MOnitoring REsynchronization deviCes and cARdiac patiEnts: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for MOnitoring REsynchronization deviCes and cARdiac patiEnts (NCT00885677), a randomized na study. The primary outcome is Phase 1: Median Time Between Event Onset Time and Clinical Decision for Each Subject..

2. Clinical Question

The broader study objective was to compare remote monitoring with scheduled routine in-patient follow-ups in terms of clinical effectiveness and total healthcare system utilization. The endpoint described in the results is narrower: it measures the interval between the onset of a device-detected event and a clinical decision. It does not directly summarize all clinical outcomes or healthcare use named in the objective.

The comparison is relevant to how information from implanted devices is followed up. Remote alerts and routine office visits represent different management strategies, and the endpoint captures the speed of a clinical response to detected events. The posted values describe the distribution of subject-level median delays; they are not a count of events or a measure of how many patients experienced a clinical outcome.

The registry record does not report an inferential comparison, such as a p-value or hazard ratio, for this endpoint. The values therefore support a descriptive comparison of the recorded medians and their interquartile ranges, but do not establish the statistical uncertainty around a group contrast or answer every part of the broader study objective.

3. Trial Design

The registry record describes a randomized, parallel-group trial with no masking. The overall enrollment is 918. The study status is terminated; the reason for termination is not reported in the registry record. The start date is 2009-06 and primary completion is 2015-12.

The primary endpoint results are specific to Phase 1, rather than a report of all 918 enrolled participants. That cohort included 154 patients enrolled from May 2009 through April 2010 at 32 centers in 6 countries: France, Hungary, Israel, Italy, Spain, and Switzerland. The final cohort analyzed for the endpoint comprised 148 patients, with 76 in the Remote group and 72 in the Control group. The registry record does not explain the difference between the Phase 1 enrollment and the final analysis cohort.

In the Study Group, patients with CRT-D devices were followed through the Medtronic CareLink Network, with automatic alerts enabled for fluid accumulation, AT/AF episodes and system integrity. The Control Group received management based on current standard clinical practice and routinely performed in-office visits. The registry record identifies Medtronic Cardiac Rhythm and Heart Failure as the sponsor.

Random allocation is intended to make treatment groups comparable, on average, at the time of assignment. It does not guarantee that the groups are identical, particularly in a smaller analyzed cohort. Because the trial was unmasked, participants and clinical teams were not described as blinded to management assignment. The registry record does not report additional details about allocation procedures, concealment, protocol deviations, or the statistical plan.

The trial objective included clinical effectiveness and healthcare system utilization, but the primary result is a time interval. Although the registry record lists two outcome measures, it does not provide a secondary outcome result in the posted results. The relationship between the Phase 1 cohort and the overall trial enrollment is not further explained.

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: 918 subjects signed the Informed Consent Form. One of those subjects withdraw from the study prior randomization, therefore 917 subjects were randomized either to Study (462) or to Control (455) groups.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Phase 1: A total of 154 patients were enrolled from May 2009 through April 2010 from 32 centers in 6 different countries (France, Hungary, Israel, Italy, Spain, and Switzerland). The final patient cohort object of analysis comprised 148 patients (76 in the Remote group and 72 in the Control group)

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 Phase 1: Median Time Between Event Onset Time and Clinical Decision for Each Subject., measured over 1 year since the randomization.

The primary endpoint is the median time between device-detected event onset and a clinical decision for each subject, measured in days. Its timeframe is 1 year since randomization. In practical terms, the measure describes how long it took for a clinical decision to follow an event detected by the device. It is a process measure of response timing, rather than a direct measure of survival, hospitalization, symptoms, or total healthcare utilization.

The registry record reports a median of 2 days for the Study Group, with an interquartile range of 1 to 4 days. For the Control Group, it reports a median of 29 days, with an interquartile range of 3 to 51 days. An interquartile range describes the middle half of observed values and conveys how spread out those values are; it is not a confidence interval for the median or a range containing every participant.

