Substance P Antagonist in the Treatment of Posttraumatic Stress Disorder: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Substance P Antagonist in the Treatment of Posttraumatic Stress Disorder (NCT00383786), a randomized phase 2 study. The primary outcome is Changes in CAPS Scores..

2. Clinical Question

3. Trial Design

This was a phase 2, randomized, triple-masked, parallel-group study of GR205171 for PTSD. The registry lists Baylor College of Medicine as the sponsor and describes the study as conducted at the NIH and the Mount Sinai School of Medicine. The record lists enrollment of 47 and a completed status. The recorded start was 2006-09, and primary completion was 2009-06.

The registry’s brief description states that participants were initially given placebo and then randomly assigned at some point within the first 3 weeks either to GR205171 or to continue placebo. It describes the remainder of the treatment period as 10 weeks. Separately, the arm descriptions specify GR205171 or placebo for 8 weeks, and the primary outcome timeframe is baseline and 8 weeks. These descriptions do not fully align on treatment duration; the record does not explain the difference.

The primary analysis included 20 participants in the GR205171 group and 19 in the placebo group. The registry says 2 of the 22 randomized to GR205171 and 6 of the 25 randomized to placebo were excluded because they did not receive a week 1 assessment. Thus, the posted primary outcome comparison is based on fewer participants than were randomized to the respective groups.

Participants were scheduled for weekly clinic visits during treatment, with interviews, self-report questionnaires, and psychiatric rating scales at every visit. Physical examinations and blood and urine tests were also listed. Follow-up visits were described as continuing for up to 3 months after treatment, with standard clinical treatment offered during follow-up. The registry does not report the randomization procedure, how masking was implemented, or the original design assumptions.

4. Participant Flow and Accounting

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

Before assignment: Of 235 potential participants screened for eligibility, 171 (73%) were excluded prior to placebo lead-in. 128 did not meet eligibility criteria, 24 were lost to follow-up, and 19 withdrew consent. Sixty-four patients began placebo lead-in, of whom 47 patients (73%) were randomized (11 were ineligible and 6 withdrew consent).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 20 patients randomized to drug were included in the primary analysis as 2 our of the 22 randomized were excluded because they did not receive a week 1 assessment. 19/25 randomized to placebo were included in the analysis after 6 were excluded due to not receiving week 1 assessments.

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 Changes in CAPS Scores., measured over Baseline, 8 weeks.

The primary endpoint was change in Clinician-Administered PTSD Scale (CAPS) scores, measured at baseline and 8 weeks. CAPS is described in the registry as a structured interview used to assess PTSD symptoms and corresponding to the DSM-IV criteria. Its core symptom scale measures the frequency and intensity of symptoms. The record describes the full score range as 0 to 136, with 0 indicating the best possible outcome and 136 the worst possible outcome.

Using a clinician-administered symptom scale gives the trial a defined way to quantify symptom severity rather than relying only on a general impression of improvement. Comparing the group means at the specified timepoint describes the average scores in the analyzed treatment groups. The reported standard deviations describe the spread of scores among participants within each group; they are not the uncertainty around the group mean.

The endpoint is reported as a mean, so the main contrast concerns average scores rather than the proportion of participants meeting a response threshold or diagnostic criteria. The registry gives the scale’s diagnostic context but does not report a clinically important difference threshold for interpreting a change in score. Nor does it provide individual participant trajectories or the distribution of score changes. The posted summary therefore supports interpretation of the group-level means and their estimated difference, but not a detailed account of how many individuals improved or how changes varied across participants.

7. Results Posted in the Registry

• GR205171: mean 43.50 versus 51.10 on control; difference -7.60 (95% CI -11.00 to -4.20), standardized effect d = -1.41; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: each participant’s CAPS score is numerical, and the registry reports group means and standard deviations. A mean is the arithmetic average within a group. A standard deviation describes how dispersed individual scores are around that average. A larger standard deviation indicates greater variation among observed scores; it is not an interval around the mean and should not be read as a confidence interval.

What does the mean difference represent?

The reported mean difference compares the GR205171 mean with the placebo mean, with the direction expressed as GR205171 minus placebo. The estimate of -7.6 corresponds to the reported means of 43.5 and 51.1. The negative sign indicates a lower average score in the GR205171 group, and lower scores are described as better on the CAPS scale. The estimate concerns the difference between group averages, not the change experienced by every participant and not a percentage change.

