Understanding Treatment Response With Naltrexone Among White Alcoholics: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Understanding Treatment Response With Naltrexone Among White Alcoholics (NCT00817089), a randomized phase 4 study. The primary outcome is Biphasic Alcohol Effects Scale:Total Mood.

2. Clinical Question

3. Trial Design

This is a Phase 4 randomized study with a parallel model and quadruple masking, according to the registry record. Enrollment was 24. The study began in 2007-12, reached primary completion in 2010-04, and is listed as completed. University of Pennsylvania is named as the sponsor. The record describes two inpatient alcohol challenge sessions and random assignment to naltrexone or placebo, with outcomes organized into four groups according to Asn40 or Asp40 status and treatment sequence.

For the placebo-placebo groups, each session was preceded by placebo. For the naltrexone groups, the first session was preceded by placebo and the second by a single 50 mg dose of naltrexone. Thus the posted primary measure is tied to the second session, after the treatment sequences had diverged. The registry labels the study parallel, while also describing two sessions and treatment sequences within groups; it does not provide enough detail to reconstruct all aspects of the assignment and analysis structure.

The record does not report how randomization was generated, whether assignment was stratified by the Asn40 or Asp40 labels, or which participants, clinicians, or assessors were included in quadruple masking. It also does not report a protocol-level sample-size rationale, the planned primary contrast, or a detailed statistical plan. The reported enrollment and the outcome-specific group counts describe different record entries and should not be treated as interchangeable measures of the analysis population.

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.

First Alcohol Challenge

Reasons for not completing this period:

Second Alcohol Challenge

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 Biphasic Alcohol Effects Scale:Total Mood, measured over during 2nd alcohol challenge session.

The primary endpoint is titled Biphasic Alcohol Effects Scale: Total Mood and is expressed in units on a scale. The registry states that the scale ranges from 0 to 106 and that higher scores indicate better outcomes. The measure is intended to capture participants’ subjective mood response in relation to the alcohol challenge, rather than a laboratory concentration by itself. The registry describes the endpoint as a mean with standard deviation and gives the timeframe as during the second alcohol challenge session.

There is an important ambiguity in the endpoint description: it calls the measure a change from baseline to peak cortisol response, then identifies subjective response measured by the Total Mood scale. Cortisol is not the same construct as a mood-scale score, and the posted record does not explain how the stated change was defined or how cortisol relates to the named scale outcome. The registry also lists Adrenocorticotropic Hormone (ACTH) Levels as a secondary outcome, but that does not resolve the wording of the primary endpoint. Consequently, the scale name, direction, and timeframe are identifiable, while the exact derivation of the primary value is not reported in the registry record. The measure could be relevant to the study’s stated interest in treatment response, but the reported summaries alone do not clarify the biological interpretation intended by the endpoint description.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What do the posted summaries describe?

The primary outcome is reported as a mean and standard deviation for each of four groups. A mean describes the center of the observed scores in a group. A standard deviation describes how dispersed those scores are around that mean. Neither quantity alone is a treatment-effect estimate: to estimate a treatment effect, an analysis must define and estimate a contrast between relevant groups. The registry does not post such a contrast for Total Mood.

The outcome counts attached to the means are 6, 7, 4, and 5 for the four listed groups, respectively. These counts are specific to the outcome summaries. They should not be assumed to represent every participant enrolled, every participant randomized, or every participant included in safety reporting. The record does not explain the reasons for the differences between outcome counts and the enrollment figure, nor does it describe participant flow or missing outcomes.

Why are standard deviations not confidence intervals?

In general, a standard deviation summarizes variation among individual observations. A confidence interval instead describes uncertainty around an estimated quantity, such as a group mean or a between-group contrast, under a specified analysis. The posted standard deviations therefore do not supply the uncertainty interval needed to assess the precision of a treatment comparison. No confidence intervals are reported for the primary outcome.

Small group counts make careful interpretation particularly important: summaries may be sensitive to the observations included, and the precision of group estimates cannot be judged fully without inferential results. This is a general statistical consideration, not a claim that any particular posted value is erroneous. The registry does not report distributional diagnostics or a model for the outcome.

What comparison would answer the treatment question?

A treatment comparison would need to specify how the placebo-placebo sequence is compared with the placebo-then-naltrexone sequence, and how the Asn40 and Asp40 groupings enter that comparison. If the scientific question is whether treatment response differs by genotype category, the analysis would also need to estimate that variation directly. Comparing group means by inspection is not a substitute for an estimate of the relevant contrast, with its uncertainty. The registry contains no analysis results for these questions.

The record identifies a randomized study and a parallel model, but does not describe the statistical model, adjustment variables, handling of repeated-session measurements, or exact contrast. It is therefore not possible to determine from the posted results whether an analysis accounted for the two-session structure or used baseline values. The primary endpoint wording itself does not clearly state whether the displayed values are raw session scores or change scores.

What does over-dispersion mean in general?

