This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for D-cycloserine and Virtual Reality Exposure to Treat Iraq War Veterans With PTSD (NCT00356278), a randomized phase 2, phase 3 study. The primary outcome is Clinician-Administered PTSD Scale (CAPS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00356278 |
| Phase | Phase 2, Phase 3 |
| Condition | Stress Disorder, Post Traumatic |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 156 |
| Arms in the primary outcome | 3 |
| Lead sponsor | Emory University |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerns Iraq War veterans with post-traumatic stress disorder. The registry lists 156 participants as the enrollment and describes the primary outcome population as intent-to-treat analyses using all available information, with full information maximum likelihood estimation to handle missing data.
Intervention
One group received virtual reality exposure therapy (VRE) with D-cycloserine. The clinical question was whether adding D-cycloserine to VRE would reduce PTSD symptoms.
Comparator
The other groups received VRE with alprazolam or VRE with placebo. Thus, the registry describes comparisons among three medication conditions, all paired with VRE, rather than a comparison of VRE against no VRE.
Primary question
The stated study aim was to determine whether VRE combined with D-cycloserine would reduce PTSD symptoms in Iraq War veterans. The posted primary measure is the Clinician-Administered PTSD Scale (CAPS), but its stated timeframe is baseline. The registry record does not report a post-treatment CAPS result or a treatment-effect estimate for the primary question.
That distinction is central to interpreting the results. The baseline CAPS means describe symptom scores at the start of the trial; they do not show whether scores changed during treatment or whether change differed among the randomized groups. The record lists PTSD Symptom Scale Self-Report as a secondary outcome repeatedly, but does not provide associated secondary results in the information summarized for this analysis. It therefore supports a description of the trial question and baseline scores, but not a conclusion about the comparative effects of the treatment combinations.
3. Trial Design
This was a randomized, quadruple-masked, parallel-group trial sponsored by Emory University. The registry lists phase 2 and phase 3. The study began in 2006-09, had a primary completion date of 2014-06, and is marked completed. Its registered enrollment is 156.
All three groups received virtual reality exposure therapy. The first group received D-cycloserine, the second received alprazolam, and the third received placebo. The registry labels the comparison group as VRE Therapy and Placebo. This design can address the relative outcomes of these medication conditions when used alongside VRE, but the listed arms do not isolate the effect of VRE itself because VRE is present in every group.
Random allocation and quadruple masking are recorded, but the registry record does not report the allocation sequence method, allocation concealment procedure, or which roles were masked. The parallel model indicates that participants were assigned to a group rather than described as crossing among conditions. Further details about treatment delivery, dose, duration, visit schedule, and adherence are not reported in the registry record.
The group counts associated with the posted baseline CAPS results are 53 for VRE Therapy and D-cycloserine, 50 for VRE Therapy and Alprazolam, and 53 for VRE Therapy and Placebo. These counts accompany baseline outcome summaries and should not be treated as evidence of how many participants contributed to any unreported follow-up analysis. The registry record does not provide a treatment-group comparison for a post-baseline primary outcome.
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
| Stage | VRE Therapy and D-cycloserine | VRE Therapy and Alprazolam | VRE Therapy and Placebo |
|---|---|---|---|
| STARTED | 53 | 50 | 53 |
| COMPLETED | 28 | 35 | 34 |
| NOT COMPLETED | 25 | 15 | 19 |
Reasons for not completing this period:
| Reason | VRE Therapy and D-cycloserine | VRE Therapy and Alprazolam | VRE Therapy and Placebo |
|---|---|---|---|
| Withdrawal by Subject | 25 | 15 | 19 |
Analysis population for the primary outcome, as defined in the registry: Intent to Treat Analyses using all available information with Full Information Maximum Likelihood Estimation (FIML)to handle missing data
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.
| Characteristic | Unit | VRE Therapy and D-cycloserine | VRE Therapy and Alprazolam | VRE Therapy and Placebo | Total |
|---|---|---|---|---|---|
| Participants analysed | 53 | 50 | 53 | 156 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 53 | 50 | 53 | 156 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 4 | 1 | 3 | 8 |
| Sex: Female, Male: Male | Participants | 49 | 49 | 50 | 148 |
| Region of Enrollment: United States | participants | 53 | 50 | 53 | 156 |
6. Primary Endpoint
The registry lists the primary outcome as Clinician-Administered PTSD Scale (CAPS), measured over Baseline.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary measure is the Clinician-Administered PTSD Scale (CAPS), a continuous measure of PTSD symptom severity. The registry describes scores from 0 (no symptoms) to 136 (severe symptoms), based on the first 17 CAPS items administered. Higher scores therefore correspond to greater symptom severity within the stated scale description.
