Efficacy and Safety Study of QAW039 in the Treatment of Patients With Moderate to Severe Atopic Dermatitis.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety Study of QAW039 in the Treatment of Patients With Moderate to Severe Atopic Dermatitis. (NCT01785602), a randomized phase 2 study. The primary outcome is Change From Baseline in Eczema Area and Severity Index (EASI).

2. Clinical Question

The registry identifies the study as phase 2 and completed. Its stated purpose was to assess whether QAW039 is safe and has beneficial effects in people with moderate to severe atopic dermatitis. The posted primary outcome addresses change in disease severity over the stated period. It does not, by itself, describe other dimensions of the condition, longer-term outcomes, or how individual participants responded. Those details are not reported in the registry record.

3. Trial Design

This was a randomized, double-blind, placebo-controlled, parallel-group phase 2 study of QAW039 in people with moderate to severe atopic dermatitis. Participants were assigned to QAW039 or matching placebo, and the registry lists 103 participants enrolled. The QAW039 arm received 450 mg daily by mouth. The outcome population is described as all randomized participants.

The registry records a study start of 2013-06 and primary completion of 2014-11, with status marked completed. The posted primary outcome is change from baseline in EASI at 12 weeks. EASI is a continuous score, and the reported arm-level summaries are means with standard errors. A secondary outcome is listed as change from baseline in EASI, but further details about that outcome are not reported in the registry record.

Randomization supports a comparison between assigned groups, while double masking is intended to limit the influence of treatment knowledge on participant experience and study conduct. These are general features of the design; the registry record does not describe the randomization procedure, the masking procedures in detail, or whether masking was assessed. It also does not report the original sample-size justification or other original design assumptions.

The registry lists two outcome measures and zero posted analyses. It does not report additional model specifications or adjusted estimates in the record. The posted numerical results therefore need to be read as the registry’s arm-level outcome summaries and the associated unadjusted recalculation, rather than as a complete account of every analysis that may have been undertaken.

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: All randomized participants

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 Change From Baseline in Eczema Area and Severity Index (EASI), measured over Baseline, 12 weeks.

The primary endpoint is change from baseline in Eczema Area and Severity Index (EASI), assessed at baseline and 12 weeks. EASI combines assessments of four signs—erythema, induration/papulation, excoriation, and lichenification—with the extent of affected skin across head/neck, upper limbs, trunk, and lower limbs. Investigators assigned severity scores from 0 to 3 for each sign and body area, with half-points permitted. Area scores ranged from 0, meaning no atopic dermatitis lesion in that area, to 6, meaning the entire area was affected.

The regional severity and area scores were weighted by body region: 0.1 for head/neck, 0.2 for upper limbs, 0.3 for trunk, and 0.4 for lower limbs. The resulting EASI total ranges from 0 to 72. Higher scores represent greater disease severity, so a negative change from baseline indicates improvement in the score.

EASI is used as a continuous measure because it combines signs and affected area into a numerical summary that can be compared between groups. The registry reports the mean change in each arm, which describes the average change in the outcome population. The measure does not imply that every participant changed by the group mean, and the registry record does not provide participant-level distributions or additional information about how individual outcomes varied.

7. Results Posted in the Registry

• QAW039: mean -8.65 versus -6.95 on control; difference -1.70 (95% CI -1.74 to -1.66), standardized effect d = -19.43; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: each participant’s EASI score is numerical, and the registry reports the mean change from baseline in each arm. A mean is an average, useful for summarizing the group’s central change on a scale. It can conceal variation in individual results, so arm means alone do not show how consistently participants changed or whether some had increases while others had decreases.

What does a mean difference represent?

The comparison is the difference between the QAW039 and placebo mean changes. The recalculated estimate is -1.7. In this direction of subtraction, a negative value means the QAW039 arm’s reported mean change was more negative than the placebo arm’s. Because a negative EASI change indicates a lower score, the contrast describes a greater average reduction in EASI in the QAW039 arm in these posted summaries. It does not describe the difference for each participant, and it should not be interpreted as an individual treatment effect.

The recalculation is unadjusted: it uses posted summary statistics rather than adjusting for other variables. General explanation: an adjusted analysis can account for specified baseline characteristics or design factors, whereas an unadjusted comparison does not make such adjustments. The registry record does not report an adjusted estimate or the study’s full analysis model, so no conclusion about how adjustment would affect the result can be drawn.

