Environmental Control as Add-on Therapy in Childhood Asthma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Environmental Control as Add-on Therapy in Childhood Asthma (NCT02251379), a randomized phase 2 study. The primary outcome is The Medication Treatment Step Assigned.

2. Clinical Question

The clinical question is whether adding an individually tailored, multifaceted Environmental Control Strategy (ECS) at home to guideline-based controller medication is associated with a different controller medication treatment step at the 6 month clinic visit than controller medication alone. The study description also states a hypothesis about controller medication requirements and allergic inflammation among urban children with asthma.

The treatment-step score ranges from 0-6: 0 indicates no controller medication and 6 indicates high dose inhaled corticosteroids plus a long-acting beta agonist. The trial compares the group means on this scale. This is a question about the assigned level of controller treatment at follow-up, not a direct measure of medication adherence or a stand-alone measure of asthma symptoms.

3. Trial Design

The registry describes a completed phase 2, randomized, parallel-group trial sponsored by Johns Hopkins University. The recorded enrollment is 155. The study started on 2014-10-01, and the primary completion is recorded as 2018-11. Masking is listed as none, so the record does not describe a masked comparison.

One group received the Environmental Control Strategy in addition to controller medication; the comparison group received controller medication alone. In both groups, controller treatment could be inhaled corticosteroids or inhaled corticosteroids plus a long-acting beta agonist, with Flovent Diskus or Advair Diskus listed as medication options. The registry describes the environmental intervention as a home-based strategy.

The primary outcome is the medication treatment step assigned at the 6 month clinic visit. The primary outcome population is participants completing the final 6 month follow-up visit. The posted group summaries include 63 participants in the ECS plus medication group and 62 in the medication-alone group for this outcome. These are the outcome-specific reported counts and should not be treated as a substitute for the enrollment figure.

The record lists five secondary outcomes: daily inhaled corticosteroid dose, exhaled nitric oxide, asthma symptom days, asthma exacerbations, and FEV1/FVC. Numerical comparison results are available for daily inhaled corticosteroid dose, asthma symptom days, and FEV1/FVC. Numerical findings for exhaled nitric oxide and asthma exacerbations are not reported in the registry record. The original design assumptions, including any planned sample-size justification or interim analyses, 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

Analysis population for the primary outcome, as defined in the registry: participants completing the final 6 month follow-up visit

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 The Medication Treatment Step Assigned, measured over 6 month clinic visit.

The primary endpoint is the controller medication treatment step assigned at the 6 month clinic visit. The assignment is based on the participant’s current controller medication step and current asthma control. The registry defines a score from 0-6, where 0 indicates no controller medication and 6 indicates high dose inhaled corticosteroids plus a long-acting beta agonist. The reported measure is a group mean, with standard deviations describing variability among participants.

This endpoint is used to represent the level of controller treatment required or assigned under the study’s treatment approach. It therefore addresses medication step rather than reporting only symptoms, lung function, or a specific drug dose. A lower score corresponds to a lower step on the defined scale, while interpretation of a group difference still depends on its uncertainty and on the endpoint’s clinical context.

The primary endpoint applies to participants completing the final 6 month follow-up visit. It is not described as an intention-to-treat outcome for every enrolled participant, and the registry record does not report details about how missing follow-up measurements were handled. The endpoint also does not, by itself, establish why a treatment step was assigned or whether an observed difference reflects the intervention rather than chance or other influences.

7. Results Posted in the Registry

• Medication Group Alone: mean 4.05 versus 4.03 on control; difference 0.02 (95% CI -0.64 to 0.68), standardized effect d = 0.01; z-test p = 0.953.

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.

Daily Inhaled Corticosteroid Dose

• 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:
  • Medication Group Alone: mean 527.70 versus 557.50 on control; difference -29.80 (95% CI -161.61 to 102.01), standardized effect d = -0.08; z-test p = 0.658.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Medication Group Alone and the control. The interval gives the range of effects that remain compatible with the data.

