Family Palliative and End-of-Life Care for Advanced Heart Failure: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Family Palliative and End-of-Life Care for Advanced Heart Failure (NCT04153890), a randomized na study. The primary outcome is Patient Heart Failure Health Status (KCCQ)- Baseline.

2. Clinical Question

3. Trial Design

The registry describes a randomized, double-masked, parallel-group trial of FamPALcare versus Standard Care. The listed enrollment is 78. The trial is marked completed, with a start date of 2020-01-13 and a primary completion date of 2023-07-31. The condition entries are Heart Failure NYHA Class III and Heart Failure NYHA Class IV. West Virginia University is listed as the sponsor. The phase is listed as NA.

FamPALcare participants were to receive standard care plus five weekly coaching sessions and telephone follow-up intended to reinforce heart-failure palliative home care. Standard Care participants were to receive routine heart-failure care and instruction at a university hospital or clinic. The registry identifies the intervention as behavioral. It does not report the specific roles of the people who were masked, how masking was maintained, or how allocation was generated or concealed. Those details are not reported in the registry record.

The study objective refers to improved rural home end-of-life and palliative care at 6 months. However, the posted primary measure analyzed in these results is KCCQ health status at Baseline. Its reported group counts are 21.0 for FamPALcare and 18.0 for Standard Care. Those outcome counts do not match the listed overall enrollment, and the reason for the difference is not reported in the registry record. The registry says the outcome population remains the same across study timepoints under an ITT principle; it does not explain how that statement relates to the baseline counts displayed for this measure.

The record lists 19 outcome measures, one posted secondary outcome, and zero analyses. The listed secondary outcome is the FamPALcare Helpfulness Scale. The registry’s completion status and stated objective do not substitute for a posted analysis of the 6-month question. The statistical plan, original sample-size justification, and analysis details beyond the information described for the posted outcome are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The overall number of participants will remain the same throughout the study timepoints as the data analysis was performed with the Intent-To-Treat (ITT) principle.

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 Patient Heart Failure Health Status (KCCQ)- Baseline, measured over Baseline.

The primary endpoint shown in the registry is Patient Heart Failure Health Status measured with the Kansas City Cardiomyopathy Questionnaire at Baseline. The description says the KCCQ uses 12 Likert-scale items, each ranging from 0-4, and that total scores range from 0-100. Higher scores indicate better heart-failure health status. The reported summary is a mean and standard deviation for each arm.

A health-status questionnaire provides a standardized way to describe how patients experience their condition. A continuous score can preserve variation across participants rather than reducing responses to a simple event count. Comparing group means is one way to summarize the average score in each arm, while the standard deviations describe the spread of individual scores around those means. These are general properties of continuous measures, not additional findings from this trial.

The timing is important for interpretation. Baseline scores characterize participants at the starting measurement; they do not measure a response to coaching. Although the registry objective refers to an assessment at 6 months, the primary outcome result posted in this record is explicitly labeled Baseline. A result for the stated 6-month objective is not reported in the registry record. Therefore, the baseline KCCQ comparison should be read as a description of the groups’ starting health-status scores, not as evidence about later change or the effect of FamPALcare.

7. Results Posted in the Registry

• FamPALcare: mean 26.79 versus 27.11 on control; difference -0.32 (95% CI -10.66 to 10.02), standardized effect d = -0.02; z-test p = 0.952.

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a continuous primary outcome summarized by arm means and standard deviations. A mean is the arithmetic average of the measured scores in an arm. A standard deviation describes how dispersed individual scores are around that arm’s mean. These summaries address different features: the mean locates the center of the observed scores, while the standard deviation describes their spread. The KCCQ total score is described as ranging from 0-100, with higher values indicating better heart-failure health status.

What does a mean difference represent?

The posted comparison expresses the FamPALcare mean relative to the Standard Care mean. Its reported estimate is -0.32 KCCQ points. A negative sign means the FamPALcare mean is lower in this stated ordering; it does not by itself imply a treatment benefit or harm. Here the measure is at Baseline, so the sign describes the direction of the starting-score contrast and not a change caused by the intervention. The arm means are 26.79 and 27.11, respectively.

In general, a mean difference is useful because it remains in the outcome’s original units. The posted interval likewise uses KCCQ points, which permits interpretation against the 0-100 scale. The registry does not provide a threshold for interpreting a difference as clinically important, so the statistical contrast cannot be classified as clinically important or unimportant on the basis of a threshold in this record.

What do the confidence interval and p-value address?

In general, a confidence interval gives a range of estimates compatible with the observed data under the statistical procedure and its assumptions. The posted interval for this mean difference runs from -10.66 to 10.02. Since the interval includes zero, the data do not clearly distinguish a positive mean contrast from a negative one. Its breadth also means that a range of possible differences remains compatible with the estimate. The interval is an uncertainty statement about the mean contrast, not a range containing a specified proportion of individual patient scores.

