Predictors of Response to Biventricular Pacing in Heart Failure: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Predictors of Response to Biventricular Pacing in Heart Failure (NCT00156390), a randomized na study. The primary outcome is Minnesota For Living With Heart Failure Questionnaire.

2. Clinical Question

3. Trial Design

The registry describes a randomized, single-masked, parallel-group study. Participants were assigned to echo-guided left ventricular lead placement or left ventricular lead placement as per standard of care without echo guidance. The record lists the study phase as NA. It lists heart failure and wide QRS complex as the conditions under study.

The recorded enrollment is 187. For the primary outcome, the posted group summaries report 96 participants in the echo-guided group and 69 in the standard-care group. Those endpoint group counts should not be treated as a full account of participant flow: the reasons for the difference between the enrollment figure and the endpoint counts, and the handling of participants who did not contribute endpoint data, are not reported in the registry record.

The primary endpoint was the Minnesota Living with Heart Failure Questionnaire at 1 year, summarized using group means and standard deviations. The registry also lists echocardiographic changes as a secondary outcome. It records two outcome measures, one posted secondary outcome, and no analyses in its analysis count. The detailed statistical plan, allocation-concealment procedures, and the identity of the masked party are not reported in the registry record.

The study status is completed. The recorded start is 2005-06 and the primary completion is 2012-06. The sponsor is Samir Saba. These record details describe the study as registered; they do not provide additional information about how the trial was conducted or how its analysis was specified.

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

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 Minnesota For Living With Heart Failure Questionnaire, measured over 1 year.

The primary endpoint is the Minnesota Living with Heart Failure Questionnaire score at 1 year. The registry describes a list of 21 questions, with each question scored on a scale from 0 to 5. A score of 0 means heart failure did not prevent the person from living as they wanted; a score of 5 means it prevented them very much. Overall scores range from 0 to 105, with 105 representing worse quality of life.

This measure is used to summarize the effect of heart failure on a person's perceived ability to live as they want. It gives a patient-reported perspective, rather than measuring only a physiological or imaging feature. The posted outcome is a continuous measure, reported as a mean and standard deviation in each group. Comparing the group means describes the average difference in questionnaire scores at the recorded time point.

The group means were 31.0 for echo-guided placement and 24.0 for standard-care placement. Since larger scores indicate worse quality of life, the higher posted mean is in the less favorable direction on this scale. The registry record does not report a threshold for a clinically important difference, nor does it provide enough information to interpret individual changes or the distribution of scores beyond the reported summaries.

7. Results Posted in the Registry

• Echo-guided LV Lead Placement: mean 31.00 versus 24.00 on control; difference 7.00 (95% CI -0.02 to 14.02), standardized effect d = 0.30; z-test p = 0.051.

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean difference represent?

For a continuous outcome, the mean is the arithmetic average of participants' scores in a group. The posted mean was 31.0 for echo-guided placement and 24.0 for standard-care placement. The registry's stated mean difference is 7.0, calculated in the direction of echo-guided minus standard care. A positive difference therefore corresponds to a higher average questionnaire score in the echo-guided group. Since higher scores on this questionnaire indicate worse quality of life, the direction of the estimate is important to its interpretation.

The mean gives a concise description of the center of a group, but it does not show the score of any particular participant. Nor does it describe how many participants had scores above or below a chosen value. The standard deviations, 26.0 and 20.0, describe the variability of scores within the two groups. General statistical interpretation: a larger standard deviation means that scores tend to be more dispersed around the group mean. The reported spreads are important context because a mean difference needs to be read alongside the variation among individual scores.

What does the standard error describe?

The registry-derived comparison reports standard errors of 2.408 for the standard-care mean and 2.654 for the echo-guided mean. General statistical interpretation: a standard error describes the uncertainty in an estimated mean due to sampling variation. It is not the same as the standard deviation, which describes variation among observed participant scores. Standard errors contribute to the uncertainty around estimates and help form confidence intervals and test statistics. The registry record does not report the detailed inferential method used by the trial investigators.

The comparison also reports a pooled standard deviation of 23.68 and a standardized effect estimate of 0.296. General statistical interpretation: a standardized effect expresses a difference relative to a measure of score variability, making it possible to describe the difference on a scale that does not use the questionnaire's original units. These quantities can help inform planning illustrations, but they do not replace the original-scale difference or establish clinical importance.

How should the confidence interval be read?