Number of Asthma Symptom Days

• 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:
  • Medication Group Alone: mean 2.70 versus 2.50 on control; difference 0.20 (95% CI -0.99 to 1.39), standardized effect d = 0.06; z-test p = 0.743.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Medication Group Alone and the control. The interval gives the range of effects that remain compatible with the data.

FEV1/FVC

• 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:
  • Medication Group Alone: mean 80.80 versus 79.30 on control; difference 1.50 (95% CI -1.47 to 4.47), standardized effect d = 0.18; z-test p = 0.322.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Medication Group Alone and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes address related but distinct dimensions: daily inhaled corticosteroid dose reflects medication amount, asthma symptom days reflect reported symptom burden, and FEV1/FVC is a lung-function measure. The registry also lists exhaled nitric oxide and asthma exacerbations, but their numerical findings are not reported in the registry record. Together, these outcomes could provide context for the primary treatment-step measure, but they do not replace it.

For the three outcomes with numerical comparisons, the posted group estimates are close relative to their uncertainty, and each unadjusted interval includes zero. In broad terms, this resembles the primary result in that the available summary statistics do not establish a clear between-group difference. The outcomes are not interchangeable, however: a finding about medication dose does not directly answer the question about assigned treatment step, and symptom or lung-function measures capture different aspects of asthma status.

Secondary outcomes generally carry less evidential weight when several are examined and no adjustment for multiple comparisons or prespecified hierarchy is reported. In general, testing a collection of outcomes makes chance findings more likely, and selective emphasis on a single favorable result can overstate the evidence. The registry record does not report a multiplicity procedure or identify which secondary outcomes were intended to be confirmatory. These findings are therefore best treated as supportive or exploratory observations rather than independent proof of an intervention effect.

The unadjusted estimates should also be considered in light of outcome-specific participant counts and the lack of reported missing-data methods. The record does not report numerical results for all listed secondary measures, so the overall secondary pattern cannot be assessed across the complete outcome list. The available secondary results do not materially alter the cautious interpretation of the primary comparison.

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

• Daily Inhaled Corticosteroid Dose
• Exhaled Nitric Oxide
• Number of Asthma Symptom Days
• Number of Asthma Exacerbations
• FEV1/FVC

9. Statistical Interpretation

10. Statistical Methods Explained

The primary measure is continuous and is reported as a mean with a standard deviation. The mean gives the average medication treatment step in each group. A standard deviation describes how dispersed individual values are around that group mean; it is not the uncertainty in the estimated mean difference. Here, the group means are 4.03 and 4.05, and the reported standard deviations are 1.91 and 1.87.

The comparison is a mean difference. Its direction is defined as the medication-alone group minus the ECS plus medication group. A positive value therefore means a higher average treatment-step score in the medication-alone group; a negative value means a higher average in the ECS plus medication group. The recalculated estimate is 0.02. This simple difference in means is unadjusted: it does not account for covariates or other features of the trial that are not represented in the posted summary statistics.

The 95% confidence interval for the unadjusted mean difference is -0.643 to 0.683. In general, a confidence interval expresses the uncertainty around an estimate under the statistical method used. It identifies values reasonably compatible with the observed data and method; it is not a guarantee that the true effect lies in the interval. Because the interval includes zero, the posted comparison does not give clear evidence of a difference in either direction. Its width also matters: the data allow differences larger than the point estimate.

The unadjusted p-value is 0.953. In general, a p-value describes how unusual a result at least as extreme as the observed result would be under a specified no-difference model and its assumptions. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. A large p-value is not evidence that the groups are identical. Interpretation should consider the estimate and interval as well as the p-value.

The calculations labeled recalculated are simple unadjusted recalculations from the posted group summaries. The registry record does not report a sponsor inferential analysis for this outcome, and no discrepancy is flagged. They should therefore be understood as summary-statistic comparisons, not as a claim about an unreported adjusted or prespecified analysis. The original statistical analysis plan, including details of any covariate adjustment, is not reported in the registry record.

