Effect of Propranolol on Preventing Posttraumatic Stress Disorder: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Propranolol on Preventing Posttraumatic Stress Disorder (NCT00158262), a randomized phase 4 study. The primary outcome is Physiological Posterior Probability of Posttraumatic Stress Disorder (PTSD) as Determined From Psychophysiologic Responses During Script-Driven Mental Imagery at Month 1.

2. Clinical Question

3. Trial Design

NCT00158262, titled “Effect of Propranolol on Preventing Posttraumatic Stress Disorder,” is recorded as a Phase 4 randomized, double-masked, parallel-group trial. Massachusetts General Hospital is listed as the sponsor. The study began in 2004-09, had primary completion in 2008-05, and is recorded as completed. Enrollment is listed as 43.

The two interventions were propranolol and placebo. The registry descriptions specify an initial short-acting oral dose, followed one hour later by a long-acting capsule on Day 1, then a 19-day course. The propranolol description gives an initial course dose of 120 mg every morning. The description ends before giving the rest of the dosing schedule, so later dose details are not reported in the registry record. The placebo description indicates matching formulations, but its full regimen is likewise not reported.

The primary endpoint was assessed at Month 1. The reported group summaries include 18.0 participants in the placebo group and 19.0 in the propranolol group. The primary analysis population is described as randomized participants with data available for analysis at Month 1; data were missing for 2 participants in each group. The registry record does not report the trial’s original sample-size justification, detailed allocation procedure, or the method used to maintain masking.

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: Participants who experienced a qualifying acute psychological trauma were randomized to receive up to 240 mg/day of propranolol or placebo.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All randomized participants with data available for analysis at Month 1. Data were missing in 2 placebo and 2 propranolol participants.

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.

Population: All randomized participants with data available for analysis. 1 participant in each arm dropped out prior to analysis and are excluded.

6. Primary Endpoint

The registry lists the primary outcome as Physiological Posterior Probability of Posttraumatic Stress Disorder (PTSD) as Determined From Psychophysiologic Responses During Script-Driven Mental Imagery at Month 1, measured over Month 1.

The primary endpoint is the physiological posterior probability of PTSD, expressed as a percent probability and assessed at Month 1. It is a continuous measure: a mean and standard deviation are reported for each group. It is not a count of participants who received a PTSD diagnosis.

For each participant, the probability was derived from a composite of psychophysiological responses during script-driven mental imagery of traumatic events. The assessment used two traumatic-script exemplars and included heart rate, skin conductance, and corrugator and left lateral frontalis facial muscle electromyogram responses. Responses across the two traumatic scripts were averaged and square-root transformed for analysis. Responses during personal traumatic imagery from previously studied individuals with and without current PTSD were used to calculate the probability of being classified as PTSD.

As a general statistical point, a continuous physiological score can preserve variation in the magnitude of responses instead of reducing each participant to a yes-or-no category. Such a score may be useful for studying physiological patterns related to classification. Its interpretation remains tied to the measurement and classification procedure: it does not by itself establish whether a participant later met clinical diagnostic criteria or whether the intervention changed PTSD incidence. The registry record does not report a separate primary endpoint based on diagnosed PTSD incidence.

7. Results Posted in the Registry

• Propranolol: mean 33.70 versus 40.70 on control; difference -7.00 (95% CI -16.09 to 2.09), standardized effect d = -0.50; z-test p = 0.131.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is described as the mean of a continuous measure. The posted group summaries are the mean physiological probability score and its standard deviation for placebo and propranolol participants with Month 1 data. A mean indicates the group’s average score; the standard deviation describes how spread out individual scores were around that average. The standard deviation is not the uncertainty interval for the mean.

What does the mean difference express?

A mean difference subtracts one group mean from the other. The re-calculation uses propranolol minus placebo, giving -7.0. The negative sign follows from that ordering and indicates that the observed propranolol mean was lower. Reversing the order reverses the sign without changing the underlying contrast. The registry’s reported mean difference is 7.0, which uses the opposite direction of comparison. Keeping the direction explicit prevents a sign from being misread as a different result.

What does the confidence interval add?

A confidence interval describes uncertainty around an estimated difference. In general, it is produced by a statistical procedure that, under its assumptions, would capture the population quantity at the stated rate over repeated applications. It is not a range containing a stated proportion of individual participants, nor does it mean there is a particular probability that the fixed population difference lies within this one interval. The re-calculated interval runs from -16.09 to 2.095. Because it includes zero, the posted summary data are compatible with no mean difference as well as with differences in either direction within the interval.

