Veteran Stress and Learning Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Veteran Stress and Learning Study (NCT00674570), a randomized phase 4 study. The primary outcome is Proportion of Maximum Skin Conductance Response (SCR) in Microsiemens (µS).

2. Clinical Question

3. Trial Design

This completed study, titled the Veteran Stress and Learning Study, is registered as a phase 4 randomized, triple-masked, parallel-group trial. Its official title describes the effects of hydrocortisone and D-cycloserine on fear extinction in veterans with posttraumatic stress disorder. The registry lists 111 participants enrolled and identifies the VA Office of Research and Development as the sponsor.

The three listed arms were hydrocortisone, D-cycloserine, and placebo. The registry summary says the study examined the medications in comparison with an inactive substance, using a computer-administered fear-learning and memory task. Randomization indicates that assignment was intended to use a chance-based process; the record does not report the allocation ratio or the specific randomization procedure. The record labels masking as triple, but does not identify which roles were masked or describe how masking was maintained.

The registry records the study as completed. Its listed start date is 2009-01-13 and its primary completion date is 2015-06-22. The record does not report the protocol details needed to interpret those dates as the duration of an individual participant’s treatment or follow-up.

The outcome description refers to skin-conductance measurements during fear conditioning, fear extinction, and extinction retention. There is an inconsistency in the record’s timing: the outcome timeframe states 15 minute measurement intervals on Study Days 7, 9, and 16, while the outcome description places extinction retention on day 11. The registry record does not explain or reconcile this difference. It also does not report details such as medication schedules, eligibility criteria, or the planned analysis populations.

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: Participation involved 4 study visits, with randomization to intervention arm and drug administration occurring on visit 3. The discrepancy between 111 participants who were initially enrolled and 106 at randomization resulted from 5 participants who dropped out between screening and visit 3, when they were to have been assigned into a group.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Proportion of Maximum Skin Conductance Response (SCR) in Microsiemens (µS), measured over 15 minute measurement intervals on Study Days 7, 9, and 16.

The primary endpoint is titled “Proportion of Maximum Skin Conductance Response (SCR) in Microsiemens (µS).” It is a continuous measure of skin conductance, a physiological signal collected during a fear-learning task. The outcome description says that a response score was calculated for conditioned stimuli by comparing the maximum skin-conductance level during the stimulus with the mean level immediately before it. It describes a separate calculation for the unconditioned response following the stimulus and the unconditioned stimulus. The responses were range corrected using each participant’s maximum response during acquisition trials.

The endpoint is used to quantify physiological responses across specified parts of the task, rather than to measure a clinical diagnosis or a participant’s overall symptoms. The record identifies results for the first and last conditioned-stimulus trials during fear conditioning and extinction, and for the first two trials during retention. Those repeated trials and phases can describe different aspects of responding, but the registry record does not report a single consolidated endpoint comparison.

The outcome is reported as a mean with standard error. In general, the mean summarizes the group’s average measured response, while the standard error describes the precision of that estimated mean. The record does not include the actual endpoint values or their uncertainty, so the magnitude and precision of the observed responses cannot be assessed from the registry information. The difference between the stated timeframe and the day identified for retention also makes the intended timing unclear.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, triple-masked, parallel-group study with hydrocortisone, D-cycloserine, and placebo arms. These design labels explain the broad structure of the comparison, but they do not supply the detailed statistical analysis plan. The registry record does not report the allocation ratio, the method used to generate or conceal assignments, the roles covered by masking, or the planned model for the primary analysis.

What does a continuous endpoint mean?

The primary outcome is continuous: it is expressed as a measured skin-conductance response rather than as a yes-or-no event. The registry identifies the summary parameter as a mean. In general, a mean is the arithmetic average of the observations included in a group summary. It can help describe the typical level in the analyzed observations, but it does not show the spread of individual responses on its own. The registry identifies standard error as the dispersion measure accompanying the mean. In general, standard error describes uncertainty in an estimated mean, not the range of individual participant values. The record does not report the individual-level data or any separate measure of participant-to-participant variability.

