Prefrontal Cortex Stimulation as Treatment for Crack-cocaine Addiction: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Prefrontal Cortex Stimulation as Treatment for Crack-cocaine Addiction (NCT01337297), a randomized phase 1, phase 2 study. The primary outcome is Abstinence.

2. Clinical Question

The clinical question is whether the recorded abstinence outcome differed between participants assigned to active and sham stimulation. The posted outcome values are 71.4% for Active-tDCS and 16.6% for Sham-tDCS. These are descriptive percentages for the outcome groups reported in the registry, not a complete account of the trial's statistical evidence. The record does not include a confidence interval, p-value, or other inferential comparison for this endpoint.

The study also listed intensity of the urge to use crack-cocaine, event-related potentials, cognitive tests, and state of depression as secondary outcomes. Their results are not reported in the registry record. Thus, the available record addresses the primary question only through the two group percentages; it does not establish how the groups compared on the secondary measures or explain whether any outcome was used in a formal analysis.

3. Trial Design

The registry classifies the study as a randomized, triple-masked, parallel-group trial with Phase 1 and Phase 2 designations. It lists 20 participants as the enrollment and identifies the study status as completed. The listed study dates are 2011-06 for start and 2012-11 for primary completion. The sponsor is Federal University of Espirito Santo.

Participants were assigned to Active-tDCS or Sham-tDCS. The active intervention was low-intensity stimulation over the dorsolateral prefrontal cortex. In the sham condition, electrodes were placed in the same manner and briefly activated for 20 s before being switched off. The primary description specifies 5 sessions, one every other day, and calls the treatment period two weeks. The registry does not report the randomization sequence method, allocation concealment procedures, or the identities of the groups covered by triple masking.

The reported outcome denominators are 7 for Active-tDCS and 6 for Sham-tDCS, while overall enrollment is listed as 20. The record does not explain the relationship between enrollment and these outcome denominators. It does not provide a participant flow account, reasons for non-inclusion in the posted outcome groups, or an analysis population definition. Those omissions prevent a reader from determining from the registry alone how many enrolled participants contributed to each outcome and why.

The record lists four secondary outcomes in addition to the primary abstinence outcome: intensity of urge to use crack-cocaine, event-related potentials, cognitive tests, and state of depression. Although five outcome measures are listed overall, results for those secondary measures are not reported in the registry record. Details of the trial protocol, including the sample-size justification and any planned interim analyses, are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Of 70 patients, 20 filling including criteria and without excluding criteria were recruited. The remaining 50 either refused to participate or accepted but never showed up to the researcher center.

Overall Study

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 Abstinence, measured over Two days after the end of tDCS treatment (one session every other day, 5 sessions), that is, on the 12nd day from the beginning..

The primary endpoint is abstinence, recorded as the percentage of participants with the event. The registry describes the event as abstinence from crack-cocaine use up to 3 months after completion of the treatment sessions. Its timeframe gives a specific assessment point as two days after the end of tDCS treatment, on day 12 from the beginning. The wording does not make clear whether the day-12 assessment defines the endpoint, whether abstinence was assessed over a period extending to 3 months, or how these descriptions were combined.

A binary endpoint classifies each participant according to whether the stated event occurred. Reporting the percentage gives a direct description of how common the event was in each outcome group. In this trial, the posted percentages are 71.4% in the active group and 16.6% in the sham group. The record does not provide the underlying participant-level observations or further details about how abstinence was established, such as the measurement procedure or criteria for classifying the outcome.

Abstinence is relevant to the stated study question because the trial concerns crack-cocaine use. However, a percentage alone does not communicate the precision of the estimate or establish the strength of evidence for a difference between groups. A confidence interval would describe uncertainty around an estimate; none is reported in the registry record. The record also does not report an inferential comparison for the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary: participants are classified according to whether abstinence occurred, and the result is expressed as a percentage. For a binary outcome, a group percentage is a descriptive estimate of the proportion with the event in that group. It does not by itself show how uncertain the estimate is, nor does it establish whether the groups differ statistically. Here, the registry reports 71.4% for Active-tDCS and 16.6% for Sham-tDCS, with outcome denominators of 7 and 6, respectively.

What does uncertainty mean for a percentage?

In general, uncertainty reflects the fact that a study observes a sample rather than every person to whom its result might be relevant. A confidence interval is one common way to express this uncertainty around an estimate. Its width depends on the data and the method used; wider intervals indicate less precision. The registry record gives no confidence interval or limits for either percentage, so the precision of the estimates cannot be assessed from the posted results. A confidence interval would not, by itself, resolve questions about missing data, endpoint definition, or bias.

What can be concluded without a reported test?

In general, an inferential comparison evaluates whether the observed group contrast is compatible with a specified statistical model and assumptions. A p-value is one summary sometimes reported for such a test; it is not a measure of the size or clinical importance of an effect. The registry contains zero analyses and does not report a p-value, test statistic, or inferential estimate for the primary outcome. The group percentages can therefore be described, but the registry does not document a formal test of the comparison.