What do the standard errors describe?

The registry gives a standard error for each arm mean: 0.01 for QAW039 and 0.017 for placebo. General explanation: a standard error describes the estimated sampling variability of a statistic, such as a mean, rather than the spread of individual participant values. It is not the same as a standard deviation. The record does not give the standard deviations of participant-level EASI changes, so the amount of individual variation cannot be read directly from these standard errors.

The mean-difference interval and p-value are recalculated from posted summary statistics. The interval runs from -1.739 to -1.661, and the reported unadjusted p-value is < 0.001. General explanation: a confidence interval gives a range of values compatible with the data under the calculation and its assumptions; it communicates uncertainty around an estimate. A p-value describes how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the calculation assumptions held. Neither measure gives the probability that the null hypothesis is true, nor does either measure establish clinical importance.

Why can over-dispersion matter?

General explanation: over-dispersion occurs when observed variability is greater than a statistical model assumes. If a model underestimates variability, standard errors may be too small, confidence intervals too narrow, and p-values too small. This concept is particularly relevant to count outcomes or models whose variance assumptions are restrictive. The primary EASI endpoint is continuous, and the registry record does not report a model or an assessment of over-dispersion. It would therefore be inappropriate to assert that over-dispersion occurred or to use it to explain the reported interval.

What does the design contribute?

Randomization is intended to support a fair comparison by assigning participants to study arms without choosing treatment based on expected outcome. Double masking is intended to reduce the influence of treatment knowledge on reporting and assessment. These are general design principles, not evidence that all sources of bias were eliminated. The registry does not describe allocation concealment, how masking was maintained, or whether participants or investigators correctly guessed assignment.

The parallel-group structure compares outcomes in groups assigned to different study regimens over the same trial period. The registry names placebo as the control and says it matched QAW039. Further information about adherence, concomitant care, protocol deviations, or the timing of individual assessments is not reported in the registry record. Such information can matter when interpreting differences between assigned groups.

Finally, the registry lists all randomized participants as the primary outcome population, but it does not explain how missing measurements were handled or whether all randomized participants contributed to the posted means. General explanation: an intention-to-treat analysis generally preserves the randomized assignment for analysis, while missing outcome data still require explicit handling. The population label alone does not reveal the missing-data method or establish that every participant had a 12-week measurement.

10. Confidence Intervals and Precision

The recalculated mean difference is -1.7, with a 95% confidence interval from -1.739 to -1.661. The interval lies below zero and is narrow around the point estimate. In general, a confidence interval describes the uncertainty of an estimated effect under the data and calculation assumptions. Its endpoints are not a range of participant outcomes, and the interval does not indicate where a specified proportion of individual changes fell.

The interval’s narrowness should be interpreted cautiously alongside the arm-level standard errors reported in the registry: 0.01 for QAW039 and 0.017 for placebo. The registry record does not explain the interval calculation or provide a sponsor analysis to clarify it; the recalculation is unadjusted and based on posted summary statistics. The discrepancy flag is false, but the available record still does not establish the full analytic method behind the posted comparison.

The p-value is reported as < 0.001. This is evidence against a null hypothesis of no mean difference under the recalculation’s assumptions, but it does not measure the probability that the result is due to chance, establish clinical importance, or resolve uncertainty about missing data and analysis choices. The registry does not report a clinical-importance threshold for EASI change.

Precision also depends on what is being estimated. This interval concerns a difference between group means, not the variability of individual outcomes, the probability of response for an individual, or persistence of a difference after 12 weeks. Participant-level distributions and later outcome results are not reported in the registry record. The numerical precision of the recalculated interval should therefore not be mistaken for comprehensive certainty about the study’s clinical implications.

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 sample-size planning figures are participants per arm, not total events. They are illustrations based on the observed effect, not the trial’s original design assumptions. The listed assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The registry does not report the original sample-size justification or original design assumptions.

The planning table gives results for planning for 100%, 75%, and 50% of the observed effect. For each of these scenarios, the listed figures are 1 participant per arm for 80% power and 1 participant per arm for 90% power. The 80% column means the planning calculation targets an 80% chance of detecting the specified effect under its assumptions if that effect is present. The 90% column targets a higher chance under the same general framework. These are planning targets, not guarantees about a future study.

