Study Using Pregnenolone to Treat Bipolar Depression: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Using Pregnenolone to Treat Bipolar Depression (NCT01409096), a randomized phase 4 study. The primary outcome is The 17-item Hamilton Rating Scale for Depression (HRSD17).

2. Clinical Question

3. Trial Design

The registry describes a completed, randomized, parallel-group Phase 4 study sponsored by the University of Texas Southwestern Medical Center. It lists an enrollment of 80 and compares pregnenolone with placebo. The registry lists triple masking. The official title uses the wording “double blind,” but the listed masking classification is triple; which study roles were masked is not reported in the registry record. Allocation concealment details are also not reported.

The planned treatment period was 12 weeks. The pregnenolone arm received a stepped regimen: 50mg twice per day for 2 weeks, 150mg twice per day for 2 weeks, and 250mg twice per day for 8 weeks. The placebo arm received matching placebo at the same frequency for 12 weeks. The registry identifies the primary purpose as assessing depressive symptoms in patients with bipolar disorder, while also listing anxiety, manic symptoms, and cognition as areas of interest.

The registry lists an enrollment of 80, while the posted primary outcome has 38 participants in the pregnenolone group and 35 in the placebo group. The reasons these posted outcome counts differ from the enrollment figure, the analysis-population definitions, participant flow, and handling of missing outcome data are not reported in the registry record. The planned recruitment target, the rationale for that target, and the original sample-size assumptions are also not reported in the registry record. The registry lists study status as completed. Its posted results include one primary continuous outcome and three secondary continuous measures at 12 weeks.

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 The 17-item Hamilton Rating Scale for Depression (HRSD17), measured over 12 weeks.

The primary endpoint is the 17-item Hamilton Rating Scale for Depression, or HRSD17, assessed at 12 weeks. The registry describes the HRSD as an observer-rated measure of depressive symptomatology. It is reported in units on a scale with a minimum of 0 and a maximum of 50. Lower scores are identified as better, and a normal score is described as 7 or less. The posted values are least-squares means, with standard errors as the accompanying measure of dispersion.

A standardized, observer-rated instrument provides a defined way to quantify depressive symptoms and compare group-level scores. The endpoint is therefore suited to a continuous-outcome comparison: the analysis estimates how far the group means differ on the scale, rather than counting participants who meet a yes-or-no criterion. The registry record does not report the clinical interpretation of a given score difference, a responder definition, or a threshold for a meaningful change.

The reported endpoint is a score at 12 weeks. Whether the analysis also accounted for baseline score, other participant characteristics, or repeated measurements is not reported in the registry record. The reported sponsor analysis is labeled ANCOVA, but its model details are not posted. The numerical comparison should consequently be read as a group-level estimate with uncertainty, not as a complete account of each participant’s course or of the clinical importance of a particular score.

7. Results Posted in the Registry

• Pregnenolone: mean 9.18 versus 9.41 on control; difference -0.23 (95% CI -4.06 to 3.60), standardized effect d = -0.03; z-test p = 0.906.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Inventory of Depressive Symptomatology-Self Report (IDS-SR)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Pregnenolone: mean 15.78 versus 18.23 on control; difference -2.45 (95% CI -9.63 to 4.73), standardized effect d = -0.16; z-test p = 0.504.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Pregnenolone and the control. The interval gives the range of effects that remain compatible with the data.

Young Mania Rating Scale (YMRS)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Pregnenolone: mean 5.84 versus 6.63 on control; difference -0.79 (95% CI -3.76 to 2.18), standardized effect d = -0.12; z-test p = 0.602.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Pregnenolone and the control. The interval gives the range of effects that remain compatible with the data.

Hamilton Rating Scale for Anxiety (HRSA)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Pregnenolone: mean 8.80 versus 10.32 on control; difference -1.52 (95% CI -5.96 to 2.92), standardized effect d = -0.16; z-test p = 0.502.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Pregnenolone and the control. The interval gives the range of effects that remain compatible with the data.

The three posted secondary measures assess self-reported depressive symptoms, manic symptoms, and anxiety at 12 weeks. Across these outcomes, the recalculated mean differences are negative, corresponding to lower posted scores in the pregnenolone group. Their intervals include zero, and the sponsor-reported p-values are 0.519 for IDS-SR, 0.606 for YMRS, and 0.511 for HRSA. Taken together, the secondary results do not provide a clearly separated pattern of group outcomes. They are broadly consistent with the primary result in that none of the posted comparisons establishes a precise difference between the groups.

