Acute D2 Receptor Blockade Induced Neuronal Network Changes in Human Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Acute D2 Receptor Blockade Induced Neuronal Network Changes in Human Volunteers (NCT01931059), a randomized na study. The primary outcome is Repeatable Battery for the Assessment of Neuropsychological Status.

2. Clinical Question

3. Trial Design

The registry describes a randomized, double-blind, crossover study. Participants were assigned to one of two treatment orders: risperidone followed by placebo, or placebo followed by risperidone. Each sequence involved treatment on consecutive days. The crossover structure allows a participant to experience both conditions, while randomization determines the order in which those conditions occur. The posted outcome summaries, however, are organized by sequence, rather than as a single direct treatment-condition comparison.

The registry reports enrollment of 11. The primary outcome summaries list 6 participants in the risperidone-then-placebo sequence and 4 in the placebo-then-risperidone sequence. The record does not explain the relationship between the enrollment figure and the participants represented in those summaries, or identify the analysis population. It also does not report whether any participants withdrew, were excluded, or had incomplete measurements.

Risperidone and placebo are the listed interventions. The record describes weight-based oral risperidone doses, but does not report detailed procedures for monitoring adherence or the timing of cognitive assessments in relation to administration. The crossover description does not specify whether a washout period was used; this information is not reported in the registry record. Nor are details of the randomization procedure, allocation concealment, or how masking was maintained reported.

The trial is marked completed. Its start is recorded as 2013-07 and its primary completion as 2016-07. The phase is listed as NA. The record identifies the Simpson-Angus Extrapyramidal Side Effects Scale as a secondary outcome, but does not post an analysis of that outcome. It lists 3 outcome measures and 0 analyses. A detailed statistical analysis plan, including any prespecified model for the crossover data, is 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.

Before assignment: Subjects were immediately randomized to either Arm 1 or Arm 2.

Day 1

Reasons for not completing this period:

Day2

Day3

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 Repeatable Battery for the Assessment of Neuropsychological Status, measured over The change of RBANS scores between placebo and treatment conditions on two consecutive days.

The primary endpoint is the difference in T-scaled RBANS Total Score between the risperidone and placebo conditions on consecutive days. RBANS is described as a measure of cognitive performance across multiple domains. The Total Score combines index scores for immediate memory, language, visuospatial ability, attention, and delayed memory. The registry describes the score as standardized, with higher scores reflecting better performance.

A total score can provide a single summary of performance across several cognitive domains. That can be useful when the research question concerns overall cognitive performance rather than one domain alone. It also means that a total-score result does not, by itself, show how each individual domain changed. The registry record does not post separate results for the five component indices.

The endpoint is expressed in RBANS T-scale points. The record describes a difference between scores under the two conditions, but does not clearly state the subtraction order. That makes it important not to assign a treatment-favoring direction to a negative value based on the sign alone. The listed group summaries are organized by sequence and do not provide a direct inferential estimate of the contrast between treatment conditions.

The registry describes RBANS as repeatable and as measuring a range of cognitive domains. Those properties explain why it was selected as an outcome; they do not establish that any observed difference is clinically important. A threshold for clinical importance, and a rationale for selecting this endpoint as primary, are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design and outcome call for careful distinction between a treatment-condition comparison and summaries grouped by treatment order. The record gives means and standard deviations for the two sequences, but does not report a direct inferential contrast between risperidone and placebo. The following concepts explain why those are different kinds of information and what cannot be concluded from the posted statistics.

What does a crossover design compare?

In general, a crossover design measures outcomes under more than one condition for the same participant. Comparing conditions within the same person can account for stable characteristics that differ between people. The sequence of conditions remains important: changes over time, carryover from an earlier condition, and differences between treatment orders may affect interpretation. A suitable analysis needs to reflect the paired measurements and the design assumptions.

In this trial, the registry reports two orders: risperidone followed by placebo, and placebo followed by risperidone. It posts a mean difference and standard deviation within each sequence. Such summaries describe the reported data for each order, but they do not themselves provide the pooled within-person treatment contrast or its uncertainty. The statistical model, treatment of sequence, and handling of any period or carryover effects are not reported in the registry record. No particular crossover analysis should be presumed.

What do the mean and standard deviation describe?

In general, a mean is a measure of the center of a set of numerical observations. A standard deviation describes how dispersed observations are around that center. The reported means are -1.5 and -0.5, and the reported standard deviations are 6.6 and 7.5, respectively, for the two treatment sequences. These summaries offer information about the recorded endpoint values within those groups. They do not give the uncertainty of a treatment-condition estimate, because that estimate and its sampling uncertainty are not posted.

A confidence interval is a range constructed by a statistical procedure to express uncertainty around an estimated quantity. In general, an interval for the treatment contrast would help show which effects remain compatible with the data under the model used. No confidence interval is reported for the primary comparison. The record also does not report a p-value or test statistic. Consequently, the precision of the treatment contrast cannot be evaluated from the registry summaries.