A confidence interval gives a range of values that are compatible with the estimate under the assumptions of the statistical method. Here the posted interval for the mean difference is approximately -0.023 to 14.02. Its inclusion of zero means that a zero difference is within the interval. The interval also extends toward positive differences, which correspond to higher scores in the echo-guided group under the reported subtraction direction. General statistical interpretation: a wide interval indicates less precision than a narrow interval, although the implications depend on the scale and the clinical context. The registry does not report a threshold for a clinically important difference on this questionnaire.

What does the p-value add?

The posted p-value is unadjusted and is 0.051. General statistical interpretation: a p-value measures how unusual the observed result, or a result more extreme, would be under a specified null model and its assumptions. It is not the probability that the null hypothesis is true, nor does it quantify the probability that the observed difference is clinically meaningful. A value near a conventional threshold should not be treated as a sharp boundary between important and unimportant evidence. The registry record does not state the trial's prespecified significance threshold or whether this result was part of a broader set of planned comparisons.

Why can the posted result differ from a simple recalculation?

The displayed comparison is an unadjusted recalculation from posted summary statistics. Such a calculation uses group means, standard deviations, and group counts to estimate an unadjusted difference and its uncertainty. General statistical interpretation: analyses using participant-level data can differ if they incorporate baseline measurements, covariates, missing-data methods, or other model features. The registry record does not report a sponsor analysis or detailed model specification for this endpoint, so the recalculated summary should not be mistaken for an adjusted trial analysis.

What does variability imply for group comparisons?

When participant scores vary considerably within groups, the group mean is less informative about any one person's likely score, and a given mean difference can be estimated with less precision. General statistical interpretation: statistical methods need to account for the outcome's distribution and the way participants were sampled and assigned. The posted endpoint is analyzed as a continuous measure, but assumptions and diagnostic checks are not reported in the registry record. The record also does not report baseline score distributions or participant-level data, so it is not possible to assess how those factors relate to the posted comparison.

What can the randomization and masking labels establish?

The registry identifies the allocation as randomized and the masking as single. Randomization is intended, in general, to reduce systematic differences between groups at assignment. Masking is intended, in general, to reduce the influence of awareness of assignment on some aspects of care, assessment, or reporting. The registry does not identify who was masked, how allocation was concealed, or whether masking was maintained. The labels alone do not answer those questions, and they do not substitute for the missing analysis details.

Overall, the posted mean, spread, confidence interval, and p-value give complementary descriptions: the estimated direction and size of the group-average difference, the variability of observed scores, and the uncertainty around the estimate. None alone establishes clinical importance or resolves the unreported questions about analysis population, missing outcomes, and prespecified methods.

10. Confidence Intervals and Precision

The posted mean difference is 7.0 questionnaire units, with a confidence interval from approximately -0.023 to 14.02. The lower limit is just below zero, while the upper limit is well into the positive direction for the reported subtraction of echo-guided minus standard care. The interval therefore includes no average difference as well as positive differences of varying size. It does not confine the plausible difference to a narrow range around the point estimate.

General statistical interpretation: a confidence interval conveys precision by displaying the range of values compatible with the estimate under a statistical model. The interval is not a guarantee that the true value lies within its bounds, and its width should be considered alongside the outcome scale and any threshold for meaningful change. No clinically important-difference threshold is reported in the registry record, so the interval cannot be classified against such a threshold from this record.

The group standard deviations were 26.0 and 20.0, indicating variability in scores within both groups. The group counts for the endpoint were 96.0 and 69.0. The posted unadjusted p-value is 0.051. Taken together, the estimate, interval, and p-value indicate uncertainty around the observed difference; the p-value should not replace consideration of the interval or the scale's meaning.

The registry record does not report an adjusted confidence interval, a baseline-adjusted estimate, or enough analysis detail to assess the robustness of the interval to alternative methods. The interval describes uncertainty in the posted comparison, not uncertainty about every possible bias or limitation in trial conduct.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. The registry's planning illustration assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It uses the observed effect as its reference and considers effects set at 100%, 75%, and 50% of that observed effect. These are planning assumptions for an illustration; the trial's original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the specified effect under the stated assumptions, if that effect is real and the assumptions hold. The 90% power column describes the corresponding planning target for a 90% chance. For planning at 100% of the observed effect, the figures are 180 participants per arm for 80% power and 241 participants per arm for 90% power. For planning at 75% of the observed effect, they are 320 and 428 participants per arm. For planning at 50% of the observed effect, they are 719 and 963 participants per arm.