How is the skin-conductance response defined?

The outcome description explains that conditioned-response scores were formed by subtracting the mean skin-conductance level in the two-second interval immediately before a conditioned stimulus from the maximum level during its eight-second presentation. For the unconditioned response, the description uses a post-stimulus baseline and a maximum increase during a specified interval corresponding to the onset of the unconditioned stimulus. It then says responses were range corrected using each participant’s maximum response during acquisition trials. These definitions indicate that the reported measure is derived from task-period changes and scaled relative to a participant-specific maximum; it is not simply a raw skin-conductance level.

The record’s description includes time windows and task details, but does not report measurement-device procedures, rules for unusable signals, or the handling of missing trial measurements. Those details can matter because measurement quality and data-processing choices affect which observations contribute to an endpoint.

Why are trial phase and trial position important?

The record lists outcomes for the first and last conditioned-stimulus trials during fear conditioning and extinction, and for the first two trials during retention. These are distinct observations within the task. In general, measurements taken at different task phases or trial positions may represent different response patterns. A result for one selected trial should therefore be interpreted as a result for that contrast, not automatically as a summary of all task performance.

The record also has an unresolved timing discrepancy: its timeframe names Study Days 7, 9, and 16, whereas its description places extinction retention on day 11. No explanation is reported. The record’s note that the primary outcome has several categories or time points and is not reduced to one comparison reinforces the need to keep those outcomes distinct. It does not say which comparison was primary for inferential testing or how the multiple measurements were modeled.

What can a confidence interval tell a reader?

A confidence interval is a general way of expressing uncertainty around an estimated quantity. It gives a range of values compatible with the estimate under the method’s assumptions. A narrow interval indicates greater precision than a wide interval, but neither interval width nor the estimate itself answers whether the result is important in a clinical or scientific sense. The registry record does not report confidence intervals for the primary outcome, so precision cannot be assessed from this record alone.

Similarly, a p-value, when reported, addresses how compatible observed data are with a specified statistical model under a null hypothesis. It does not measure the size of an effect or the probability that a hypothesis is true. The registry record does not provide primary-outcome p-values or describe the tests used for the ten listed analyses.

What do the planning illustrations represent?

The sample-size section is described as a planning illustration computed from an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It considers effects stated as fractions of the observed effect. These are planning scenarios, not observed power and not a record of the trial’s original design justification. The registry record does not report the trial’s own sample-size justification, and the two-arm equal-allocation assumption in the illustrations should not be confused with the study’s listed three-arm design.

In general, a sample-size calculation asks how many participants per arm would be needed for a specified power to detect a defined effect under stated assumptions. Such a calculation depends on the target effect, variability, significance level, allocation, and analysis approach. The planning illustrations are conditional on their assumptions; they do not establish what the trial was designed to detect, whether the trial achieved a particular power, or whether a result is precise. No numerical illustration values are described because the registry information summarized for this page does not state them.

What analysis details remain unavailable?

The registry reports ten analyses but does not give their specifications. It does not report whether the primary analysis adjusted for baseline values or other covariates, how repeated measurements were handled, whether a particular model was used, or whether assumptions such as the distribution of residuals were evaluated. In general, a model for repeated measurements can account for the fact that observations from the same participant are related; treating them as independent when they are not can misstate uncertainty. The record does not say whether such a model was used.

Likewise, the record does not report an interim-analysis plan, a stopping rule, or a pre-specified hierarchy of tests. It does not explain how missing outcome measurements were handled or define the analysis population. Those omissions limit reproducibility and make it difficult to judge whether the posted analyses follow the intended plan.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint covers multiple task phases and trial positions: conditioning, extinction, and retention, with specified early or late trials in each phase. The registry record notes that the outcome has several categories or time points and is not reduced to one comparison. It also lists ten analyses, but does not describe what each analysis tested, which result was designated primary for inference, or whether any multiplicity adjustment was planned or used.