In general, randomized allocation can help balance prognostic factors across groups, but a randomized design does not remove uncertainty in a particular trial or guarantee that every factor is balanced. This record identifies allocation as randomized and the model as parallel. It lists masking as none. The registry does not report further details about allocation concealment, stratification, or the implementation of randomization, so those design features cannot be evaluated from this record.

The study’s primary population is participants completing the final 6 month follow-up visit. The comparison uses outcome-specific group counts of 63 and 62. The registry record does not report whether the analysis used imputation, a model for repeated measurements, or another method to address missing outcomes. Nor does it state whether all randomized participants were included in a primary intention-to-treat analysis. These omissions matter because analysis populations and missing-data methods can affect interpretation, especially when outcomes are available only for participants who complete follow-up.

The secondary outcomes are also presented as continuous means with standard deviations and unadjusted mean differences where numerical results are posted. General statistical reasoning applies: testing several outcomes increases the chance that at least one result may look notable by chance, so secondary findings are usually interpreted cautiously unless a multiplicity strategy was prespecified. No such adjustment or hierarchy is reported in the registry record. The posted secondary comparisons should therefore be regarded as exploratory rather than as a set of independently confirmatory tests.

Planning illustrations use the observed effect as a reference and show hypothetical participant requirements under stated assumptions. In general, power is the chance that a study would detect a specified effect under a particular model and significance threshold if that effect were present. It depends on the assumed effect size and variability, among other design inputs. A planning calculation does not establish the power actually achieved by this completed study; the registry record does not report the original sample-size justification or design assumptions.

For the primary mean difference, the posted recalculation uses the reported group means and standard deviations without an adjustment. The record’s discrepancy indicator is false. Under the stated reporting conventions, sponsor analyses would take precedence if a discrepancy were flagged; none is flagged. That does not convert a recalculation into a sponsor-reported analysis, and the record does not list a reported inferential analysis for the outcome.

11. Confidence Intervals and Precision

The primary mean difference is 0.02, and its 95% confidence interval runs from -0.643 to 0.683. The interval includes zero, so the posted summary statistics do not resolve whether the average treatment step was higher in one group or the other. It also spans values on both sides of zero, making clear that the estimate is not precise enough to pin down a single direction or a narrowly defined effect.

The interval should be read in the units of the endpoint: score points on the treatment-step scale. It describes uncertainty about the difference in group means, not the range of individual participants’ scores. Individual variability is reflected separately in the standard deviations, 1.91 for ECS plus medication and 1.87 for medication alone. A confidence interval for the mean difference and a standard deviation answer different questions.

The unadjusted p-value of 0.953 is consistent with the interval’s inclusion of zero, but it does not make the possible differences inside the interval equally likely or establish equivalence. The registry record does not report a clinically important difference threshold or a margin for equivalence. Without such a threshold, statistical precision cannot establish whether the range of values is small or large enough to matter clinically.

The estimates are based on the participants with reported primary outcome data at the final 6 month visit. Missing-data handling and the original analysis plan are not reported in the registry record. The interval therefore conveys uncertainty under the simple unadjusted calculation, not all uncertainty about selection, missingness, or the trial’s design and analysis.

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 sample-size figures are planning illustrations based on the observed effect, not the trial’s own original design calculation. For these continuous outcomes, the displayed requirements are participants per arm, not total events. The assumptions stated for the illustration are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect equal to the stated fraction of the observed effect. The original design assumptions are not reported in the registry record.

The 80% power column gives the hypothetical participants per arm under which the calculation would have an 80% chance of detecting the specified effect, if that effect and the planning assumptions were correct. The 90% power column uses a higher target chance of detection, and therefore generally requires more participants under otherwise matching assumptions. These columns are conditional planning quantities, not forecasts of the result.

Rows for 100%, 75%, and 50% of the observed effect represent progressively smaller effects to detect. A smaller target effect is harder to distinguish from random variation, so the calculated requirement rises as the assumed effect gets smaller. This is especially important when the observed effect is small: scaling a small estimate can produce very large planning requirements. The figures are illustrations of that relationship, not recommendations for a future study.

