An 8 Week Open-Label Study to Evaluate the Efficacy and Safety of Acamprosate Calcium (Campral) as Augmentation Therapy in Patients With Anxiety Symptoms Who Are Only Partial Responders to SSRI or SNRI Antidepressants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An 8 Week Open-Label Study to Evaluate the Efficacy and Safety of Acamprosate Calcium (Campral) as Augmentation Therapy in Patients With Anxiety Symptoms Who Are Only Partial Responders to SSRI or SNRI Antidepressants (NCT00591565), a na na study. The primary outcome is Change From Baseline at 8 Weeks in the HAM-A Scale.

2. Clinical Question

The clinical question is about change during treatment, not a comparison between acamprosate and placebo or another assigned treatment. Because all participants received acamprosate and there was no control group, the study can describe outcomes observed during the treatment period but cannot establish how those outcomes compare with what would have occurred without acamprosate.

The record describes participants as having anxiety symptoms despite only partial response to SSRI or SNRI therapy. It also says the study assessed a broader set of domains, including depression, sleep, alcohol use, and social functioning. However, the registry lists one outcome measure, the HAM-A change from baseline at 8 weeks, and does not provide numerical outcome results. The question can therefore be stated from the endpoint definition, but the posted results do not answer it with an estimate.

3. Trial Design

This was a completed, prospective, single-group study of acamprosate augmentation in patients with anxiety symptoms who were described as partial responders to SSRI or SNRI antidepressants. The registry lists 13 participants enrolled, one intervention—acamprosate tablets—and no separate control arm. Allocation is listed as NA, and the design is listed as single group. The study title and brief summary describe an 8-week treatment period.

The brief summary calls the study patient open-label and rater-blinded. The registry’s masking entry, however, is NONE. These descriptions do not align fully, so the masking arrangement is not clear from the registry record alone. The record does not describe how any rater blinding was implemented.

The primary endpoint is change from baseline at 8 weeks in the HAM-A scale, reported as a mean with standard deviation. Its stated timeframe is baseline and 8wk. The endpoint population is described as LOCF if two initial visits were completed. The registry lists the phase as NA. It records the study status as completed, with start listed as 2006-06 and primary completion as 2009-12.

The sponsor is State University of New York - Upstate Medical University. The record does not identify a randomized allocation, placebo group, or active comparator. It also does not report the protocol details, sample-size justification, or a fuller statistical analysis plan. The sample-size calculations associated with this study are planning illustrations, not a description of the study’s own enrollment plan.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: LOCF if two initial visits were completed

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 Change From Baseline at 8 Weeks in the HAM-A Scale, measured over baseline and 8wk.

The primary endpoint is change from baseline at 8 weeks in the HAM-A scale. HAM-A is described in the registry as a validated, clinician-administered scale ranging from 0-44, with scores spanning mild to severe illness. The result is intended to be expressed as a mean change, with standard deviation as the measure of dispersion. The stated measurement timeframe is baseline and 8wk.

Repeated measurement of a symptom scale can describe how scores differ between the start and end of a treatment period. The mean summarizes the average change across participants included in the analysis, while the standard deviation describes how dispersed individual changes are around that mean. These are different quantities: the mean is an estimate of the group’s average change, and the standard deviation characterizes variation among participants.

The registry record does not give the observed mean change, its standard deviation, a confidence interval, or a significance test. It also does not state the direction of change in the outcome description. Consequently, the endpoint definition is available, but the magnitude and precision of the observed result are not reported in the registry record. The scale range alone cannot establish what change occurred during the study.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change represent?

For a continuous measure such as HAM-A, a mean change is an average of participants’ differences between the endpoint measurement and the baseline measurement, using the analysis definition adopted for the study. It condenses individual data into one group-level estimate. That estimate is useful for describing the center of the observed changes, but it does not show the full spread of participant outcomes. The registry specifies standard deviation as the dispersion measure, which describes how variable the changes are around the mean.

The HAM-A range is given as 0-44, with scores spanning mild to severe illness. A scale range provides context for interpreting possible values, but it does not supply the actual baseline score, follow-up score, or change. The record also does not specify the direction of improvement in its outcome definition. No numerical mean change or standard deviation is reported, so neither the magnitude nor the variability of the result can be evaluated.

How would uncertainty be described?

In general, a confidence interval gives a range of values compatible with the data and the method used to calculate it. A narrower interval indicates greater precision under the assumptions of that method; a wider interval indicates greater uncertainty. A confidence interval is not a guarantee that the true value falls within its limits, and it does not resolve limitations in study design. No confidence interval for the HAM-A change is reported in the registry record.

A p-value, in general, measures how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the statistical model were correct. It does not measure the size or clinical importance of an effect. The record does not report a primary endpoint p-value or a hypothesis test. The two-sided significance level of 0.05 appears among assumptions for planning illustrations; it is not a reported test result from the study.

What does the single-group design allow?

A single-group analysis can describe outcomes over time among participants who received the intervention. It does not estimate a randomized contrast between treatment groups because there is no separate comparator in the registry record. Even when an average score changes, the design cannot separate the contribution of the study intervention from other explanations for change. This is a general limitation of interpreting within-group change as a treatment effect, rather than a claim about what happened to these participants.

