Org 25935 Versus Placebo as Augmentation to Cognitive-behavioral Therapy to Treat Panic Disorder (P05705): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Org 25935 Versus Placebo as Augmentation to Cognitive-behavioral Therapy to Treat Panic Disorder (P05705) (NCT00725725), a randomized phase 2 study. The primary outcome is Change in Panic Disorder Severity Scale (PDSS) Score From Baseline to End-of-Treatment (EOT).

2. Clinical Question

3. Trial Design

This was a randomized, quadruple-masked, parallel-group Phase 2 trial sponsored by Merck Sharp & Dohme LLC. Its official title describes a multicenter, double-blind, fixed-dose comparison of Org 25935 and placebo as additions to cognitive-behavioral therapy in people with panic disorder. The registry lists three arms: Org 25935 4 mg, Org 25935 12 mg, and placebo.

The record gives enrollment as 46. It does not state the number assigned to each arm for the primary analysis, nor does it report details of the randomization sequence or allocation concealment. The masking designation is quadruple, but the record does not identify which roles or groups were masked. It therefore supports describing the trial as randomized and quadruple-masked, but not inferring the operational procedures used to implement those features.

The arm descriptions say that participants took three doses of their assigned study medication before therapy sessions over a two-week period. The primary endpoint timeframe is Screening and Day 36, while the study summary describes the hypothesis in relation to three weeks of therapy. These are the time descriptions recorded for different parts of the study; the registry record does not explain their relationship. The study began on 2008-07-23, had a primary completion date of 2010-04-23, and is listed as terminated. A reason for termination is not reported in the registry record.

The available description establishes the broad design and treatment groups, but does not report further protocol details such as the number or schedule of therapy sessions, medication adherence, criteria for stopping treatment, or the rationale for the enrollment target. Those matters should not be inferred from the trial title or the reported arm descriptions.

4. Participant Flow and Accounting

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

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Intent-to-Treat (ITT) population consisted of all participants who received ≥1 dose of double-blind study medication and had PDSS assessments at Screening and EOT.

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Change in Panic Disorder Severity Scale (PDSS) Score From Baseline to End-of-Treatment (EOT), measured over Screening and Day 36.

The primary endpoint was change in Panic Disorder Severity Scale score from baseline at Screening to end of treatment at Day 36. The PDSS is described as a seven-item clinician-rated measure covering multiple dimensions of panic disorder severity, including the frequency of panic attacks. Each item uses a five-point Likert scale scored from 0 to 4, and the total score ranges from 0 to 28. Higher scores indicate greater panic disorder severity.

Change in score is used to describe how the measured symptom severity differs between the starting assessment and the end-of-treatment assessment. Comparing mean change across randomized groups can address whether average measured change differed between the assigned treatment strategies. It does not, by itself, describe every participant’s experience, and a group mean can conceal variation among individuals. The standard deviation is the reported measure of dispersion specified for this endpoint, but arm-level means and standard deviations are not reported in the registry record.

The primary-outcome population was the Intent-to-Treat population as defined in the record: participants who received at least one dose of double-blind study medication and had PDSS assessments at Screening and end of treatment. The registry record does not provide the number meeting that definition or the endpoint results for any arm. Consequently, the outcome definition is clear, but the observed magnitude and precision of change cannot be evaluated from the reported endpoint information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design and endpoint description permit a limited explanation of the statistical question, but the registry record does not report the detailed analysis procedures or primary outcome results. General statistical concepts can clarify what those missing results would ordinarily be used to communicate; they cannot replace them.

What does the mean change represent?

The endpoint is defined as a mean change in PDSS score between Screening and Day 36. A mean describes the average value in a group. In this setting, the group mean change would summarize the average difference between end-of-treatment and baseline scores for participants included in the analysis. The registry record specifies the mean as the parameter and standard deviation as the dispersion measure, but it does not provide those values by arm. The direction convention for the subtraction is not separately stated in the record, so it is best to retain its description as change from baseline rather than assign a sign interpretation to an unreported estimate.

A mean is a useful summary, but it does not describe the whole distribution. Participants may have different changes, and the mean alone does not show how clustered or variable those changes are. The standard deviation describes spread among observations in a group; it is not the same as the uncertainty in a group mean or in a difference between groups. Both the estimate and an appropriate measure of its uncertainty are needed for a full interpretation.

What would a between-group estimate show?

The central comparison would be the difference in mean change between an Org 25935 arm and placebo. A between-group estimate focuses on the contrast relevant to the trial question, rather than relying only on whether each group changed from its own baseline. Random allocation is intended to support a comparison of assigned groups, although the registry record does not provide details of the randomization procedure or the primary analysis model. No numerical contrast is reported, so its direction and magnitude cannot be described.