A clinician-administered symptom scale can quantify symptom burden using a consistent measure, allowing researchers to describe scores across participants and treatment groups. Because it is continuous, its result is summarized as a mean with a 95% confidence interval in the registry record. A confidence interval conveys uncertainty around an estimated mean; it is not a range containing every participant’s score.
The registered timeframe for this primary outcome is baseline. That makes the posted means useful as descriptions of starting symptom scores, not as evidence of symptom reduction during treatment. The record does not report a post-treatment CAPS mean, a change-from-baseline result, or an estimated between-group treatment effect for this primary endpoint. The intent-to-treat description says all available information was used, with full information maximum likelihood estimation to handle missing data, but the detailed estimation procedure is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary outcome values are baseline CAPS means. For VRE Therapy and D-cycloserine, the mean is 85.3 units, with a 95% confidence interval from 79.3 to 91.9. For VRE Therapy and Alprazolam, the mean is 88.0 units, with a 95% confidence interval from 82.3 to 93.6. For VRE Therapy and Placebo, the mean is 82.6 units, with a 95% confidence interval from 75.8 to 89.4. Each interval describes uncertainty around its group’s estimated baseline mean.
These values do not answer whether one treatment combination reduced symptoms more than another. The registered timeframe is baseline, and the posted results do not include follow-up CAPS values, changes from baseline, or a treatment contrast. In particular, the baseline means must not be interpreted as treatment responses or as evidence of comparative efficacy. The registry record also does not report a primary-outcome hypothesis test or a confidence interval for a treatment effect.
The confidence intervals communicate precision for the group means, but not the full spread of individual scores. They are not standard deviations, and the record does not give standard deviations for these groups. Nor should the intervals be used as a substitute for a direct statistical comparison. A group comparison requires an estimate of the difference or another prespecified contrast, together with its uncertainty and analysis details; such a result is not reported in the registry record.
The results are therefore descriptive at baseline. They document the symptom-score levels reported for each randomized group at the stated starting assessment. Although randomization is part of the trial design, a baseline-only summary does not establish how the groups’ symptoms subsequently changed. It also does not establish that any observed baseline differences were statistically meaningful. No numerical difference or ratio between the posted means is calculated.
The registry lists 10 outcome measures and five posted secondary outcomes, with PTSD Symptom Scale Self-Report named for those secondary outcomes. It reports zero analyses in the analysis listing. This means a set of outcome-specific analysis results is not available in the registry record; it does not establish whether analyses were conducted elsewhere. The posted information is thus insufficient to assess the stated treatment question, rather than evidence for or against a treatment effect.
9. Statistical Methods Explained
What does a mean describe?
For a continuous outcome, the mean is an average on the outcome’s scale. Here, the CAPS is reported in units on a scale whose stated range is 0 to 136, with higher scores described as more severe symptoms. A mean gives a concise summary of a group’s scores, but it does not show the distribution of individual scores. Participants may have scores above and below the mean, and the mean alone does not describe how widely those scores vary. The registry’s outcome summaries do not report a standard deviation or another measure of individual-level dispersion.
What does a 95% confidence interval mean?
A confidence interval expresses uncertainty around an estimated quantity, in this case each group’s baseline mean. In general statistical terms, a narrower interval indicates greater precision for that estimate under the method used, while a wider interval indicates less precision. The interval is not a statement that most individual participants had scores inside its limits. It also is not a direct interval for a comparison between groups. The registry lists a 95% confidence interval as the dispersion measure for these results, but does not describe how the interval was calculated.
Why does the outcome timeframe matter?
The timeframe attached to an outcome defines when the measurement applies. The CAPS timeframe in this record is baseline. Baseline summaries describe the measurement at the start of the study; they do not show subsequent change. A claim about reduction during treatment would require a relevant later measurement or a change estimate, and an assessment of how those results compare across randomized groups. Those results are not reported in the registry record. Consequently, the baseline mean and its confidence interval should be read as starting-point descriptions only.
What is the intent-to-treat and FIML description?
The record describes the primary outcome population as intent to treat, using all available information, and says full information maximum likelihood estimation (FIML) was used to handle missing data. In general, an intent-to-treat approach aims to analyze participants according to their randomized group, preserving the comparison created by randomization. FIML is a statistical approach that can use available observations in estimating a model when some outcome data are missing, subject to assumptions about the data and the model. It is not equivalent to filling in each missing score with a simple value. The registry record does not describe the model, missingness assumptions, amount or pattern of missing data, or sensitivity analyses, so the precise implementation and robustness cannot be assessed.