The secondary outcomes can add context because depressive symptoms are also measured by self-report, while the other scales address manic symptoms and anxiety. They do not replace the primary HRSD17 result or independently resolve its uncertainty. The registry describes cognition as an area the study would explore, but the posted secondary measures listed in the results are IDS-SR, YMRS, and HRSA; a cognition result is not reported in the registry record.

Each secondary comparison is an additional opportunity to observe an apparently notable result by chance. General: when many outcomes or comparisons are tested, the chance of at least one small p-value can increase unless the analysis accounts for multiplicity. The registry does not report a multiplicity adjustment or a hierarchy for interpreting secondary outcomes. Accordingly, the secondary p-values should be treated as unadjusted and exploratory in interpretation, rather than as independent confirmatory evidence. Their pattern is descriptive and does not establish that the intervention changes any of these symptom domains.

The sponsor methods differ across secondary outcomes: ANCOVA for IDS-SR, ANOVA for YMRS, and ANCOVA for HRSA. Model specifications and covariates are not reported in the registry record. The summary comparisons are recalculated from posted group statistics and are unadjusted; they should not be conflated with the sponsor’s model-based analyses.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Inventory of Depressive Symptomatology-Self Report (IDS-SR)
• Young Mania Rating Scale (YMRS)
• Hamilton Rating Scale for Anxiety (HRSA)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a score measured on a numeric scale. The posted group summaries are least-squares means with standard errors. A least-squares mean is a model-based group mean, but the registry does not report the covariates or other details used to obtain these values. The standard error describes uncertainty in an estimated mean; it is not the spread of individual participants’ scores. The registry’s dispersion label is Standard Error.

What does a mean difference represent?

The mean difference expresses the pregnenolone group’s score relative to the placebo group’s score. For the primary outcome, the recalculated difference is -0.23 units. The negative sign indicates that the pregnenolone group’s posted mean is lower. Since the registry identifies lower HRSD17 scores as better, that direction favors the lower score, but the difference is small and uncertain. The difference is a group-level summary and does not show how many individual participants improved or worsened.

The recalculated comparisons are simple, unadjusted calculations from the posted summary statistics. They are not a reproduction of the sponsor’s ANCOVA model. The reported sponsor analysis for the primary measure is ANCOVA, but the registry does not give the model’s effect estimate, covariates, or other specifications. For that reason, the recalculated estimate and the sponsor’s reported p-value answer related but not necessarily identical statistical questions.

How should a p-value be read?

A p-value describes how unusual results at least as far from a null comparison as the observed result would be under the statistical model and its assumptions, if the null comparison were true. It is not a measure of the probability that the null is true, nor does it measure the magnitude or clinical importance of a difference. The recalculated primary p-value is 0.906, while the sponsor’s reported ANCOVA p-value is 0.908. These values are close, but the sponsor’s result comes from a different, model-based analysis. Neither p-value gives a direct estimate of the range of plausible effects; the effect estimate and its interval are needed for that.

General: a confidence interval is a range of estimates compatible with the data under the method used to construct it. Wider intervals indicate less precision than narrower intervals. The primary recalculated interval runs from -4.056 to 3.596 and includes zero. The confidence level and construction method for the posted comparison intervals are not reported in the registry record, so those details cannot be assumed.

Why do model choices matter?

ANCOVA is a general method for comparing a continuous outcome between groups while adjusting for one or more additional variables. The registry labels the sponsor’s primary analysis ANCOVA. It does not report which variables were included, how assumptions were assessed, how missing values were treated, or whether the analysis followed a prespecified statistical plan. For the secondary outcomes, the sponsor methods are ANCOVA for IDS-SR, ANOVA for YMRS, and ANCOVA for HRSA. The details of those models are likewise not reported in the registry record.

General: adjustment can change an estimated group contrast and its precision, depending on the variables included and their relationship to the outcome. A reported model-based p-value should therefore be distinguished from an unadjusted calculation based on summary statistics. The registry does not provide enough information to reproduce the sponsor models or assess all their assumptions.

What does over-dispersion mean?

General: over-dispersion arises when observed variability is greater than a statistical model expects. It can make standard errors too small if the model does not accommodate the extra variability, producing uncertainty estimates that are too narrow. The primary HRSD17 outcome is continuous, and the registry does not report an over-dispersion assessment or identify over-dispersion as a model issue. This concept is relevant to statistical modeling generally, but no conclusion about its presence in this trial can be drawn from the registry record.

