Clinical Trial of Efficacy and Safety of Prospekta in the Treatment of Attention Deficit/Hyperactivity Disorder in Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Trial of Efficacy and Safety of Prospekta in the Treatment of Attention Deficit/Hyperactivity Disorder in Children (NCT04569357), a randomized phase 3 study. The primary outcome is Percentage of Patients With Total ADHD-RS-V Reduction ≥25%.

2. Clinical Question

3. Trial Design

The registry record describes a phase 3, randomized, quadruple-masked, parallel-group clinical trial comparing Prospekta with placebo. Its official title identifies the study as multicenter. The trial is listed as completed, with enrollment of 363 participants. The registry lists Attention Deficit Hyperactivity Disorder as the condition and Materia Medica Holding as the sponsor.

The primary endpoint was assessed after 8 weeks of treatment. It is a binary outcome: each participant either met the threshold of a total ADHD-RS-V reduction of at least 25%, or did not. For the posted endpoint counts, the Prospekta group has 170 participants and the placebo group has 187. The registry notes that questionnaire data after 8 weeks were unavailable for 4 participants in the Prospekta group and 2 in the placebo group.

The intervention and placebo descriptions specify matching tablet schedules and administration instructions. The record lists additional outcomes involving ADHD-RS-V total and subscale scores, CGI-EI efficacy, vital signs, and clinically relevant laboratory abnormalities. It lists 12 outcome measures and 15 analyses. The registry record does not report the original sample-size justification, detailed allocation procedures, the masking roles, or the analysis populations used for each result.

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: There is no data on the ADHD-RS-V questionnaire after 8 weeks of treatment from 4 patients in the Prospekta group and 2 patients in the Placebo group.

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 Percentage of Patients With Total ADHD-RS-V Reduction ≥25%, measured over After 8 weeks of treatment.

The primary endpoint is the percentage of participants with a total ADHD-RS-V reduction of at least 25% after 8 weeks of treatment. The ADHD-RS-V home version assesses 18 symptoms through brief descriptions of behaviour and emotional responses in situations at home. It is used separately for children aged 7-10 years and teenagers aged 11-12 years, according to the registry description.

Turning a score change into a threshold outcome makes the endpoint straightforward to interpret as a count of participants who crossed a specified level of improvement. It also means that participants with different score changes can be placed in the same category if both meet the threshold. Conversely, a participant just short of the threshold and one with little change both fall outside the endpoint category. The result therefore describes threshold attainment, not the full distribution of score changes.

The registry posts counts of 95 participants meeting the endpoint in the Prospekta group and 81 in the placebo group. It does not provide the individual score changes or the full distribution of ADHD-RS-V changes in the primary result. Secondary outcomes include change in total and subscale scores, which address score change in a different way.

7. Results Posted in the Registry

• Prospekta: 55.9% (95/170) versus 43.3% (81/187) on control; risk difference 12.6 percentage points (95% CI 2.3 to 22.9), risk ratio 1.29 (1.04–1.59); unadjusted two-proportion z-test p = 0.018.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is binary because it records whether each participant did or did not reach a reduction of at least 25% in total ADHD-RS-V score. The posted counts are 95 participants meeting the threshold in the Prospekta group and 81 in the placebo group. The analysis compares the proportions in the two groups, rather than comparing average score changes.

What does a risk difference describe?

The risk difference is the difference between the event proportions in two groups. Here, the event is meeting the ADHD-RS-V reduction threshold. The registry reports a risk difference of 0.126, with interval bounds of 0.023 and 0.229. A risk difference is expressed on the probability scale and describes the absolute separation between group proportions. It differs from a risk ratio, which compares proportions by division, and an odds ratio, which compares odds rather than proportions.

How do the relative measures differ?

The reported risk ratio is 1.29, with interval bounds of 1.044 and 1.594. It compares the proportion meeting the endpoint in the Prospekta group with the corresponding proportion in the placebo group. The reported odds ratio is 1.658, with interval bounds of 1.091 and 2.52. Odds and probabilities are related but are not the same quantity; the odds ratio should not be read as a direct ratio of probabilities. The registry reports all three measures to describe the binary comparison from complementary perspectives.

What does the Fisher Exact test assess?

