Virtual Reality & D-cycloserine (DCS) for Posttraumatic Stress Disorder (PTSD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Virtual Reality & D-cycloserine (DCS) for Posttraumatic Stress Disorder (PTSD) (NCT00632632), a randomized na study. The primary outcome is Clinician Administered PTSD Scale(CAPS).

2. Clinical Question

3. Trial Design

This was a randomized, quadruple-masked, parallel-group study listed as completed. The registry reports enrollment of 25 participants and identifies D-cycloserine (DCS) and placebo as the two interventions. The posted primary outcome includes 13 participants in the DCS group and 12 in the placebo group. The registry record does not explain which roles were masked or how masking was implemented, and it does not provide further details about randomization procedures.

The study summary describes participants with PTSD following either the events of September 11, 2001, or military service in the war in Iraq. It proposes evaluating DCS combined with virtual reality exposure therapy. The arm descriptions themselves are blank, so details such as the therapy schedule, treatment dose, and the relationship between the drug and therapy sessions are not reported in the registry record.

The registry lists a start of 2005-01 and primary completion of 2012-12. It gives the trial phase as NA. The reported primary endpoint is mean CAPS severity immediately following treatment. Other aims in the study summary include symptom change over time, symptomatology at a six-month follow-up, and whether the BDNF Val66Met single nucleotide polymorphism predicts response. The posted results do not report findings for those aims.

The record lists one secondary outcome, the Structured Clinical Interview for DSM-IV - Major Depressive Disorder (SCID-MDD), and three outcome measures overall. It does not report an analysis count. The registry record does not give the trial's original sample-size justification, detailed analysis plan, or further information on how participants were followed or included in analyses.

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

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 Clinician Administered PTSD Scale(CAPS), measured over Immediately following treatment.

The primary endpoint is the Clinician Administered PTSD Scale (CAPS) total severity score immediately following treatment. It is a continuous measure reported as a group mean and standard deviation. The record states that the total score ranges from 0-136 and that higher values indicate worse outcomes, meaning greater severity of posttraumatic symptoms.

CAPS combines three symptom-cluster subscales into a total severity score: cluster B for reexperiencing symptoms, cluster C for avoidance and numbing symptoms, and cluster D for hyperarousal symptoms. The registry gives ranges of 0-40, 0-56, and 0-40 for those subscales, respectively.

Using a continuous score retains information about the degree of reported symptom severity rather than reducing participants to categories. Comparing group means is one way to describe the average score in each arm and the difference between those averages. The scale's direction is important when interpreting that difference: a lower mean represents less measured symptom severity. The endpoint is assessed immediately following treatment, so it describes that time point rather than establishing how outcomes changed during treatment or persisted later. Although the study summary mentions a six-month follow-up aim, follow-up results are not reported in the registry record.

7. Results Posted in the Registry

• D-Cycloserine (DCS): mean 32.38 versus 42.17 on control; difference -9.79 (95% CI -29.25 to 9.67), standardized effect d = -0.39; z-test p = 0.324.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous, and the registry reports its mean and standard deviation separately for the two randomized groups. A mean describes the group's average CAPS score; the standard deviation describes the spread of individual scores around that average. The posted means are 32.38 for DCS and 42.17 for placebo, with standard deviations of 28.55 and 20.75, respectively. Since higher CAPS scores indicate worse severity, the direction of the group means has a straightforward descriptive interpretation. Still, a mean comparison does not show the range of individual responses or whether the score distributions have a particular shape.

What does the mean difference represent?

The posted contrast is DCS minus placebo, with an estimate of -9.79. A negative estimate means that the observed average score was lower in the DCS group. The contrast is in CAPS score units and retains the endpoint's direction: lower scores mean less measured symptom severity. The estimate is a summary of the observed groups, not an explanation of why their means differ. Random assignment is intended to support a causal comparison, but the registry record does not provide enough detail about implementation, analysis populations, or missing observations to assess all features of that comparison.

How should the p-value be read?

