PRC-063 Classroom Study in Children (6-12 Years of Age) With ADHD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PRC-063 Classroom Study in Children (6-12 Years of Age) With ADHD (NCT03172481), a randomized phase 3 study. The primary outcome is Swanson, Kotkin, Agler, M-Flynn and Pelham (SKAMP)-Combined Scores During the Full-Day Laboratory Classroom.

2. Clinical Question

The statistical question concerns the difference between group means on a continuous behavioral measure, rather than a comparison of the number of children meeting a threshold. The posted group means are 11.4 for PRC-063 and 18.2 for placebo. The reported mean difference is -6.8, with a confidence interval from -9.395 to -4.205. The negative direction reflects a lower mean score in the PRC-063 arm under the comparison used in the registry record.

This question is specific to the endpoint, visit, and population described. It does not by itself address outcomes outside the full-day laboratory classroom assessment, longer-term outcomes, or other populations. Those questions are not answered by the posted primary result.

3. Trial Design

The registry record describes NCT03172481, a phase 3, randomized, double-blind, placebo-controlled, parallel-group study of PRC-063 in children aged 6–12 years with ADHD. It lists quadruple masking. The record does not identify which study roles were masked, or provide further details about the randomization or masking procedures.

The two arms were PRC-063 and placebo, both administered as oral capsules. The active-treatment description lists doses of 25, 35, 45, 55, 70 or 85 mg and characterizes the study as dose optimized. The placebo arm has no further dose description. The details of treatment assignment, dose optimization, treatment duration, adherence, and any permitted co-interventions are not reported in the registry record.

Enrollment is listed as 156. The primary outcome results give 74 participants for PRC-063 and 73 for placebo. The registry record does not explain the relationship between the enrollment figure and the group counts contributing to this outcome, nor does it identify the analysis population or explain any exclusions.

The study status is completed. The listed start date is 2017-05-01 and the listed primary completion date is 2017-08-19. The sponsor is Purdue Pharma, Canada. These record details describe the registered study but do not supply information about conduct beyond what is explicitly recorded.

A parallel-group design compares participants assigned to separate treatment groups. Randomization is intended, as a general statistical principle, to make treatment groups comparable on average with respect to measured and unmeasured baseline characteristics. It does not guarantee that every characteristic will be balanced in a particular trial. Baseline characteristics and the method used to generate or conceal the random sequence 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.

Open-label

Double-blind

Reasons for not completing this period:

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 Swanson, Kotkin, Agler, M-Flynn and Pelham (SKAMP)-Combined Scores During the Full-Day Laboratory Classroom, measured over Full-day Classroom - 13 hrs.

The primary endpoint is the mean Swanson, Kotkin, Agler, M-Flynn and Pelham (SKAMP)-Combined score during the full-day laboratory classroom, listed as 13 hours. The SKAMP rating scale assesses behavioral symptoms of ADHD in a classroom setting. Its combined score includes 13 items covering attention, deportment, quality of work, and compliance. Each item is rated on a 7-point impairment scale, from 0 for none to 6 for maximal impairment, and the item scores are summed. The total possible combined score is 0 to 78. Lower scores indicate fewer ADHD symptoms.

The record says SKAMP-C was assessed before dosing and approximately 1, 2, 4, 6, 8, 10, 12, and 13 hours after dosing during the full-day classroom visit. Average post-dose score and change from the pre-dose score were analyzed on the individual SKAMP-C scores. The posted primary result is expressed as a mean with a standard deviation for each arm; the description of the outcome also refers to average post-dose score and change from pre-dose score. Further details about how the posted group-level result relates to those repeated assessments are not reported in the registry record.

A classroom rating scale is used to quantify observed behavior in the setting relevant to the assessment. As a general measurement principle, a continuous score can retain gradations across participants and visits rather than reducing results to a yes-or-no classification. The endpoint captures the measured classroom behavior on this scale; it should not be interpreted as a direct measure of every aspect of ADHD or of outcomes not assessed during the visit.