How should the p-value be read?

The unadjusted p-value is 0.131. In general, a p-value describes how unusual data at least as discordant with a null hypothesis would be if that hypothesis and the analysis assumptions were true. It is not the probability that the null hypothesis is true, and it does not measure the probability that the result occurred by chance. The registry record does not report a p-value for its own analysis. The re-calculated value is unadjusted and should not be treated as evidence that any multiple-outcome or multiple-analysis considerations were addressed.

What is an unadjusted re-calculation?

The re-calculation uses the posted summary statistics to estimate a simple group contrast, rather than reproducing an analysis based on participant-level data or a reported adjusted model. It does not account for covariates, stratification, repeated measurements, or other features unless those are explicitly incorporated; the registry record does not report such details for the primary analysis. This does not establish that the trial’s own analysis did or did not use those approaches. The method for the sponsor’s reported result is not reported in the registry record.

A standardized effect size is also available in the recalculation, but the mean difference is more directly interpretable in the endpoint’s own percent-probability scale. Standardization expresses a difference relative to a measure of variability and can help compare effects measured on different scales. It does not remove uncertainty, validate the measurement, or establish clinical importance. The registry record does not report a threshold for a clinically important difference in this score.

Why do planning calculations use different assumptions?

Sample-size illustrations use a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. They use stated fractions of the observed effect as the effect to detect. These are planning assumptions for the illustration, not evidence that the original trial was designed with those assumptions. The original design assumptions are not reported in the registry record. General planning calculations describe how a future study’s target size can depend on its effect assumption and desired power; they do not alter the uncertainty in the current trial result.

Statistical significance and clinical meaning are distinct questions. A confidence interval and p-value characterize evidence about a statistical contrast under stated or assumed methods. Clinical interpretation additionally depends on what the score represents, whether it corresponds to outcomes important to participants, and what magnitude would matter. A clinically meaningful threshold for this score is not reported in the registry record. The numerical result therefore should be read as an estimate with uncertainty, not as a complete judgment about benefit or harm.

10. Confidence Intervals and Precision

The re-calculated mean difference is -7.0, with a 95% confidence interval from -16.09 to 2.095. The interval is the main description of precision for this unadjusted contrast: it shows that the point estimate is not known with high exactness from the posted data. Its lower end is a difference favoring a lower mean in the propranolol group under the stated contrast, while its upper end extends to a small difference in the opposite direction. Since zero lies inside the interval, the data do not rule out no mean difference.

The size of a confidence interval depends on the amount of information and on variability in the measured outcome. As a general principle, more precise estimates have narrower intervals, while greater variability or less information tends to widen them. The group standard deviations were 17.0 for placebo and 10.2 for propranolol, with reported analysis group sizes of 18.0 and 19.0. These statistics help describe the observed data but do not remove the uncertainty expressed by the interval.

The registry’s reported estimate is 7.0, with a 95% confidence interval from -2.7 to 16.7. That interval also includes zero. The registry record does not state the method used to calculate it, so its precision should be interpreted as reported rather than reconstructed from an assumed model. The re-calculated interval is based on posted summary statistics and is an unadjusted estimate; it is not identical to the registry interval.

Confidence intervals are not guarantees that a particular future study will produce a result inside the current interval. Nor do they convey the spread of individual participant scores. They describe uncertainty around a group contrast under the analysis used. The record does not report a clinically important threshold for the physiological probability score, so statistical precision cannot be translated into a conclusion about whether the observed range would matter clinically.

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 apply to a continuous-outcome comparison and are presented for planning at 80% power and 90% power. In plain terms, each power column describes the planned chance of detecting the assumed effect if that effect were present and if the planning assumptions held. Higher target power requires more participants under otherwise unchanged assumptions.

The calculation uses a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The target effect is set to a stated fraction of the observed effect: 100%, 75%, or 50%. The entries show increasing participant requirements as the assumed effect becomes smaller. This is a general feature of planning: a subtler target difference is harder to distinguish from variability, so more participants are needed to achieve the same planned power. The figures are illustrations based on the observed effect, not evidence about the original trial’s design.

The original sample-size assumptions and justification are not reported in the registry record. These figures are not observed power, and they do not revise the interpretation of the trial’s confidence interval or p-value. They indicate how planning changes under the stated assumptions and effect fractions. They also do not account for design features beyond those listed in the planning assumptions.

