint population are not interchangeable by assumption. The record lists enrollment as 216 and calls the endpoint population “Implant + Attempt Subjects,” but does not explain the population’s membership or provide a flow of participants through implantation, attempts, follow-up, or analysis. It also does not report how many participants contributed data to the primary endpoint.

Because no concurrent comparator is described, the study design can characterize outcomes in the evaluated group but cannot by itself separate device-related outcomes from background clinical events or other influences. Allocation is listed as NA, rather than as a specified assignment process. The registry record does not report a protocol-level rationale for the design, a target sample-size justification, or details of any monitoring or interim analysis. The completed status and dates describe the study record, not the completeness or precision of its outcome estimates.

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: Implant + Attempt Subjects

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 Primary Safety Endpoint is to Evaluate the System-related Complication-free Rate, measured over 3 months.

The primary endpoint is the system-related complication-free rate at 3 months post-implant. Its stated purpose is to evaluate safety of the AUTOGEN system. The endpoint description includes the implanted AUTOGEN CRT-D pulse generator, the RV and LV leads, and the RA lead if implanted. The named population is “Implant + Attempt Subjects.”

A complication-free rate summarizes the share of an identified population that does not experience the specified complication during the defined period. As a binary outcome, each participant’s status is classified according to whether the event definition is met. The interpretation depends on the event definition, follow-up window, and population used as the denominator. Those features determine what the rate represents and which clinical experiences it includes.

The registry lists the endpoint unit as a percentage of participants and identifies a 95% confidence interval as the dispersion measure. In general, a confidence interval expresses uncertainty around an estimate; it does not remove uncertainty about how outcomes were collected or who was included. The registry record does not report the observed complication-free rate, its confidence interval limits, or the number of participants with and without a qualifying complication. Consequently, the endpoint’s intended measurement is clear, but its observed value and precision cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group result describe?

In a single-group study, an outcome estimate describes the participants assessed under the study’s conditions. For a binary endpoint, each eligible participant is classified according to whether the defined event occurred; a percentage summarizes the frequency within the analysis population. Such an estimate is descriptive of that population and follow-up period. Without a comparison group, it does not estimate a contrast between treatments or establish what would have happened under an alternative.

This study is identified as a single-group model, with allocation recorded as NA and masking as NONE. The record does not describe a comparator. Accordingly, the stated design does not support a randomized treatment contrast. The study’s primary endpoint is a complication-free rate, rather than a comparison of rates between assigned groups.

What does the confidence interval add?

The primary endpoint description identifies a 95% confidence interval as its dispersion measure. In general, a confidence interval communicates the uncertainty associated with an estimated quantity under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval, but neither width nor coverage can be assessed without the estimate and interval limits. The registry record does not report those values for the primary endpoint.

A confidence interval also does not resolve ambiguity in the underlying endpoint. Its interpretation depends on which participants are included, how complications are defined and ascertained, and how missing follow-up is handled. The record names the “Implant + Attempt Subjects” population and the 3-month timeframe, but does not provide enough detail to evaluate the analysis population or missing-outcome procedures.

Why does the denominator matter?

A percentage has a numerator and a denominator. For this endpoint, the numerator would depend on the number meeting the complication-free definition, while the denominator would depend on the endpoint population and availability of follow-up. The registry’s enrollment figure does not establish that denominator. Although the adverse-event entries list 210 at risk for the CRT-D group, that figure belongs to the adverse-event reporting and is not identified as the primary endpoint denominator.

In general, excluding participants without an observed outcome can affect the meaning of an estimate, particularly if missingness is related to outcome status. Alternative assumptions about missing outcomes can yield different interpretations. The registry record does not report the amount or handling of missing primary endpoint data, so the effect of missingness cannot be evaluated.

How should the secondary endpoints be understood?

The secondary descriptions concern the percentage of RVAT- and LVAT-commanded tests that resulted in an appropriate outcome. A test-level percentage is conceptually different from a participant-level percentage: a participant may contribute tests, and the number and distribution of tests can affect what the summary represents. The record does not provide test counts, a definition of an appropriate outcome, or analysis details that would clarify whether results were summarized by test, participant, or another method. No secondary endpoint estimates are reported.

