Families Taking Control (FTC): Family-based Problem-solving Intervention for Children With Sickle Cell Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Families Taking Control (FTC): Family-based Problem-solving Intervention for Children With Sickle Cell Disease (NCT02273310), a randomized na study. The primary outcome is Child-Reported Health Related Quality of Life-School Functioning Subscale.

2. Clinical Question

3. Trial Design

The registry describes a randomized, parallel-group study with no masking. It lists the phase as NA. The study was conducted from 2009-07 to a primary completion date of 2012-08, and its status is completed. The registry lists University of Pennsylvania as the sponsor and enrollment of 83.

The intervention was behavioral: Families Taking Control, a one-day problem-solving skills training for disease management. The comparison group was a delayed intervention control, whose families were offered the training after assessment time 2. The brief study description says the intervention included booster phone calls, while the arm description itself identifies the one-day training. Further details about the calls are not reported in the registry record.

The primary endpoint was scheduled at 6 months and measured child-reported health-related quality of life in the school-functioning subscale of the Pediatric Quality of Life Inventory. The posted outcome summaries list 24 participants for Families Taking Control and 38 for delayed intervention control. These outcome-specific group counts are distinct from the registry's overall enrollment figure. The record does not explain the difference between enrollment and the group counts appearing in the primary outcome summary.

Random assignment is reported, but the method used to generate the sequence, allocation concealment procedures, and any stratification factors are not reported in the registry record. The record also does not report whether analyses followed intention-to-treat principles, how missing outcome data were handled, or the original design's sample-size assumptions. The posted summaries are descriptive and include unadjusted comparisons; reported analysis details are not available 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

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 Child-Reported Health Related Quality of Life-School Functioning Subscale, measured over 6 months.

The primary endpoint was the child-reported Health Related Quality of Life-School Functioning Subscale, assessed at 6 months with the Pediatric Quality of Life Inventory. The score ranges from 0-100, and higher scores indicate better quality of life. The posted summary reports a mean and standard deviation for each group.

This endpoint focuses on the child's experience of school functioning as part of health-related quality of life. It is relevant to the study's stated aim of addressing both quality of life and school functioning for children with sickle cell disease and their families. A child report offers a perspective on the child's own experience; it is not interchangeable with attendance records, school accommodations, or a caregiver's assessment.

A mean describes the average score in a group, while the standard deviation describes how spread out individual scores are around that average. The endpoint therefore gives a group-level comparison, not a description of every child's experience. The registry record does not report a threshold for a meaningful change in this subscale, so the numerical difference alone cannot establish whether its size would matter to children or families. Nor does the outcome summary describe change from baseline; baseline values and the approach to any baseline adjustment are not reported in the registry record.

7. Results Posted in the Registry

• Delayed Intervention Control: mean 64.60 versus 60.40 on control; difference 4.20 (95% CI -6.77 to 15.17), standardized effect d = 0.21; z-test p = 0.453.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

School Functioning-Absences

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Delayed Intervention Control: mean 1.10 versus 0.48 on control; difference 0.62 (95% CI 0.17 to 1.07), standardized effect d = 0.66; z-test p = 0.007.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Delayed Intervention Control than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Number of Accommodations Provided to Families by Schools

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Delayed Intervention Control: mean 1.38 versus 1.44 on control; difference -0.06 (95% CI -0.72 to 0.60), standardized effect d = -0.05; z-test p = 0.858.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Delayed Intervention Control and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes broaden the scope beyond the primary child-reported quality-of-life score. They address school absences, accommodations provided to families by schools, and acceptability of the intervention. The posted quantitative summaries include results for absences and accommodations; the registry lists acceptability as a secondary outcome, but a quantitative result for it is not reported in the registry record.

Across the school-related secondary measures, the pattern is not uniformly aligned: one comparison shows a clearer separation between group summaries, while the other is much closer. These outcomes capture different constructs, so they need not move together. Absence is a measure of time away from school, accommodations reflect support provided by schools, and the primary endpoint is the child's report of school functioning within quality of life. None can be treated as a direct substitute for another.

The secondary findings do not overturn or resolve the uncertainty in the primary comparison. They may help describe domains that the primary endpoint does not capture, but they do not turn an imprecise primary result into a definitive overall conclusion. The registry record identifies four outcome measures in total and lists three secondary outcomes. It does not report analyses for the secondary endpoints.