This is not observed power. It does not measure how likely the completed trial was to produce a statistically significant result after the data were collected. The registry record does not report the trial’s original sample-size justification, and the planning values should not be used as evidence about whether the completed study was adequately designed.

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 = 0.020; pooled standard deviation σ = 1.890.
2. n = 2 × (1.96 + 0.842)² × 1.890² / 0.020² = 140,224.7, rounded up to 140,225 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 <- 0.0199999999999996                      # observed difference in means
sigma <- 1.89026840267364                     # 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(2251379)
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 = 140,225 (80% power), 187,722 (90% power)
 75% of observed effect: n per arm = 249,289 (80% power), 333,727 (90% power)
 50% of observed effect: n per arm = 560,899 (80% power), 750,885 (90% power)
power.t.test: 140225.7 
Simulated power at n = 140,225 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 a primary outcome and five secondary outcomes. The primary comparison is the medication treatment step at the 6 month visit. Secondary measures include daily inhaled corticosteroid dose, exhaled nitric oxide, asthma symptom days, asthma exacerbations, and FEV1/FVC. The record does not report a testing hierarchy, a familywise error procedure, a false-discovery procedure, or another multiplicity adjustment.

In general, when several outcomes are tested, the chance of at least one apparently notable result arising by chance increases. Multiplicity methods or a clearly defined hierarchy can help control that issue. Without a reported plan, secondary p-values and intervals should be interpreted as unadjusted comparisons, and isolated results should not be treated as confirmatory. This is relevant even when the available secondary findings do not show a clear difference, because the record does not describe how outcomes were selected or prioritized for interpretation.

The registry reports the primary endpoint population as participants completing the final 6 month follow-up visit. Outcome-specific counts are given for the posted comparisons, but the record does not explain why participants may be absent from an outcome summary or how missing observations were addressed. It does not report imputation, sensitivity analyses, or a missing-data model. These details would help assess whether the analyzed participants remain comparable to the randomized groups.

The record also does not state whether the primary analysis followed an intention-to-treat principle, whether any participants were excluded after randomization, or how protocol deviations were handled. These analysis-population details are not reported in the registry record. Their absence limits assessment of how closely the posted comparison reflects the randomized assignment, especially for a follow-up outcome defined among participants completing the visit.

Original sample-size justification, interim analyses, and the complete statistical analysis plan are also not reported in the registry record. Their absence does not invalidate the posted summaries, but it prevents evaluation of whether the analyses and outcome emphasis followed a prespecified plan.

15. 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 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: asthma hospitalization (10.3%), hospitalization (1.3%).

The registry reports serious adverse events in 2 of 77 participants at risk in the ECS plus medication group and 10 of 78 participants at risk in the medication-alone group. It reports no other adverse events in either group among the listed participants at risk, and no deaths in either group. These are descriptive counts from the registry record, not adjusted comparisons of risk.

The listed serious adverse event terms include “asthma hospitalization” at 10.3% and “hospitalization” at 1.3%. The record does not clarify in this summary whether event terms overlap, how repeated events were handled, or how the term-level percentages relate to the group-level counts. Those labels should therefore be read as registry-reported event categories, not as a complete account of individual event histories.

The counts alone do not establish that the intervention caused or prevented an event. The record does not provide a statistical comparison, attribution details, or further clinical descriptions of the serious events. Safety interpretation should remain descriptive and should not be conflated with the efficacy-oriented comparison of treatment-step means.

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

The posted primary results show nearly identical group means for the assigned medication treatment step at the final 6 month visit: 4.03 for ECS plus medication and 4.05 for medication alone. The unadjusted recalculated mean difference is 0.02, with a 95% confidence interval from -0.643 to 0.683 and an unadjusted p-value of 0.953. The data therefore do not establish a clear difference between the group means, while still allowing a range of possible differences.

This is not proof that the intervention has no effect, and it is not proof that the groups are equivalent. Equivalence requires a prespecified margin and a design and analysis suited to that question; no equivalence margin is reported in the registry record. Conversely, the small point estimate should not be interpreted as a precise estimate of no difference, because the interval includes values in both directions.