Using a median is appropriate when a distribution of waiting times may be asymmetric or contain unusually long delays. The median is less affected by extreme values than the arithmetic mean. The endpoint is defined at the subject level: each subject’s median delay is the quantity being summarized. It should not be read as the time to a first event for the group as a whole.

The endpoint can describe the speed of clinical decisions after device detections, but it does not by itself establish the consequences of those decisions. A shorter recorded delay does not reveal whether the decision was appropriate, whether it changed a patient’s health outcome, or how much healthcare was used. Those questions require other results, which are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is a time measure, but its reported summary is a median delay for each subject and a median across subjects in each group. Those are related but distinct levels of summarization. First, each subject has a median interval between event onset and a clinical decision. The group-level median then summarizes those subject-level medians. It is not necessarily the same as pooling every event-level interval and taking one median across all events.

What does the median describe?

In general, a median is the middle value of an ordered set of observations. It is useful when values are skewed, because a few unusually long or short observations have less influence on it than they would on a mean. Here, the group medians summarize the subject-level delays: 2 days in the Study Group and 29 days in the Control Group.

The interquartile range gives the interval from the lower quartile to the upper quartile. It describes the spread of the central portion of the observations, not the precision of the estimated median. The reported interquartile ranges are 1 to 4 days for the Study Group and 3 to 51 days for the Control Group. A confidence interval would instead describe uncertainty in an estimate under a statistical procedure. No confidence interval for the group medians or their contrast is reported.

Why are time-to-event methods sometimes used?

General explanation: time-to-event methods are useful when the event of interest may not have occurred for every participant by the end of observation, or when follow-up ends before the event is observed. Such methods can account for incomplete observation using censoring information. A time-to-event comparison may be expressed as a hazard ratio, but the registry record does not report a hazard ratio for this endpoint. The posted result is a median-time summary, so it should not be interpreted as if it were a hazard ratio.

The registry record states that values are missing or not estimable for a two-arm comparison of this median-time endpoint. That note prevents an unadjusted between-group recalculation from being presented as though it were a sponsor analysis. The displayed medians are still interpretable as descriptive summaries, but the registry does not give an inferential test or an uncertainty interval for the contrast. The sponsor’s own analysis would take precedence if a discrepancy between it and a recalculation were reported; no discrepancy is identified in this record.

What does randomization contribute?

General explanation: random allocation is used to reduce systematic differences between groups at baseline. It helps support a causal interpretation of a group comparison when the assigned strategies are followed and outcomes are analyzed appropriately. It does not remove uncertainty, guarantee balance in every characteristic, or address missing outcomes automatically. This trial is identified as randomized and parallel, but the allocation procedure and detailed analysis population are not reported in the registry record.

The trial was unmasked. In general, knowledge of group assignment can affect behavior, follow-up, or outcome assessment, especially for an endpoint involving a clinical decision. The endpoint is based on the interval from a detected event to a decision, and the record does not describe whether decision timing was assessed by blinded reviewers or through a standardized process. It is therefore not possible to assess those safeguards from the registry record.

What can the available analysis establish?

The reported summaries establish the observed group medians and interquartile ranges for the analyzed cohort. They do not alone establish the statistical significance of a difference, an adjusted effect, or the effect of assignment for every enrolled participant. A formal group comparison would need a specified model or test, a defined analysis population, and an estimate of uncertainty. Those details are not reported in the registry record.

The record lists two outcome measures but reports no secondary outcome results. It also reports no analyses in the registry record. This means there is no stated adjustment for covariates, no reported handling strategy for multiple outcomes, and no basis to judge whether the displayed endpoint was selected after examination of the data. These absences do not prove that such methods were never used; they mean they are not documented in the registry record.

Any sample-size illustrations associated with these results are planning exercises, not evidence about the trial’s observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. For time-to-event calculations, the illustration is based on a total number of events using the Schoenfeld approach; other illustrations are expressed as participants per arm. These assumptions do not describe the trial’s own design justification, which is not reported in the registry record.