7. Results Posted in the Registry

• PRC-063: mean 11.40 versus 18.20 on control; difference -6.80 (95% CI -9.39 to -4.21), standardized effect d = -0.85; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous, and the posted arm summaries report a mean and standard deviation. A mean represents the arithmetic average of the scores in a group. A standard deviation describes how dispersed individual scores are around that mean. It is not the uncertainty interval for the mean and does not show the full shape of the score distribution. The registry record gives 74 participants for PRC-063, with a mean of 11.4 and standard deviation of 6.9, and 73 for placebo, with a mean of 18.2 and standard deviation of 9.0.

The mean difference is reported as -6.8 for the comparison of PRC-063 with placebo. The sign depends on the order of the groups in the comparison: a negative value indicates that the PRC-063 mean is lower than the placebo mean in this coding. Because lower SKAMP-C scores indicate fewer ADHD symptoms on the scale, the direction of the numerical contrast can be translated into the direction of the measured score. That interpretation remains specific to this classroom rating outcome.

A confidence interval is a range of values compatible with the observed data and the assumptions of the method used to calculate it. In repeated use of the same procedure under its assumptions, intervals constructed this way would cover the underlying parameter at the stated confidence level at the corresponding long-run frequency. It is not a range containing a fixed proportion of individual scores, nor does it assign a probability to the true value after the data have been observed. For the reported mean difference, the 95% confidence interval is -9.395 to -4.205.

The registry record reports an ANOVA and p < 0.001. ANOVA, in general, compares variation between groups with variation within groups under a specified model. It can be used to test whether group means differ, while the precise interpretation depends on the model and the design. The registry record does not give details of the ANOVA model, including any covariates, repeated-measures structure, or adjustments. Those features should not be inferred from the method label alone.

The separately displayed unadjusted recalculation uses posted summary statistics to estimate a simple group difference. It reports a mean difference of -6.8 and a confidence interval from -9.395 to -4.205, with p < 0.001. This kind of recalculation is a straightforward comparison of the reported group summaries; it does not recover unreported model details or adjust for characteristics that are not included in the summaries. It is not a replacement for the sponsor's analysis. The sponsor's ANOVA result is the reported primary analysis, and the recalculation is best treated as a check based on the summary data.

The recalculated comparison also reports a standardized effect estimate, but its posted value has more than three decimal places. It is not repeated. In general, a standardized effect expresses a group difference relative to a measure of score variability. This can help describe magnitude on a scale independent of the endpoint's original units, but it does not remove the need to understand the clinical meaning of the original score or the study context.

In general, the standard error describes the estimated sampling variability of a statistic, such as a mean. Larger standard errors usually correspond to less precision in the estimate. A confidence interval is commonly built from an estimate and its standard error, together with a method-specific multiplier or distributional assumption. The registry record does not give enough detail to identify every calculation choice behind the sponsor's reported ANOVA result. The recalculation's posted standard errors are 1.053 for placebo and 0.802 for PRC-063; the latter value has more than three decimal places and is not repeated.

Over-dispersion is a general concern when observed variability is greater than a model assumes. If a model understates variability, standard errors can be too small and inferential results can appear more precise than they should. The posted outcome is a continuous score, and the registry record does not state that over-dispersion was assessed or describe a model for it. It would not be appropriate to claim that over-dispersion was present or absent on the basis of the record.

Repeated assessment is relevant because the score was collected at multiple post-dose times as well as before dosing. In general, observations from the same participant are related rather than independent. A method that models repeated observations can account for that within-participant correlation, while a summary such as an average post-dose score can reduce repeated observations to one participant-level quantity. The registry description mentions average post-dose score and change from pre-dose score, but the exact construction of the group outcome and the handling of correlations are not reported in the registry record.

The posted p-values are small under their respective analyses. In general, a p-value depends on the null hypothesis, the model, and the assumptions used for inference. It does not report the probability that an observed result will repeat, the probability that treatment assignment caused the result, or the clinical importance of the estimate. Interpretation therefore combines the estimate's direction and size, its confidence interval, the trial design, and the limits of the posted analysis details.

Multiplicity refers to the increased chance of false-positive findings when many statistical tests are conducted. In general, studies may address this through a prespecified testing hierarchy or adjustment procedure. The registry record lists one outcome measure and one analysis and does not report a multiplicity plan. It also does not report interim analyses or the original statistical analysis plan. The absence of those details in the registry record should not be taken as proof that no such procedures existed.