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 = -7.000; pooled standard deviation σ = 13.924.
2. n = 2 × (1.96 + 0.842)² × 13.924² / -7.000² = 62.1, rounded up to 63 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                      # observed difference in means
sigma <- 13.9239977838879                     # 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(158262)
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 = 63 (80% power), 84 (90% power)
 75% of observed effect: n per arm = 111 (80% power), 148 (90% power)
 50% of observed effect: n per arm = 249 (80% power), 333 (90% power)
power.t.test: 63.1 
Simulated power at n = 63 per arm: 0.796 (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. Analyses Reported by the Sponsor

The registry’s own reported analysis gives a mean difference in final values of 7.0 and a 95% confidence interval from -2.7 to 16.7. The comparison is listed between placebo and propranolol, but the registry record does not state the method used to obtain this estimate or its interval. No p-value is reported for this analysis.

The unadjusted re-calculation uses propranolol minus placebo and reports a difference of -7.0, a 95% confidence interval from -16.09 to 2.095, and an unadjusted p-value of 0.131. The point estimates have opposite signs because the contrast is expressed in the reverse order. The intervals are not identical after reversing their signs, so they should not be presented as the same calculation. The registry record does not report enough methodological detail to explain the difference between the intervals.

The sponsor’s reported result is the trial’s own analysis and should be distinguished from the simple re-calculation based on posted summary statistics. The re-calculation is useful as a transparent unadjusted comparison, but it does not establish that it reproduces the sponsor’s analysis or its assumptions. Both reported intervals include zero, and the registry’s own analysis should remain the primary reference for what the trial reported.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists three outcome measures and one posted secondary outcome, the Clinician-Administered PTSD Scale Total Score. It also lists four analyses. The multiplicity plan—how conclusions were to account for examining more than one outcome or analysis—is not reported in the registry record. Without that information, the unadjusted p-value for the primary score should not be interpreted as if it necessarily accounts for all comparisons made in the study. The record also does not report whether any outcomes or analyses were designated as exploratory.

For the primary endpoint, the analysis population is described as all randomized participants with data available at Month 1. The record states that data were missing for 2 placebo participants and 2 propranolol participants. The reported endpoint group sizes are 18.0 and 19.0. The method used to handle missing data, the reasons for missingness, and any sensitivity analyses are not reported in the registry record. It is therefore not possible to assess from these details whether missingness could have affected the estimate.

The description of the analysis population does not establish that every randomized participant was included in the primary endpoint analysis. The record does not specify whether the primary analysis followed an intention-to-treat approach, whether any participants were excluded for reasons other than missing endpoint data, or how adherence was handled. These details matter because the population analyzed can influence the interpretation of a randomized comparison.

The registry record does not report an interim-analysis plan, stopping rules, or the trial’s detailed statistical analysis plan. Their absence from the record is not evidence that such procedures were or were not used. It means the posted information does not support a conclusion about them. The sponsor’s method for its reported mean difference is also not stated, limiting direct methodological comparison with the unadjusted re-calculation.

15. 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.

The registry reports zero serious adverse events among the participants listed as at risk in each group: 20 in placebo and 21 in propranolol. It also reports zero other adverse events among those at risk in each group. These are event counts as recorded for the registry, not estimates of comparative safety with a stated uncertainty interval.

The absence of reported events in these groups should be read narrowly. It does not establish that no adverse events occurred outside the registry’s reported categories or observation period, and it does not show that the groups have identical risk. The registry record does not provide further details about adverse-event definitions, collection procedures, follow-up duration for safety, or statistical comparisons. Deaths are not reported in the registry record.

As a general statistical point, a zero count in a study does not demonstrate that the underlying event risk is zero. The degree of certainty depends on the amount and quality of safety follow-up, as well as on event definitions and reporting. The figures should therefore be understood as the adverse-event counts posted for this trial, not as a broad guarantee about safety or a basis for treatment advice.

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

The result describes a difference in the mean Month 1 physiological probability score between the analyzed groups. The propranolol group had a reported mean of 33.7 and the placebo group a mean of 40.7. The unadjusted contrast, defined as propranolol minus placebo, is -7.0. Its 95% confidence interval extends from -16.09 to 2.095, so the estimate is uncertain and includes no mean difference.