The registry lists allocation as NA and describes a single group. It therefore does not report random assignment to acamprosate versus a control condition. The study title and summary characterize the intervention as augmentation, but the record does not provide a comparative estimate of acamprosate augmentation against continuing existing therapy alone.

How should the planning calculations be read?

The planning assumptions describe hypothetical two-arm sample-size calculations: two-sided significance level 0.05, equal allocation between arms, a normal approximation, and effects defined as stated fractions of an observed effect. These assumptions concern planning illustrations, not the design actually recorded for this single-group study. The illustrations are not evidence that the study had a particular probability of detecting an effect, and sample sizes derived under such assumptions are not observed trial outcomes.

The record does not provide numerical sample-size illustration results or a numerical observed effect on which to base their interpretation. It also does not report the study’s own sample-size justification. Thus the assumptions can be described, but the illustrations cannot be used to infer why 13 participants were enrolled or what precision the actual endpoint estimate would have had.

What is the role of the standard deviation?

For a continuous outcome, standard deviation describes dispersion among individual values or changes, depending on the quantity being summarized. It is not the same as a standard error or a confidence interval. The standard deviation reflects variation among participants; a standard error reflects uncertainty in an estimated mean and depends on both variation and the amount of data. The registry names standard deviation for the primary outcome but does not report its value, so the degree of participant-to-participant variation is unknown.

In general, unusually variable data can make a simple normal model less suitable for some analyses, and count outcomes may show over-dispersion when their variability exceeds what a basic count model expects. Over-dispersion is not relevant to interpreting a mean HAM-A change in the same direct way as it is to count data, and the registry does not report an over-dispersion assessment or a model for the primary endpoint. No specific distributional assumptions for that analysis are reported.

What can be said about missing-data handling?

The endpoint description states LOCF if two initial visits were completed. In general, last observation carried forward uses a participant’s last available measurement as a substitute for a later missing measurement. This creates an analysis value, not a new observed measurement. Its validity depends on assumptions about how missingness and outcomes relate; those assumptions may not hold in every study. The registry record does not explain the reason for this rule, how many participants it affected, or whether other missing-data methods were used.

The phrase about two initial visits limits the stated endpoint population, but the record does not clarify the operational details beyond that phrase. There is no reported count of participants with missing follow-up measurements, no analysis population size, and no sensitivity analysis. These omissions prevent evaluation of how the stated approach may have influenced the endpoint estimate.

What is and is not inferentially available?

The record gives a primary endpoint definition but no numerical result or analysis record. A statistical method cannot recover an unreported outcome from the scale range, the enrollment count, or the design description. As a result, the posted information permits discussion of what the endpoint was intended to measure and what kinds of statistical summaries would be informative, but not a calculation or interpretation of an effect estimate.

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("Acamprosate")
n   <- c(8)
m   <- c(6.12)
sp  <- c(1.39)
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  Acamprosate  8  6.120  1.390  4.958  7.282

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure: change from baseline at 8 weeks in HAM-A. Its brief summary says the investigators planned to use a comprehensive set of rating scales covering anxiety, co-occurring depression, sleep disorders, alcohol use, and social functioning. However, the registry does not list those additional measures as registered outcomes in the outcome information. The record does not report a multiplicity strategy, such as how multiple outcome tests would be handled or which outcomes would be prioritized beyond the named primary measure.

The registry lists zero analyses and does not report a numerical result for the primary endpoint. It therefore provides no analysis-level detail about model choice, hypothesis tests, confidence intervals, or adjustments for multiple comparisons. The planning significance level of 0.05 is part of sample-size assumptions and should not be treated as a reported endpoint testing procedure.

For missing data, the endpoint population is described as LOCF if two initial visits were completed. The number of participants with missing measurements, the number included in analysis, and the reasons for missingness are not reported in the registry record. Further details about implementation of the method and sensitivity analyses are also not reported in the registry record.

These gaps matter because outcome selection, repeated testing, and missingness can affect how estimates and uncertainty are interpreted. They do not show that a particular bias occurred; they limit the ability to assess the analysis from the record.

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 1% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events for the acamprosate group among 13 participants at risk: 0 participants were affected. It reports other adverse events among the same 13 participants at risk: 2 participants were affected. These are participant counts, not event rates calculated for a different observation period. The registry does not provide the event terms for the serious adverse events, and the listed serious-event terms are empty.

The death count is not reported in the registry record. A blank list of serious-event terms should not be read as additional detail about the types or timing of events. The record also does not describe event severity definitions, duration, relationship assessments, or how adverse events were collected. The figures alone cannot establish whether an event was caused by acamprosate.

These counts describe what the registry reports for this group; they do not compare safety with another treatment because no control group is listed. With 13 participants enrolled, the counts are limited observations from this study and do not characterize uncommon events. The distinction between 0 serious-event-affected participants and 2 participants affected by other adverse events should be retained rather than combining the categories.

