Targeting Reconsolidation to Prevent Return of Fear: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Targeting Reconsolidation to Prevent Return of Fear (NCT01623830), a randomized na study. The primary outcome is Fear of Flying Inventory (FFI).

2. Clinical Question

The comparison isolates the cue condition within a study where both groups were described as receiving virtual reality exposure therapy using a virtual airplane. The central contrast is therefore not exposure therapy versus no exposure, but exposure preceded by a fear-related reminder versus exposure preceded by a neutral cue. The proposed rationale was to reactivate the fear memory before exposure treatment and investigate whether this approach could reduce anxiety or the return of fear.

The registry record lists 89 participants enrolled. The brief summary describes a proposal to treat 64 patients, while the posted primary outcome summaries report 38 participants in the Reactivation + VRE arm and 35 in the Neutral Cue + VRE arm. The registry record does not report why these counts differ or how participants without posted primary outcome values were handled. The question addressed by the posted endpoint is limited to the measured score after treatment; a post-treatment score alone does not establish whether fear later returned.

3. Trial Design

This was a randomized, triple-masked, parallel-group behavioral trial sponsored by Emory University. The registry lists the study as completed and its phase as NA. The posted enrollment is 89. The registry record gives a start date of 2012-07 and a primary completion date of 2015-06.

Both groups received virtual reality exposure therapy for fear of flying. In the Reactivation + VRE arm, a virtual reality clip of an airplane taxiing and taking off was presented in a head-mounted display 10 minutes before all exposure therapy sessions. In the Neutral Cue + VRE arm, the corresponding cue was a virtual reality clip of a living room, also presented 10 minutes before all sessions. The brief summary states that all patients would receive the same exposure treatment using a virtual airplane.

The primary outcome was the Fear of Flying Inventory after treatment, at 9 weeks. The registry also lists the Beck Depression Inventory, State Trait Anxiety Inventory-State, and State Trait Anxiety Inventory-Trait at post-treatment. The posted primary outcome summaries include 38 participants in the reactivation arm and 35 in the neutral-cue arm. The registry record does not report the allocation ratio, details of the masking procedures, the original target sample-size rationale, or the statistical analysis plan. Although the study is described as a pilot randomized clinical trial in its official title, further details about pilot objectives or progression criteria are not reported in the registry record.

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:

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 Fear of Flying Inventory (FFI), measured over Post treatment (9 weeks).

The primary endpoint is the mean Fear of Flying Inventory score after treatment, at 9 weeks. The inventory has 33 items measuring the intensity of fear of flying. Items are rated from 0, meaning not at all, to 8, meaning very severely disturbing. The possible total score range is 0-264, and higher totals indicate greater fear-of-flying intensity. The posted outcome is measured in units on a scale and is summarized as a mean with a standard deviation.

A continuous score preserves gradations in reported fear rather than reducing responses to a simple yes-or-no outcome. Comparing arm means can describe whether average scores differed at the specified assessment time. The registry description reports test-retest reliability of .92 in 15 waiting-list patients and states that the measure has been sensitive to change with treatment. Those measurement properties explain why the inventory was selected as an outcome, but they do not determine whether a difference between these trial arms is clinically important.

The endpoint is measured after treatment, so it addresses the post-treatment score rather than the longer-term return of fear described among the study’s aims. Later follow-up results for this primary measure are not reported in the registry record.

7. Results Posted in the Registry

• Neutral Cue + VRE: mean 76.57 versus 65.55 on control; difference 11.02 (95% CI -11.31 to 33.35), standardized effect d = 0.23; z-test p = 0.333.

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.

The Beck Depression Inventory (BDI)

• 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 deviations.
• Result:
  • Neutral Cue + VRE: mean 3.60 versus 4.26 on control; difference -0.66 (95% CI -2.77 to 1.45), standardized effect d = -0.14; z-test p = 0.541.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Neutral Cue + VRE and the control. The interval gives the range of effects that remain compatible with the data.

State Trait Anxiety Inventory- State (STAI-State)

• 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 deviations.
• Result:
  • Neutral Cue + VRE: mean 46.29 versus 45.97 on control; difference 0.32 (95% CI -2.08 to 2.72), standardized effect d = 0.06; z-test p = 0.794.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Neutral Cue + VRE and the control. The interval gives the range of effects that remain compatible with the data.