Multiplicity is a general concern when many related hypotheses are examined. The more comparisons made, the greater the chance that at least one result may appear notable by chance alone if the analyses are interpreted without accounting for the number of tests. Different approaches can control this concern, but the record does not report an approach for this study. It is therefore not possible to determine from the registry record how the ten analyses were prioritized or how their inferential results should be interpreted together.

The registry does not report the number of participants contributing data to each endpoint analysis, the amount or pattern of missing outcome data, or the method used to address missing measurements. Enrollment of 111 does not establish that every enrolled participant contributed every trial measurement. It also does not specify whether the analyses followed an intention-to-treat, per-protocol, or other population definition. These details are important for understanding which participants and observations underlie an estimate and how results might be affected by incomplete follow-up.

The record does not report a statistical analysis plan, an interim-analysis strategy, or a missing-data sensitivity analysis. Those items should be treated as not reported in the registry record, rather than inferred from the study design or the number of analyses. Without them, readers cannot fully assess analysis selection, the handling of incomplete data, or the robustness of the reported findings.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry lists serious and other adverse-event counts separately for the three arms. In the hydrocortisone arm, 37 participants are listed as at risk; the counts shown are zero serious adverse events, zero other adverse events, and zero deaths. In the D-cycloserine arm, 32 participants are listed as at risk, with zero in each of those three categories. In the placebo arm, 35 participants are listed as at risk, also with zero in each category. No top serious-event terms are listed.

These are reported counts, not estimates of comparative risk. A zero count means no events in that category are recorded for the listed group in this registry entry. It does not mean that the study proves the possibility of an event is absent, nor does it establish that every event was captured. The record does not report the safety observation period, detailed event definitions, the method of collecting adverse events, or whether the at-risk counts correspond to all enrolled participants or only those included in safety follow-up.

The adverse-event entries should also be kept distinct from the skin-conductance endpoint, which measures task responses rather than safety events. The posted safety figures can be described as reported, but the registry record does not provide enough detail to evaluate completeness or make a broader comparative safety assessment.

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

This trial’s stated purpose was to examine hydrocortisone and D-cycloserine in relation to fear responses and memory of fear among veterans with posttraumatic stress disorder symptoms. Its primary outcome was a series of skin-conductance response measurements taken during a fear-learning task. The registry record identifies three arms, a randomized and triple-masked parallel design, and the broad outcome procedures.

Those details describe the study question and its measurement strategy; they are not themselves evidence that either medication changed the measured responses. The registry information does not report the primary-outcome estimates, their uncertainty, or the results of the ten analyses. Consequently, it is not possible from this record to say whether the groups differed, in which direction any differences went, or how precisely they were estimated. The trial title and rationale should not be read as a substitute for outcome data.

Even when numerical group results are available, a statistical difference and a meaningful difference are not automatically the same. General interpretation would require attention to the size of the contrast, its uncertainty, the task phase and trial position, and the relevance of the measured signal to the study question. The record does not provide a threshold for a meaningful change in this endpoint or explain how a task response should be related to broader symptoms or functioning. The endpoint measures physiological responses during a computer task, not a complete account of a participant’s clinical state.

The timing discrepancy between the stated outcome timeframe and the day assigned to extinction retention also matters when interpreting any result by study day. The record does not resolve that inconsistency. Likewise, the absence of reported analysis populations, missing-data procedures, and multiplicity methods limits interpretation of how the posted findings were generated.

The safety entries report zero serious adverse events, zero other adverse events, and zero deaths in each arm’s listed at-risk group. These counts describe the registry record, but they do not establish that no adverse events could occur or that the groups have equivalent safety. The record does not give the duration or completeness of safety observation.

In short, the available information supports a careful description of design and measurement, but not a claim about the comparative outcome or its clinical significance. Any conclusion about the observed data would need to be grounded in the posted estimates and their precision, with the limitations of the registry record kept in view.