The unadjusted p-value is 0.324. In general, a p-value describes how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the test assumptions held. It is not a measure of effect size, the probability that the observed result arose by chance, or the probability that a treatment works. A p-value also does not show whether an estimate is precise. The registry record does not report the test procedure or assumptions used for the posted comparison, so those details should not be inferred.

What does an interval add?

The mean-difference interval runs from -29.25 to 9.67. In general, a confidence interval expresses uncertainty in an estimate under a statistical procedure and its assumptions. It identifies a range of values compatible with the observed data and method, rather than a guaranteed range for the true effect. Here the interval includes zero and spans negative and positive differences. That means the reported results do not pinpoint the direction of the underlying group difference. Its breadth is also important: plausible values across the interval differ substantially in direction and magnitude.

Why do variability and group size matter?

In general, the precision of a group comparison depends on how much observations vary and how many participants contribute data. Greater variability makes the average less informative about the group, while more observations can improve precision when other conditions are comparable. The posted standard deviations are large relative to the difference estimate, and the outcome counts are 13 and 12. These features help explain why the interval is broad, though the record does not report a formal decomposition of the uncertainty.

In general, over-dispersion occurs when observed variation is greater than a model expects. It can make standard errors too small if the model does not account for that extra variation. The registry record does not report a model-based analysis or an over-dispersion assessment, so this is a general statistical consideration, not a claim about this trial.

The posted comparison is identified as unadjusted. The record does not specify covariate adjustment, analysis population, missing-data methods, or a multiplicity strategy. There is therefore no basis to describe an adjusted estimate or to assert that multiple testing was controlled. The record also lists no analyses, so the exact statistical workflow underlying the posted summary is not reported in the registry record.

10. Confidence Intervals and Precision

The posted mean difference is -9.79 CAPS units, with an interval from -29.25 to 9.67. This interval is central to understanding precision. It is not confined to negative values: zero and positive values are also within its limits. Thus, the reported estimate does not narrowly establish which group had the lower underlying mean. In the negative direction, the contrast favors a lower score in the DCS group; in the positive direction, it favors a lower score in the placebo group, given the stated subtraction order and score direction.

In general, an interval reflects both the estimated effect and its uncertainty under a statistical method. A narrow interval indicates greater precision than a broad interval, assuming comparable methods and scales. The interval is broad, so a range of materially different differences remains compatible with the result. It should not be read as a probability statement that the true difference lies within these exact endpoints, nor as a clinical threshold. The registry record does not report a minimum clinically important difference against which the estimate could be judged.

The group sizes contributing to the posted primary outcome are 13 and 12, and the standard deviations are 28.55 and 20.75. In general, modest group sizes and variation in individual scores can limit precision. The available summary does not show individual observations, score distributions, or details of missingness, so it is not possible to assess whether a small number of observations strongly influenced the means.

The interval should be interpreted alongside the point estimate and the unadjusted p-value of 0.324, not in isolation. Together they describe an observed lower mean in the DCS arm but substantial uncertainty around the size and direction of the group contrast. They do not establish that there is no difference, and they do not demonstrate a dependable difference.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect, not the trial's original enrollment plan. The registry record does not report the original sample-size justification or its design assumptions. These illustrations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect targeted is the stated fraction of the observed effect.

The entries are participants per arm, not total participants and not total events. For planning around 100% of the observed effect, the illustration gives 104 participants per arm for 80% power and 139 participants per arm for 90% power. For planning around 75% of the observed effect, it gives 184 participants per arm for 80% power and 247 participants per arm for 90% power. For planning around 50% of the observed effect, it gives 414 participants per arm for 80% power and 554 participants per arm for 90% power.

In plain terms, the 80% power column indicates the approximate number of participants per arm that the planning method estimates would be needed to detect the specified effect with 80% power under the stated assumptions. The 90% column gives the corresponding illustration for 90% power. Higher planned power generally calls for more participants for the same target effect. The rows also illustrate that smaller effects need more participants to detect, all else held constant.