State Trait Anxiety Inventory- Trait (STAI-Trait)

• 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 deviations.
• Result:
  • Neutral Cue + VRE: mean 45.81 versus 44.83 on control; difference 0.98 (95% CI -0.98 to 2.94), standardized effect d = 0.23; z-test p = 0.327.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Neutral Cue + VRE and the control. The interval gives the range of effects that remain compatible with the data.

The three posted secondary measures are the Beck Depression Inventory, State Trait Anxiety Inventory-State, and State Trait Anxiety Inventory-Trait, each assessed after treatment. Across these outcomes, the observed arm means are relatively close in scale units, and the posted confidence intervals for the mean differences include zero. Taken together, this pattern does not provide a clear separation between the cue conditions on the listed secondary measures at that assessment.

These outcomes complement the primary fear-of-flying measure by describing depression and state and trait anxiety. They do not measure the same construct as the Fear of Flying Inventory, so their results should not be treated as substitutes for the primary outcome or as direct confirmation of a later return-of-fear effect. Their broad pattern is consistent with the primary comparison in the limited sense that none of the posted intervals excludes zero; it does not prove that the effects are identical across outcomes.

Unadjusted secondary results carry less weight because evaluating several outcomes creates multiple opportunities for apparently notable findings to arise through chance. The registry record does not report a prespecified hierarchy among the secondary measures, a multiplicity correction, or an analysis plan for these outcomes. The reported analyses list is empty for each secondary measure. For these reasons, the secondary results are best treated as descriptive and exploratory rather than as independent confirmatory evidence. They can help characterize the posted results, but should not be used alone to make strong claims about the effect of the cue condition.

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

• The Beck Depression Inventory (BDI)
• State Trait Anxiety Inventory- State (STAI-State)
• State Trait Anxiety Inventory- Trait (STAI-Trait)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a scale score that can take values across a range. A mean gives the average score within each arm, while a standard deviation describes how spread out individual scores are around that arm’s mean. The posted standard deviations are 49.88 for Reactivation + VRE and 47.46 for Neutral Cue + VRE. These describe variation among participants; they are not uncertainty intervals for the arm means.

What does the mean difference represent?

The comparison is expressed as the neutral-cue arm mean minus the reactivation arm mean. The estimate is 11.02 units. With this subtraction order, a positive value means the neutral-cue arm had a higher observed mean score. Because the inventory assigns higher scores to greater fear-of-flying intensity, the direction is interpretable in relation to the measure. The estimate remains a difference between observed group averages, not a direct measure of individual change from baseline.

What does the confidence interval add?

A confidence interval describes the range of values compatible with the data and the calculation procedure under its assumptions. For this comparison, the 95% confidence interval is -11.31 to 33.35. It includes zero, which corresponds to no mean difference, and spans values on both sides of zero. This breadth indicates that the estimate is imprecise: the posted data do not narrowly locate the size or direction of the mean contrast. A confidence interval is not a guarantee that the true value lies within its endpoints, nor does it state the probability that a particular treatment effect is true.

How should the p-value be read?

The unadjusted p-value is 0.333. In general, a p-value measures how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the model assumptions held. It is not the probability that the null hypothesis is true, and it does not describe the clinical importance of the estimate. The registry record does not report a multiplicity adjustment for this result, so the p-value is identified as unadjusted.

What role do the standard deviations play?

In general, larger spread among individual measurements makes an arm mean less precise when sample sizes are held constant. Standard deviations also help put a mean difference in context relative to the variability in the measure. The comparison reports a pooled standard deviation of 48.74 and a standardized effect estimate of 0.226. These summaries are descriptive aids; they do not replace the original scale units or establish clinical importance.

The reported comparison uses a simple unadjusted calculation from the posted summary statistics. The registry record does not report whether the original analysis used baseline adjustment, covariates, a different analysis population, or another model. The record also does not report the statistical analysis plan, prespecified hypotheses, assumptions checks, or how missing endpoint values were handled. Those omissions mean that the posted summary data cannot show whether this calculation matches the sponsor’s intended analysis.

General statistical interpretation also depends on the study design and outcome collection. Randomization supports comparison of assigned groups, but the registry record does not give enough detail to evaluate the allocation process, adherence to assigned cue conditions, or masking success. The posted group summaries alone cannot answer whether those design features affected the result. The distinction between an observed arm contrast and a causal effect estimate matters: causal interpretation depends on design conduct and analysis choices as well as the arithmetic of the group means.

