Protego DF4 Post Approval Registry: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Protego DF4 Post Approval Registry (NCT02243696), a registered phase not stated study. The primary outcome is Percentage of Subjects With No Protego DF4 Lead Adverse Event.

2. Clinical Question

These details frame a device-safety question rather than a comparative-effectiveness question. The endpoint focuses on events attributed to the lead or header, while the registry also lists secondary measures concerning lead pacing threshold, shock impedance, sensing, pacing impedance, and adverse events excluded from the primary objectives. Those measures address different aspects of device performance and safety; they should not be treated as substitutes for the primary endpoint.

The record does not report the primary endpoint’s observed percentage or its confidence interval. It therefore does not answer, from the posted information, what proportion remained free of a lead- or header-related adverse event over the stated follow-up. Nor does the absence of a comparator show what would have occurred with another device. The clinical question can be identified from the registry description, but its numerical answer is not reported in the registry record.

3. Trial Design

The Protego DF4 Post Approval Registry is described as a registry study intended to confirm long-term safety and reliability of the Protego DF4 right ventricular lead. Biotronik, Inc. is listed as the sponsor. The record gives an enrollment of 1694 and lists implantable defibrillator user as the condition. It does not report additional eligibility criteria, participant characteristics, the recruitment process, or the analysis population.

The registry lists a BIOTRONIK Protego DF4 Lead group. It does not describe random assignment or a concurrent control group, and the allocation is not stated. The record explicitly cautions that this is not a randomized comparison and that the arms are not a like-for-like control comparison. Accordingly, any interpretation should focus on what the registry reports for the device group, not on a causal contrast between treatments.

The study start date is 2014-09-27, and the primary completion date is 2019-04-17. Its status is TERMINATED. The record does not report why the registry was terminated, whether follow-up ended as planned, or whether termination affected the completeness of outcome collection. The primary endpoint timeframe is stated as up to 4.5 years, while its description says the endpoint is evaluated through 5 years. The record does not explain this difference.

The primary outcome concerns the percentage of participants with no Protego DF4 lead adverse event. Other listed outcomes include pacing threshold measurement, shock impedance, sensing, pacing impedance, and a percentage of subjects with no adverse events excluded from primary objectives. The registry lists seven outcome measures, but no statistical analyses are reported. The record does not describe the protocol’s sample-size justification, the methods used for outcome assessment, or a detailed statistical analysis plan. These omissions limit what can be inferred about how the study was conducted and how complete the reported evidence is.

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:

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Subjects With No Protego DF4 Lead Adverse Event, measured over Up to 4.5 years.

The primary endpoint is the percentage of participants without an adverse event related to the Protego DF4 lead or header. The registry describes it as an adverse event-free rate. This endpoint is intended to capture whether a lead- or header-related adverse event occurred during the stated follow-up, rather than to summarize a continuous measurement such as impedance or pacing threshold.

An event-free percentage can provide a direct description of the proportion of participants who did not experience the defined event. Its interpretation depends on the event definition, how events are attributed to the lead or header, and how follow-up is handled. The registry description identifies the relationship to the lead or header as part of the endpoint, but does not report the detailed adjudication rules, censoring approach, or handling of participants with incomplete follow-up.

The record gives a timeframe of up to 4.5 years and separately describes evaluation through 5 years. It does not explain how those timeframes relate. Although the primary outcome specifies a 95% confidence interval as its dispersion measure, no endpoint estimate or confidence interval is reported in the registry record. Thus, the endpoint’s intended meaning is clear at a broad level, but its observed value and precision cannot be assessed from the posted information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a binary outcome summarized as a percentage: participants either meet the definition of having no qualifying lead- or header-related adverse event, or they do not. A percentage is a way to describe the frequency of a category in a specified population. For a complete interpretation, the numerator, denominator, event definition, and observation period all matter. The registry identifies the endpoint type and intended timeframe, but does not report the endpoint estimate or its analysis denominator.

What does a confidence interval add?

A confidence interval expresses the statistical uncertainty around an estimate. For a percentage, it indicates a range of values reasonably compatible with the observed data under the method used. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. It does not eliminate uncertainty about study design, measurement, or missing data, and it is not a guarantee that the true value lies within the interval.

The registry specifies a 95% confidence interval for the primary endpoint, but no interval bounds or point estimate are reported. Therefore, its precision cannot be evaluated. The confidence level alone is not a result: it says what type of uncertainty summary was intended, not what range the data support.

How should the timeframe be understood?

The primary outcome lists a timeframe of up to 4.5 years, while the endpoint description refers to evaluation through 5 years. These are both stated in the registry, but their relationship is not explained. In general, follow-up duration matters because an event-free percentage can change depending on how long participants are observed. A percentage over a shorter observation period does not necessarily answer the same question as a percentage over a longer period.

For time-to-event data, analysts may account for differing follow-up by estimating the probability of remaining event-free over time. That approach requires information about event times and censoring, meaning the point at which a participant’s event status is no longer observed. The registry record does not report whether the primary endpoint used a time-to-event method, how censoring was handled, or what follow-up data were available. The endpoint is called an adverse event-free rate, but that label alone does not identify the statistical procedure.