Unadjusted secondary results generally carry less weight when several outcomes are examined without a reported plan for controlling the chance of false-positive findings. Considering multiple comparisons can make an isolated apparently strong result less persuasive, especially when the number of planned tests and the interpretation strategy are not documented. The record does not report a multiplicity adjustment or a hierarchy for the outcomes. Accordingly, the secondary summaries are best read as exploratory context rather than as independent confirmation of the primary finding.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• School Functioning-Absences
• Number of Accommodations Provided to Families by Schools
• Acceptability of Intervention

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a score on a 0-100 scale, summarized using a mean and standard deviation. A mean gives the arithmetic average within a group. A standard deviation describes the amount of variation among the scores around that average; it is not the uncertainty in the mean itself. The registry reports the group means as 60.4 and 64.6 and the standard deviations as 23.89 and 16.94.

What does the mean difference represent?

The posted comparison expresses the mean difference as delayed intervention control minus Families Taking Control. Its estimate is 4.2 units. With this ordering, a positive estimate indicates a higher average in delayed intervention control; the score definition says that higher values indicate better quality of life. This directional description is specific to the chosen outcome scale and does not establish why the group averages differ. The comparison is unadjusted and does not account for any additional factors in the calculation shown.

How should the confidence interval be read?

A confidence interval describes uncertainty around an estimated difference. In general, a wider interval indicates less precision than a narrower interval. The primary interval runs from -6.771 to 15.17. It contains zero, which represents no difference between the group means under the stated direction of subtraction. It also includes values on both sides of zero, so the posted estimate alone does not determine the direction of the underlying difference. A confidence interval is not a guarantee that the true value lies within its limits, nor does it describe the range of individual scores.

What does the p-value contribute?

The unadjusted p-value for the primary comparison is 0.453. In general, a p-value measures how unusual data at least as incompatible with a specified null model would be if that model and the assumptions used for the calculation were correct. It is not the probability that the null model is true, and it does not measure the clinical importance of a result. The registry record does not report a detailed testing procedure or analysis plan, so interpretation of this posted p-value should remain tied to the unadjusted summary comparison.

What is a standardized effect?

A standardized effect expresses a difference relative to a measure of variability, rather than in the original scale units. This can make effects from scales with different units easier to compare in general, but it can also make an effect less directly interpretable in terms of the original measure. The posted primary comparison includes a standardized effect estimate, but the scale-unit mean difference and its confidence interval provide the more direct description of the primary outcome. The registry record does not state a threshold for a meaningful standardized or scale-unit difference.

Why distinguish recalculated estimates from reported analyses?

The posted comparison statistics are unadjusted recalculations from the group summary statistics. The registry record lists no reported analyses, so these summaries should not be mistaken for a documented sponsor analysis. The record does not describe the exact test used for the original trial analysis, any covariate adjustment, or how repeated measurements or baseline scores were handled. Those details are not reported in the registry record. The recalculated comparison provides a transparent reading of the available group means, standard deviations, and outcome counts, but it cannot recover analysis choices that are not documented.

Why can over-dispersion matter?

As a general statistical point, an outcome with more variability than a model assumes can lead to standard errors that are too small and confidence intervals that are too narrow if that extra variability is ignored. Conversely, an analysis that recognizes additional variation may produce wider uncertainty estimates. This concern is especially relevant for outcomes whose distributions are uneven or clustered, but it should not be assumed that a particular problem occurred in this trial. The primary endpoint is reported as a continuous score with standard deviations, and the registry record does not describe a model that assumes a particular count distribution or report an over-dispersion assessment.

All inferential summaries depend on assumptions about the data and analysis. The registry record does not report enough detail to evaluate those assumptions fully, including the original analysis population, missing-data approach, or whether the reported comparison was prespecified. The estimates should therefore be interpreted as unadjusted summaries rather than as a complete account of the trial's statistical methods.

11. Confidence Intervals and Precision

The primary mean difference is 4.2 units, with a 95% confidence interval from -6.771 to 15.17. This interval is broad enough to include no difference and values in both directions. It therefore gives limited precision about the direction and size of the group contrast. The interval is more informative than the point estimate alone because it displays a range of values compatible with the uncertainty in the comparison under the calculation used.

The confidence interval is not an interval for individual children's scores. Individual scores varied within both groups, as reflected by the standard deviations of 23.89 and 16.94. Nor does the interval indicate whether a difference would be important in practice. The registry record does not report a minimally important difference or other threshold for interpreting the size of a change on the school-functioning subscale.

The comparison is based on the posted outcome counts of 24 and 38. The registry record does not explain how these counts relate to overall enrollment or whether any outcome values were missing. Without that information, it is difficult to assess whether the analyzed summaries represent all randomized participants or a subset selected by outcome availability. The record also does not report an adjusted estimate or a detailed method for calculating the interval.