The endpoint is an assigned treatment step based on current medication step and asthma control. It is not itself a direct measure of every aspect of asthma, and a group average does not capture each participant’s experience. The secondary measures address medication dose, symptoms, and lung function, but numerical results are not reported for every listed secondary outcome and the available comparisons are unadjusted.

The findings apply to the posted outcome data for participants completing the final 6 month follow-up visit. The record does not report enough detail to assess missing-data methods, the full analysis population, or any adjusted sponsor analysis. The results should therefore be understood as a limited statistical description of the registry’s posted data, rather than a definitive statement about treatment effects in all children and adolescents with asthma.

17. Why This Trial Matters Statistically

This trial is statistically interesting because its primary endpoint represents a treatment decision rather than a single symptom or laboratory measurement. The medication step combines current treatment and current asthma control, making it relevant to the study’s stated question about controller medication requirements. At the same time, this composite clinical assignment is not a direct measure of every mechanism or outcome named in the study hypothesis.

The comparison illustrates why a point estimate and its uncertainty must be read together. The observed mean difference is close to zero, but the confidence interval is wide enough to include differences in either direction. A non-small p-value alone cannot establish that groups are alike; the interval and the absence of a reported equivalence margin are essential to a careful interpretation.

The trial also highlights the distinction between completed-study results and planning calculations. The sample-size illustrations use the observed effect under stated assumptions, whereas the registry record does not report the original design justification. Large hypothetical requirements derived from a small observed effect do not measure the trial’s observed power and cannot retrospectively show whether the design was adequate.

Finally, the record includes multiple secondary outcomes but does not report a multiplicity plan or numerical findings for every listed measure. This makes outcome prioritization and cautious interpretation important. The information available supports a transparent description of uncertainty, while leaving important questions about missing data, analysis populations, and the prespecified statistical strategy unanswered.

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 available record. The primary outcome is reported for participants completing the final 6 month visit, but the record does not describe how missing follow-up outcomes were handled or whether the analysis included every randomized participant. This makes it difficult to evaluate the potential effect of missing data on the group comparison.

The primary comparison is an unadjusted recalculation from group means and standard deviations. The record does not report a sponsor inferential analysis, a full statistical analysis plan, or whether covariate-adjusted analyses were prespecified. The discrepancy indicator is false, but that does not supply details about an unreported analysis.

The trial is listed as randomized and parallel, with masking listed as none. Further information about allocation procedures, concealment, adherence, intervention fidelity, and potential contamination between groups is not reported in the registry record. The study description identifies a tailored home intervention, but the record excerpt does not provide enough detail to assess how consistently it was implemented.

The registry lists five secondary outcomes, yet numerical findings are not reported for exhaled nitric oxide and asthma exacerbations. It also does not report multiplicity adjustment or a hierarchy for secondary outcomes. The serious adverse event summary gives counts and event terms but limited detail about attribution, overlap, and individual event histories. These limitations constrain interpretation of both the outcome pattern and safety findings.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Environmental Control as Add-on Therapy in Childhood Asthma — NCT02251379.
• Registry record last updated 2019-11-20; status last verified 2019-11.
• Results first posted 2019-11-04.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

22. Record Summary

NCT02251379 is a completed phase 2 randomized, parallel-group study of an environmental home intervention added to controller medication for children and adolescents with asthma. It was sponsored by Johns Hopkins University, with enrollment recorded as 155. The registry lists no masking.

The primary outcome is the medication treatment step assigned at the 6 month clinic visit among participants completing the final follow-up. The mean was 4.03 in the ECS plus medication group and 4.05 in the medication-alone group. The unadjusted recalculated mean difference was 0.02, with a 95% confidence interval from -0.643 to 0.683 and an unadjusted p-value of 0.953.

The registry also lists secondary measures of medication dose, exhaled nitric oxide, asthma symptom days, asthma exacerbations, and FEV1/FVC. Numerical comparisons are available for three of these measures. The record does not report the original sample-size justification, complete analysis plan, multiplicity strategy, or methods for missing data.