Repeated tests from the same participant may be statistically related rather than independent. In general, an analysis that treats correlated observations as independent can misstate uncertainty. Methods that account for clustering or repeated observations may be relevant, depending on the data structure, but the registry record does not report which approach was used. The same applies to any adjustment for participant characteristics or other covariates: no such analysis is described.

What can be inferred from the analysis listing?

The registry lists 7 outcome measures and 0 analyses. That administrative summary does not provide an inferential method, model, test statistic, p-value, or estimate for the primary endpoint. The record does not report a prespecified statistical analysis plan, the method used to calculate the confidence interval, or whether any interim analyses were conducted. These details should not be inferred from the endpoint wording or the existence of a listed confidence interval.

In general, statistical interpretation requires keeping the endpoint definition, study population, observed estimate, and uncertainty measure together. Here, the endpoint definition and timeframe are documented, but the observed result and analysis details are not reported in the registry record. The available information supports describing the intended measurement and design limits, not reconstructing an unreported analysis.

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("CRT-D")
n      <- c(210)
events <- c(177)
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  CRT-D  210  177  84.3  78.6  88.9  78.8  88.6  78.7  88.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 outcome measures, including the primary safety endpoint and secondary endpoints for RVAT and LVAT. It does not report how the study addressed multiplicity, such as whether outcomes were ranked in a testing hierarchy, whether significance levels were adjusted, or whether the secondary endpoints were considered descriptive. Without those details and without outcome results, the chance of false-positive findings across multiple tests cannot be assessed.

The record lists 0 analyses and does not report p-values or inferential results for the endpoints described. It also does not report a statistical analysis plan or explain whether endpoint definitions or analyses changed during the study. No conclusion about the presence or absence of multiplicity adjustment is warranted from the endpoint list alone.

The primary endpoint population is named “Implant + Attempt Subjects,” but the record does not explain its membership or give a participant flow. It does not report how many endpoint observations were missing, whether participants were excluded from analysis, or what assumptions or procedures were used for missing data. The effect of missingness on the reported endpoint is therefore not assessable.

In general, missing-data handling matters because an estimate based only on observed outcomes may differ from the outcome that would have been obtained if all participants had complete follow-up. This is especially relevant when the likelihood of missing data may be related to health status or an event. The registry record does not provide information to evaluate such relationships. It also does not report analysis populations beyond the named primary endpoint population, so the relationship between enrollment and each outcome analysis remains unclear.

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 (11.9%), gastrointestinal (6.7%), pulmonary (6.7%), dyspnea - heart failure (4.3%), cardiac arrest (3.8%).

The CRT-D adverse-event entry lists 210 at risk and 101 affected for serious adverse events; it lists 210 at risk and 81 affected for other adverse events. The entry also lists 17 deaths. These are registry adverse-event figures and should be read as separate entries, not as components of the primary complication-free rate. The record does not report whether these events were system-related or whether the deaths were related to the device or study.

The listed serious-event terms and percentages are Multiple Heart Failure Symptoms, 11.9%; Gastrointestinal, 6.7%; Pulmonary, 6.7%; Dyspnea - Heart Failure, 4.3%; Cardiac Arrest, 3.8%; and Atrial Fibrillation (Af), 3.3%. The record does not specify the denominator or further counting rules for these term-level percentages. They should not be added together or interpreted as mutually exclusive categories.

These figures describe adverse-event reporting in the registry. They do not show event timing, severity beyond the serious/non-serious grouping, relatedness, or the primary endpoint result. Those details are not reported in the registry record.

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

The study’s stated purpose was to evaluate PaceSafe RVAT and LVAT features in AUTOGEN CRT-D devices. The primary endpoint was a system-related complication-free rate at 3 months post-implant, while the secondary endpoint descriptions focused on appropriate outcomes for commanded RVAT and LVAT tests. These descriptions identify the planned questions, but the registry record does not report the corresponding outcome estimates.

Consequently, the record does not establish the observed primary safety rate, its confidence interval, or the results for either secondary endpoint. It does not permit assessment of how precisely the primary endpoint was estimated. The adverse-event entries provide separate counts and term-level percentages, but they do not replace the missing endpoint results and do not establish whether events were system-related.