In general, over-dispersion occurs when observed variability is greater than a statistical model expects. It can make standard errors from an unsuitable model too small and uncertainty appear more precise than it is. This is a general concept only. The registry does not report a model fit, a dispersion assessment, or evidence that over-dispersion was present in this study. The posted standard deviations are descriptive and do not establish a model problem.

How should sample-size illustrations be understood?

Any sample-size figures associated with planning scenarios are illustrations based on the observed effect under stated assumptions, not evidence of observed power and not the trial’s original design justification. In general, such illustrations depend on the effect chosen for planning, allocation assumptions, a significance level, and the statistical approximation. They do not show that the study had a particular probability of detecting an effect after results were observed. The registry record does not report the trial’s own sample-size justification. No planning figure can replace a reported effect estimate and its uncertainty.

What is absent from the inferential record?

The analysis count is 0, and no primary-outcome comparison, model estimate, p-value, or confidence interval is posted. This absence limits what can be said: descriptive group values can be reported, but statistical evidence for a treatment contrast cannot be characterized from these entries. The registry does not report whether analyses were planned but omitted, whether results were not estimable, or why no analysis is posted. Those explanations should not be inferred.

In general, a sound reading separates the observed summaries, the target comparison, and uncertainty about that comparison. Here, the observed summaries are available, but the contrast and its uncertainty are not. The endpoint-description ambiguity and unreported analysis details further constrain interpretation. These limitations are distinct from whether the study’s underlying scientific question is important.

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("Group 1: Asn40 Placebo Placebo", "Group 2: Asn40 Placebo Naltrexone", "Group 3: Asp40 Placebo Placebo", "Group 4: Asp40 Placebo Naltrexone")
n   <- c(6, 7, 4, 5)
m   <- c(6.94, 3.57, 6.5, 3.2)
sp  <- c(9.53, 18.46, 4.04, 8.11)
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  Group 1: Asn40 Placebo Placebo  6  6.940  9.530  -3.061  16.941
CARM  Group 2: Asn40 Placebo Naltrexone  7  3.570  18.460  -13.503  20.643
CARM  Group 3: Asp40 Placebo Placebo  4  6.500  4.040  0.071  12.929
CARM  Group 4: Asp40 Placebo Naltrexone  5  3.200  8.110  -6.870  13.270

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and identifies Adrenocorticotropic Hormone (ACTH) Levels as a secondary outcome. It does not report a multiplicity plan describing how inference across outcomes, treatment contrasts, or genotype groups was handled. Without that information, the level of protection against false-positive findings across multiple tests cannot be assessed. Since the posted analysis count is 0, no multiplicity-adjusted or unadjusted inferential results are available to interpret.

Missing-data handling is not reported in the registry record. The primary outcome counts are 6, 7, 4, and 5 across the four groups, while the enrollment figure is 24. These entries do not explain which participants lacked a measurement, why any measurement was absent, or whether exclusions occurred. No imputation method, complete-case rule, sensitivity analysis, or participant-flow account is reported. The safety counts use separate at-risk figures, so they should not be assumed to define the outcome-analysis population.

The record does not identify an intention-to-treat, per-protocol, or other analysis population for the primary endpoint. It also does not report how randomization was preserved in analysis, how repeated sessions were handled, or whether participants were analyzed according to assigned sequence. These details matter because the analysis population and missing-data approach can affect both the estimate and its interpretation.

In general, multiplicity concerns arise when several outcomes or comparisons are tested, and missing-data methods depend on why observations are absent and on the analysis target. Those general considerations cannot be resolved from the registry entries. The record does not say whether the secondary outcome was analyzed, and no secondary-outcome results are posted in the registry record described for these results.

12. 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.

The registry reports serious adverse events, other adverse events, and deaths separately for each group. For the placebo-placebo groups, the serious-event count is 0 among 6 at risk for the Asn40 group and 0 among 4 at risk for the Asp40 group. For the placebo-naltrexone groups, the serious-event count is 0 among 8 at risk for the Asn40 group and 0 among 6 at risk for the Asp40 group. The reported count for other adverse events is also 0 in each group, and deaths are reported as 0 in each group.

These are registry counts for the reported at-risk groups. They describe what was recorded in the safety fields; they do not prove that no event of any kind occurred, nor do they establish comparative safety. The at-risk counts differ from the outcome counts listed for the primary measure, and the record does not explain the population definitions or follow-up completeness for safety reporting. The registry lists no serious-event terms.

In general, a zero count in a small study is not an estimate that risk is zero. The size of the exposed population, duration of observation, event definitions, and completeness of reporting all affect what zero reported events can tell a reader. No safety comparison, confidence interval, or formal analysis is reported. These counts should therefore be read as descriptive registry entries, not as evidence that one treatment sequence is safer than another.

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

The record contributes descriptive information about a small randomized alcohol-challenge study organized around Asn40 and Asp40 groups and placebo or naltrexone treatment sequences. It gives group means and standard deviations for the named Total Mood endpoint, along with counts for the primary outcome. It also reports zero serious adverse events, zero other adverse events, and zero deaths in each listed safety group. These are the results that can be stated directly from the posted entries.