Why does the endpoint’s sign need care?

The registry defines the measure as a difference between risperidone-day and placebo-day RBANS scores, but does not clearly specify which score is subtracted from which. The score description says that higher RBANS scores reflect better performance. In general, the sign of a difference indicates direction only when the subtraction convention is known. Because that convention is not clear in the registry record, the negative means should not be interpreted as indicating which condition had higher scores.

What does double blinding tell the reader?

In general, masking is intended to reduce the influence of knowledge about treatment assignment on participant experience, study conduct, and outcome assessment. The record labels the study double-blind, but does not describe how masking was implemented or assessed. The label is useful information about the stated design, but it does not resolve questions about the analysis, missing observations, or the precision of the reported comparison.

How should planning calculations be read?

In general, sample-size calculations estimate how many participants a future study might need under specified assumptions. The planning illustration described for this record uses a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence about the result of this trial. They depend on assumptions, including the effect size chosen for planning.

For a crossover study, the assumptions underlying a future sample-size calculation need to align with the design and the variability of within-person differences. The registry description does not provide enough detail to assess how the planning illustration handles the crossover structure. The numerical participant requirements for the planning scenarios are not reported in the registry record. They should not be treated as part of the observed findings.

What can be inferred without a reported comparison?

Descriptive summaries can report the values recorded in each sequence. An inferential analysis would add an estimate of the treatment-condition contrast and a measure of uncertainty, using a method appropriate to the design. In general, a p-value addresses compatibility between data and a specified null hypothesis under a statistical model; it is not a measure of effect size or clinical importance. Neither a p-value nor a model-based treatment contrast is reported.

The registry lists 0 analyses and indicates that values are missing or not estimable for a two-arm comparison of this continuous endpoint. That limits interpretation to the posted descriptive statistics. It does not justify reconstructing an adjusted analysis or assuming a particular statistical plan. The registry record does not report a prespecified model, an analysis population, a missing-data approach, or an inferential result for the primary comparison.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Risperidone Then Placebo", "Placebo Then Risperidone")
n   <- c(6, 4)
m   <- c(-1.5, -0.5)
sp  <- c(6.6, 7.5)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Risperidone Then Placebo  6  -1.500  6.600  -8.426  5.426
CARM  Placebo Then Risperidone  4  -0.500  7.500  -12.434  11.434

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity concerns the risk of misleading results when several outcomes, comparisons, time points, or analyses are examined. In general, a statistical plan may identify a primary outcome and specify how other tests will be handled. This record identifies RBANS as the primary outcome and the Simpson-Angus Extrapyramidal Side Effects Scale as a secondary outcome. It lists 3 outcome measures, but does not report a multiplicity adjustment or a plan for interpreting multiple analyses. The registry lists 0 analyses, and no inferential results are posted for the secondary outcome.

The missing-data approach is not reported in the registry record. The record does not say whether all measurements were collected, how unavailable values were handled, or whether any imputation or sensitivity analysis was used. It also does not report an analysis population, such as whether the primary result was intended to include all randomized participants or only participants with complete measurements. The enrollment figure and the sequence-specific summary counts are reported, but the record does not explain their relationship.

These omissions matter because incomplete outcome data can affect both the estimate and its uncertainty. In general, an analysis that uses only observed measurements relies on assumptions about why data are missing, while imputation methods make their own assumptions. Without a stated approach and information about missingness, readers cannot assess whether missing data could have influenced the reported summaries.

The registry does not report a detailed statistical analysis plan, interim analyses, or the handling of protocol deviations. These elements should not be inferred from the randomized, double-blind, crossover labels. The posted information supports description of the registered endpoint and available summaries, but not a conclusion about multiplicity control or the robustness of an analysis to missing observations.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry reports no serious adverse events among the participants listed in either treatment sequence: the serious-event count is 0 in the risperidone-then-placebo group and 0 in the placebo-then-risperidone group. It also reports no other adverse events in those groups, with a reported count of 0 for each. The record lists 6 participants at risk for each event category in the first sequence and 4 in the second.

These figures are counts as recorded in the registry. They do not show that risk is absent, nor do they establish that the treatments have equivalent safety. In general, an observed count of zero in a small study can coexist with uncertainty about the range of possible event rates. This is especially relevant when the record does not report detailed event ascertainment procedures or follow-up beyond the described treatment days.

Deaths are not reported in the registry record; the death fields are not populated. That is different from a reported finding of zero deaths. The record also does not list any serious adverse event terms. The absence of a posted term list should be read as a limitation of the registry information, not as a conclusion about events beyond the recorded counts.

These safety summaries are descriptive. They do not provide a comparative statistical analysis between risperidone and placebo, and the sequence-based reporting does not isolate treatment-condition event risk. No clinical recommendation follows from these figures alone.