These figures are not observed power. They are prospective planning calculations using an effect estimated from this small trial, so the observed effect may not be a stable estimate for future planning. The curve is another presentation of the planning relationship and should be read in light of those same assumptions, rather than as a description of the trial's observed outcomes.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -9.790; pooled standard deviation σ = 25.124.
2. n = 2 × (1.96 + 0.842)² × 25.124² / -9.790² = 103.4, rounded up to 104 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -9.79                      # observed difference in means
sigma <- 25.1235360810812                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(632632)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 104 (80% power), 139 (90% power)
 75% of observed effect: n per arm = 184 (80% power), 247 (90% power)
 50% of observed effect: n per arm = 414 (80% power), 554 (90% power)
power.t.test: 104.3 
Simulated power at n = 104 per arm: 0.802 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and identifies one secondary outcome: the Structured Clinical Interview for DSM-IV - Major Depressive Disorder (SCID-MDD). It does not report a result for that secondary outcome. The study summary also describes aims involving symptom-change timing, six-month follow-up, and whether the BDNF Val66Met variant predicts response, but findings for those questions are not reported in the registry record.

When a study examines multiple outcomes, time points, subgroups, or analyses, the chance of at least one apparently notable result can increase. Statistical methods for multiplicity can account for a specified family of comparisons. The registry record does not report whether any such adjustment or prespecified hierarchy was used. The posted primary comparison is explicitly unadjusted; it should not be treated as evidence that multiplicity was addressed.

The record reports no analyses. It does not describe a statistical analysis plan, analysis population, handling of missing values, or whether outcomes were analyzed according to randomized assignment. These omissions limit the ability to determine how the reported means and contrast relate to the intended protocol analysis. The outcome counts are reported for each arm, but those counts alone do not establish whether all randomized participants had complete follow-up or how any missing outcome data were treated.

The record also does not report whether there were interim analyses, how the genetic predictor aim was analyzed, or whether subgroup analyses were planned. These details should not be inferred from the study summary. In the absence of reported methods, the unadjusted primary comparison can be described as posted, but its relationship to other potential analyses and decisions in the study remains unclear.

14. 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 adverse-event record lists 13 participants at risk in the DCS group and 12 in the placebo group. It reports zero participants affected by serious adverse events in each group and zero affected by other adverse events in each group. These entries describe what the registry record reports for the listed groups; they do not establish that no adverse events occurred outside the recorded categories or observation period.

The deaths field is not populated for either arm, so deaths are not reported in the registry record. The record does not provide event terms, severity definitions beyond the serious/other categories, exposure duration, or a detailed collection period. It also does not explain how events were solicited or whether any participants had incomplete safety follow-up.

Zero recorded affected participants should be read as a count in this registry entry, not as proof that an event is impossible or that the two groups have identical safety profiles. With the small recorded groups, absence of reported events provides limited information about uncommon events. The safety entries are descriptive and do not support a broad comparison beyond the reported counts.

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

The posted primary result describes a mean CAPS score of 32.38 in the DCS group and 42.17 in the placebo group immediately following treatment. The observed mean difference is -9.79, in the direction of a lower score in the DCS group, and higher scores represent greater symptom severity. The interval from -29.25 to 9.67 shows substantial uncertainty and includes both zero and values in the opposite direction. The unadjusted p-value is 0.324.

These statistics do not establish whether DCS changes PTSD symptoms, and they do not establish that there is no effect. They describe the posted primary comparison and its imprecision. The interval leaves room for a range of underlying differences; the point estimate alone should not be treated as the definitive effect. The registry record does not report a clinically important threshold that would show how to interpret a particular number of CAPS units in practical terms.

The stated primary time point is immediately following treatment. The study summary's aims about earlier symptom decrease, six-month outcomes, and prediction by BDNF Val66Met are not answered by this result, because results for those aims are not reported in the registry record. Nor can the primary outcome alone address every measure of mental health or longer-term outcomes.

The trial was randomized and masked, but the registry entry does not provide enough detail to evaluate implementation, missing data, analysis populations, or the full analysis plan. Those omissions matter when judging how broadly the posted estimate can be interpreted. The record's small outcome groups and broad interval mean that the primary comparison is best understood as an uncertain estimate rather than a conclusive finding in either direction.