The unadjusted p-value is 0.952. In general, a p-value measures how unusual data at least as discordant with a null hypothesis would be if that hypothesis and the test assumptions held. It is not a measure of the probability that the null hypothesis is true, nor does it quantify the probability of a treatment effect. The registry does not report a multiplicity-adjusted p-value or a full statistical analysis plan.

Why does variability matter?

The standard deviations are 18.3 for FamPALcare and 14.63 for Standard Care. In general, greater variability makes it harder to estimate an arm mean precisely when the number of observations is limited. The uncertainty of a difference depends on variability in both arms and on the amount of information available in each. The reported outcome counts are 21.0 and 18.0. The comparison also reports a pooled standard deviation of 16.71, used in the posted planning illustrations. No further details of the statistical model used for the registry comparison are reported in the registry record.

Over-dispersion is a general concern when a statistical model assumes less variation than the data contain. If variability is underestimated, uncertainty can be understated, producing intervals that are too narrow or tests that are too optimistic. This is a general principle, not a finding that over-dispersion occurred in this trial. The posted outcome is continuous and summarized with means and standard deviations; no over-dispersion assessment is reported in the registry record.

What is the scope of this comparison?

The primary endpoint is labeled Baseline, so the comparison concerns starting scores. Randomization is intended to make groups comparable on average, but it does not ensure identical observed summaries in every realized trial. In general, a baseline comparison can describe the observed groups; it is not a substitute for comparing outcomes after treatment or changes over time. The posted baseline estimate should not be recast as a treatment estimate.

The registry describes an ITT principle for the outcome population and states that the overall number remains the same throughout timepoints. It does not report the missing-data procedures, the exact analysis population construction, or how the stated ITT approach was implemented for the displayed baseline counts. It also lists zero analyses. These omissions limit the ability to assess the analysis in detail. No adjusted result, repeated-measures model, or follow-up estimate is reported in the registry record.

How should recalculated results be understood?

Recalculated estimates are simple, unadjusted calculations from posted summary statistics rather than a substitute for a trial’s full statistical analysis. In this record, the comparison is not flagged as discrepant. No sponsor analysis takes precedence in the posted record. The displayed mean difference, interval, and p-value should nevertheless be interpreted within their stated scope: the baseline KCCQ comparison. General statistical explanations in this discussion describe concepts and do not add analyses or findings for the trial.

10. Confidence Intervals and Precision

The reported mean difference is -0.32, and its confidence interval extends from -10.66 to 10.02 KCCQ points. The estimate is a single summary of the observed contrast; the interval communicates that the underlying mean difference is uncertain. The interval crosses zero, so it includes no difference as well as contrasts in either direction. Its width cautions against treating the point estimate as a precise determination of the size or direction of a baseline difference.

In general, a confidence interval is constructed by a method that would cover the target parameter at a stated rate over repeated applications when its assumptions hold. It does not mean that there is a 95% probability that this particular fixed parameter lies within the observed interval. Nor does it describe the spread of individual KCCQ scores; that is what the arm standard deviations characterize. The registry identifies the displayed range as a confidence interval but does not report a detailed method for its construction.

The interval is expressed in the original KCCQ score units, whose total-score range is 0-100. The lower and upper limits are far enough apart that the result remains compatible with a range of possible baseline mean contrasts. The registry does not report a clinical-importance threshold for the KCCQ difference, so the interval alone cannot establish whether any particular contrast would matter clinically.

The p-value is 0.952 and is explicitly unadjusted. It complements, but does not replace, the interval: it summarizes compatibility with a specified null model, whereas the interval displays a range of estimates. Neither establishes equality, and neither answers the 6-month question. Because the endpoint is at Baseline, precision concerns the baseline means, not an intervention effect or a change during follow-up.

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 illustrations express requirements as participants per arm, not as total events. They are based on the observed mean difference and then consider planning for 100% of that observed effect, 75% of the observed effect, and 50% of the observed effect. For 100% of the observed effect, the figures are 42,826 participants per arm for 80% power and 57,332 participants per arm for 90% power. For 75% of the observed effect, they are 76,135 and 101,924 participants per arm, respectively. For 50% of the observed effect, they are 171,304 and 229,327 participants per arm, respectively.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. The registry’s sample-size assumptions specify participants per arm for this continuous outcome; the note about total events applies to time-to-event illustrations, not these figures. The trial’s own original design assumptions and sample-size justification are not reported in the registry record.