In general, more precise estimates tend to have narrower confidence intervals, while smaller samples or greater variability tend to increase uncertainty. Those general considerations do not identify the cause of the interval's width in this study. The posted interval supports a cautious reading: the estimated difference is not precise enough to establish a clear direction or rule out a range of potentially different values.

12. 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 event counts. They are illustrative calculations based on the observed effect, rather than the trial's original sample-size design. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning row considers detecting the stated fraction of the observed effect. The original design assumptions for this trial are not reported in the registry record.

The 80% power column describes a planning scenario in which a study designed with the listed assumptions would have an 80% chance of detecting an effect of the specified size, if that effect and the assumptions were correct. The 90% power column describes the corresponding planning target with a 90% chance. These are design calculations, not estimates of the chance that the trial's observed result is true or the chance that a treatment works.

The rows use the observed effect and smaller fractions of it. Planning to detect a smaller effect requires more participants per arm, because a smaller difference is harder to distinguish from random variation under the same assumptions. For the primary outcome, the displayed planning figures are 353 and 472 participants per arm for 80% and 90% power when planning for 100% of the observed effect; 627 and 839 when planning for 75%; and 1,409 and 1,886 when planning for 50%.

These calculations are not observed power. They are planning illustrations based on the observed effect and specified assumptions. They do not show what the trial was originally designed to detect, and they should not be used as a retrospective measure of whether the trial succeeded. Because the observed estimate itself is uncertain, planning directly from it can also be unstable; a design would ordinarily need a justified target effect and assumptions appropriate to its purpose.

13. 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 = 4.200; pooled standard deviation σ = 19.893.
2. n = 2 × (1.96 + 0.842)² × 19.893² / 4.200² = 352.2, rounded up to 353 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 <- 4.2                      # observed difference in means
sigma <- 19.8932532533017                     # 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(2273310)
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 = 353 (80% power), 472 (90% power)
 75% of observed effect: n per arm = 627 (80% power), 839 (90% power)
 50% of observed effect: n per arm = 1,409 (80% power), 1,886 (90% power)
power.t.test: 353.1 
Simulated power at n = 353 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.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and three secondary outcomes, and it reports four outcome measures in total. However, the registry record lists zero reported analyses. It does not describe a prespecified testing hierarchy, a family of outcomes for multiplicity control, or an adjustment method for multiple comparisons. Without those details, the interpretation of separate unadjusted p-values is less secure, particularly for secondary outcomes. If many outcomes or analyses are considered, the chance of at least one apparently notable result can increase even when there is no real difference; this is a general statistical concern, not a claim that a particular false-positive result occurred in this trial.

Missing-data handling is also not reported in the registry record. The primary outcome summary lists 24 participants in Families Taking Control and 38 in delayed intervention control, while total enrollment is 83. The record does not explain the relationship between those figures, identify the reasons for any absent outcome data, or state whether missing measurements were imputed, excluded, or addressed in another way. It therefore cannot establish whether the posted comparison reflects all randomized participants or only participants with available outcome measurements.

The analysis population is not reported in the registry record. It is not stated whether the primary comparison used intention-to-treat, per-protocol, or another population definition. Nor are the handling of crossovers, intervention adherence, baseline adjustment, or other exclusions described. These omissions matter because analysis choices can affect both the estimate and its uncertainty.

The registry gives a randomized design and a delayed intervention comparison, but does not report enough statistical-plan detail to assess which analyses were planned in advance or how deviations were treated. As a result, the posted unadjusted summaries can be described, but their relationship to the original analysis plan cannot be verified from the registry record.

15. 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.

The adverse-event summaries list 42 participants at risk in Families Taking Control and 41 in delayed intervention control. For each group, the registry reports zero participants affected by serious adverse events and zero affected by other adverse events. These are the figures recorded in the safety summary; they do not establish that no event occurred outside the reported monitoring or reporting scope.

The deaths entries are null, which means a death count is not reported in the registry record; it should not be read as a reported zero. The registry does not list serious adverse-event terms. It also does not provide event descriptions, severity categories beyond the serious-versus-other distinction, timing, or a narrative of safety monitoring in the posted record.

These summaries are descriptive counts, not a comparison designed to establish that the groups had the same safety experience. The record does not explain how the safety population relates to the primary outcome populations, and no conclusions about safety beyond the posted figures are justified by these data alone.

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

The primary result describes child-reported school functioning within health-related quality of life at 6 months. The posted group means were 60.4 for Families Taking Control and 64.6 for delayed intervention control. The unadjusted mean difference was 4.2 units in the direction of a higher average in delayed intervention control. Its confidence interval, -6.771 to 15.17, includes zero and spans values in both directions. The result is therefore uncertain about the size and direction of the group contrast.