In general, a smaller effect is harder to distinguish from random variation and needs more participants to reach the same power target, all else equal. Here, the displayed figures remain 1 per arm across the stated effect fractions, so they do not illustrate an increase as the assumed effect becomes smaller. The numbers are planning illustrations computed from the observed result and should not be taken as evidence that the original study was designed with those assumptions. This is not observed power.

The corresponding curve should be read as a planning aid under the stated assumptions, not as a summary of what happened in the completed trial. Its interpretation depends on the effect size and model assumptions used for planning. It does not account for design details or analysis features that are not reported in the registry record.

12. How the Sample Size Is Derived

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

Formula

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

Worked calculation for this trial

1. Observed difference Δ = -1.700; pooled standard deviation σ = 0.087.
2. n = 2 × (1.96 + 0.842)² × 0.087² / -1.700² = 0.0, rounded up to 1 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 <- -1.7                      # observed difference in means
sigma <- 0.0874771823148333                     # 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(1785602)
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 = 1 (80% power), 1 (90% power)
 75% of observed effect: n per arm = 1 (80% power), 1 (90% power)
 50% of observed effect: n per arm = 1 (80% power), 1 (90% power)
power.t.test: 1.5 
Simulated power at n = 1 per arm: NA (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 two outcome measures, including the primary EASI change outcome and a secondary outcome also described as change from baseline in EASI. It lists zero posted analyses. The record does not describe a multiplicity adjustment, an outcome hierarchy, or a pre-specified strategy for interpreting multiple outcomes. Without such information, it is not possible to determine whether the reported p-value was considered alongside other statistical tests or how the study controlled the chance of false-positive findings across analyses.

General explanation: multiplicity arises when several outcomes, time points, treatment contrasts, or statistical tests are considered. Testing multiple hypotheses without an appropriate strategy can make a nominal p-value less informative about the overall chance of a false-positive conclusion. This does not show that multiplicity affected this study; the registry record does not report the relevant analysis plan.

The primary outcome population is stated as all randomized participants. However, missing-data handling is not reported in the registry record. The record does not state how many participants contributed measurements at baseline and 12 weeks, how missing values were treated, whether imputation was used, or whether sensitivity analyses were performed. These details matter because a mean change based on available measurements can differ in interpretation from an analysis that addresses missing outcomes under explicit assumptions.

The registry also does not explain whether the numerical outcome results were analyzed according to randomized assignment, whether protocol deviations affected inclusion, or whether any additional analysis populations were defined. The phrase “all randomized participants” describes the listed outcome population but does not, on its own, establish how incomplete measurements or deviations were handled. The posted results can be interpreted as the reported group summaries, while broader claims about the statistical plan and missingness are not supported by the registry record.

14. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dermatitis atopic (11.1%), diverticulitis (3.7%), atrial fibrillation (1.3%).

The serious adverse event counts are reported separately by arm. In the QAW039 group, 1 participant was affected among 76 at risk; in the placebo group, 4 were affected among 27 at risk. These are counts of participants affected by serious adverse events, not counts of all events. The registry does not provide a deaths value for either group, so deaths are not reported in the registry record.

The registry lists serious adverse event terms and percentages, including Dermatitis atopic (11.1%), Diverticulitis (3.7%), and Atrial fibrillation (1.3%). The record does not clarify in this listing how the terms’ percentages map to arms or whether people could appear under more than one term. They should not be treated as arm-specific rates without that context.

Serious adverse event counts are a limited view of safety. They do not describe all symptoms or events, their timing, duration, severity grading, attribution, or whether treatment was stopped. Other adverse events affected 44 participants in the QAW039 group and 16 in the placebo group, but the registry excerpt does not give a full event-by-event account. These results describe what is posted and do not establish a complete comparison of safety.

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

The registry results show mean EASI changes of -8.65 in the QAW039 arm and -6.95 in the placebo arm from baseline to 12 weeks. A negative change means a lower EASI score, and the recalculated unadjusted mean difference is -1.7, with a 95% confidence interval from -1.739 to -1.661 and p < 0.001. These results describe an average between-group contrast in the posted outcome summaries.

They do not show that every participant improved, identify the range of individual responses, or establish how many participants experienced a change of any particular size. The registry record does not report a threshold for clinical importance, so statistical evidence for a difference should not be equated with a judgment about how meaningful the difference is to participants. The results also concern the stated 12-week timeframe; they do not establish whether the observed pattern persisted beyond it.