In plain language, 80% power is a planning target for the chance of detecting an effect of the specified size under the calculation’s assumptions, if that effect is the true effect. The 90% column uses a higher detection target and therefore requires more participants in each listed scenario. Smaller effects require more participants to distinguish them from random variation at the same planning thresholds. These are planning illustrations based on the observed baseline contrast, not observed power.

The figures should not be read as the trial’s enrollment target or as evidence that the trial was designed around these assumptions. The posted estimate comes from a baseline endpoint, and the registry does not report the original design calculation or the effect the trial intended to detect. These illustrations are therefore conditional examples, not a reconstruction of the trial’s design process.

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 = -0.320; pooled standard deviation σ = 16.714.
2. n = 2 × (1.96 + 0.842)² × 16.714² / -0.320² = 42,825.9, rounded up to 42,826 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 <- -0.32                      # observed difference in means
sigma <- 16.7141526856733                     # 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(4153890)
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 = 42,826 (80% power), 57,332 (90% power)
 75% of observed effect: n per arm = 76,135 (80% power), 101,924 (90% power)
 50% of observed effect: n per arm = 171,304 (80% power), 229,327 (90% power)
power.t.test: 42826.9 
Simulated power at n = 42,826 per arm: 0.801 (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 19 outcome measures, but only one secondary outcome is identified as posted: the FamPALcare Helpfulness Scale. It lists zero analyses. The primary outcome result available for interpretation is the baseline KCCQ comparison. The registry does not give a complete list of planned tests, specify which outcomes were designated primary at each timepoint, or explain how the displayed comparison relates to the listed analysis count. Those details are not reported in the registry record.

Multiplicity is a general issue that arises when several outcomes, timepoints, or statistical tests are examined. The more tests conducted, the greater the opportunity for some results to appear notable by chance if each is judged without adjustment. Statistical approaches can control or describe that issue, but the appropriate approach depends on the prespecified plan and the questions being tested. No multiplicity strategy is reported in the registry record. The posted p-value is unadjusted, so it should not be treated as an adjustment for other outcomes or analyses.

The registry says that the outcome population follows an Intent-To-Treat (ITT) principle and that the overall number remains the same across timepoints. In general, ITT refers to analyzing participants according to their randomized groups, regardless of adherence to assigned intervention. The registry does not report the operational definition used, how the stated approach was implemented, or how missing observations were handled. The reported baseline KCCQ counts are 21.0 for FamPALcare and 18.0 for Standard Care, while overall enrollment is 78; the reason for the difference is not reported in the registry record.

Missing-data handling can affect estimates if some measurements are unavailable. In general, analysts may use different assumptions and methods for missing outcomes, and conclusions can depend on those choices. The registry does not report the amount or pattern of missing KCCQ data, imputation methods, sensitivity analyses, or reasons for unavailable measurements. No particular missing-data mechanism or procedure should therefore be assumed.

The record does not report a full statistical analysis plan, prespecified covariates, a baseline-adjusted follow-up analysis, or a plan for repeated observations. It also does not report an inferential result for the stated 6-month objective. These omissions restrict assessment of selective outcome reporting, multiplicity, and the treatment of missing follow-up data. They do not establish that a particular procedure was or was not performed outside what is recorded.

14. 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

Serious events with the highest arm-level rate: death (11.1%).

Safety entries are reported separately for patients and caregivers in each arm. Among FamPALcare patients, 21 were listed at risk for serious adverse events and none were affected; 21 were listed at risk for other adverse events and none were affected. Among Standard Care patients, 18 were listed at risk for serious adverse events, with 2 affected, and 18 were listed at risk for other adverse events, with none affected. No serious or other adverse events were listed for caregivers in either arm: the caregiver at-risk counts were 21 for FamPALcare and 18 for Standard Care.

The serious-event term listed is Death, at 11.1%. The record also reports 2 deaths in Standard Care patients and none in FamPALcare patients. This is a descriptive registry entry, not evidence that group assignment caused or prevented an event. The registry does not report event-level timing, adjudication, attribution to intervention, or an analysis comparing safety between arms. The small reported counts also limit the precision of any interpretation. Absence of a reported event in a group should not be read as proof that no risk exists.

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

The result establishes that the registry posted baseline KCCQ means of 26.79 for FamPALcare and 27.11 for Standard Care, along with a mean difference of -0.32 and a confidence interval from -10.66 to 10.02. These data describe starting health-status scores among the outcome counts shown. They indicate uncertainty around the baseline mean contrast rather than a precise estimate of a later intervention effect.

The figures do not show whether FamPALcare improved heart-failure health status, changed palliative or end-of-life care, or altered outcomes at 6 months. The endpoint is explicitly Baseline, and a result for the registry’s stated 6-month objective is not reported in the registry record. A baseline comparison cannot be substituted for a comparison of follow-up scores or changes over time.