What can the randomized, masked design establish?
Randomization is intended to make treatment groups comparable at the point of assignment, on average, by allocating participants through chance. Masking is intended to limit influences on care, measurement, or reporting when people involved do not know the assigned condition. The registry identifies the trial as randomized and quadruple masked, but does not report the sequence-generation or concealment procedures, or specify which people were masked. The parallel design assigns groups to different medication conditions alongside VRE. Because VRE appears in each arm, the listed contrasts concern medication conditions in the context of VRE, not VRE versus no VRE.
How should planning illustrations be read?
The record describes sample-size planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The target effect is described as a stated fraction of the observed effect. These are planning assumptions, not evidence about the trial’s original design or its observed power. The registry record does not report the trial’s own sample-size justification or the statistical plan behind its design. Any planning result based on an observed effect is illustrative: it depends on the effect estimate used and should not be presented as a measured probability that the completed trial detected an effect. No planning estimate is inferred or recalculated in this explanation.
Why are direct comparisons needed?
To evaluate a treatment question, an analysis generally needs to estimate a contrast between relevant randomized groups at an appropriate outcome time, then quantify uncertainty around that contrast. A direct contrast can use a model appropriate to the outcome and design, while accounting for the analysis population and missing observations as specified. The registry record does not report such a post-baseline CAPS contrast, its model, or a test result. The reported group means and confidence intervals therefore cannot be converted into a claim about a treatment difference by visual inspection or by subtracting the means. The record’s analysis listing contains zero analyses, and it notes that values are missing or not estimable for a two-arm comparison of a continuous endpoint. These omissions restrict interpretation to the baseline summaries and registered design information.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 10 outcome measures and five secondary outcomes, each described as PTSD Symptom Scale Self-Report. It does not report the detailed outcome definitions, timeframes, analysis results, or a statistical plan explaining how multiple outcomes were handled. When a study assesses multiple outcomes, or makes multiple comparisons, the chance of obtaining at least one apparently notable result can increase. General approaches to this issue include prespecifying a primary comparison or adjusting inference, but the registry record does not say whether such an approach was used. No multiplicity adjustment can therefore be attributed to this trial from the posted record.
For the primary outcome, the record describes intent-to-treat analyses using all available information and FIML to handle missing data. That is relevant to the analysis population and missing observations, but it does not reveal how much data were missing, why they were missing, whether assumptions were checked, or whether sensitivity analyses were performed. Those details are not reported in the registry record.
The record reports zero analyses in its analysis listing, and the posted information does not contain secondary-outcome estimates. This absence should be read as a lack of reported analysis results in the registry record, not as proof that no analyses occurred. The primary CAPS result is at baseline, and no post-baseline primary treatment comparison is reported. Without the analysis plan and relevant outcome estimates, it is not possible to assess prespecification, multiplicity handling, or the consequences of missing data for treatment-effect inference.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| VRE Therapy and D-cycloserine | 0 | 53 | 0.0% |
| VRE Therapy and Alprazolam | 0 | 50 | 0.0% |
| VRE Therapy and Placebo | 0 | 53 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| VRE Therapy and D-cycloserine | 0 of 53 |
| VRE Therapy and Alprazolam | 0 of 50 |
| VRE Therapy and Placebo | 0 of 53 |
The adverse-event figures list zero participants affected by serious adverse events in the D-cycloserine group, among 53 at risk; zero in the alprazolam group, among 50 at risk; and zero in the placebo group, among 53 at risk. The figures also list zero participants affected by other adverse events in each group, with the same group-specific numbers at risk. These are the counts recorded in the registry results; they should not be taken to establish that no events occurred outside the reported definitions, observation period, or reporting process.
The registry record does not report the adverse-event timeframe, event definitions, ascertainment procedures, or a detailed breakdown of non-serious events. No serious-event terms are listed. Death counts are not reported in the registry record. A zero affected count is a count, not a guarantee of zero risk, and the record does not provide an estimate of uncertainty for these safety figures. The available information supports only a description of the posted counts, not a broad comparison of safety among the groups.
12. What the Result Does, and Does Not, Mean
The posted results mean that the registry contains baseline CAPS summaries for three randomized groups receiving VRE alongside D-cycloserine, alprazolam, or placebo. The reported group means and 95% confidence intervals describe baseline symptom scores. They provide information about the starting measurements and their statistical precision as estimated means.
They do not show whether symptoms improved after treatment, whether the change differed by group, or whether D-cycloserine altered the effect of VRE. The primary outcome timeframe is baseline, and no post-treatment CAPS result or treatment-effect estimate is reported. The baseline results cannot be substituted for a treatment comparison, even though the trial was randomized and masked.