General explanation: over-dispersion occurs when observed variability exceeds what a statistical model expects. If present, it can make conventional uncertainty estimates too small unless the model accounts for it. The registry does not report an over-dispersion assessment, and the endpoint summaries do not provide enough information to evaluate one. No claim about over-dispersion or its consequences can be made for this analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures, but a secondary outcome result is not reported in the registry record. It reports no analyses, and does not describe a prespecified hierarchy of outcomes, a multiplicity adjustment, or another method for controlling the chance of false-positive findings across multiple comparisons. The absence of these details does not show that an adjustment was or was not used outside the registry record; it means the approach cannot be assessed from the record.

The primary endpoint results describe a Phase 1 cohort of 148 patients, drawn from 154 enrolled in that cohort. The record does not explain why the final analysis cohort excluded some Phase 1 enrollees, whether any endpoint values were missing, or how missing or unevaluable observations were handled. It also does not state whether the analysis was based on assignment as randomized, treatment received, or another analysis population.

The overall enrollment is 918, while the endpoint population is a smaller Phase 1 cohort. The record does not provide the relationship between that cohort and all trial participants or explain why the endpoint result is limited to Phase 1. This limits assessment of attrition and of how representative the endpoint analysis is of the full trial population.

Missingness can affect a result if the chance of having an observed endpoint is related to treatment assignment or to the endpoint itself. General explanation: statistical methods can address some forms of missingness, but they rely on assumptions that should be stated and examined. Such assumptions and sensitivity analyses are not reported in the registry record. The available information therefore does not support a conclusion about the impact of missing data on the reported medians.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: heart failures (16.5%), procedural and device related injuries and complications nec (6.9%), fatal outcome (4.5%), cardiac arrhythmias (4.2%), cardiac disorder signs and symptoms (3.5%).

The registry record lists serious adverse event counts for the Study Group and Control Group, alongside counts described as at risk. For serious adverse events, it reports 184 affected and 462 at risk in the Study Group, and 168 affected and 455 at risk in the Control Group. It separately reports other adverse event counts of 68 affected and 462 at risk for the Study Group, and 85 affected and 455 at risk for the Control Group. These are registry counts, and the record does not explain how the safety populations relate to the Phase 1 endpoint cohort.

The record identifies the most frequently listed serious event terms as Heart failures (16.5%), Procedural and device related injuries and complications NEC (6.9%), Fatal outcome (4.5%), Cardiac arrhythmias (4.2%), Cardiac disorder signs and symptoms (3.5%), and Renal disorder (3.2%). The record does not provide enough detail to determine whether those percentages refer to participants, events, or another denominator. They should be read as registry-listed percentages, not converted into counts.

Safety counts do not, by themselves, show whether an event was caused by the assigned management strategy. Interpretation requires the event definitions, follow-up duration, exposure, ascertainment procedures, and a comparable analysis of groups. The registry record does not report deaths by group in the safety fields, nor does it provide a detailed safety analysis plan. These figures should not be treated as a causal comparison or as a complete account of safety.

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

The endpoint gives a descriptive account of how quickly clinical decisions followed device-detected events in the Phase 1 analysis cohort. The median was 2 days in the Study Group and 29 days in the Control Group. The corresponding interquartile ranges were 1 to 4 days and 3 to 51 days. The sponsor narrative also characterizes the remote-group delay as considerably shorter.

This result concerns a response process, not the full set of outcomes in the study objective. It does not show whether patients had fewer heart failure events, lived longer, felt better, or required less healthcare. It does not indicate whether individual decisions were appropriate or whether faster decisions changed subsequent care. Those conclusions require other outcome data and analyses, which are not reported in the registry record.

The result also does not establish a statistically significant difference. A test statistic, p-value, confidence interval for the contrast, and sponsor-reported hazard ratio are not reported for this endpoint. The medians and interquartile ranges communicate the observed summaries, but do not quantify the uncertainty around a between-group effect. Their descriptive contrast should not be mistaken for a formal inferential result.

The analyzed cohort is not the same as the overall enrollment. The endpoint result applies to the Phase 1 cohort described in the registry, with 148 patients in the final analysis, rather than automatically to all 918 enrolled participants. The record does not explain the cohort selection or exclusions. This limits conclusions about generalizability within the trial and to patients outside the study.