The interval includes zero and values in either direction. This means the posted estimate does not resolve whether the underlying baseline mean contrast favors one group or the other. It also does not prove that baseline scores were exactly equal. The registry does not give a threshold for a clinically important KCCQ difference, so the numerical estimate cannot be assigned clinical importance using a threshold from this record.

The trial is described as randomized, which is relevant to how the study was designed, but the available endpoint result is not the post-assignment outcome needed to assess an intervention effect. The record does not report enough about the analysis plan, missing data, or follow-up estimates to establish how the stated objective was evaluated. The posted result should therefore be understood narrowly: it is a baseline health-status description with an imprecise between-arm mean contrast.

Likewise, the adverse-event entries are descriptive and do not establish causation. The registry reports serious events and deaths in Standard Care patients and none in the FamPALcare patient group, but it does not provide an adjusted safety comparison, event timing, or attribution. These entries cannot by themselves establish that either care approach caused or prevented the reported events.

16. Why This Trial Matters Statistically

This trial raises statistical questions common in behavioral and supportive-care research: how to measure patient health status, how to compare randomized groups, and how to distinguish a starting description from an intervention outcome. The KCCQ is a continuous score with a stated range and direction, so its mean difference can be expressed in familiar score units. That makes the contrast interpretable as a difference in average reported health status, while the standard deviations and confidence interval convey variation and uncertainty.

The central statistical point is the timing of the posted primary endpoint. The study objective concerns care at 6 months, but the posted primary result is at Baseline. Statistical interpretation depends not just on the outcome name but on when it was measured. A baseline result describes the groups’ starting scores; it cannot answer a question about subsequent change. Recognizing this distinction prevents an initial group comparison from being mistaken for evidence about the intervention.

The confidence interval also illustrates why a point estimate alone is insufficient. The mean difference is -0.32, but the interval from -10.66 to 10.02 encompasses zero and a range of contrasts in either direction. The result therefore has limited precision as a description of the underlying baseline difference. The p-value of 0.952 does not erase that uncertainty or establish equivalence.

The planning illustrations demonstrate another general principle: required sample size depends on the effect a study seeks to detect and on its power target and statistical assumptions. Smaller target effects require more participants under the stated planning framework. These illustrations use the observed baseline effect, however, and are not evidence of the trial’s original design assumptions or its ability to detect the intervention effect.

Finally, outcome multiplicity, missingness, analysis populations, and safety attribution all affect interpretation. The record gives limited detail on these matters. Identifying what is and is not documented is part of sound statistical reading: it avoids filling gaps with assumed methods and keeps conclusions aligned with the endpoint and analysis actually posted.

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 primary limitation for interpreting the posted result is that the KCCQ endpoint is labeled Baseline, whereas the study objective refers to assessment at 6 months. A baseline contrast does not estimate an intervention effect or a change over follow-up. A 6-month primary result is not reported in the registry record.

The outcome counts shown by arm are 21.0 for FamPALcare and 18.0 for Standard Care, while enrollment is listed as 78. The record says the outcome population follows an ITT principle and remains the same across timepoints, but does not explain the relationship between that statement, overall enrollment, and the reported baseline counts. This limits assessment of the analyzed population.

The registry does not report the statistical analysis plan, the construction method for the confidence interval, missing-data procedures, covariate adjustment, multiplicity handling, or sensitivity analyses. It lists zero analyses despite posting a comparison, and the reason for this is not reported. The comparison has a wide interval, leaving uncertainty about the direction and size of the baseline mean contrast. No clinical-importance threshold is recorded.

Details of masking, allocation concealment, intervention adherence, and the exact implementation of coaching and telephone follow-up are not reported in the registry record. Safety entries are descriptive; event timing, relationship to intervention, and comparative analysis are not reported. These limitations do not show that a particular method was absent, but they constrain what can be inferred from the registry record.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Family Palliative and End-of-Life Care for Advanced Heart Failure — NCT04153890.
• Registry record last updated 2025-02-19; status last verified 2025-02.
• Results first posted 2025-02-19.
• 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

NCT04153890 is a completed, randomized, double-masked, parallel-group study sponsored by West Virginia University. It compares FamPALcare, a behavioral program of five weekly coaching sessions plus telephone follow-up, with Standard Care for advanced heart failure. The listed enrollment is 78, and the study objective concerns home palliative and end-of-life care at 6 months.

The posted primary outcome is baseline KCCQ health status. Mean scores were 26.79 for FamPALcare and 27.11 for Standard Care; the reported mean difference was -0.32, with a confidence interval from -10.66 to 10.02 and an unadjusted p-value of 0.952. This is a baseline comparison, not a follow-up treatment effect. The registry does not report the primary outcome result at 6 months or detailed methods for missing data, multiplicity, and the analysis plan.