The record also does not establish that the groups were exactly alike at baseline, nor does it provide a formal test of baseline differences. A baseline mean is a descriptive statistic, not an outcome of treatment. Likewise, the absence of posted analysis results does not prove that no statistical analyses were undertaken; it means those analyses are not reported in the registry record.
The adverse-event counts document zero affected participants in the posted serious and other event categories for each arm, but the registry record does not provide the definitions and observation details needed to interpret those counts fully. Death counts are not reported. These safety summaries should therefore be understood as limited registry reporting, not as proof of an absence of harm.
Overall, the record describes a completed randomized trial and its baseline primary-outcome measurements, but it does not report the follow-up evidence needed to answer the stated comparative treatment question. No conclusion about symptom reduction or relative treatment effects follows from these baseline values alone.
13. Why This Trial Matters Statistically
This trial is statistically important to interpret carefully because the headline research question concerns symptom reduction, while the posted primary endpoint is explicitly measured at baseline. That mismatch between the intended clinical question and the available primary-outcome result sharply limits what can be learned from the reported numbers. It illustrates why outcome timeframes matter as much as outcome names: a valid measure taken before treatment cannot itself quantify a treatment response.
The study’s randomized, quadruple-masked, parallel design is relevant to the intended comparison among VRE medication combinations. Yet a design label does not replace the results of a comparison. Statistical interpretation requires estimates at an appropriate follow-up time, a clearly defined contrast, and uncertainty around that contrast. Those items are not reported in the registry record. The baseline means and confidence intervals should not be used to manufacture a treatment effect.
The record also highlights the importance of transparent reporting. It identifies a primary outcome, multiple outcome measures, an intent-to-treat population, and FIML for missing data, but does not provide the detailed analysis plan or posted analysis results. Without those details, readers cannot evaluate model choices, multiplicity handling, or the sensitivity of findings to missing observations. This is a general lesson in trial reporting: design and methods information helps frame a question, but conclusions depend on outcome-specific results and sufficiently described analyses.
For researchers and clinicians reading registry data, the distinction between “not reported” and “no effect” is essential. Here, the record provides baseline descriptions and limited adverse-event counts, not a reported comparative treatment result. Recognizing that boundary avoids overstating what the data establish.
14. 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 limitation is that the posted primary CAPS results are baseline measurements, while the study aim concerns symptom reduction. The registry record does not report a post-treatment CAPS result, a change estimate, or a direct treatment comparison. Consequently, the central comparative question cannot be answered from the posted primary-outcome data.
Further details needed to evaluate the study are not reported in the registry record. These include the treatment dose and duration, visit schedule, allocation sequence and concealment procedures, the specific roles included in quadruple masking, and the statistical model used for the primary analysis. The record describes FIML for missing data but does not give the amount or pattern of missingness, the assumptions used, or sensitivity analyses. The sample-size justification and the trial’s detailed statistical plan are also not reported.
The registry lists 10 outcome measures and five secondary outcomes, but does not provide results for the secondary outcomes in the information. The record also does not explain how multiplicity was handled. For safety, affected counts are posted, but event definitions, observation timeframe, and death counts are not reported. These omissions limit interpretation of both efficacy and safety reporting.
Finally, the baseline means and their confidence intervals summarize group averages, not individual score distributions. The record does not provide standard deviations or other measures of score dispersion. These limitations do not establish that the trial had no findings; they define what can be concluded from the results reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: D-cycloserine and Virtual Reality Exposure to Treat Iraq War Veterans With PTSD — NCT00356278.
- Registry record last updated 2016-01-08; status last verified 2016-01.
- Results first posted 2014-11-19.
- 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.
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18. Record Summary
NCT00356278 is a completed randomized, quadruple-masked, parallel-group phase 2 and phase 3 trial sponsored by Emory University. The registered enrollment is 156, and the study dates are 2006-09 to primary completion in 2014-06. Each arm received VRE with D-cycloserine, alprazolam, or placebo.
The primary outcome is the CAPS, reported as a continuous score from 0 to 136, with a baseline timeframe. The registry gives a mean and 95% confidence interval for each group, but does not report a post-baseline primary outcome comparison. It describes intent-to-treat analyses using FIML for missing data. Five secondary outcomes are listed, and the analysis listing reports zero analyses.
Posted adverse-event counts show zero affected participants in the serious and other event categories in each group; death counts are not reported. The registry record supports descriptions of trial design, baseline scores, and posted safety counts, but does not report results that answer whether the treatment combinations differed in symptom reduction.