The outcome title refers to changes in CAPS scores, and the timeframe identifies baseline and 8 weeks. However, the posted group values are presented as means and standard deviations, and the registry record does not separately show baseline means, group-specific changes from baseline, or a model estimating change adjusted for baseline. The comparison should therefore be described according to the reported estimate rather than assigning it an unreported adjustment or analysis method.

How should the p-value be read?

The unadjusted p-value is <0.001. In general, a p-value measures how unusual the data, or data at least as incompatible with a specified null model, would be if that model were true and the test assumptions held. It is not the probability that the treatment has no effect, and it does not measure the probability that the finding will replicate. The word “unadjusted” matters because the registry does not describe a correction for testing multiple outcomes or comparisons in this result.

Statistical significance and clinical importance are different questions. A small p-value does not establish that a score difference is important to patients, and a mean difference alone does not show how many participants experienced a meaningful change. The registry does not give a minimum clinically important difference or a responder definition for this endpoint.

Why does randomization matter?

In general, random assignment is intended to make comparison groups similar, on average, with respect to factors known and unknown at the time of assignment. This supports interpretation of differences between groups as related to assigned treatment, provided the analysis and follow-up preserve the randomized comparison. Here, the primary analysis excluded participants lacking a week 1 assessment. Excluding participants after randomization can weaken comparability if inclusion is related to prognosis, treatment, or the outcome. The record does not report enough information to determine whether that occurred.

The registry identifies the design as randomized, triple-masked, and parallel, but does not state the random sequence method, allocation concealment procedure, which people were masked, or whether masking remained intact. These are relevant design details, but their absence from the registry record does not establish that the procedures were or were not adequate.

What do the confidence limits add?

In general, a confidence interval combines an estimate with a range of values compatible with the data and the method used to calculate the interval. It conveys uncertainty about the group contrast more directly than a p-value alone. The reported interval runs from -11.0 to -4.199, entirely on the negative side of zero. This is consistent with a lower mean score in the GR205171 group for the reported comparison. The confidence level and the exact interval procedure are not reported in the registry record, so they should not be inferred.

Standard deviations and confidence intervals answer different questions. The group standard deviations, 5.1 for GR205171 and 5.7 for placebo, describe participant-to-participant variation. The confidence interval around the mean difference describes uncertainty in the estimated contrast. A relatively narrow interval can support greater precision about the group difference than a wide interval, but precision does not remove uncertainty due to missing data, selection, measurement, or the design’s applicability beyond the study.

What is not documented?

The registry record does not report the statistical analysis plan, the test or model used for the primary comparison, any baseline adjustment, assumptions checked for the analysis, an approach to missing outcome data, or an interim analysis plan. It also does not report how the original sample size was justified. General methods such as modeling repeated measurements or adjusting for baseline can be useful in clinical research, but there is no basis in this record to say that the trial used them.

The primary comparison has a single posted unadjusted p-value, while the record lists two outcome measures and no posted secondary results in this analysis. Without a prespecified hierarchy or multiplicity plan, the extent of adjustment across all planned tests is unknown. The reported result should be interpreted as the endpoint comparison available in the registry, not as proof that every possible analysis or outcome was accounted for.

10. Confidence Intervals and Precision

The estimated mean difference is -7.6 CAPS points, with a confidence interval from -11.0 to -4.199. The interval gives a range of values compatible with the estimate under the method used. Its endpoints are both negative, so the reported interval supports a lower mean score in the GR205171 group for this comparison. The registry does not report the confidence level or the procedure used to construct the interval; these should not be assumed.

Precision concerns how tightly an estimate is determined, not whether it is clinically important or free from bias. The reported standard deviations are 5.1 for GR205171 and 5.7 for placebo. These describe spread in participant scores, while the interval describes uncertainty around the difference in group means. The analysis included 20 participants in the GR205171 group and 19 in placebo, after exclusions for lack of a week 1 assessment. The small analysis groups make it especially useful to consider the interval rather than focusing only on the p-value.

The interval does not account for every possible source of uncertainty. In particular, the registry record does not explain missing outcome handling, provide group-specific baseline and follow-up distributions, or document the analysis model. It also does not identify a clinically important threshold for CAPS scores. Thus, the interval conveys statistical uncertainty in the posted contrast, but it cannot alone resolve the importance of the difference or the effect of exclusions and other design limitations.