The posted record identifies the trial as randomized and parallel. Random assignment is a design feature intended to support comparisons between groups, but the record does not describe how the random sequence was generated or how assignments were concealed. The triple-masked designation indicates that the registry labels the design as triple-masked; which roles were masked and how masking was maintained are not reported in the registry record. These design labels should not be mistaken for a complete account of trial conduct.

How should sample-size planning be understood?

In general, a sample-size calculation is a planning exercise based on assumptions about the outcome, the effect a study aims to detect, the significance level, statistical power, allocation, and analysis method. The registry describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It also describes planning for a stated fraction of the observed effect. These are planning assumptions, not evidence about the probability that the completed trial detected an effect.

Such illustrations should not be read as observed power. Observed power is not a substitute for an uncertainty interval around the actual result. A planning calculation can show how assumed effect size and design choices relate to a target sample size, but it cannot repair a small or incompletely described outcome dataset. The trial's own sample-size justification, target effect, and planning rationale are not reported in the registry record. Numerical planning outputs are not reported in the registry record.

The registry also notes that recalculated quantities are simple, unadjusted recalculations from posted summary statistics and that some comparisons may not be estimable. For this binary endpoint, the record states that values are missing or not estimable for a two-arm comparison. Consequently, there is no recalculated comparison to interpret alongside the sponsor's analysis. No sponsor analysis for this endpoint is reported in the registry record.

Why do outcome definitions and denominators matter?

Statistical interpretation depends on knowing who was included and what counted as the event. Overall enrollment is listed as 20, while the posted endpoint denominators are 7 and 6. The record does not explain the relationship between these values, identify reasons for absent outcomes, or define an analysis population. A complete account would distinguish all enrolled participants from those randomized, treated, followed, or included in an endpoint analysis. Those details are not reported in the registry record.

For a binary endpoint, the event definition and observation window also determine what the percentage represents. The record refers both to abstinence up to 3 months after treatment and to an assessment two days after the end of treatment, on day 12 from the beginning. Without clarification about ascertainment and the observation period, it is difficult to know exactly what interval of abstinence the percentages represent. This is a definition and reporting issue, not a calculation that can be resolved from the percentages.

Finally, the registry lists several outcomes, but only the primary percentages are posted. Statistical methods for secondary outcomes, handling of multiple comparisons, missing-data methods, and any model-based adjustments are not reported in the registry record. These absences mean readers cannot reconstruct a comprehensive analysis plan from the posted record. General statistical methods can explain what such choices are intended to do, but they cannot establish which choices were made in this trial.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Active-tDCS", "Sham-tDCS")
n      <- c(7, 6)
events <- c(5, 1)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Active-tDCS  7  5  71.4  29.0  96.3  35.9  91.8  34.9  91.5
ARM  Sham-tDCS  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists abstinence as the primary outcome and names four secondary outcomes: intensity of the urge to use crack-cocaine, event-related potentials, cognitive tests, and state of depression. Results for those secondary outcomes are not reported in the registry record. The record does not describe a multiplicity strategy, such as prioritizing selected comparisons or adjusting the interpretation of multiple statistical tests. Without that information, it is not possible to determine how the investigators intended to address the chance of apparently notable findings when examining several outcomes.

There is also no reported analysis plan or inferential analysis for the primary endpoint. The registry lists zero analyses. The statistical method used for the posted percentages and whether any covariate adjustment was planned or performed are not reported in the registry record. The record does not report interim analyses or stopping rules.

Enrollment is listed as 20, while the primary outcome denominators are 7 and 6. The record does not explain this difference, give participant flow, report reasons for missing outcomes, or specify whether the analysis followed an intention-to-treat or another population definition. It also does not describe imputation, complete-case analysis, or sensitivity analyses for missing data. These omissions prevent assessment of whether the reported percentages represent all randomized participants or a subset.

These are reporting gaps, not proof that particular methods were or were not used in the trial. The registry record does not establish how missing observations or multiple outcomes were handled. Readers should therefore treat the posted percentages as descriptive and avoid inferring unreported analytical procedures.

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 7 participants at risk in Active-tDCS and no serious adverse events among the 6 participants at risk in Sham-tDCS. It also reports no other adverse events among the 7 and 6 participants at risk in the respective groups. These figures describe the safety information recorded for the listed groups.

A count of zero observed events does not establish that an event cannot occur. In general, safety estimates based on small groups have limited ability to characterize uncommon events, and the absence of a reported event is not the same as evidence that risk is absent. The registry does not provide further detail about how adverse events were collected, the observation period used for safety reporting, or whether all enrolled participants contributed to the safety groups.

Deaths are not reported in the registry record; the death counts are not presented as zero. The registry also lists no serious adverse-event terms. The available figures should therefore be read narrowly as the recorded event counts and denominators, rather than as a complete characterization of safety.

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

The results establish that the registry posted different abstinence percentages for the two outcome groups: 71.4% in Active-tDCS and 16.6% in Sham-tDCS. The denominators were 7 and 6, respectively. Those figures are a description of the recorded outcomes in those groups. They do not, on their own, establish the precision of the contrast or provide a formal statistical assessment.