10. Confidence Intervals and Precision

The reported mean difference is -6.8, with a 95% confidence interval from -9.395 to -4.205. The interval communicates uncertainty about the estimated group difference under the method's assumptions. Its bounds are both on the negative side of the comparison, indicating that the range of values in this interval corresponds to a lower mean SKAMP-C score in the PRC-063 group than in the placebo group, given the reported contrast direction.

Precision is distinct from the size of an estimate. A narrow interval indicates more precision than a wide interval, while the estimate itself describes the location of the result. A confidence interval does not describe how much scores vary among children; the arm-level standard deviations, 6.9 for PRC-063 and 9.0 for placebo, describe that observed spread. Nor does the interval indicate whether the difference is clinically important. The registry record does not report a threshold for a clinically meaningful difference on SKAMP-C.

As a general concept, a confidence interval reflects both the observed data and the assumptions of the method used. Its interpretation may be affected by the analysis model, the handling of repeated assessments, missing data, and which participants were included. The registry record identifies ANOVA as the sponsor's method but does not provide enough detail to assess all of those elements. The unadjusted recalculation yields the same posted mean difference and confidence interval, and its p-value is p < 0.001; the sponsor reports p < 0.001 from ANOVA.

The interval does not quantify uncertainty about outcomes that were not measured or about populations not represented by the study. It pertains to the primary score comparison in the described full-day laboratory classroom assessment. The record does not report a confidence interval for the difference in adverse events or additional outcome estimates.

11. Planning a Similar Trial: Sample Size

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

The planning figures are participants per arm, not total event counts. They are illustrations based on the observed effect and use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For each planning scenario, the effect to detect is the stated fraction of the observed effect. The original sample-size justification and design assumptions for the trial are not reported in the registry record.

The 80% power column gives the illustrated number of participants per arm under the stated assumptions for an analysis with an 80% chance of detecting the specified effect if that effect were the true one. The 90% power column gives the corresponding per-arm planning figure for a 90% chance under those assumptions. These are design calculations, not descriptions of what happened in this completed study.

Planning for 100% of the observed effect gives 22 participants per arm for 80% power and 30 participants per arm for 90% power. Planning for 75% of the observed effect gives 39 participants per arm for 80% power and 52 participants per arm for 90% power. Planning for 50% of the observed effect gives 88 participants per arm for 80% power and 117 participants per arm for 90% power. The figures illustrate that a smaller target effect requires more participants under the same assumptions; a higher desired power also requires a larger planning sample.

These calculations are not observed power. They do not indicate the probability that the completed trial found a result, and they should not be used as a retrospective measure of evidential strength. They are planning illustrations tied to the observed effect and stated assumptions. The registry record does not report whether the original trial design used these assumptions or these calculations.

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 = -6.800; pooled standard deviation σ = 8.012.
2. n = 2 × (1.96 + 0.842)² × 8.012² / -6.800² = 21.8, rounded up to 22 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 <- -6.8                      # observed difference in means
sigma <- 8.01185759165535                     # 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(3172481)
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 = 22 (80% power), 30 (90% power)
 75% of observed effect: n per arm = 39 (80% power), 52 (90% power)
 50% of observed effect: n per arm = 88 (80% power), 117 (90% power)
power.t.test: 22.8 
Simulated power at n = 22 per arm: 0.782 (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. Analyses Reported by the Sponsor

The registry record reports the sponsor's primary analysis as ANOVA, with p < 0.001. A separate unadjusted recalculation from the posted group summaries gives a mean difference of -6.8, a 95% confidence interval from -9.395 to -4.205, and p < 0.001. The recalculation is a simple comparison based on the posted means, standard deviations, and group sizes; it is not the sponsor's analysis model.

The p-value thresholds are not identical. The sponsor's ANOVA result takes precedence as the trial's reported analysis. The recalculation can be read as a summary-statistic check on the direction and scale of the group comparison, not as evidence that the sponsor's model used the same assumptions or handled the repeated assessments in the same way. The registry record does not provide enough detail to reconstruct the ANOVA model or explain the difference between the reported p-value thresholds.