Smaller effects are harder to distinguish from random variation, so the illustration requires more participants per arm for the smaller assumed effects. These figures are not observed power, do not describe the trial's actual enrollment target, and do not show that the trial did or did not have adequate power. The original trial design assumptions are not reported in the registry record.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 7.000; pooled standard deviation σ = 23.682.
2. n = 2 × (1.96 + 0.842)² × 23.682² / 7.000² = 179.7, rounded up to 180 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 7                      # observed difference in means
sigma <- 23.6824596633357                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(156390)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 180 (80% power), 241 (90% power)
 75% of observed effect: n per arm = 320 (80% power), 428 (90% power)
 50% of observed effect: n per arm = 719 (80% power), 963 (90% power)
power.t.test: 180.6 
Simulated power at n = 180 per arm: 0.794 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists the Minnesota Living with Heart Failure Questionnaire as the primary outcome and echocardiographic changes as a secondary outcome. It records two outcome measures and one posted secondary outcome. The posted primary comparison has an unadjusted p-value of 0.051. A multiplicity adjustment, hierarchy of outcomes, or strategy for controlling the chance of false-positive findings across tests is not reported in the registry record.

General statistical interpretation: when several outcomes, time points, subgroups, or comparisons are examined, the chance of at least one apparently unusual result can increase. A prespecified approach to multiplicity helps readers understand how a set of inferential results should be interpreted. The registry record does not establish whether other analyses were planned or conducted beyond those represented in the posted results, so the extent of any multiplicity concern cannot be determined from this record alone.

The record does not report the amount or pattern of missing primary-outcome data, reasons for missingness, or the method used to handle missing values. It also does not identify whether the primary result came from an intention-to-treat population, a per-protocol population, or another analysis population. The endpoint group counts are posted, but participant flow and the relationship between enrollment and endpoint availability are not described in detail.

These omissions matter because missing outcomes and choices about which participants to include can affect the estimated group difference. General statistical interpretation: when missingness is related to outcome or treatment assignment, an analysis that excludes participants with missing data may not represent the original randomized comparison. The registry does not provide enough information to evaluate that possibility or to judge whether sensitivity analyses were performed.

The statistical analysis plan, model details, baseline adjustment, prespecified threshold for significance, and handling of secondary outcomes are not reported in the registry record. Therefore, the posted comparison can be described, but its status within a complete prespecified analysis strategy cannot be established from the record.

14. 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 failure hospitalization (27.3%), death (19.5%).

The adverse-event record lists serious events among 110 participants at risk in the echo-guided group and 77 participants at risk in the standard-care group. It reports 31 serious events for the echo-guided group and 36 for the standard-care group. Other adverse events are listed as 8 and 7, respectively, among the same group-specific numbers at risk. These are the posted counts; they should not be interpreted as rates or compared by calculating proportions without a specified analysis and context.

The record also lists “Heart Failure Hospitalization” at 27.3% and “Death” at 19.5% among the top serious-event terms. The denominator and method underlying those term percentages are not reported in the registry record. Group-specific death counts are not reported in the adverse-event summary. The record therefore does not support a detailed comparison of death occurrence between groups from these entries.

General statistical interpretation: adverse-event counts describe events recorded during the study, but their meaning depends on definitions, follow-up duration, ascertainment, and whether counts represent people or repeated events. Those details are not reported in the registry record. These safety entries are descriptive and should not be read as establishing that either lead-placement strategy caused or prevented an event.

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

The posted primary result describes a difference between group-average questionnaire scores at 1 year. The echo-guided group had a mean score of 31.0, compared with 24.0 for standard-care placement, and the posted mean difference was 7.0. Because higher questionnaire scores correspond to worse quality of life, the observed means are directionally higher in the echo-guided group. The confidence interval extends from approximately -0.023 to 14.02, and the unadjusted p-value is 0.051.

These statistics do not establish that the observed difference was caused by the lead-placement approach, nor do they establish whether it is important to participants. The interval includes zero, and the registry does not report a threshold for a clinically important difference. The result also does not describe every participant's experience: group means and standard deviations cannot show how individual scores were distributed or changed.

The study was randomized and single-masked according to the registry, but further details about masking, allocation procedures, participant flow, and endpoint analysis are not reported in the registry record. Missing-data handling, analysis populations, baseline adjustment, and a complete statistical plan are also not reported. These uncertainties restrict how far the posted comparison can be taken as a definitive causal estimate.