The record does not provide an estimated treatment contrast, confidence interval, p-value, or model-based result for the primary outcome. It therefore does not establish the magnitude or precision of a treatment effect. It also does not establish whether response differs by Asn40 versus Asp40 status, or whether either label defines an endophenotype. Such conclusions would require clearly specified analyses and uncertainty estimates that are not reported.

The endpoint description leaves uncertainty about whether the primary outcome is a mood-scale score, a change from baseline, or linked in some way to peak cortisol response. The posted scale range and direction help identify the named measure, but do not resolve that discrepancy. Outcome counts and safety at-risk counts are not interchangeable, and the record does not give reasons for their differences.

In general, a randomized design can support causal comparisons when the outcome, contrast, analysis population, and analysis method are clearly specified and results are reported with appropriate uncertainty. The registry’s design labels alone cannot fill in these missing details. Any sample-size figures framed as planning illustrations are not observed power and do not provide the trial’s design rationale. The findings should be understood as limited descriptive data rather than a definitive treatment or genetic conclusion.

14. Why This Trial Matters Statistically

This study is statistically notable because it combines a treatment comparison with a question about variation by Asn40 and Asp40 status. Those are distinct inferential questions. One asks about the treatment-sequence contrast; the other asks whether that contrast differs across the listed categories. A set of group means can describe the data, but it does not by itself answer either question or quantify uncertainty. The absence of posted analyses makes that distinction especially important.

The small outcome counts in the four groups also make transparent reporting of uncertainty, analysis populations, and endpoint construction consequential. Standard deviations are available, but confidence intervals and formal comparisons are not. The registry does not state whether baseline values or the repeated-session structure were incorporated into an analysis. Nor does it clarify how the named mood outcome relates to the description of change in cortisol response.

The record illustrates why trial design labels and outcome summaries are not substitutes for an analysis plan and interpretable results. Randomization and masking are reported, yet the assignment procedure, primary contrast, and missing-data approach are not. A reader cannot infer those details from the group labels. In general, a biologically motivated subgroup question benefits from an analysis that explicitly tests the relevant interaction and reports its precision, rather than relying on separate descriptive summaries.

The study’s stated aim—to investigate a possible genetic link to alcohol-treatment response through an endophenotype—makes these reporting distinctions central. The posted information permits a careful account of what was measured and summarized, but leaves the inferential question unresolved. That boundary is statistically meaningful: it helps prevent descriptive patterns from being mistaken for evidence about treatment effects or genetic mechanisms.

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.

Several limitations are specific to the registry entries. First, the primary endpoint description is internally unclear: the title names Total Mood on the Biphasic Alcohol Effects Scale, while the description refers to change from baseline to peak cortisol response and then to subjective response. The registry does not specify the precise calculation or reconcile those concepts.

Second, the record posts descriptive means and standard deviations but no primary-outcome analysis. No treatment contrast, confidence interval, p-value, or model specification is reported. The analysis count is 0, leaving the intended estimand and the inferential approach unavailable. Results cannot support conclusions about treatment differences or effect modification by the Asn40 and Asp40 labels.

Third, the group outcome counts are 6, 7, 4, and 5, while the enrollment entry is 24. Safety at-risk counts also differ from the outcome counts. The registry does not report participant flow, reasons for missing endpoint data, analysis-population definitions, or the duration and completeness of safety observation. These omissions limit interpretation of both the outcome summaries and the zero safety counts.

The record does not describe eligibility details beyond the study summary, baseline characteristics, randomization procedure, masking roles, or protocol-level sample-size rationale. It does not explain how repeated-session data were handled or whether baseline adjustment was used. Multiplicity handling for the listed outcomes and subgroup comparisons is also not reported. These missing details constrain reproducibility and precision of interpretation; they should not be replaced by assumptions about the protocol or analysis.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Understanding Treatment Response With Naltrexone Among White Alcoholics — NCT00817089.
• Registry record last updated 2019-11-21; status last verified 2019-10.
• Results first posted 2019-11-21.
• 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

The registry describes a completed Phase 4 randomized, quadruple-masked study sponsored by University of Pennsylvania, with enrollment of 24 and a parallel model. It concerns alcohol dependence in males described as of European or Asian descent and includes two inpatient alcohol challenge sessions. Groups are organized by Asn40 or Asp40 status and by placebo at both sessions or placebo followed by a single 50 mg naltrexone dose at the second session.

The primary outcome is named Biphasic Alcohol Effects Scale: Total Mood, with group means, standard deviations, and outcome counts posted. The endpoint description is ambiguous about its relation to baseline and peak cortisol response. No inferential analysis is reported. The secondary outcome listed is ACTH Levels. Safety entries report zero serious adverse events, zero other adverse events, and zero deaths in each group. Missing-data methods, analysis populations, multiplicity handling, and the trial’s own sample-size justification are not reported in the registry record.