13. Why This Trial Matters Statistically

Statistically, this study is useful to consider because it combines a three-arm randomized design with a continuous physiological endpoint measured at several points in a structured task. That combination raises practical interpretation questions: which arm contrasts matter, which task measurements represent the primary inference, and how repeated observations should be summarized without obscuring differences between phases or trials.

The endpoint description also illustrates how a measured outcome can be constructed rather than directly recorded as a single raw value. The conditioned-response score uses a pre-stimulus reference, a maximum response during the stimulus, and range correction based on a participant-specific maximum. Understanding those choices is necessary before interpreting a group mean. The record supplies some of the calculation details, while leaving other measurement and analysis procedures unreported.

The registry’s note that the endpoint has several categories or time points and is not reduced to one comparison makes multiplicity a central interpretive issue. A collection of results requires a clear account of which comparisons were planned and how their uncertainty is handled. The record lists ten analyses but does not explain their relationship to the outcome categories or report a multiplicity strategy. That gap illustrates why an analysis plan is important alongside results.

The planning illustrations can also help distinguish a design calculation from an observed result. They are described as scenarios based on an observed effect and particular assumptions, not as observed power or the original trial’s sample-size justification. This distinction matters because a planning calculation cannot replace estimates and uncertainty from the actual trial.

Finally, the timing discrepancy between the outcome timeframe and the description of retention shows why registry entries should be checked for internal consistency. Accurate timing, analysis definitions, participant flow, and missing-data reporting are necessary to interpret and reproduce a study. The record offers a useful outline of the trial, but its unreported details constrain what can be concluded statistically.

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.

Several trial-specific limitations of interpretation arise from what the registry record does and does not describe. First, it gives no numerical results for the primary skin-conductance endpoint. The direction, magnitude, and precision of the group comparisons therefore cannot be assessed from this information. Although ten analyses are listed, the record does not provide their results or explain which analysis corresponds to which outcome contrast.

Second, the outcome spans multiple phases and trial positions, and the registry explicitly does not reduce these to one comparison. Without a reported analysis hierarchy or multiplicity approach, it is difficult to know how to interpret a set of analyses as a whole. The record also does not describe the statistical model, any covariate adjustment, or how repeated measurements from the same participant were handled.

Third, the measurement schedule is inconsistent within the record. The stated timeframe gives Study Days 7, 9, and 16, while the description assigns extinction retention to day 11. The record does not explain whether this reflects different labels, a correction, or another issue, so the intended timing cannot be resolved.

Further limitations include the absence of reported eligibility details, allocation ratio, randomization procedures, masking roles, participant flow, analysis-population definitions, missing-data methods, and the trial’s sample-size justification. The record does not report interim analyses or a statistical analysis plan. These absences limit assessment of bias, reproducibility, and the extent to which analyses reflect pre-specified intentions.

For safety, the registry reports zero serious and other adverse events and zero deaths in the listed groups, but does not report observation duration or the detail needed to assess completeness. These limits do not negate the reported entries; they define how narrowly those entries should be interpreted.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Veteran Stress and Learning Study — NCT00674570.
• Registry record last updated 2019-05-30; status last verified 2019-05.
• Results first posted 2019-05-30.
• 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.

18. Record Summary

The Veteran Stress and Learning Study is registered as a completed, phase 4 randomized, triple-masked, parallel-group study sponsored by the VA Office of Research and Development. Enrollment was 111. The listed arms were hydrocortisone, D-cycloserine, and placebo, and the study concerned fear responses and memory of fear in veterans with posttraumatic stress disorder symptoms.

The primary endpoint was the proportion of maximum skin-conductance response, summarized as a mean with standard error. Measurements were described across fear conditioning, extinction, and extinction retention. The timeframe and outcome description differ on the retention day, and the record does not reconcile that inconsistency.

The registry lists ten analyses but does not report the primary outcome estimates or explain the analyses in detail. It also does not report missing-data procedures, analysis populations, or a multiplicity strategy. Safety entries show zero serious adverse events, zero other adverse events, and zero deaths in each listed arm. The record supports a description of the design and measures, but not a conclusion about comparative primary-outcome results.