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

The registry record establishes that a completed, 8-week, single-group study evaluated acamprosate tablets as augmentation for patients described as partial responders to SSRI or SNRI antidepressants. It specifies change from baseline at 8 weeks in clinician-administered HAM-A as the primary endpoint. It also reports enrollment of 13 participants and limited adverse-event counts for the acamprosate group.

What the record does not establish is the observed HAM-A change. There is no numerical mean, standard deviation, confidence interval, or p-value for the primary endpoint. The absence of a result is not evidence that participants did not change, and it is not evidence that they did. It means the magnitude and precision of change are not reported in the registry record.

Even if a within-group change were available, it would describe change over time among participants receiving acamprosate, not a causal treatment effect. A single-group design has no concurrent control group to indicate what would have happened without acamprosate. In general, symptom changes can have multiple explanations, and the design cannot distinguish them on its own. The posted record does not determine which explanations, if any, applied.

The serious adverse-event count is reported as 0 affected participants out of 13 at risk, while 2 participants were affected by other adverse events. These observations are not comparative safety evidence and do not establish that there were no unreported risks. Deaths are not reported in the registry record.

The appropriate conclusion is narrow: the study’s design and intended primary measure are described, but the posted results do not provide the primary outcome estimate needed to quantify change. The registry information therefore cannot support a conclusion about the size, precision, or cause of any HAM-A change, nor can it establish comparative efficacy or safety.

14. Why This Trial Matters Statistically

This study illustrates why a clearly defined endpoint and a reported endpoint result are both necessary for statistical interpretation. The registry specifies the instrument, timing, summary measure, dispersion measure, and a condition for the analysis population. Those details identify what the investigators intended to measure. Without the numerical mean change and its variability, however, readers cannot judge the observed magnitude or precision.

The design also shows the distinction between describing change and estimating a comparative effect. In a single-group study, an outcome measured at baseline and follow-up can characterize the group’s course during treatment. It cannot by itself attribute that course to the intervention. This distinction is particularly important when a study has no separate control group and no randomized allocation recorded.

The registry’s sample-size assumptions provide another statistical lesson. Planning illustrations use a stated significance level, equal allocation, a normal approximation, and fractions of an observed effect. Such assumptions describe a hypothetical planning framework; they do not substitute for a trial’s design details, outcome results, or uncertainty estimates. In this case, the record does not report its own sample-size justification or numerical primary endpoint result.

Finally, the endpoint population description explicitly references LOCF, while the record does not report how many observations required that approach. Missing-data methods can affect estimates, so reporting the method without its application details leaves important uncertainty. Together, these features make the study useful for understanding what information is needed to interpret a small, uncontrolled clinical study, while limiting what can be concluded from the registered results.

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 main trial-specific limitation is the absence of a numerical result for the primary HAM-A endpoint. The registry defines change from baseline at 8 weeks but does not report the mean change, standard deviation, confidence interval, or test result. This prevents assessment of the direction, magnitude, variability, and precision of the primary outcome.

The study is listed as single group, with allocation NA and no separate comparator. As a result, the record does not provide a controlled estimate of the difference between acamprosate augmentation and another treatment strategy. The small enrollment of 13 participants further constrains how broadly the observed experience could represent the population of interest, even if the endpoint result were available.

There is an inconsistency in descriptions of masking: the brief summary calls the study rater-blinded, whereas the registry masking entry is NONE. The record does not explain this difference or describe how rating was conducted. The formal eligibility criteria and the extent to which existing SSRI or SNRI treatment continued are not detailed beyond the summary description.

The endpoint population is described as LOCF if two initial visits were completed, but the record does not give the number of participants analyzed, missing-measurement counts, reasons for missingness, or sensitivity analyses. It also does not report the analysis model or multiplicity approach. Safety information is limited to participant counts, with no serious-event terms listed and deaths not reported in the registry record. These limitations restrict interpretation; they do not establish that any specific bias or safety issue occurred.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: An 8 Week Open-Label Study to Evaluate the Efficacy and Safety of Acamprosate Calcium (Campral) as Augmentation Therapy in Patients With Anxiety Symptoms Who Are Only Partial Responders to SSRI or SNRI Antidepressants — NCT00591565.
• Registry record last updated 2014-12-18; status last verified 2014-12.
• Results first posted 2014-12-18.
• 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 record describes a completed, prospective, open-label, single-group study of acamprosate tablets as augmentation therapy for patients with anxiety symptoms who were only partial responders to SSRI or SNRI antidepressants. It lists 13 participants enrolled and an 8-week study period. The primary endpoint is mean change from baseline at 8 weeks in the clinician-administered HAM-A scale, with standard deviation as the dispersion measure.

The registry does not report the numerical primary endpoint result or a statistical analysis. The endpoint population is described as LOCF if two initial visits were completed, but further missing-data and analysis details are not reported. Serious adverse events affected 0 of 13 participants at risk; other adverse events affected 2 of 13. Deaths are not reported in the registry record.

Because there is no separate comparator and no reported endpoint estimate, the posted information does not quantify change or establish a comparative treatment effect.