The registry lists echocardiographic changes as a secondary outcome, but detailed results for that outcome are not included in the registry record described for the primary comparison. The adverse-event record gives group-specific serious and other event counts, plus two top serious-event terms, but does not report enough detail to infer comparative risk or causation.

In short, the posted evidence is a summary of observed group scores and their uncertainty, not a clinical recommendation or a complete account of all trial outcomes. It should be interpreted in light of the endpoint's direction, the interval's breadth, and the analysis and reporting information that is not available in the registry record.

16. Why This Trial Matters Statistically

This trial raises a statistical question that goes beyond whether the groups have different averages: how precisely can a randomized comparison estimate a patient-reported outcome when scores vary substantially among participants? The posted standard deviations, 26.0 and 20.0, are large relative to the mean difference of 7.0. General statistical interpretation: variation within groups affects the precision of a comparison, and the confidence interval is an important way to see that uncertainty.

The result also illustrates why estimates, intervals, and p-values answer different questions. The mean difference gives the estimated direction and size on the questionnaire scale. The confidence interval shows a range of values compatible with the comparison under its assumptions. The unadjusted p-value describes evidence relative to a null model, but it is not a measure of clinical importance. Reading these together avoids reducing the result to a threshold judgment.

Planning also depends on the effect a study aims to detect. The sample-size illustration shows that smaller assumed effects require more participants per arm under its stated assumptions. This is a general design principle, not evidence about the original rationale for this trial. The registry record does not report the original sample-size justification or planning assumptions.

Finally, registry interpretation depends on transparent reporting of analysis populations, missing outcomes, multiplicity, and model choices. Their absence does not invalidate the posted result, but it limits independent assessment of how robustly the randomized comparison was analyzed. This distinction—between what the numerical result says and what the record allows readers to verify—is central to statistical reading of clinical trials.

17. 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 endpoint comparison is based on posted group summaries rather than participant-level data. The registry record does not report baseline questionnaire scores, so the balance of groups on the primary measure at study entry and any adjustment for baseline values cannot be assessed. It also does not report demographic or clinical characteristics that would help describe the analyzed population.

There is a difference between the recorded enrollment of 187 and the endpoint group counts of 96.0 and 69.0. The registry record does not explain participant flow, reasons for missing endpoint data, or whether the endpoint counts reflect all randomized participants who were eligible for analysis. This limits assessment of attrition and the population represented by the primary result.

The registry records single masking but does not say who was masked or how masking was implemented. It does not report allocation concealment, detailed placement procedures, or the statistical model used for the primary comparison. The prespecified analysis plan, significance threshold, multiplicity strategy, and analysis population are also not reported in the registry record.

The confidence interval crosses zero, and the record does not provide a clinically important-difference threshold for the questionnaire. The result is therefore uncertain both statistically and in its practical interpretation. The record does not provide enough information to assess questionnaire completion, score distributions, or whether statistical assumptions were checked.

Safety reporting is also limited in the available summary: group-specific numbers at risk differ, the basis of the serious-event term percentages is not reported, and group-specific death counts are not reported. These limitations do not imply a particular direction of bias or harm; they identify details needed for a fuller assessment of the posted findings.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Predictors of Response to Biventricular Pacing in Heart Failure — NCT00156390.
• Registry record last updated 2019-11-06; status last verified 2019-11.
• Results first posted 2014-11-24.
• 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.

21. Record Summary

The completed study, NCT00156390, is titled “Predictors of Response to Biventricular Pacing in Heart Failure.” The registry describes randomized, single-masked, parallel-group allocation, with an enrollment of 187 and a recorded phase of NA. The study compared echo-guided left ventricular lead placement with standard-care placement without echo guidance.

The primary outcome was the Minnesota Living with Heart Failure Questionnaire at 1 year. The posted means were 31.0 for echo-guided placement and 24.0 for standard care, with a mean difference of 7.0, a confidence interval from approximately -0.023 to 14.02, and an unadjusted p-value of 0.051. The questionnaire score is worse at higher values.

Echocardiographic changes are listed as a secondary outcome. The record also lists serious and other adverse-event counts, but the available details do not support a complete comparative safety analysis. Missing-data handling, analysis population, multiplicity strategy, and the trial's original sample-size assumptions are not reported in the registry record.