This does not establish that the intervention improved or worsened the primary outcome, nor does it establish equivalence between the groups. A failure to demonstrate a clear difference is not proof that there is no difference. Conversely, a numerical difference between group means is not by itself proof of a meaningful effect. The registry record does not report a threshold for a clinically meaningful difference on this scale.

The primary endpoint is one dimension of the study's aims. The secondary outcomes concern absences, school accommodations, and intervention acceptability. These outcomes address related but distinct experiences, and the registry does not report results for acceptability or an analysis plan connecting the outcomes. The primary comparison cannot answer every question about school functioning, family experience, or the intervention's implementation.

The result also depends on who contributed outcome data and how those data were analyzed. The registry record does not explain the endpoint counts relative to enrollment, describe missing-data handling, or identify the analysis population. It lists no reported analyses. These limitations mean that the posted summaries should be interpreted as group-level descriptive and unadjusted comparisons, rather than as a complete account of all trial analyses.

In short, the record reports an imprecise primary comparison and secondary outcomes that add context without resolving the primary uncertainty. The figures do not support a broad claim about treatment effects beyond these specific recorded measures and time point.

17. Why This Trial Matters Statistically

This trial illustrates why a randomized comparison should be read through both its estimate and its uncertainty. The primary means differ numerically, but the confidence interval extends across zero and includes values in either direction. Focusing only on the point estimate or on a single p-value would conceal how little precision the comparison provides about the underlying difference.

It also demonstrates the importance of separating outcome domains. Child-reported school-functioning quality of life, school absences, and accommodations are related but not identical measures. A trial can show different patterns across these domains without contradiction, because each captures a different aspect of children's school experience. Statistical interpretation should retain those distinctions rather than compress them into a single claim.

The registry record also highlights the value of transparent analysis reporting. Randomization is identified, but the original analysis plan, missing-data approach, multiplicity strategy, and analysis population are not reported. Without those details, readers can describe the posted summaries but cannot fully assess how they relate to planned analyses or who was included.

Finally, planning calculations based on observed effects require careful reading. They show how sample-size targets change under specified assumptions and smaller target effects; they do not reveal the original design rationale or the probability that the observed conclusion is correct. Together, these features make the study a useful example of reading estimates, intervals, outcomes, and registry reporting as complementary parts of statistical evidence.

18. 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 are specific to the information recorded for this trial. The registry reports overall enrollment of 83, while the primary outcome summaries list 24 and 38 participants in the two groups. The registry record does not explain the relationship between these counts, reasons for unavailable outcome measurements, or whether those included differed from those not included. This prevents a clear assessment of potential selection from missing outcome data.

The primary result is an unadjusted comparison of group means. The registry record does not report the original statistical analysis plan, whether the comparison was prespecified in its posted form, or any adjusted analysis. The analysis population, baseline score handling, and methods for missing data are also not reported. Therefore, the posted estimate may not capture all analysis choices used during the trial.

The primary outcome is child-reported and focuses on one school-functioning subscale. It does not by itself measure attendance, accommodations, or all aspects of quality of life. Although these are represented among secondary outcomes, the registry record does not report a quantitative acceptability result or details sufficient to connect the outcome domains into a single overall assessment.

The record describes a randomized design without masking. Sequence generation and allocation concealment are not reported in the registry record. It also does not provide a detailed account of intervention uptake, adherence, or the booster phone calls mentioned in the brief summary. Those omissions limit evaluation of how the intervention was delivered and how closely the comparison reflected the intended contrast.

Finally, multiplicity procedures and original sample-size assumptions are not reported. The secondary summaries are unadjusted, and the primary confidence interval is broad. These limitations call for restrained interpretation of the posted estimates rather than extrapolation to outcomes or populations not documented in the registry record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Families Taking Control (FTC): Family-based Problem-solving Intervention for Children With Sickle Cell Disease — NCT02273310.
• Registry record last updated 2016-01-07; status last verified 2015-12.
• Results first posted 2016-01-07.
• 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.

22. Record Summary

NCT02273310, Families Taking Control (FTC), is a completed randomized, parallel-group study sponsored by University of Pennsylvania. It studied a family-based problem-solving intervention for children with sickle cell disease and their families. The registry lists enrollment of 83, no masking, and a study period from 2009-07 to primary completion in 2012-08.

The primary outcome was child-reported health-related quality of life in the school-functioning subscale at 6 months. The posted unadjusted mean difference was 4.2 units, with a 95% confidence interval from -6.771 to 15.17 and an unadjusted p-value of 0.453. Secondary outcomes included school absences, school accommodations, and intervention acceptability. The registry record lists no reported analyses and does not report the original statistical plan, missing-data methods, or analysis population.