A confidence interval, when reported, gives a range of values compatible with the data under the assumptions of the statistical method. Its width communicates precision: a narrower interval indicates greater precision than a wider interval, all else equal. The interval also helps readers distinguish an estimate from the uncertainty around it. No confidence interval is reported for the primary endpoint in the registry record.

A p-value, when reported, measures how incompatible the observed data are with a specified null hypothesis under the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. The registry record does not report a primary endpoint p-value or identify the test used. The trial’s hypothesis statement should not be read as a reported test result.

Why does dispersion matter?

The standard deviation is relevant because participant outcomes can vary even when they receive the same assigned treatment. Greater variability makes an average less informative about any one participant and can make a group contrast less precise. If outcome variation is substantially greater than expected under a simple model, standard methods may understate uncertainty unless their assumptions are addressed. This is a general statistical consideration, not evidence that over-dispersion occurred in this trial. The registry record does not report a distributional assessment, diagnostics, or a method for handling unusual outcome distributions.

What can be said about the analysis model?

The record identifies a continuous endpoint summarized by a mean and standard deviation. It does not state whether the primary analysis compared change scores directly, adjusted for baseline score, used a repeated-measures model, or used another method. It also does not report assumptions, covariates, handling of site, or a prespecified estimator. Those choices can affect estimates and their uncertainty, so they should not be reconstructed from the endpoint definition alone.

The record defines the primary analysis population as participants who received at least one dose of double-blind study medication and had PDSS assessments at Screening and end of treatment. This definition describes eligibility for that analysis; it does not tell readers how many participants met it, how randomized participants without both assessments were handled, or whether additional analysis populations were used. No information on missing-data methods or sensitivity analyses is reported in the registry record.

What does the sample-size illustration mean?

The record describes planning illustrations based on a fraction of the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such an illustration is a hypothetical planning calculation: it explores how a sample-size target would vary under stated assumptions about an effect and a statistical procedure. It is not an observed result, and it is not the trial’s own sample-size justification. The registry record does not report the protocol’s sample-size rationale. No numerical planning estimates are reported in the registry record.

Any sample-size illustration based on an observed effect should be interpreted cautiously as a planning aid, not as evidence that the trial had adequate power or as a statement about the probability of a positive result. It is not observed power. Without the primary effect estimate and its uncertainty, the assumptions behind such an illustration cannot be independently evaluated from the outcome information in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The trial has three listed arms, and the stated primary hypothesis concerns each Org 25935 dose in relation to placebo. The record also lists secondary outcomes involving PDSS at other time points, diagnostic interview scores, clinical global severity, anxiety, anxiety sensitivity, and depression. It reports 12 outcome measures and 14 analyses. Considering several doses, outcomes, or time points raises a multiplicity question: when many statistical comparisons are made, the chance of at least one apparently noteworthy result can increase. A prespecified strategy may address this, but the strategy is not reported in the registry record.

The record does not say whether there was a formal hierarchy of endpoints, an adjustment for multiple comparisons, or a distinction between confirmatory and exploratory analyses. No particular procedure should be assumed. Because the primary results are not reported, it is also not possible to assess how multiplicity may bear on any claimed finding.

Missing-data handling is likewise not reported in the registry record. The primary analysis population requires at least one dose and PDSS assessments at Screening and end of treatment, but the record does not state how many participants met this definition, how missing endpoint measurements were treated, or whether imputation or sensitivity analyses were used. It does not describe reasons for missing assessments or whether missingness differed by arm. These details matter because an analysis restricted to participants with the required measurements can be affected if availability of those measurements is related to outcomes.

The registry’s ITT label is accompanied by a specific definition. It should be read using that definition, rather than assuming that it necessarily includes every randomized participant regardless of treatment exposure or outcome availability. The record does not report other analysis populations or how results across populations were compared.

11. 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 serious adverse event counts of 0 among 11 participants at risk in the Org 25935 4 mg group, 0 among 15 in the Org 25935 12 mg group, and 0 among 14 in the placebo group. These are observed counts for the listed groups. They do not establish that the underlying risk is zero, particularly because the group sizes are limited. No serious adverse event terms are listed among the top serious terms.

For other adverse events, the record reports 8 affected participants among 11 at risk in the 4 mg group, 12 among 15 at risk in the 12 mg group, and 5 among 14 at risk in the placebo group. These are counts, not a causal comparison. The record does not provide event-level descriptions here, severity details, exposure-adjusted comparisons, or a statistical analysis of differences between groups. Participants may also experience more than one event, so counts of affected participants should not be mistaken for counts of all events.

Deaths are not reported in the registry record; the missing death entries should not be interpreted as zero deaths. Safety counts describe the posted observations and do not establish comparative safety or explain why the trial was terminated.

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

The registry record establishes that a randomized, quadruple-masked, parallel-group Phase 2 study was designed to examine Org 25935 at 4 mg and 12 mg against placebo as an augmentation to cognitive-behavioral therapy for panic disorder. It defines a primary endpoint based on mean change in PDSS score from Screening to Day 36 and describes the scale’s content and score interpretation. These details explain the research question and the outcome measure.