The recalculated planning illustrations use an approximate pooled standard deviation derived from the posted standard errors and group counts. That approximation is not the sponsor’s outcome analysis and is used only for the planning display. The registry’s own modeling details, including diagnostics and any prespecified analysis decisions, are not reported in the registry record.

11. Confidence Intervals and Precision

The primary recalculated mean difference is -0.23 HRSD17 units, with interval limits of -4.056 and 3.596. The interval includes zero, so it is compatible with no group difference as well as differences in either direction. Because lower HRSD17 scores are identified as better, the negative estimate points toward a lower score for pregnenolone, while the upper end of the interval points in the opposite direction. The interval’s breadth makes the point estimate an imprecise summary of the possible contrast.

General: an interval communicates uncertainty around an estimate. A narrow interval can indicate greater precision, while a wide interval leaves more uncertainty about the magnitude and direction of an effect. It is important to consider the interval alongside the point estimate rather than treating a p-value as a complete description of the result. The confidence level and method used for the recalculated interval are not reported in the registry record.

Both group means are reported with standard errors: 9.18 with 1.41 for pregnenolone and 9.41 with 1.35 for placebo. Those standard errors characterize uncertainty around the group means, not the range of individual participant scores. The pooled standard deviation used in the recalculation is approximate, as indicated in the calculation details; it should not be mistaken for a directly reported trial estimate of participant-level variability.

The registry reports 38 and 35 participants for the primary outcome, against an enrollment of 80. It does not report why those counts differ, how missing outcomes were handled, or whether additional participants were included in another analysis population. Those omissions limit assessment of how the observed precision relates to the full enrolled group. The posted interval describes uncertainty under its calculation assumptions; it does not account for every possible source of uncertainty, such as missing-data or model-selection concerns.

12. 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 are illustrations derived from the observed effect, not the trial’s original design calculation. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The original sample-size justification and design assumptions are not reported in the registry record.

The 80% power column gives the number of participants per arm that the planning calculation estimates would be needed to have an 80% chance of detecting the specified effect under those assumptions, if that effect were the true one. The 90% power column gives the corresponding planning estimate for a 90% chance. These are planning probabilities conditional on the calculation’s assumptions; they are not probabilities that a treatment effect exists or that a future study will reach a particular conclusion.

For the primary HRSD17 result, planning for 100% of the observed effect gives 20,748 participants per arm for 80% power and 27,775 participants per arm for 90% power. Planning for 75% of the observed effect gives 36,884 participants per arm for 80% power and 49,378 participants per arm for 90% power. Planning for 50% of the observed effect gives 82,989 participants per arm for 80% power and 111,099 participants per arm for 90% power. The pattern illustrates that smaller effects require more participants to detect under the same assumptions.

The curve represents the same planning relationship across effect sizes: when the target effect is made smaller, the calculated participant requirement rises. The calculations use the observed effect from a small posted comparison, so the planning estimates are highly sensitive to that observed estimate and are not guarantees about a future study. This is not observed power. The registry’s original design rationale, including whether its planned sample size targeted another effect or outcome, is not reported in the registry record.

13. 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 = -0.230; pooled standard deviation σ = 8.362.
2. n = 2 × (1.96 + 0.842)² × 8.362² / -0.230² = 20,747.2, rounded up to 20,748 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 <- -0.23                      # observed difference in means
sigma <- 8.36158519912663                     # 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(1409096)
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 = 20,748 (80% power), 27,775 (90% power)
 75% of observed effect: n per arm = 36,884 (80% power), 49,378 (90% power)
 50% of observed effect: n per arm = 82,989 (80% power), 111,099 (90% power)
power.t.test: 20748.1 
Simulated power at n = 20,748 per arm: 0.801 (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.

14. Analyses Reported by the Sponsor

The registry reports an ANCOVA for the sponsor’s primary comparison, with p = 0.908. It does not post the sponsor’s effect estimate, confidence interval, model covariates, or further model details. The recalculated comparison uses the posted arm-level summaries and is unadjusted: its mean difference is -0.23, its interval runs from -4.056 to 3.596, and its p-value is 0.906.

The recalculated p-value is close to the sponsor’s reported p-value, but the numerical closeness does not make the methods interchangeable. The sponsor’s ANCOVA may account for model terms that are not represented in a simple summary-statistic recalculation. Since the sponsor analysis is the reported analysis, it takes precedence when describing the trial’s own statistical result. The unadjusted calculation is useful as a transparent check based on the posted group summaries, not as a replacement for the sponsor’s analysis.