Both results indicate a group difference in the direction of a lower mean SKAMP-C score for PRC-063, as coded in the comparison. Neither p-value alone establishes clinical importance. The estimate and its confidence interval describe the magnitude and precision of the comparison; interpretation remains limited to the posted endpoint and analysis information.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and one analysis. It does not list posted secondary outcomes. This allows the primary result to be described as the posted main outcome comparison, but the record does not establish the full set of outcomes or tests considered during trial conduct.

Multiplicity is a general statistical issue that arises when several hypotheses or outcomes are tested. Without an adjustment or a prespecified testing sequence, repeated testing can increase the chance of at least one false-positive result. The registry record does not report a multiplicity procedure, a hierarchy of tests, or the original statistical analysis plan. It also does not report interim analyses. These items are not reported in the registry record; their absence from the record is not evidence that no such procedures were used.

Missing-data methods are not reported in the registry record. The outcome counts are 74 for PRC-063 and 73 for placebo, while enrollment is listed as 156. The record does not explain which participants were included in the primary analysis, whether any randomized participants lacked outcome measurements, how missing observations were handled, or whether sensitivity analyses were conducted. It is therefore not possible from the registry record to determine the influence of missing outcome data on the estimate.

The analysis population is not reported in the registry record. The record does not state whether the primary analysis followed an intention-to-treat, modified intention-to-treat, per-protocol, or other population definition. It also does not describe exclusions, treatment adherence, or protocol deviations relevant to the analysis. Those details affect the interpretation of which participants the reported estimate represents.

The outcome description says SKAMP-C was assessed before dosing and at approximately 1, 2, 4, 6, 8, 10, 12, and 13 hours after dosing, with average post-dose score and change from pre-dose score analyzed on the individual scores. The exact statistical treatment of those repeated observations is not reported in the registry record. The sponsor's method is identified as ANOVA, but the record does not say whether the model included repeated-measures terms, baseline values, or other covariates. Accordingly, the posted summary supports a description of the reported result, not a complete reconstruction of the analysis 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 2% reporting threshold.

Most frequent non-serious adverse event terms

The registry record reports serious adverse events in 0 of 74 participants at risk in the PRC-063 group and 0 of 73 participants at risk in the placebo group. Deaths are listed as 0 in both groups. These figures describe the serious adverse event counts recorded for the groups; they do not imply that no non-serious adverse events occurred.

Other adverse events are listed for 10 of 74 participants at risk in the PRC-063 group and 3 of 73 participants at risk in the placebo group. These are counts of participants affected, not a complete description of event types, timing, severity, or relatedness. The record does not list serious adverse event terms, and further detail about the other adverse events is not included in the posted safety summary.

As a general principle, a count of zero serious adverse events in a trial does not prove that a serious event cannot occur; it describes what was recorded among the participants and observation period represented in the data. The registry record does not provide detailed exposure duration or a fuller safety analysis, so the event counts should be interpreted within the limits of the posted information.

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

The primary result describes a lower mean SKAMP-C score in the PRC-063 arm than in the placebo arm during the full-day laboratory classroom assessment. The arm means are 11.4 and 18.2, respectively, and the reported mean difference is -6.8. The 95% confidence interval, -9.395 to -4.205, describes the statistical precision of that group comparison under the method's assumptions. Lower scores on this scale indicate fewer ADHD symptoms as assessed in the classroom setting.

The result does not by itself establish how meaningful the score difference is in everyday life. The registry record does not report a threshold for clinical importance, individual-level response patterns, or outcomes outside the specified classroom measurement. A group average does not mean that every participant had a lower score, and the posted summaries do not show how individual scores were distributed beyond their standard deviations.

The finding is specific to the children and study context described: ages 6–12 years, ADHD, a dose-optimized PRC-063 regimen, a placebo comparator, and the full-day laboratory classroom assessment. The registry record does not provide detailed eligibility criteria or participant characteristics that would establish how closely the enrolled group represents other settings or populations. The result cannot, from this record alone, be extended to other ages, settings, durations, or outcomes.

The randomized, double-blind, placebo-controlled design is relevant when interpreting the comparison, but the registry record does not report enough information to assess all aspects of trial conduct, including the analysis population, missing-data handling, or the full statistical model. The sponsor's ANOVA result is the reported analysis, and the recalculated unadjusted comparison is a summary-statistic check. Neither the small p-values nor the confidence interval answers every question about bias, clinical relevance, or generalizability.