What can the adverse-event counts tell readers?

The safety listing gives counts for participants at risk and affected by serious and other adverse events, along with a separate death count. Counts describe how many events or affected participants were recorded under the registry’s definitions; they do not automatically establish cause. A serious event may occur during follow-up without being caused by the device. The registry’s selected serious-event terms include percentages, but the record does not provide enough detail to establish their denominators, whether participants could appear under more than one term, or how events were attributed.

General statistical interpretation also distinguishes a count from a rate. A rate requires a defined denominator and, in many settings, the amount of time participants were observed. Even when a denominator is listed, unequal follow-up can affect comparisons of simple proportions. The registry does not report person-time or a detailed method for translating event records into the primary adverse event-free endpoint. Accordingly, the adverse-event listing should be read as descriptive safety information, not as a substitute for a fully specified endpoint analysis.

What does the planning information represent?

The record describes sample-size assumptions as a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also distinguishes planning for participants per arm from total events for time-to-event calculations. These assumptions describe an illustration, not necessarily the registry’s original design. The record does not report the study’s own sample-size justification, and it does not report statistical analyses or an observed primary endpoint effect from which to assess the illustration.

Planning calculations ask how much information a future study might need under specified assumptions. They are not observed power, do not describe the study’s actual ability to detect an effect, and do not establish that a study was adequately powered. Here, the record does not describe a randomized two-arm comparison, so assumptions involving equal allocation between two arms should not be mistaken for the registry’s reported design. No planning sample-size values are stated in the record information.

Why are analysis details essential?

A statistical result is interpretable only when readers can connect it to the participants analyzed, the outcome definition, the handling of missing information, and the method used to calculate uncertainty. The registry does not report those details for the primary endpoint. It lists seven outcome measures and no statistical analyses. It does not report model assumptions, adjustment procedures, interim analyses, or the treatment of repeated observations. None of these methods should be inferred from the endpoint label or the stated confidence-interval type.

General principles can explain why these details matter, but cannot fill in the missing analysis. For example, if participants have different follow-up, a method that accounts for follow-up may be more suitable than a simple proportion; if event observations are incomplete, assumptions about censoring or missingness can influence the estimate. The record does not establish which conditions applied or how they were handled. As a result, there is no basis for independently reproducing or validating the primary endpoint from the posted information.

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("BIOTRONIK Protego DF4 Lead")
n      <- c(1694)
events <- c(1672)
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  BIOTRONIK Protego DF4 Lead  1694  1672  98.7  98.0  99.2  98.0  99.1  98.0  99.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures, including the primary adverse event-free endpoint and secondary measures of pacing threshold, shock impedance, sensing, pacing impedance, and adverse events excluded from primary objectives. Examining multiple outcomes can raise a multiplicity issue: when many statistical tests are conducted, the chance of at least one apparently notable result can increase. Methods such as prespecifying a primary outcome or adjusting for multiple comparisons can address particular multiplicity concerns, but the registry record does not report a multiplicity strategy.

No statistical analyses are reported. Consequently, the record does not show whether the outcomes were tested, whether any adjustment was used, or how results were selected for reporting. The presence of several outcome measures alone does not establish that a particular correction was necessary or applied.

Missing-data handling is not reported in the registry record. It does not describe how participants with incomplete follow-up, missing endpoint assessments, or uncertain event attribution were treated. These details matter because an event-free percentage depends on which participants contribute information and how incomplete observation is handled. No assumptions about missingness or imputation should be inferred.

The primary endpoint’s population field is blank, and the record does not describe the analysis population or provide an endpoint denominator. Enrollment is reported as 1694, but enrollment does not itself establish that every participant was eligible for or included in the endpoint analysis. The record also does not report whether analyses used an intention-to-treat, per-protocol, or other population. Without these details, the scope of any primary result cannot be defined; in this record, the primary result itself is not reported.

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: rv lead dislodgement (1.5%), atrial lead dislodgement (1.2%), primary infection (1.2%), rv lead oversensing not due to external noise (0.5%), hematoma (0.5%).

The safety listing for the BIOTRONIK Protego DF4 Lead group reports 1694 participants at risk for serious adverse events and 145 affected, and 1694 at risk for other adverse events and 144 affected. It separately reports 282 deaths. These are the recorded counts; they should not be converted into percentages or combined into a total. The record does not explain whether the categories overlap, whether the death count includes deaths following an adverse event, or how much follow-up each participant contributed.

The listed serious-event terms and percentages are RV lead dislodgement, 1.5%; atrial lead dislodgement, 1.2%; primary infection, 1.2%; RV lead oversensing not due to external noise, 0.5%; hematoma, 0.5%; and secondary infection, 0.4%. The record does not provide further detail on the denominator or ascertainment basis for each percentage. These terms are not necessarily mutually exclusive, and the listing does not establish that every event was caused by the lead.

Serious adverse events, other adverse events, deaths, and the primary lead- or header-related endpoint are distinct descriptions. The record does not establish that they use identical definitions or populations. The death count is not evidence of device causation, and the broader adverse-event counts do not reveal the primary adverse event-free percentage.