The registry does not provide enough information to reconstruct the ANCOVA or determine why its p-value differs from the recalculated one. The record also does not report whether the sponsor’s analysis followed a prespecified plan, how missing values were handled, or the exact analysis population. The sponsor result should therefore be quoted as reported, while recognizing that its effect size and precision cannot be evaluated from the posted ANCOVA output alone.

15. Multiplicity, Missing Data and Analysis Populations

The registry posts one primary endpoint and three secondary outcomes. It does not report how the primary outcome was selected relative to other measures, whether the secondary outcomes were prespecified in a hierarchy, or whether any correction for multiple testing was used. Without that information, the secondary results are best read as additional descriptive comparisons rather than a set of independent confirmatory tests. General: testing multiple outcomes can increase the chance of at least one apparently unusual result under a null hypothesis; multiplicity procedures are designed to address that issue, but no particular procedure can be attributed to this trial from the record.

The sponsor reports ANCOVA for the primary endpoint and for IDS-SR and HRSA, and ANOVA for YMRS. The registry does not provide covariates, model formulas, assumption checks, a statistical analysis plan, or details about whether analyses were prespecified. It also does not explain whether the posted least-squares means were estimated from the same models used for the sponsor p-values. Those omissions constrain reproducibility and make it difficult to compare the unadjusted recalculations directly with sponsor analyses.

The registry enrollment is 80, while the posted primary outcome counts are 38 for pregnenolone and 35 for placebo. The record does not explain the participant flow that led to those outcome counts, identify an intention-to-treat or other analysis population, state how missing outcomes were handled, or describe the amount or pattern of missingness. The record also does not report whether imputation, sensitivity analyses, or other methods were used to evaluate missing-data assumptions.

These gaps matter because results can depend on which participants contribute outcome data and on assumptions about unavailable measurements. They do not demonstrate that a particular bias occurred; they mean that the registry record does not allow its presence or absence to be assessed. Similarly, no interim analyses, stopping rules, or monitoring of statistical boundaries are reported in the registry record. None should be inferred from the trial’s completed status or from its posted p-values.

16. 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.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: cholecystitis (2.9%), injuries secondary to motor vehicle accident (2.9%), fall (2.9%), corneal ulceration (2.6%), skin abscess followed by allergic reaction to antibiotic used to treat it (2.6%).

The registry lists serious adverse events affecting 4 of 38 participants at risk in the pregnenolone group and 3 of 35 in the placebo group. It lists 0 other adverse events in each group. Death counts are not reported in the registry record. The adverse-event summaries are counts within the listed groups; they do not on their own describe event timing, duration, severity beyond the serious classification, or whether events were judged related to treatment.

The registry lists serious-event terms with percentages: Cholecystitis, 2.9%; Injuries secondary to motor vehicle accident, 2.9%; Fall, 2.9%; Corneal ulceration, 2.6%; Skin abscess followed by allergic reaction to antibiotic used to treat it, 2.6%; and Skin rash, 2.6%. The registry record does not identify the group attribution for each listed term in this summary, nor does it provide further case descriptions. These terms should therefore be read as registry-listed serious adverse event categories, not as evidence that a particular event was caused by the study treatment.

Safety counts are descriptive and should be interpreted in light of the available participant counts and the registry’s reporting detail. The record does not give enough information to infer comparative risk or establish causation from these summaries.

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

The posted result describes a 12-week comparison of HRSD17 scores between participants assigned to pregnenolone and placebo. The pregnenolone group’s least-squares mean was 9.18, compared with 9.41 for placebo. The recalculated mean difference was -0.23, with an interval from -4.056 to 3.596. The sponsor-reported ANCOVA p-value was 0.908. These statistics show a small estimated difference and substantial uncertainty about its magnitude and direction.

The result does not prove that the groups are exactly alike. The interval includes zero but also extends to differences on either side, and the registry does not provide the confidence level or sponsor-model interval. Nor does the result establish a clinically important benefit or harm: the record does not report a minimum important difference, responder threshold, or interpretation of a change of this size. A score difference is a measure on the HRSD17 scale, not by itself a judgment about clinical significance.

The p-value should not be read as the probability that pregnenolone works, nor as the probability that it does not. It is a statistic tied to a particular analysis and its assumptions. The sponsor’s ANCOVA result is the trial’s reported statistical analysis, while the recalculated unadjusted estimate offers a separate summary-statistic comparison. The record does not give the model details needed to fully reproduce the sponsor analysis.