The safety summary reports no serious adverse events and no deaths in either arm, while other adverse events are recorded in both groups. These counts are limited to the registry's posted summary and do not provide a comprehensive account of the nature or timing of events. Taken together, the posted results describe a statistically distinguishable group comparison on the specified score and limited safety counts; they do not establish conclusions beyond the measured outcomes and reported study information.

17. Why This Trial Matters Statistically

This trial offers a useful statistical example of how to read a continuous behavioral endpoint in a randomized, placebo-controlled design. The group means alone show the observed average scores, while the mean difference states the contrast directly and the confidence interval conveys uncertainty around that contrast. Keeping these quantities distinct helps prevent a p-value from being treated as a measure of effect size or clinical relevance.

The endpoint is measured repeatedly during a full-day classroom visit. That makes the connection between the measurement schedule and the analysis important: repeated observations from the same participant are generally related, and the way they are summarized or modeled can affect the estimate and its uncertainty. The registry record describes the assessment times and identifies ANOVA, but does not provide the model details needed to reconstruct how the repeated observations entered the primary analysis.

The case also illustrates the distinction between a sponsor-reported analysis and an unadjusted recalculation from published summary statistics. The recalculation can help readers inspect the numerical comparison, but it cannot substitute for the sponsor's model or recover unreported design and analysis choices. When the reported p-value thresholds differ, the sponsor's analysis takes precedence, while the recalculation remains a supplementary descriptive check.

Finally, planning illustrations derived from an observed effect are not the same as the trial's original design justification, nor are they observed power. Their role is to show how planning sample sizes change when the target effect or desired power changes under stated assumptions. That distinction matters when reading a completed study: planning scenarios are not evidence about the probability that its result is true or reproducible.

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.

The primary result is limited to the SKAMP-C score during the full-day laboratory classroom assessment. The record describes a 13-hour visit and repeated assessments, but does not report a clinically meaningful score threshold or additional posted outcomes. It is therefore not possible to use this result alone to characterize outcomes beyond the measured classroom behavior.

The record does not describe the characteristics of participants beyond the age range and ADHD condition. Detailed eligibility criteria, baseline characteristics, and the extent to which participants represent children in other settings are not reported in the registry record. Generalizability to populations or settings not described cannot be evaluated from the posted record alone.

Important analysis details are also absent: the analysis population, handling of missing data, the exact repeated-measures model, covariate adjustment, and the original analysis plan are not reported in the registry record. Although the sponsor's method is listed as ANOVA, that label does not establish which model terms were used. The posted sample counts and enrollment figure are not reconciled in the record.

The dose-optimized design lists several active doses, but the registry record does not explain how doses were selected or adjusted, how many participants received each dose, or how dose relates to the primary group result. The result is therefore a comparison for the active-treatment group as posted, not a dose-specific estimate.

The safety summary is limited to counts for serious adverse events, other adverse events, and deaths. Serious adverse event terms are not listed, and details about the other events are not reported in the registry record. The posted counts do not describe event timing, duration, severity, or attribution. These limitations restrict how fully the efficacy and safety results can be interpreted from the registry record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: PRC-063 Classroom Study in Children (6-12 Years of Age) With ADHD — NCT03172481.
• Registry record last updated 2019-11-05; status last verified 2019-05.
• Results first posted 2019-06-04.
• 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

NCT03172481 is a completed phase 3 randomized, double-blind, placebo-controlled, parallel-group study of oral PRC-063 in children aged 6–12 years with ADHD. Enrollment is listed as 156. The primary outcome is the mean SKAMP-Combined score during a full-day laboratory classroom assessment listed as 13 hours.

The posted outcome counts are 74 for PRC-063 and 73 for placebo. Mean scores are 11.4 and 18.2, respectively; the reported mean difference is -6.8, with a 95% confidence interval from -9.395 to -4.205. The sponsor's ANOVA result is p < 0.001. Serious adverse events and deaths are listed as 0 in both groups.

The record does not report the original sample-size justification, full analysis plan, analysis population, or missing-data methods. Those omissions limit assessment of the complete design and analysis, while the posted result remains specific to the stated classroom score and study population.