Finally, the trial is marked terminated, but the reason is not reported in the registry record. That status should not be interpreted as evidence for or against the endpoint finding. It is a separate fact about the study record, and without an explanation it cannot clarify the design, conduct, or interpretation of the result.

13. Why This Trial Matters Statistically

This trial illustrates why the statistical definition of an endpoint matters. The stated study objective is broad, addressing clinical effectiveness and healthcare system utilization, while the reported primary result focuses on the delay between a device-detected event and a clinical decision. That timing measure can provide information about management processes, but it is not interchangeable with a patient health outcome or a measure of total healthcare use.

It also illustrates the distinction between a descriptive result and an inferential comparison. Medians and interquartile ranges show the observed distributions in the analyzed groups. Without an estimate of uncertainty for the contrast or a reported test, readers cannot determine from those summaries alone how compatible the observed difference is with chance variation under a specified model.

The study’s overall enrollment and endpoint analysis population also make population definition important. The registry reports 918 enrolled overall, but the primary endpoint summary concerns a Phase 1 cohort with 148 patients in the final analysis. Clear reporting of who was included, who was not, and how the analysis population was chosen is essential for judging what the estimate represents.

Finally, an unmasked, randomized management comparison raises practical questions about outcome assessment and analysis methods. For an endpoint involving clinical decisions, it is useful to know whether decision criteria were standardized and whether assessment could be influenced by knowledge of assignment. The registry record does not report these details. The case demonstrates how a clinically interpretable endpoint can remain statistically difficult to evaluate when the analysis plan, missing-data methods, and uncertainty estimates are absent.

14. 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 main limitation of the posted primary result is that it is descriptive. The registry record does not report an inferential comparison, a confidence interval for the group contrast, a p-value, or a hazard ratio. The record also notes that values are missing or not estimable for a two-arm comparison of this median-time endpoint. As a result, the precision of the contrast cannot be assessed from the posted endpoint values.

The endpoint cohort is limited to Phase 1: 154 patients enrolled and 148 included in the final analysis. Although overall enrollment is 918, the registry record does not explain how Phase 1 relates to the full trial, how the final cohort was selected, or why patients were not included in the endpoint analysis. The analysis population may therefore differ from the wider enrolled population, but the nature and consequences of any such differences are not reported.

The trial is unmasked, and the endpoint involves clinical decisions. The registry record does not describe standardization of decision criteria, blinded endpoint assessment, or steps taken to limit the influence of assignment knowledge. It also does not report allocation concealment, adherence, crossovers, or deviations from the assigned management strategy. These details would help interpret the internal validity of the comparison.

The record provides no statistical analysis plan, explanation of the terminated status, or handling of missing data. It lists two outcome measures but no secondary outcome results and no analyses. The safety counts are not described in enough detail to connect their populations and denominators to the primary endpoint cohort. Together, these reporting gaps restrict assessment of selection, multiplicity, analysis choices, and the breadth of conclusions supported by the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: MOnitoring REsynchronization deviCes and cARdiac patiEnts — NCT00885677.
• Registry record last updated 2025-07-02; status last verified 2017-02.
• Results first posted 2017-04-04.
• 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.

18. Record Summary

NCT00885677 is a randomized, parallel-group, unmasked study of remote monitoring compared with routine in-office management for patients with heart failure treated with cardiac resynchronization therapy devices. The registry lists overall enrollment of 918 and status as terminated.

The primary endpoint is the median time from device-detected event onset to a clinical decision, in days, during 1 year since randomization. In the Phase 1 final analysis cohort of 148 patients, the reported median was 2 days (interquartile range 1 to 4) in the Study Group and 29 days (interquartile range 3 to 51) in the Control Group. A formal two-arm comparison is not reported.

The registry record does not report the termination reason, detailed analysis plan, missing-data methods, secondary outcome results, or inferential uncertainty for the primary endpoint. The reported summaries therefore describe response timing in the analyzed cohort, while leaving the statistical strength and broader clinical implications uncertain.