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 planning figures are participants per arm, not total events. They illustrate the group size that a future two-arm study might require under the stated planning assumptions; they are not a record of the number enrolled in this trial. The calculations use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set as a stated fraction of the observed effect.

For planning around 100% of the observed effect, the figures are 8 participants per arm for 80% power and 11 participants per arm for 90% power. For planning around 75% of the observed effect, they are 15 participants per arm for 80% power and 19 participants per arm for 90% power. For planning around 50% of the observed effect, they are 32 participants per arm for 80% power and 43 participants per arm for 90% power.

In general, a power target describes the chance that a study will detect an effect of the specified size at the chosen significance level, if that effect is present and the assumptions hold. The 80% and 90% columns represent different planning targets: 90% power calls for more participants per arm than 80% power for the same assumed effect. Smaller effects need more participants because they are harder to distinguish from random variation. These figures are planning illustrations based on the observed effect, not observed power. The registry record does not report the assumptions or justification used for the trial’s original design.

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 = -7.600; pooled standard deviation σ = 5.400.
2. n = 2 × (1.96 + 0.842)² × 5.400² / -7.600² = 7.9, rounded up to 8 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 <- -7.6                      # observed difference in means
sigma <- 5.40022522052853                     # 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(383786)
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 = 8 (80% power), 11 (90% power)
 75% of observed effect: n per arm = 15 (80% power), 19 (90% power)
 50% of observed effect: n per arm = 32 (80% power), 43 (90% power)
power.t.test: 9 
Simulated power at n = 8 per arm: 0.745 (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 record identifies changes in CAPS scores as the primary outcome and lists two outcome measures, but the record summarized for this analysis contains no posted secondary outcome results. It reports an unadjusted p-value for the primary comparison. It does not report whether there was a prespecified hierarchy of outcomes, a multiplicity adjustment, or a broader statistical analysis plan.

In general, when researchers test multiple outcomes, timepoints, or comparisons, the chance of at least one apparently unusual result can increase if every test is interpreted independently. A prespecified strategy can clarify which result is primary and how additional results are treated. Without that strategy in the registry record, it is not possible to determine what set of tests was planned, whether the primary test was selected before outcomes were examined, or whether any adjustment was intended.

The analysis population also requires attention. The registry says participants without a week 1 assessment were excluded from the primary analysis: 2 of 22 randomized to GR205171 and 6 of 25 randomized to placebo. The record does not report an intention-to-treat analysis including all randomized participants, an alternative analysis of those excluded, or the reasons for missing week 1 assessments beyond their absence. It does not describe imputation, likelihood-based handling, or sensitivity analyses for missing outcome data. Those methods are general options, not methods that can be attributed to this study.

Randomization supports a fair comparison at assignment, but post-randomization exclusions can affect that comparison. If missing assessments are related to treatment or likely outcomes, the included groups may differ in ways that influence the result. The registry record does not provide enough information to assess that possibility. The original sample-size justification, interim analyses, and stopping rules are also not reported in the registry record.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events in the GR205171 group, with 22 participants at risk, and zero in the placebo group, with 25 participants at risk. These are serious-event counts in the posted safety summary; zero reported events does not establish that no other safety concerns occurred or that the treatments have equivalent safety.

The record also lists other adverse events for 13 of 22 participants at risk in the GR205171 group and 6 of 25 at risk in placebo. These are separate from the serious adverse event counts. The registry does not provide event-level descriptions, severity grading for these other events, attribution to treatment, or the timing and duration of events in the registry record used for this analysis. No serious adverse event terms are listed.

Deaths are not reported in the registry record. The safety figures should be read alongside the study’s size and the available follow-up description, not as a complete safety profile. Counts alone do not establish whether an event was caused by treatment, and the registry summary does not support a comparative safety conclusion.

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

The posted primary result is a mean CAPS score of 43.5 in the GR205171 analysis group and 51.1 in the placebo analysis group at the reported endpoint. The estimated mean difference is -7.6, with a confidence interval from -11.0 to -4.199 and an unadjusted p-value of <0.001. Since lower CAPS scores are described as better, the observed group means and estimated contrast favor a lower average score in the GR205171 group in this analysis.

That statement is specific to the reported endpoint and analysis population. It does not show that every participant improved, establish how many participants had a meaningful change, or describe outcomes beyond the CAPS score. The registry record does not report a clinical importance threshold, a responder analysis, or posted secondary outcome results in this analysis. The confidence interval expresses uncertainty in the estimated group contrast under the method used, but its confidence level is not reported.