The outcome counts are lower than the enrollment figure, and the registry does not explain the difference or describe missing-data methods. As a result, the posted summaries cannot answer whether unavailable outcomes affected the comparison. The findings also apply to the particular study population, treatment schedule, outcome measure, and follow-up reported; the registry does not establish how results would generalize beyond those conditions.

In short, the posted data give an uncertain estimate for the primary score comparison. They neither demonstrate a clear separation between groups nor establish equivalence. Interpretation should keep the point estimate, its interval, the sponsor analysis, and the registry’s reporting gaps in view.

18. Why This Trial Matters Statistically

This trial illustrates why statistical interpretation requires more than a single p-value. The primary outcome has a point estimate, an interval, a sponsor-reported model result, and group-level standard errors. Each communicates a different feature: direction, uncertainty, model-based evidence, and precision of the means. The recalculated interval includes zero and spans values on either side, while the sponsor’s ANCOVA p-value is 0.908. Together, those details make the uncertainty visible rather than reducing the result to a binary conclusion.

The record also demonstrates the importance of distinguishing analyses. The simple recalculation based on arm summaries is not the same as the sponsor’s ANCOVA. The sponsor analysis takes precedence as the trial’s reported analysis, but its model estimate and specifications are not posted. This leaves a useful statistical lesson: a reported p-value without an effect estimate and interval can be difficult to interpret for magnitude and precision, while an unadjusted recalculation cannot stand in for a model whose details are unavailable.

The planning illustrations make another point: calculations based on an observed effect can imply very different participant requirements when the target effect is smaller or when a higher power target is chosen. Those are planning illustrations, not evidence of the trial’s original design assumptions or of what the study was powered to detect. The registry’s original sample-size justification is not reported.

Finally, enrollment and outcome counts, multiplicity details, missing-data handling, and analysis-population definitions affect how completely a result can be assessed. The record provides enough to describe the posted estimates and their limits, but not enough to resolve every design and analysis question. That distinction between what the statistics show and what the record does not document is central to sound interpretation.

19. 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 limitations arise from what the registry record reports. The primary outcome summary includes 38 participants in the pregnenolone group and 35 in the placebo group, while the listed enrollment is 80. Participant flow and the reasons for the difference are not reported in the registry record. The analysis population, missing outcome counts, missing-data methods, and sensitivity analyses are also not reported. It is therefore not possible to determine from the record how missing observations may have affected the estimates.

The sponsor’s primary result is given as an ANCOVA p-value, but its adjusted effect estimate, interval, covariates, and model specifications are not reported. The recalculated comparison is unadjusted and uses an approximate pooled standard deviation derived from the posted standard errors. It is informative as a summary-statistic check, but it does not reproduce the sponsor analysis. The confidence level and construction method for the posted recalculated interval are not reported in the registry record.

The registry does not report the original sample-size justification, target effect, power target, or statistical analysis plan. It also does not report whether interim analyses or stopping rules were used. Consequently, the planning illustrations based on the observed effect cannot establish the adequacy of the original design or indicate the trial’s observed power.

Multiple outcomes are posted, but the registry does not report a multiplicity adjustment or outcome hierarchy. The sponsor methods vary across the secondary measures, with model details absent. The listed masking classification is triple, while the official title uses “double blind”; which study roles were masked is not reported. Finally, the registry provides limited detail on serious adverse event attribution and no death counts. These reporting limitations constrain interpretation, but do not by themselves show that a particular bias, safety issue, or analytic error occurred.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Study Using Pregnenolone to Treat Bipolar Depression — NCT01409096.
• Registry record last updated 2016-03-31; status last verified 2016-03.
• Results first posted 2016-03-31.
• 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.

23. Record Summary

The registry describes a completed, randomized, parallel-group Phase 4 study comparing a stepped pregnenolone regimen with matching placebo for 12 weeks. The listed enrollment is 80, and the registry lists triple masking. The primary outcome is the 17-item Hamilton Rating Scale for Depression at 12 weeks, for which lower scores are identified as better.

The posted primary least-squares means are 9.18 for pregnenolone and 9.41 for placebo. The recalculated unadjusted mean difference is -0.23, with an interval from -4.056 to 3.596; the sponsor reports an ANCOVA p-value of 0.908. The record also posts three secondary symptom measures and serious adverse event summaries. Important details—including the sponsor model specifications, analysis population, missing-data handling, multiplicity approach, and original sample-size rationale—are not reported in the registry record.