This endpoint is derived from physiological responses during traumatic-script imagery and a classification procedure based on responses from previously studied individuals with and without current PTSD. It should not be mistaken for the proportion of trial participants who developed PTSD. The endpoint result alone does not answer whether clinical PTSD diagnoses, symptoms, or other outcomes differed. The registry lists the Clinician-Administered PTSD Scale Total Score as a secondary outcome, but its numerical result is not reported in the registry record.

The result also does not establish the effect of propranolol on outcomes beyond the reported Month 1 assessment. The registry record does not include a numerical result for a longer-term primary endpoint, a diagnosed PTSD incidence comparison, or the clinical importance threshold for this physiological score. A lower observed group mean is a description of these data, not proof of a causal or clinically important effect.

More generally, an estimate can be compatible with several possible underlying differences when its confidence interval is wide. The reported interval includes values favoring either contrast direction as well as zero. This uncertainty, the available-data analysis population, and the unreported missing-data and multiplicity procedures all matter when interpreting the result. The findings should be limited to the endpoint, time point, and analysis details reported in the registry.

17. Why This Trial Matters Statistically

This trial illustrates why an endpoint’s meaning matters as much as its numerical contrast. The primary measure is a continuous physiological probability derived from psychophysiological responses and a classification procedure. It is not equivalent to a diagnosis or an incidence count. Statistical interpretation therefore begins by identifying what was measured, at what time, and in whom.

It also shows why a point estimate should be read alongside its uncertainty. The unadjusted mean difference is -7.0, but the 95% confidence interval includes zero and extends in both directions. The estimate alone does not settle whether a population difference exists or how large it might be. The registry’s own estimate also has an interval that includes zero, while its analysis method is not reported.

The record further demonstrates the importance of distinguishing a trial’s reported analysis from a re-calculation using summary statistics. The re-calculation can make the contrast and its uncertainty easier to inspect, but it does not reproduce undocumented analysis choices. Knowledge of the analysis population and the handling of missing endpoint data is also essential to understanding what comparison the result represents.

Finally, planning illustrations are not a substitute for the original design rationale. The registry does not report that rationale, while the posted planning figures use explicit assumptions and fractions of the observed effect. Separating these planning scenarios from observed results helps prevent sample-size calculations from being misread as evidence about the trial’s achieved power or its conclusions.

18. 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 includes participants with Month 1 data, and the registry states that data were missing for 2 participants in each group. The reasons for missing data and the method used to address them are not reported in the registry record. Without those details, the possible influence of missingness cannot be evaluated from the posted information.

The registry record does not report the original sample-size justification, the detailed statistical analysis plan, or the method used for the sponsor’s reported mean difference. It also does not report how multiplicity across outcomes and analyses was handled. These omissions limit assessment of the intended analysis and of how the reported primary result fits with other analyses.

The endpoint is a physiological probability score based on script-driven imagery and a classification procedure. The registry record does not give a clinically important threshold for interpreting its magnitude, and the posted primary result is not a direct comparison of PTSD diagnoses. The numerical result therefore has a narrower interpretation than a clinical incidence or symptom outcome.

The propranolol and placebo arm descriptions do not state the complete subsequent dosing schedule. The record also does not report the reasons for missing endpoint data or a numerical result for the listed secondary outcome. Safety counts are posted without additional detail on event definitions, follow-up, or comparative analyses. These limitations concern what can be learned from the registry record; they do not establish that unreported procedures or information were absent from the conduct of the trial.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Effect of Propranolol on Preventing Posttraumatic Stress Disorder — NCT00158262.
• Registry record last updated 2017-04-10; status last verified 2017-04.
• Results first posted 2017-04-10.
• 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.

22. Record Summary

NCT00158262 is recorded as a completed Phase 4 randomized, double-masked, parallel-group trial sponsored by Massachusetts General Hospital. The study began in 2004-09 and had primary completion in 2008-05; enrollment is listed as 43. The comparison was propranolol versus matching placebo after an acute psychologically traumatic event.

The primary endpoint was the mean physiological posterior probability of PTSD classification at Month 1. The reported means were 40.7 for placebo and 33.7 for propranolol. The unadjusted re-calculated mean difference, propranolol minus placebo, was -7.0, with a 95% confidence interval from -16.09 to 2.095 and an unadjusted p-value of 0.131. The registry’s own reported mean difference was 7.0, with a 95% confidence interval from -2.7 to 16.7; its method is not reported in the registry record. Interpretation is limited by missing endpoint data and unreported analysis details.