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

The registry documents a randomized, double-blind crossover study of risperidone and placebo in human volunteers, with cognitive performance assessed using RBANS. The posted primary outcome summaries are means and standard deviations for the two treatment sequences. They show the values recorded in those sequence groups, but do not report a direct estimate of the treatment-condition contrast or its uncertainty.

That distinction limits what the result means. A treatment effect is not established simply by comparing two sequence-specific means. The design involves measurements under both conditions and the order in which they were received. A direct analysis would need to use the within-participant information and account for relevant design features. The registry record does not report that analysis, a confidence interval, a test statistic, or a p-value.

The negative signs on the reported means cannot be assigned a treatment-favoring direction because the subtraction order for the difference is not clearly specified. Although the RBANS description states that higher scores reflect better performance, that score interpretation does not resolve the missing sign convention. Nor does the posted record identify a threshold for a clinically important difference. Statistical and clinical meaning therefore cannot be determined from the means alone.

The summaries also do not show what happened in each RBANS domain, because only the Total Score is reported as the primary measure. The registry lists the Simpson-Angus scale as a secondary outcome but does not post an analysis of it. Safety counts are recorded as zero for serious and other adverse events in the sequence groups, while deaths are not reported in the registry record. Those counts are not evidence that risk is absent.

The appropriate conclusion is limited: the registry reports descriptive RBANS difference summaries by treatment sequence and event counts as recorded. It does not provide enough statistical detail to establish the direction, magnitude, precision, or clinical importance of a treatment-condition difference. These data should not be interpreted as a recommendation about treatment.

14. Why This Trial Matters Statistically

This trial is statistically notable because it uses a crossover design while reporting the primary outcome in treatment-sequence groups. A crossover design is intended to compare conditions experienced by the same participants. Sequence-specific descriptive statistics do not directly communicate that paired comparison. Readers need to distinguish the layout of the posted summaries from the estimand—the treatment contrast the analysis is intended to estimate.

The record also illustrates why reporting an endpoint definition is not the same as reporting an analysis. It identifies RBANS Total Score and describes a difference between risperidone and placebo days. However, it does not clarify the sign convention or provide an inferential estimate. Without those details, the numerical summaries have limited interpretive value for the primary question.

Another statistical issue is precision. Means and standard deviations describe observed data, but the record does not report a confidence interval for the treatment contrast. An interval would help convey uncertainty in the estimated effect. The absence of that information makes it difficult to distinguish a stable estimate from one that is highly uncertain, especially in a study with a modest enrollment and sequence-specific summaries.

Finally, the record lists a secondary outcome but no analyses. Clear reporting of analysis populations, missing-data handling, multiplicity decisions, and the crossover model would help readers understand how the findings were produced and how robust they may be. The registry entry therefore offers a useful example of the gap between a registered research question and the inferential detail needed to answer it.

15. 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 limitation for interpretation is that the registry does not report an inferential comparison between risperidone and placebo. The posted means and standard deviations are organized by treatment sequence. No treatment-effect estimate, confidence interval, test statistic, or p-value is reported. The reader therefore cannot determine the magnitude or precision of a direct comparison from the record.

The endpoint’s subtraction order is not clear, so the sign of the posted means cannot establish which condition had higher scores. The record does not report a threshold for clinical importance or a rationale for the chosen endpoint. It also does not post results for separate RBANS domains, despite describing the Total Score as combining several indices.

Important design and analysis details are not reported in the registry record. These include the randomization procedure, how masking was maintained, whether a washout period was used, the statistical model for the crossover design, the analysis population, missing-data handling, and any sensitivity analyses. The record does not explain the relationship between the enrollment figure and the sequence-specific counts.

The record lists a secondary outcome and 3 outcome measures, but reports 0 analyses. It does not describe multiplicity procedures or provide a secondary-outcome result. Serious and other adverse event counts are reported as zero in the sequence groups, but deaths are not reported in the registry record. These safety figures and the incomplete analytical detail constrain interpretation; they do not establish absence of risk or a treatment effect.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Acute D2 Receptor Blockade Induced Neuronal Network Changes in Human Volunteers — NCT01931059.
• Registry record last updated 2018-04-30; status last verified 2018-03.
• Results first posted 2018-04-30.
• 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.

19. Record Summary

NCT01931059 is a completed randomized, double-blind crossover study titled “Acute D2 Receptor Blockade Induced Neuronal Network Changes in Human Volunteers.” The registry lists enrollment of 11 and describes two treatment sequences: risperidone followed by placebo, and placebo followed by risperidone. The primary outcome is the difference in RBANS Total Score between treatment conditions on consecutive days.

The posted primary summaries report means of -1.5 and -0.5, with standard deviations of 6.6 and 7.5, respectively, for the two sequence groups. The registry does not report an inferential comparison, confidence interval, p-value, or clearly specified subtraction order. It lists the Simpson-Angus scale as a secondary outcome and 0 analyses. Serious and other adverse event counts are recorded as 0 in both groups; deaths are not reported in the registry record.