The registry lists a Fisher Exact test for the comparison and reports p = 0.020. In general, a Fisher Exact test evaluates how compatible the observed allocation of event counts between groups is with a null hypothesis of no association, using the observed margins. It is a test of evidence against that null hypothesis, not a measure of the size of the group difference. A p-value is not the probability that the null hypothesis is true, nor does it indicate the probability that the result will recur.

A simple unadjusted re-calculation from the posted summary statistics reports p = 0.018. It is a separate calculation from the registry's listed Fisher Exact analysis. Such re-calculations use the posted counts and do not incorporate adjustment for other variables unless those data and a specified adjusted model are available. The registry record does not report an adjusted estimate for this primary comparison.

What can intervals tell readers?

An interval around an estimate communicates the range of values compatible with the data under the method and assumptions used to construct it. Narrower intervals indicate greater precision, while wider intervals indicate more uncertainty about the effect size. The registry posts interval bounds for the risk difference, risk ratio, and odds ratio, but the confidence level and interval-construction method are not reported in the registry record. The bounds should therefore be read as the posted intervals without assigning an unreported confidence level.

General statistical interpretation: a confidence interval is not a range containing a fixed proportion of individual participant outcomes. It concerns uncertainty in an estimated quantity under a statistical procedure. It also does not account automatically for every possible source of bias, such as missing outcome data or selective reporting.

What information is missing from the analysis description?

The record includes 12 outcome measures and 15 analyses, but it does not report a testing hierarchy, a multiplicity adjustment, an interim-analysis plan, or a detailed statistical analysis plan. When many outcomes or tests are considered, general statistical practice recognizes that the chance of at least one apparently notable result can increase if tests are treated as independent opportunities without adjustment. Whether and how that issue was addressed in this trial is not reported in the registry record.

The record notes that primary questionnaire data after 8 weeks were unavailable for 4 participants in the Prospekta group and 2 in the placebo group. It does not say how missing primary outcomes were handled in the reported comparison. General statistical methods for missing data rely on assumptions about why values are missing; different assumptions can affect estimates. The registry record does not identify the assumptions or method used.

Finally, the comparison is based on a threshold endpoint. General statistical interpretation recognizes that categorizing a continuous score change can discard information about the size and distribution of changes. The registry also lists score-change outcomes, but the primary binary result alone cannot show the full pattern of score responses.

10. Confidence Intervals and Precision

The posted risk-difference estimate is 0.126, with interval bounds of 0.023 and 0.229. For the risk ratio, the estimate is 1.29, with bounds of 1.044 and 1.594. For the odds ratio, the estimate is 1.658, with bounds of 1.091 and 2.52. Each interval expresses uncertainty around a different effect measure, so the scales and bounds should be interpreted separately.

In general, an interval gives more information about precision than a point estimate alone: it shows a range of effect values compatible with the data under the method's assumptions. A wider interval reflects less precision; a narrower interval reflects more precision. These intervals do not show the range of individual participants' outcomes and do not eliminate uncertainty due to design limitations or missing data.

The confidence level and interval-construction method are not reported in the registry record. Consequently, the posted bounds can be quoted, but a confidence level should not be inferred from the record. The registry also reports no primary-endpoint data after 8 weeks for 4 participants in the Prospekta group and 2 in the placebo group. How those missing values were treated is not reported, so the displayed precision cannot be used to judge the sensitivity of the result to different missing-data assumptions.

The intervals are compatible with a range of effect sizes; they should not be reduced to a simple yes-or-no judgment. The point estimate is one estimate from the observed data, while the bounds indicate uncertainty around it under the unreported interval procedure.

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 events. They are illustrations based on the observed effect, not the trial's original design calculations. The registry record does not report the trial's own original sample-size assumptions or justification.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is defined as a stated fraction of the observed effect. For planning for 100% of the observed effect, the figures are 248 participants per arm for 80% power and 331 participants per arm for 90% power. For planning for 75% of the observed effect, they are 440 participants per arm for 80% power and 589 participants per arm for 90% power. For planning for 50% of the observed effect, they are 988 participants per arm for 80% power and 1,322 participants per arm for 90% power.

