Mental Stress Reduction in Defibrillator Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Mental Stress Reduction in Defibrillator Patients (NCT00624520), a randomized phase 3 study. The primary outcome is Mental Stress Induced Elevation in "Double Product" by Math Stress Task.

2. Clinical Question

The registry’s stated purpose is to assess the effectiveness of stress management versus patient education on cardiac responses to mental stress in veterans with implantable cardioverter-defibrillators. That purpose identifies the comparison and the physiological response of interest; it does not establish what the study found. The posted record does not report a numerical primary-outcome estimate for either group or a between-group comparison, so the direction and size of any difference cannot be assessed from this record.

3. Trial Design

This was a Phase 3, randomized, parallel-group study with no masking listed in the registry. The sponsor was the US Department of Veterans Affairs. The record lists enrollment of 129 and gives a start date of 2008-09 and a primary completion date of 2012-05. Its current status is terminated. The reason for termination and the timing of that decision are not reported in the registry record.

The two groups received different 10-week programs. The Cognitive Behavioral Stress Management group attended group sessions, while the Patient Education group attended once-weekly group sessions. The registry does not report the allocation ratio, how the random sequence was generated, or whether allocation was concealed. It also does not provide further detail on attendance, adherence, or whether participants in either group received other care during the study.

The primary outcome concerned a mental arithmetic task using serial subtraction. Heart rate and blood pressure were measured before, during, and after the task; the task lasted 10 minutes, with 10 minutes of recovery time. Measurements were taken at 2.5 minute intervals, and an average of 3 measurements was used as the baseline before stress tasks. The primary outcome timeframe is described as immediate to 6 months post intervention.

Although the registry labels the study randomized and lists a parallel model, it does not report the statistical analysis plan, the intended analysis population, or the planned handling of repeated measurements. The record also does not explain why the trial was terminated. These gaps limit interpretation of the design beyond the information explicitly described in the registry.

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: Some enrolled participants were excluded from the trial if determined to have severe mental illness after administration of an SCID-I questionnaire and/or interview by a clinical psychologist. Others were excluded as drop-outs due to travel issues, weather, family issues, and illness. 2 subjects died before group assignment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Response to Mental Stress by Math Stress Task.

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: Subjects randomized , including drop-outs before commencement of intervention.

6. Primary Endpoint

The registry lists the primary outcome as Mental Stress Induced Elevation in "Double Product" by Math Stress Task, measured over Immediate to 6 months post intervention.

The primary endpoint is the maximum mental-stress-induced elevation in double product during a mental arithmetic task. Double product is defined in the registry as heart rate in beats per minute multiplied by systolic arterial blood pressure in mmHg. The endpoint is the difference between the baseline value and the maximum value reached during the task, expressed in mmHg x beats/min. The registry states that higher values represent a greater stress-induced effect and lower values a lower effect.

Heart rate and blood pressure were recorded serially before, during, and after the mental stress task with an automated blood pressure recording device. The task involved serial subtraction and lasted 10 minutes, followed by 10 minutes of recovery. An average of 3 pre-task measurements was used as baseline. These details define how the physiological response was elicited and measured; they do not indicate how large a response occurred in either group.

This endpoint focuses on a cardiovascular response during a standardized mental challenge, rather than on a participant’s report of stress or mood. It is relevant to the study’s stated question because the trial sought to compare cardiac responses to mental stress between the two programs. The record lists the outcome timeframe as immediate to 6 months post intervention, but does not report the actual endpoint values, their uncertainty, or a treatment comparison. The result and its precision are therefore not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the endpoint summary mean?

The primary outcome is a continuous measure, and the registry identifies its summary as a mean with standard error as the dispersion measure. In general, a mean represents the average observed value in a group. A standard error expresses uncertainty in the estimated mean; it is not the same as the spread of individual participant measurements. For comparing groups, the central quantity of interest would ordinarily be a between-group contrast with an uncertainty interval or another measure of precision. No such primary comparison is reported in the registry record, so the mean and standard error labels alone do not establish an effect.

The outcome is based on a change from a pre-task baseline to the maximum value during mental arithmetic. As a general matter, a change score depends on both the baseline and the later measurement, and it can be affected by measurement variability at either point. The registry describes the measurement sequence and baseline construction, but does not report the values needed to examine those components or their variability.

Why does the repeated measurement schedule matter?

The registry describes serial heart-rate and blood-pressure measurements before, during, and after a task. Repeated measurements can help characterize a response over time, but analyses of such data need to account for the fact that observations from the same participant are related. This is a general statistical consideration, not a description of the method used in this trial. The statistical model or other method used to account for repeated measurements is not reported in the registry record.