The registry does not report a confidence interval, p-value, or other inferential comparison. It also does not clarify how the outcome denominators relate to the overall enrollment of 20. Without a participant flow account and a stated analysis population, the reader cannot determine from the registry how missing outcomes were handled or whether the displayed groups represent all participants assigned to treatment.

The outcome timing is not fully clear. The registry describes abstinence up to 3 months after treatment and separately specifies an assessment two days after treatment ended, on day 12 from the start. It does not explain the relation between these time references or the procedure used to ascertain abstinence. Thus, the percentages should not be assigned a more precise observation window than the record supports.

The trial record also does not report results for its four secondary outcomes, the analysis methods, or any adjustment for multiple outcomes. The study is designated randomized and triple-masked, but details of sequence generation, concealment, and which roles were masked are not reported in the registry record. These omissions limit evaluation of the evidence and the conduct of the trial.

In general, statistical evidence is best interpreted by considering the estimate, its uncertainty, the study design, outcome definition, and completeness of reporting together. Here, the posted percentages are a signal in the descriptive data, but the registry does not establish how precisely they estimate a broader effect. They do not alone prove that stimulation changes abstinence outcomes, and they do not establish that it fails to do so. No medical conclusion should be drawn from the percentages without the missing analytical and methodological context.

14. Why This Trial Matters Statistically

This trial illustrates why group percentages and inferential evidence answer different questions. The percentages describe the observed abstinence outcomes in the groups listed in the registry. They do not indicate how much sampling uncertainty surrounds those values. With outcome denominators of 7 and 6, precision is particularly important to consider, yet the registry does not report confidence intervals or another measure of uncertainty.

It also demonstrates the importance of reconciling enrollment with outcome denominators. The registry lists enrollment of 20 but reports outcome groups of 7 and 6. Without participant flow or an analysis-population definition, readers cannot tell how those numbers relate or how missing outcomes were treated. This information is necessary for understanding who the reported percentages represent.

Endpoint timing is another central statistical issue. The record refers to abstinence up to 3 months after treatment while also identifying an assessment two days after treatment ended. A clear observation window is needed to interpret a binary endpoint consistently. When timing is ambiguous, even a correctly calculated percentage may not answer a clearly specified question.

Finally, the record lists several secondary outcomes but does not report their results or a multiplicity approach. It also contains no inferential analyses for the primary outcome. These reporting limits show why statistical interpretation depends not only on the numerical result, but on a transparent account of the analysis, missing data, and outcome definitions. The trial is statistically informative as an example of a descriptive result whose uncertainty and analytic context remain unclear in the registry record.

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 is the small number of participants in the posted outcome groups: 7 in Active-tDCS and 6 in Sham-tDCS. The registry lists total enrollment as 20 but does not explain how that enrollment relates to the endpoint denominators. No participant flow, reasons for missing outcome data, or analysis population is reported in the registry record. This makes it difficult to assess the completeness and representativeness of the posted outcome data.

The primary endpoint's timing is described in two ways: abstinence up to 3 months after completion of treatment, and an assessment two days after the end of treatment, on day 12 from the beginning. The registry does not resolve this ambiguity or state how abstinence was ascertained. Further measurement details and operational criteria for classifying abstinence are not reported in the registry record.

The record does not report a confidence interval, p-value, or formal comparison for the primary endpoint. It lists zero analyses and does not describe statistical methods, missing-data procedures, multiplicity handling, interim analyses, or an analysis population. The sample-size justification and the protocol's analytical plan are not reported in the registry record. Details of random sequence generation, allocation concealment, and the roles included in triple masking are also not reported.

Results for the four secondary outcomes are not reported in the registry record. Safety figures are limited to the event counts and denominators listed; follow-up and ascertainment details are not reported. These limitations constrain interpretation of both the primary percentages and the broader trial record. They do not determine what the unreported methods or results would have shown.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Prefrontal Cortex Stimulation as Treatment for Crack-cocaine Addiction — NCT01337297.
• Registry record last updated 2014-01-30; status last verified 2013-12.
• Results first posted 2013-11-27.
• 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

NCT01337297 is a completed randomized, triple-masked, parallel-group trial with Phase 1 and Phase 2 designations. The registry lists enrollment of 20 and compares active tDCS over the dorsolateral prefrontal cortex with sham-tDCS. The treatment description specifies 5 sessions, one every other day.

The primary outcome is abstinence, expressed as a percentage. Posted values are 71.4% for Active-tDCS and 16.6% for Sham-tDCS, with outcome denominators of 7 and 6. The registry does not report a confidence interval or inferential analysis and does not explain the relationship between these denominators and total enrollment. Its descriptions of the abstinence timeframe are not fully aligned.

Four secondary outcomes are listed, but their results are not reported in the registry record. The record reports no serious or other adverse events in the listed groups; deaths are not reported in the registry record. Missing-data methods, the analysis population, and detailed statistical methods are not reported in the registry record.