The record does not report the primary endpoint results by group or a treatment-effect estimate. It therefore does not show whether either Org 25935 group had a greater or smaller mean change than placebo, how large a contrast may have been, or how precisely it was estimated. The stated hypothesis is not evidence that the hypothesized difference was observed. A conclusion about statistical significance or clinical importance cannot be made from an outcome definition alone.

The absence of reported primary results also prevents assessment of whether the groups were similar at baseline, how many participants contributed endpoint data, or how missing assessments affected the analysis. The listed safety counts offer descriptive information, but do not answer the primary symptom-change question. Nor do zero reported serious adverse events establish the absence of risk.

The study is listed as terminated, but its reason is not reported in the registry record. Termination should not be treated as a result in favor of or against either treatment. In particular, it does not identify the direction of any outcome, the conduct of the study, or whether the observed data were considered sufficient by the sponsor.

The defensible conclusion is limited to what the record describes: a trial design, an endpoint, and selected safety counts. The efficacy result and its uncertainty are not reported in the registry record. This distinction matters because study objectives and planned comparisons describe what investigators sought to learn; only reported outcome estimates can show what the data indicated.

13. Why This Trial Matters Statistically

This study raises several statistical issues that are common in clinical trials. First, the endpoint is a change score on a clinician-rated scale, and its interpretation depends on having measurements at both Screening and end of treatment. The registry gives a definition of the analysis population that requires both assessments, making participant flow and missing-data handling important to understanding the estimate. Those details are not reported in the registry record.

Second, the three-arm structure creates more than one treatment contrast. The stated question concerns two fixed doses in comparison with placebo, while a set of secondary outcomes adds further potential comparisons. Without a reported multiplicity strategy, readers cannot determine whether the testing plan controlled the overall chance of false-positive findings or treated secondary analyses as exploratory.

Third, the record distinguishes the trial’s enrollment from the safety denominators and defines a particular population for the primary endpoint. These are not interchangeable quantities. Clear reporting of analysis populations, participant flow, estimates, and uncertainty is essential to interpreting a randomized study, especially when some participants may not contribute to every endpoint.

Finally, the trial is listed as terminated, but the record does not provide a reason, and it does not report the primary outcome results. This illustrates why status, design, and outcome reporting answer different questions. A well-described endpoint and a clear hypothesis do not substitute for the estimate and uncertainty needed to interpret the data. The statistical importance of the record is therefore partly in what it specifies and partly in the limits imposed by the outcome information that is not reported.

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 most important limitation for interpreting this trial is that the registry record does not report the primary outcome values or a comparison between groups. Without arm-level mean changes, variability, and an estimate of the between-group contrast, the magnitude, direction, and precision of the primary result remain unknown. No conclusion about statistical significance can be drawn from the stated hypothesis.

The record lists enrollment of 46 but does not report the number in the primary analysis population. It defines that population in terms of medication exposure and PDSS assessments at Screening and end of treatment, yet does not describe participant flow, exclusions, missing assessments, or methods for handling missing data. The safety denominators are not a substitute for those primary-outcome counts.

The trial status is terminated, but the reason is not reported in the registry record. The record also does not state whether planned analyses changed, whether there were interim analyses, or whether the study ended before its intended completion. None of these matters should be inferred from the status alone.

Further limits include the absence of a detailed statistical analysis plan, a reported sample-size justification, a multiplicity procedure, and information about model choice or sensitivity analyses. The record does not identify the masked roles or describe the randomization implementation. It describes therapy and medication timing but does not provide additional operational detail. These omissions constrain assessment of methods and precision; they do not establish that a particular method was or was not used.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Org 25935 Versus Placebo as Augmentation to Cognitive-behavioral Therapy to Treat Panic Disorder (P05705) — NCT00725725.
• Registry record last updated 2018-10-16; status last verified 2018-09.
• Results first posted 2016-12-30.
• 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

NCT00725725 is a randomized, quadruple-masked, parallel-group Phase 2 trial sponsored by Merck Sharp & Dohme LLC. It enrolled 46 participants and is listed as terminated. The study compared Org 25935 4 mg and 12 mg with placebo as augmentation to cognitive-behavioral therapy for panic disorder.

The primary endpoint was mean change in PDSS score from Screening to Day 36. The scale is described as a seven-item clinician-rated measure, with higher total scores indicating greater panic disorder severity. The registry record defines the primary analysis population but does not report the arm-level endpoint results, a treatment-effect estimate, confidence intervals, or a p-value.

Serious adverse event counts were 0 in each listed group; other adverse events were reported in all three groups. Deaths are not reported in the registry record. The reason for termination, missing-data methods, sample-size justification, and multiplicity strategy are also not reported.