The result does not by itself establish whether the difference would persist beyond the stated assessment, whether it generalizes to other settings or populations, or how it compares with other treatment options. The registry record describes follow-up visits but does not post a follow-up efficacy result in the registry record for this comparison. It also does not provide enough detail to evaluate the effect of excluding participants without week 1 assessments.

The finding should not be converted into a claim that GR205171 works or does not work. The available result is a statistical comparison in a phase 2 trial with a limited analysis population and incomplete documentation of the analysis plan. Its meaning depends on the endpoint, the exclusions, and the uncertainty around the estimate, as well as on information that is not reported in the registry record.

16. Why This Trial Matters Statistically

This trial is statistically informative because it reports a continuous symptom-scale outcome as group means and standard deviations, along with a mean difference and a confidence interval. That combination makes it possible to distinguish the estimated direction and size of the contrast from the variation in individual scores and from the uncertainty in the estimated contrast. The p-value alone would not convey all of those features.

The record also illustrates why analysis populations matter in randomized studies. The primary comparison excludes participants who lacked a week 1 assessment, and the numbers excluded differ between the groups. Randomization applies to assignment, while the analysis reflects the participants retained for the endpoint. Understanding how post-randomization exclusions may influence comparability is essential to interpreting the result.

There is also an important distinction between a statistically clear contrast and a clinically meaningful one. The reported interval lies below zero, but the registry does not provide a clinical importance threshold for the CAPS scale. A statistically supported difference is not, by itself, evidence about whether the magnitude matters to patients or whether it translates into wider functioning or lasting change.

Finally, the planning illustrations show how assumed effect size and desired power influence sample-size planning. They are based on the observed effect and stated assumptions, not on the original trial design. Treating them as prospective design requirements would ignore the uncertainty in the observed effect and the fact that the trial’s own sample-size assumptions are not reported in the registry record.

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 primary analysis did not include every randomized participant. The registry reports that 2 participants randomized to GR205171 and 6 randomized to placebo were excluded because they did not receive a week 1 assessment. The reasons for missing those assessments, their later outcome availability, and the consequences of excluding them are not reported in the registry record. This limits assessment of whether the analyzed groups remained comparable after randomization.

The registry gives the primary endpoint timeframe as baseline and 8 weeks, but the posted summary does not include group-specific baseline scores or a separate estimate of change from baseline. It is therefore not possible from this record to determine whether the reported mean contrast was adjusted for baseline or to assess the baseline score balance. The analysis model and its assumptions are also not reported.

The treatment-duration descriptions are not fully aligned. The brief description refers to a 10-week treatment period, while the arm descriptions specify 8 weeks and the endpoint is assessed at 8 weeks. The registry record does not explain this difference. The record also does not report the random sequence method, allocation concealment, details of masking, or the original statistical plan.

The outcome summary does not provide an interpretation threshold for clinically important change, individual participant outcomes, or posted secondary results in this analysis. The confidence level for the reported interval is not reported. Safety information is limited to counts of serious and other adverse events; deaths are not reported in the registry record. These limitations restrict what can be concluded from the posted result and do not establish that unreported procedures or data were absent.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Substance P Antagonist in the Treatment of Posttraumatic Stress Disorder — NCT00383786.
• Registry record last updated 2019-07-31; status last verified 2019-07.
• Results first posted 2014-01-31.
• 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

The registry record describes a completed, randomized, triple-masked, parallel phase 2 trial of the NK1 antagonist GR205171 for PTSD, sponsored by Baylor College of Medicine. It lists enrollment of 47, a recorded start of 2006-09, and primary completion of 2009-06. The primary outcome was CAPS score at baseline and 8 weeks.

The primary analysis included 20 participants assigned to GR205171 and 19 assigned to placebo. Their reported mean scores were 43.5 and 51.1, respectively, with standard deviations of 5.1 and 5.7. The mean difference was -7.6, with a confidence interval from -11.0 to -4.199 and an unadjusted p-value of <0.001. The registry reports zero serious adverse events in either group and other adverse events in 13 of 22 at risk for GR205171 and 6 of 25 at risk for placebo. Several details needed to assess the analysis, missing data, multiplicity, and original design assumptions are not reported in the registry record.