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

The registry record documents a post-approval study focused on the long-term safety and reliability of the Protego DF4 right ventricular lead. It identifies a primary endpoint based on the percentage of participants without a lead- or header-related adverse event, gives a follow-up timeframe, and lists selected safety information. It also reports enrollment and the registry’s status. These details establish the subject and intended question of the study.

They do not provide the primary endpoint result. No adverse event-free percentage or confidence interval is reported, and no statistical analyses are listed. The record therefore cannot establish the observed frequency of the primary endpoint or how precisely it was estimated. The specified 95% confidence interval is a planned form of uncertainty summary, not an estimate in the absence of its bounds and point estimate.

The listed adverse-event counts and serious-event terms add descriptive safety context, but do not answer the primary endpoint question. The record does not establish that all listed events were related to the lead or header, and it does not establish that the reported deaths were caused by the device. Nor does it explain how event attribution was determined or how incomplete follow-up was handled.

The record also does not provide a like-for-like control comparison. It cautions that this is not a randomized comparison and that the arms are not a like-for-like control comparison. Therefore, the posted information cannot show what the event experience would have been under another device or establish a causal difference between options.

The registry status is TERMINATED, but no reason for termination or explanation of its consequences is reported. The available record supports a description of the study’s purpose and selected safety listings; it does not support a numerical conclusion about the primary outcome, a causal conclusion, or a conclusion about comparative safety.

14. Why This Trial Matters Statistically

This registry illustrates an important distinction between recording a study question and reporting evidence that answers it. A clearly described endpoint can tell readers what investigators intended to measure, but a statistical interpretation also requires the observed estimate, its uncertainty, the analysis population, and the method used. The registry record states that the primary outcome is an adverse event-free percentage with a 95% confidence interval, yet does not report the estimate or interval.

The distinction matters especially for device safety. Event counts can be useful, but their meaning depends on definitions, attribution, exposure time, and follow-up completeness. A list of serious-event terms does not by itself reveal whether an event was device-related, whether participants had more than one event, or how those events map to the primary endpoint. Reporting these elements helps readers understand what safety information can and cannot establish.

The record also underscores why comparator design matters. Without a reported randomized, like-for-like comparison, descriptive events in the device group cannot establish how outcomes would differ with another device. A single group’s experience may describe what was recorded, but it does not supply the counterfactual comparison needed for a causal claim.

Finally, the record contains multiple outcomes and a planning illustration but no posted statistical analyses. Those items should not be treated as evidence of an analysis plan, a powered comparison, or an observed effect. Transparent reporting of outcome results, denominators, uncertainty, analysis populations, and missing-data methods is necessary for a reader to judge precision and robustness. In this registry record, those details are not reported, making the limits of interpretation as important as the study’s stated objective.

15. Limitations

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

Several limitations specific to this record restrict interpretation. The primary endpoint is described, but its observed percentage and 95% confidence interval are not reported. The registry therefore does not provide a numerical primary safety result or its precision. Although enrollment is listed as 1694, the endpoint analysis denominator and analysis population are not reported.

The endpoint timeframe is stated as up to 4.5 years, while its description refers to evaluation through 5 years. The registry does not explain the difference or specify how follow-up was incorporated into the analysis. It also does not report detailed event definitions, attribution procedures, censoring rules, or methods for handling incomplete follow-up. These omissions make it difficult to determine exactly what the intended endpoint estimate would represent.

The record lists adverse-event counts, a death count, and selected serious-event terms, but does not clarify the relationship among these categories or establish causation. The term percentages are not accompanied by details of their denominator or ascertainment basis. They should not be interpreted as the primary endpoint or as a complete account of all safety outcomes.

The registry reports no statistical analyses, and its primary population field is blank. It does not state a multiplicity approach, missing-data method, interim analysis plan, or detailed statistical plan. The reason for TERMINATED status and its effect on follow-up are also not reported. Finally, the absence of a like-for-like control comparison limits comparative interpretation. These are reporting gaps in the registry record; they do not, by themselves, establish that a particular method was or was not used in the study.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Protego DF4 Post Approval Registry — NCT02243696.
• Registry record last updated 2020-06-22; status last verified 2020-06.
• Results first posted 2020-04-22.
• 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 Protego DF4 Post Approval Registry, sponsored by Biotronik, Inc., was intended to assess long-term safety and reliability of the Protego DF4 right ventricular lead. The record lists implantable defibrillator user as the condition, an enrollment of 1694, a start date of 2014-09-27, a primary completion date of 2019-04-17, and status TERMINATED.

The primary endpoint is the percentage of participants without a Protego DF4 lead or header adverse event, described as an adverse event-free rate. Its timeframe is listed as up to 4.5 years, while the description refers to evaluation through 5 years. The record specifies a 95% confidence interval but does not report the endpoint estimate, interval, analysis denominator, or statistical analyses.

Selected adverse-event counts and serious-event terms are listed, but their relation to the primary endpoint and their attribution are not fully described. The registry does not report a like-for-like control comparison. The posted information therefore defines the study’s question and gives limited safety listings, but does not quantify the primary endpoint or support a comparative causal conclusion.