The stated primary timeframe extends from immediately to 6 months post intervention, and the registry notes multiple categories or time points without reducing the outcome to one comparison. A result at one time point may not convey the pattern across all time points. In general, selecting among multiple time points or summaries can affect interpretation and the chance of a chance finding. The record does not specify which time point was intended as the primary comparison or how repeated time points were handled in the analysis.

What can be said about planning illustrations?

The planning assumptions describe an illustration based on the observed effect, not the trial’s original design justification. The stated illustration uses a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. For non-time-to-event outcomes, the stated sample-size unit is participants per arm for a specified power level; time-to-event planning uses a total number of events.

These are assumptions for interpreting a planning illustration, not evidence that the study was designed using those assumptions. The registry record does not report the original sample-size justification, the target effect used when planning the trial, or the power calculation used by the investigators. A planning illustration based on an observed effect is not observed power, and it cannot establish whether the trial was adequately powered. No additional sample-size quantities can be inferred from the assumptions alone.

How should multiplicity be considered?

The registry lists 11 outcome measures and 11 analyses, with several secondary psychological, heart-rate-variability, and device-related outcomes. When an analysis examines multiple outcomes or time points, the chance of at least one apparently unusual result can rise if each comparison is interpreted independently. As a general matter, prespecified priorities and multiplicity procedures can help clarify how multiple findings should be interpreted. The statistical plan, the primary testing hierarchy, and any multiplicity adjustment are not reported in the registry record. Therefore, it is not possible to determine whether or how the analyses accounted for multiple outcomes.

What other statistical details are missing?

The registry does not report the analysis population, the number included in the primary endpoint analysis, the handling of missing measurements, or whether analyses followed randomized assignment. It also does not describe model covariates, assumptions, or sensitivity analyses. These omissions do not show that such procedures were absent from the full study; they mean they are not reported in the registry record. In their absence, the posted material does not permit a detailed assessment of the analysis strategy or the robustness of any primary finding.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures and 11 analyses. Its secondary outcomes span state anger, tension or anxiety, perceived stress, depression or dejection, low- and high-frequency heart-rate variability, their ratio, and cardioverter-defibrillator therapies. The record does not report a testing hierarchy, identify which secondary outcomes were confirmatory, or describe any adjustment for multiple comparisons. In general, examining many outcomes or time points can increase the chance that some findings appear notable by chance when each is considered separately. Whether that issue was addressed in the trial analysis is not reported in the registry record.

The registry also states that the primary outcome has several categories or time points and has not been reduced to one comparison. The intended primary time point, the method for handling repeated measurements, and the statistical model are not reported in the registry record. This means the posted information does not define a single primary contrast that can be interpreted as the definitive comparison.

Missing-data procedures and analysis populations are also not reported in the registry record. The record does not state how many participants contributed primary-outcome data, how missing measurements were handled, whether participants were analyzed according to randomized assignment, or whether any sensitivity analyses were performed. These omissions prevent assessment of how incomplete follow-up might affect the estimated response. They should be read as limits on what can be determined from the registry record, not as evidence that the study team did not use such methods.

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 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: dizziness (4.3%), atrial flutter (3.6%), implantable defibrillator malfunction (3.6%), pneumonia (3.6%), death (2.1%).

The registry reports serious adverse events affecting 9 participants among 56 at risk in the Cognitive Behavioral Stress Management group and 12 among 47 at risk in the Patient Education group. It reports 0 other adverse events among 56 at risk in the Cognitive Behavioral Stress Management group and 0 among 47 at risk in the Patient Education group. These are the registry’s group-specific counts; they are not a comparison adjusted for follow-up, participant characteristics, or other factors. The record does not provide further information about event timing, severity beyond the serious classification, or how events were attributed.

Deaths are recorded as null for both groups, so group-specific death counts are not reported in the registry record. The registry also lists Dizziness (4.3%), Atrial flutter (3.6%), Implantable Defibrillator malfunction (3.6%), Pneumonia (3.6%), Death (2.1%), and Ventricular tachycardia (2.1%) among the top serious adverse event terms. The record does not identify group-specific percentages or denominators for these terms, so they should not be assigned to either group or directly compared across groups.

Adverse-event counts describe reported safety events; they do not by themselves establish that an intervention caused an event or that the event rates differ between groups. The registry record does not provide a comparative safety analysis or uncertainty estimates. The listed figures should therefore be read as descriptive reporting rather than as a definitive assessment of comparative safety.

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

The record establishes that the study was designed to compare a 10-week Cognitive Behavioral Stress Management program with a 10-week Patient Education program in veterans with implantable cardioverter-defibrillators. Its main outcome was a physiological response to a mental arithmetic task, defined using heart rate and systolic blood pressure. The registry also lists psychological, heart-rate-variability, and device-related secondary outcomes. These details explain the question the study set out to address, but they do not reveal the outcome of the comparison.