In general, power is the chance that a statistical test will detect an effect of the specified size under the planning assumptions, if that effect is present. The 80% and 90% columns represent different target probabilities for detecting the selected effect. A smaller target effect requires more participants in these illustrations. The corresponding curve expresses that planning relationship across effect sizes; it does not describe the observed trial outcome. These figures are not observed power.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.433; treatment proportion p₁ = 0.559; average p̄ = 0.496.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7071 = 1.3859.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.7015 = 0.5904.
4. n = (1.3859 + 0.5904)² / (0.1257)² = 247.3, rounded up to 248 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
p0 <- 0.433155080213904                          # control proportion
p1 <- 0.558823529411765                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(4569357)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 248 (80% power), 331 (90% power)
 75% of observed effect: n per arm = 440 (80% power), 589 (90% power)
 50% of observed effect: n per arm = 988 (80% power), 1,322 (90% power)
power.prop.test: 247.3 
Simulated power at n = 248 per arm: 0.804 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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 reports the primary comparison using a Fisher Exact test, with p = 0.020. A separate simple unadjusted re-calculation from the posted summary statistics gives p = 0.018. The re-calculation uses the posted counts and is not a replacement for the registry's reported test. The two p-values should be identified by their analysis source rather than combined or treated as though they came from one procedure.

The registry also reports a risk difference of 0.126, with interval bounds of 0.023 and 0.229, alongside a risk ratio and an odds ratio. These effect estimates describe the group comparison, whereas the p-values describe evidence from a test under its assumptions. The registry record does not provide a detailed account of the statistical plan or enough information to reconstruct every aspect of the reported analysis. It does not report an adjustment for covariates or for multiple testing.

The posted record does not flag a discrepancy between the reported analysis and the re-calculation. The re-calculated p-value should therefore be read as a distinct, unadjusted check based on summary statistics, not as a correction to the registry result.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures and 15 analyses. That establishes that several outcomes and analyses are recorded, but it does not specify which tests were considered confirmatory, how outcomes were prioritized, or whether a formal testing hierarchy was used. The registry record does not report a multiplicity adjustment or the planned family of tests to which one might apply.

In general, when multiple statistical tests are considered, the chance of at least one result appearing notable can rise if each test is interpreted without accounting for the number of comparisons. Methods such as prespecified hierarchies or statistical adjustments can address particular multiplicity concerns. Whether either approach was used for this trial is not reported in the registry record. The primary p-value should therefore be interpreted alongside the absence of documented multiplicity methods, rather than assuming that an adjustment was or was not made.

The record states that primary questionnaire data after 8 weeks were unavailable for 4 participants in the Prospekta group and 2 in the placebo group. It does not report whether these participants were excluded, imputed, or handled through another missing-data method. The endpoint counts are 95 of 170 and 81 of 187; the record does not explain the relationship between those analysis denominators and the missing questionnaires beyond noting the unavailable data.

The analysis population is not described in detail. The registry record does not state whether the primary result used an intention-to-treat population, a per-protocol population, or another defined set of participants. It also does not report an interim-analysis plan or the assumptions used in the original sample-size justification. These omissions make it difficult to assess alignment between the planned analysis and the posted result.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event figures use 174 participants at risk in the Prospekta group and 189 in the placebo group. The registry reports 0 serious adverse events in each group and 0 deaths in each group. It also records 23 participants with other adverse events in each group. The registry does not list any top serious adverse-event terms.

These are descriptive counts within the groups and at-risk denominators recorded for safety. A count of zero serious events or deaths in this trial does not establish that such events cannot occur; it states what was recorded in this study. The record does not provide detail about event types for the other adverse events, their timing, severity, relatedness, or how they were assessed. Those details should not be inferred from the counts alone.

The safety denominators differ from the primary endpoint denominators, which are 170 and 187. The registry lists the safety populations separately, but does not explain the reasons for the difference. Serious events, other adverse events, and deaths are distinct categories in the posted safety summary and should not be collapsed into a single outcome.

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

The primary result describes the proportion of participants meeting a prespecified threshold of at least a 25% reduction in total ADHD-RS-V score after 8 weeks. The posted counts are 95 in the Prospekta group and 81 in the placebo group. The registry's estimated risk difference is 0.126, with interval bounds of 0.023 and 0.229. The reported relative measures and Fisher Exact test provide additional descriptions of this group comparison.

This finding does not describe the full distribution of symptom-score changes. The binary endpoint groups everyone who crossed the threshold together, despite possible differences in how far they crossed it, and groups participants who did not cross it together despite possible differences in their score changes. The registry lists score-change outcomes as secondary measures, but their results are not included in the registry record described for the primary comparison.