The posted adverse-event counts are also limited: zero affected participants are listed in each group for serious and other adverse events, while deaths are not reported in the registry record. Those entries should not be generalized beyond the recorded categories and participants.

16. Why This Trial Matters Statistically

This trial is statistically informative because it shows the distinction between an observed group difference and a precise estimate of that difference. The DCS group had a lower mean CAPS score at the stated time point, but the interval extends from -29.25 to 9.67 and therefore does not pin down the direction of the underlying contrast. A point estimate can appear clear in direction while its uncertainty remains broad.

The endpoint is a continuous severity scale, and the registry reports group means and standard deviations. That makes it possible to interpret the group contrast in scale units and to consider the within-group variability. At the same time, the outcome counts of 13 and 12 are small, and the posted standard deviations show substantial variation in CAPS scores. The example illustrates why reporting uncertainty alongside means is necessary: the difference alone does not convey how much information supports it.

The planning illustrations also show how assumptions about the effect to detect affect the number of participants needed. Smaller target effects require larger per-arm planning figures in the listed scenarios. Because the illustrations use the observed effect from this trial, they should be treated as planning examples rather than a definitive design recommendation.

Finally, the registry record distinguishes between an aim and a reported result. It describes questions about symptom timing, follow-up, and genetic prediction, but posts no results for those aims. Statistical interpretation depends not only on a study's questions but on which outcomes, time points, and analyses are actually reported, along with the uncertainty and limitations of those estimates.

17. 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 registry entry provides limited detail about the trial's conduct and statistical methods. It reports randomization, quadruple masking, and a parallel design, but does not describe the randomization sequence, allocation concealment, which people were masked, or how masking was maintained. The arm descriptions are blank, leaving treatment procedures and the relationship between virtual reality exposure therapy and the assigned drug unclear.

The primary outcome comparison includes 13 participants in the DCS group and 12 in the placebo group. The interval is broad, and the available summary does not include participant-level data, distributions, or sensitivity analyses. The registry does not report missing-data handling or the analysis population, so the outcome counts cannot establish whether the results include every randomized participant.

The registry record does not report the original sample-size justification, a detailed analysis plan, adjusted estimates, or methods for managing multiple outcomes and time points. The posted p-value is unadjusted, and the record lists no analyses. As a result, it is not possible to determine whether the posted result reflects a prespecified analysis or how it relates to other analyses.

The study summary names several additional aims, including six-month follow-up and genetic prediction, but their results are not reported in the registry record. Only the immediate post-treatment primary result is available in the posted outcomes. The secondary outcome is named, but its result is not reported. Safety reporting is also limited: counts of affected participants are listed, but deaths are not reported and further event details are absent.

These limitations mean the posted statistics support a focused description of the primary comparison, not a complete evaluation of all study aims or methods.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Virtual Reality & D-cycloserine (DCS) for Posttraumatic Stress Disorder (PTSD) — NCT00632632.
• Registry record last updated 2015-08-27; status last verified 2015-07.
• Results first posted 2015-08-27.
• 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.

21. Record Summary

NCT00632632 is listed as a completed, randomized, quadruple-masked, parallel-group study sponsored by Weill Medical College of Cornell University. The record reports enrollment of 25 participants and lists D-cycloserine and placebo as the interventions. The stated population concerns PTSD following the events of September 11, 2001, or military service in the war in Iraq.

The primary outcome is mean CAPS total severity immediately following treatment. The posted means are 32.38 for DCS and 42.17 for placebo, with a mean difference of -9.79, an interval from -29.25 to 9.67, and an unadjusted p-value of 0.324. The record also names SCID-MDD as a secondary outcome, but does not report its result. Findings for the additional aims described in the study summary are not reported in the registry record.

The record lists a start of 2005-01 and primary completion of 2012-12. It does not report the original sample-size justification, detailed analysis plan, missing-data methods, or deaths.