The primary results, including group values and a between-group estimate, are not reported in the registry record. The record therefore does not establish whether the primary response was higher in one group, whether the groups were similar, or how precise any difference might have been. Lack of a reported estimate should not be interpreted as evidence of no effect. Nor does the randomized design alone establish a result: random assignment is a feature of the study method, not a substitute for outcome data.

The study’s terminated status is recorded, but the reason is not reported in the registry record. It cannot be used to infer whether termination was related to recruitment, safety, results, or any other particular circumstance. Likewise, the enrollment listing does not establish how many participants contributed to each analysis or whether follow-up was complete.

The adverse-event figures provide limited descriptive safety information, including serious-event counts by group and a list of commonly reported serious terms. They do not show causation, adjusted comparisons, or the precision of differences. The record does not report a comparative safety analysis, and null entries for deaths do not provide group-specific death counts.

For readers, the appropriate conclusion is narrow: the registry describes a randomized trial and defines its primary endpoint, but the posted results do not permit an assessment of the primary comparative effect. Additional results and analysis details are needed to interpret the study’s findings, their uncertainty, and the implications of the recorded safety information.

13. Why This Trial Matters Statistically

This study raises statistical issues that are common in behavioral trials with physiological endpoints. The intervention and comparator were both group-based 10-week programs, while the primary outcome was a continuous measure taken during a mental stress task. Interpreting such a comparison depends not only on the outcome definition but also on how repeated measurements, follow-up time points, and missing observations are handled. The registry describes the measurement process but does not report these analysis details.

The multiple listed outcomes also make prespecification and multiplicity relevant. Psychological scales, heart-rate-variability measures, device-related outcomes, and the primary double-product response address different aspects of the study question. In general, interpreting a collection of outcomes requires knowing which comparisons were primary and how additional analyses were treated. The statistical plan and any adjustment approach are not reported in the registry record, so those considerations cannot be resolved from the posted information.

The record is also a reminder that trial design labels do not convey the results. Randomization and a parallel model describe aspects of the design, while a treatment-effect estimate and its precision are needed to judge the observed comparison. Here, the registry does not report the primary results, and its note about multiple categories or time points leaves no single primary comparison to interpret.

Finally, the serious adverse-event counts are useful descriptive information but do not amount to a full comparative safety analysis. The group-specific counts, missing death entries, and unallocated serious-event terms illustrate why denominators, event definitions, follow-up, and uncertainty matter when reading safety data. The record’s gaps limit what can be concluded without resolving the statistical question the trial was designed to examine.

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.

Several limitations of interpretation arise from the registry information. Most importantly, the primary-outcome results are not reported in the registry record. There are no group means, comparative estimate, confidence interval, or p value with which to assess the size or precision of the primary result. The registry also notes that the primary outcome has several categories or time points and has not been reduced to one comparison, so the intended primary contrast is not clear from the posted record.

The status is terminated, but the reason for termination is not reported in the registry record. The record does not describe participant flow, follow-up completion, the number contributing data to the endpoint, or missing-data handling. Although enrollment is listed as 129, that information alone does not establish the size of the analysis population. The allocation ratio and procedures for sequence generation and allocation concealment are also not reported.

The record describes serial measurements and an outcome timeframe extending from immediately to 6 months post intervention, but does not explain how repeated observations or multiple time points were modeled. It does not state the analysis population, the statistical model, covariate adjustment, sensitivity analyses, or multiplicity procedures. These details may exist outside the registry record; they are not reported in it.

For safety, the registry lists serious-event counts by group and selected serious-event terms, but does not provide comparative estimates or uncertainty. Death entries are null, and the event-term percentages are not assigned to groups in the record. Consequently, these figures offer only a limited descriptive view and do not support a complete comparison of safety outcomes.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Mental Stress Reduction in Defibrillator Patients — NCT00624520.
• Registry record last updated 2014-12-22; status last verified 2014-12.
• Results first posted 2014-12-22.
• 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.

18. Record Summary

The registry describes NCT00624520, a Phase 3 randomized parallel-group study sponsored by the US Department of Veterans Affairs. It compares a 10-week Cognitive Behavioral Stress Management group program with a 10-week once-weekly Patient Education group program for veterans with implantable cardioverter-defibrillators. The record lists enrollment of 129, a start date of 2008-09, a primary completion date of 2012-05, and status terminated.

The primary outcome is the maximum mental-stress-induced elevation in double product during a mental arithmetic task, assessed from immediately to 6 months post intervention. The registry lists 11 outcome measures and 11 analyses, but does not report the primary comparative result or key analysis details, including the analysis population and missing-data procedures. It reports serious adverse events affecting 9 participants among 56 at risk in the stress-management group and 12 among 47 at risk in the education group; group-specific death counts are not reported in the registry record.