The single-group design also places a limit on interpretation. The record does not describe a control group or randomized allocation, so the study cannot provide a randomized comparison against another device or condition. An outcome in the evaluated group, even if reported, would describe that group under the study conditions rather than establish a causal difference from an alternative.

The record does not report the analysis population details, missing-data methods, endpoint adjudication procedures, or statistical analysis plan. Those omissions limit evaluation of how the outcomes were defined, collected, and analyzed. The enrollment figure and adverse-event counts cannot be used to reconstruct the unreported primary or secondary results.

Accordingly, the registry record supports a description of the study’s design and intended endpoints. It does not support a conclusion that the algorithms did or did not achieve a particular safety or efficacy result. The distinction is between an endpoint being specified and an endpoint result being reported; only the former is documented for the primary outcome in this record.

14. Why This Trial Matters Statistically

This study illustrates an important distinction in clinical trial reporting: a clearly named endpoint is not the same as a reported endpoint result. The registry specifies a system-related complication-free rate, a 3-month timeframe, a named analysis population, and a 95% confidence interval as the dispersion measure. Without the estimate and interval, readers cannot evaluate either the observed rate or its statistical precision.

The design information is also essential to interpretation. The study is listed as single group, with allocation recorded as NA and no masking. That context matters because outcomes from a single evaluated group do not provide a randomized comparison with an alternative device or control condition. A descriptive rate and a comparative treatment effect answer different questions.

The adverse-event entries demonstrate why outcome categories should not be conflated. Serious and other adverse-event counts, deaths, and term-level percentages are reported separately from the primary endpoint definition. The record does not establish that these entries correspond to system-related complications, so they cannot stand in for the missing complication-free rate.

Finally, an enrollment figure alone does not explain which participants contributed to each analysis. The named endpoint population, unreported participant flow, and missing outcome details all affect how a percentage would be interpreted. For biostatisticians and clinical researchers, this record is a useful reminder to distinguish study aims, design descriptors, safety listings, and analyzed endpoint results. Here, the first three are described to some extent, while the primary and secondary outcome estimates are not reported in the registry record.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most direct limitation is that the registry record does not report the primary endpoint result. Although it specifies a 3-month system-related complication-free rate and a 95% confidence interval, neither the estimate nor the interval limits are available in the record. The endpoint’s observed frequency and precision therefore cannot be evaluated.

The record also does not report results for the secondary RVAT and LVAT efficacy endpoints. Their descriptions refer to the percentage of commanded tests resulting in an appropriate outcome, but the definition of appropriate, test counts, and analysis methods are not given. Repeated tests may require methods that account for within-participant dependence; the record does not indicate how this issue was handled.

Although enrollment is listed as 216, the endpoint population is described separately as “Implant + Attempt Subjects.” The record does not define that population, provide participant flow, or identify endpoint-specific denominators. The adverse-event listing’s at-risk count does not resolve the primary endpoint denominator. Missing-data amounts and procedures are also not reported.

The single-group design and absence of a described comparator limit comparative interpretation. Masking is recorded as NONE, while outcome ascertainment and adjudication procedures are not reported in the registry record. The record does not report a statistical analysis plan, sample-size justification, multiplicity approach, or interim analysis details. These gaps prevent evaluation of important design and analysis choices; they should not be filled by assumptions based on the endpoint labels or study status.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of Automatic Threshold Algorithms — NCT02097290.
• Registry record last updated 2018-04-19; status last verified 2018-01.
• Results first posted 2017-09-01.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry describes a completed, single-group evaluation of PaceSafe RVAT and LVAT features in AUTOGEN CRT-D devices, sponsored by Boston Scientific Corporation. It lists 216 participants enrolled, a start date of 2014-04, and primary completion in 2016-01. The primary safety endpoint is the system-related complication-free rate at 3 months post-implant in the “Implant + Attempt Subjects” population, with a 95% confidence interval specified.

The record does not report the primary endpoint estimate or results for the secondary RVAT and LVAT endpoints. It lists adverse-event counts and serious-event terms separately. Allocation is NA, masking is NONE, and the study model is single group. The registry record does not report the analysis plan, missing-data methods, or comparator outcomes.