The findings are limited to the population and study context described in the registry: a phase 2 randomized, double-blind, placebo-controlled parallel-group study in moderate to severe atopic dermatitis. The record does not provide detailed eligibility criteria or enough information to determine how closely participants resemble any other population. It also does not report the full statistical analysis plan, missing-data methods, or an adjusted estimate.

Safety interpretation is similarly limited. The registry reports serious adverse event counts by arm and lists serious event terms, but deaths are not reported in the registry record and the event listing does not provide a complete account of timing, attribution, and severity. The outcome and safety results together are not a basis for medical advice or a definitive judgment about treatment. They are a registry-record description with important unanswered questions about analysis, precision, and the scope of outcomes.

16. Why This Trial Matters Statistically

This trial illustrates why a numerical treatment comparison needs context beyond a p-value. The EASI outcome is a continuous measure that combines severity signs and affected body area into a score, and the registry reports mean change in each randomized group. Reading the two group means alongside their contrast helps distinguish an absolute change within each arm from the difference between arms.

It also demonstrates the difference between statistical evidence and clinical interpretation. The recalculated mean difference is -1.7, and the reported p-value is < 0.001, but the registry does not identify a clinically important EASI difference. A small p-value does not answer whether a difference matters to participants, nor does it describe individual variation. The confidence interval is also unusually narrow relative to the posted arm standard errors, making attention to calculation details important.

The record’s limited analysis reporting matters as well. It identifies the primary outcome population and gives arm summaries, but it does not report missing-data methods, a multiplicity strategy, or a full analysis model. These omissions constrain how confidently a reader can reconstruct the inferential analysis from the registry record.

Finally, the sample-size illustrations show how planning depends on assumptions about the effect to detect and the desired power. The listed planning values are not a record of the original design process and do not establish the adequacy of the completed study. Taken together, these features make the trial useful for teaching careful separation of observed summaries, statistical uncertainty, design intentions, and conclusions that the record cannot support.

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.

Several trial-specific limitations follow from what is not reported. The registry does not provide the original sample-size justification, detailed randomization or masking procedures, or a complete statistical analysis plan. It does not explain how missing EASI measurements were handled, whether the posted means include every randomized participant, or whether analyses were adjusted for baseline values or other factors. Those omissions limit independent reconstruction of the primary comparison.

The recalculated confidence interval is unusually narrow in relation to the arm-level standard errors in the record, and the underlying interval calculation is not explained. The discrepancy flag is false, but this does not resolve the absent method details. The recalculated result should therefore be interpreted as an unadjusted calculation from posted summaries, not as a fully documented sponsor model.

The record provides a 12-week primary outcome timeframe and does not report later EASI results in the outcome details described. It does not report a clinical-importance threshold or participant-level outcome distributions. As a result, the summaries do not establish the spread of responses, durability, or the proportion of participants whose changes met any particular criterion.

Safety information is also incomplete for broad interpretation. Serious adverse event counts and selected terms are posted, but deaths are not reported in the registry record. Details such as event timing, duration, attribution, and the relationship between listed terms and study arms are not fully described. These limitations concern the registry information available; they do not establish what was or was not collected during the trial.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Efficacy and Safety Study of QAW039 in the Treatment of Patients With Moderate to Severe Atopic Dermatitis. — NCT01785602.
• Registry record last updated 2015-12-15; status last verified 2015-11.
• Results first posted 2015-12-15.
• 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

NCT01785602 is a completed phase 2 randomized, double-blind, placebo-controlled, parallel-group study of QAW039 in moderate to severe atopic dermatitis. The registry reports enrollment of 103 participants and a primary completion date of 2014-11. The QAW039 arm received 450 mg daily by mouth, and the comparator received matching placebo.

The primary outcome was mean change from baseline in EASI at 12 weeks. The registry reports mean changes of -8.65 for QAW039 and -6.95 for placebo. The unadjusted recalculated mean difference is -1.7, with a 95% confidence interval from -1.739 to -1.661 and p < 0.001. Serious adverse events affected 1 participant in the QAW039 group and 4 in the placebo group. Further details about the analysis plan, missing data, and deaths are not reported in the registry record.