The result is specific to the trial's recorded population, treatment schedule, comparator, endpoint definition, and assessment time. The registry describes children with attention deficit hyperactivity disorder and a home version of the ADHD-RS-V for children aged 7-10 years and teenagers aged 11-12 years. It does not establish what results would be in populations, settings, or time periods not represented in the record.

Interpretation is also limited by unreported analysis details. The registry does not state the confidence level for the posted intervals, the handling of missing primary-endpoint data, the analysis population, or whether multiplicity was addressed. These gaps do not change the reported counts, but they limit independent assessment of the methods and of the sensitivity of the result to analytic choices. The trial result is a statistical comparison, not by itself a complete assessment of benefit, harm, or clinical importance.

17. Why This Trial Matters Statistically

This trial illustrates how the choice of endpoint shapes the statistical question. The primary outcome is not the mean change in ADHD-RS-V score; it is whether a participant reached a reduction threshold of at least 25%. That framing yields an interpretable count of threshold responders, but it also discards information about the amount of change within each response category. The registry's additional score-change outcomes address a different aspect of the data.

It also demonstrates why absolute and relative effect measures are useful together. The registry reports a risk difference, risk ratio, and odds ratio for the same binary endpoint. Each expresses the comparison on a different scale, and the odds ratio should not be mistaken for a ratio of probabilities. Reporting several measures can aid interpretation, provided their meanings are kept distinct.

The record further highlights the importance of precision and analysis transparency. Effect estimates and interval bounds convey more than a p-value alone, but the confidence level and interval method are not reported. The registry identifies missing primary questionnaire data and gives group counts, yet does not describe how missing data or the analysis population were handled. It also lists multiple outcomes and analyses without reporting multiplicity procedures. These details matter because they affect how confidently readers can interpret a nominal comparison and relate it to the full set of planned questions.

Finally, planning illustrations based on an observed effect are not the same as the original sample-size rationale. Their assumptions are explicitly stated, but the trial's own design justification is not reported. Keeping those two uses of sample-size information separate prevents a retrospective planning illustration from being mistaken for evidence about the trial's design adequacy.

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 registry record provides limited detail about how the primary endpoint was analyzed. It does not report the analysis population, the handling of the 4 missing questionnaires in the Prospekta group and 2 in the placebo group, or whether any model adjustment was used. These omissions make the endpoint denominators and the sensitivity of the comparison to missing data harder to assess.

The record lists 12 outcome measures and 15 analyses, but does not describe a prespecified testing hierarchy or multiplicity adjustment. It also does not report the confidence level or construction method for the posted interval bounds. The registry's reported Fisher Exact test is identified, but the broader statistical analysis plan is not available in the record.

The primary outcome is a threshold measure assessed after 8 weeks. It does not, by itself, show the size or distribution of score changes, and the primary result does not give subgroup results by the two age bands described for the questionnaire. The registry does list change in total and subscale scores among secondary outcomes, but their findings are not included in the primary comparison information.

Safety information is also limited to summary counts. The record reports no serious adverse events or deaths in either group and 23 participants with other adverse events in each group, but does not give further detail on event type, severity, timing, or relatedness. The record does not report the original sample-size justification or interim-analysis plan. These limitations concern what can be learned from the registry record and should not be taken as evidence that unreported methods or analyses did or did not occur.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Clinical Trial of Efficacy and Safety of Prospekta in the Treatment of Attention Deficit/Hyperactivity Disorder in Children — NCT04569357.
• Registry record last updated 2024-08-01; status last verified 2021-11.
• Results first posted 2024-08-01.
• 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

NCT04569357 is a completed phase 3 randomized, quadruple-masked, parallel-group trial of Prospekta versus placebo in children with attention deficit hyperactivity disorder. The registry lists enrollment of 363 and identifies Materia Medica Holding as the sponsor.

The primary endpoint was a reduction of at least 25% in total ADHD-RS-V score after 8 weeks. The posted counts are 95 of 170 in the Prospekta group and 81 of 187 in the placebo group. The registry reports a risk difference of 0.126 and a Fisher Exact test p-value of 0.020. It notes missing primary questionnaire data for 4 participants in the Prospekta group and 2 in the placebo group.

Safety summaries report 0 serious adverse events and 0 deaths in each group, with 23 participants recorded with other adverse events in each group. Details of several analysis procedures and planning decisions are not reported in the registry record.