11. Confidence Intervals and Precision

The primary mean difference is 11.02 units, with a 95% confidence interval from -11.31 to 33.35. The interval is wide enough to include a negative contrast, zero, and a positive contrast. Because the subtraction is Neutral Cue + VRE minus Reactivation + VRE, a negative value would favor a lower mean in the neutral-cue arm, while a positive value indicates a higher mean in that arm. The observed estimate is positive, but the interval shows that its direction and magnitude are not precisely determined.

Precision depends in part on the amount of variation in scores and the number of participants contributing outcome data. The posted standard deviations are 49.88 and 47.46, with outcome summaries for 38 and 35 participants, respectively. The registry record does not explain the difference between these outcome counts and the enrollment total, or report whether other participants lacked post-treatment measurements. It is therefore not possible to determine from the record why the interval has its particular width or how missing measurements may have influenced it.

The interval is a measure of statistical uncertainty under the calculation used; it is not a range of individual participant scores and does not settle whether any particular difference would matter clinically. The registry record does not report a threshold for a clinically meaningful difference on the Fear of Flying Inventory. Consequently, the estimate and interval describe statistical precision but do not establish clinical importance. They also relate to the post-treatment assessment only, not to unreported later outcomes.

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. The assumptions for these illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario uses a stated fraction of the observed effect as the effect to detect. The original trial’s own sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the estimated number of participants per arm for a future study to have an 80% chance of detecting the assumed effect under those planning assumptions, if that effect and the calculation assumptions hold. The 90% power column gives the corresponding number for a 90% chance. These are planning probabilities under a model, not probabilities that a treatment effect exists. The figures are planning illustrations based on observed effects; they are not observed power.

Read the effect scenarios as planning for the full observed effect, planning for 75% of the observed effect, and planning for 50% of the observed effect. When a smaller effect is the target, a larger sample is generally required to distinguish it from random variation at the same significance level and power target. Thus, the participant counts rise as the assumed effect becomes a smaller fraction of the observed estimate. These calculations do not show what sample size the completed pilot should have had, and they do not establish whether its enrollment was adequate for a different target effect or analysis plan.

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 = 11.020; pooled standard deviation σ = 48.736.
2. n = 2 × (1.96 + 0.842)² × 48.736² / 11.020² = 307.0, rounded up to 308 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 <- 11.02                      # observed difference in means
sigma <- 48.7361229364138                     # 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(1623830)
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 = 308 (80% power), 412 (90% power)
 75% of observed effect: n per arm = 546 (80% power), 731 (90% power)
 50% of observed effect: n per arm = 1,229 (80% power), 1,645 (90% power)
power.t.test: 308 
Simulated power at n = 308 per arm: 0.800 (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. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and three secondary endpoints, but does not report how the analysis plan handled multiple outcomes. In general, testing several hypotheses can increase the chance of at least one apparently notable result even when no true differences exist. A prespecified hierarchy or a multiplicity adjustment can address that issue, but neither approach is reported in the registry record. The secondary comparisons are described as unadjusted, and their interpretation should account for that uncertainty.

Missing-data methods are also not reported in the registry record. The posted primary endpoint summaries include 38 participants in the Reactivation + VRE arm and 35 in the Neutral Cue + VRE arm, while the registry lists enrollment of 89. The record does not state why the outcome counts differ from enrollment, whether participants discontinued, whether measurements were unavailable, or how any missing measurements were addressed. No assumption about the reasons for missing outcomes or their likely values can be made from the posted summaries.

The analysis population is not reported in the registry record. It does not specify whether the posted summaries include all randomized participants, only participants who completed treatment, or another population. Likewise, the record does not describe adherence to the assigned cue, exclusions, protocol deviations, or sensitivity analyses. These details matter because analysis choices can affect how a randomized comparison is interpreted. Without them, the posted arm summaries and unadjusted comparison are informative descriptions, but they do not provide a complete account of the intended or conducted analysis.

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 lists 0 serious adverse events among 45 participants at risk in the Reactivation + VRE group, and 0 among 44 participants at risk in the Neutral Cue + VRE group. It also lists 0 other adverse events among 45 and 44 participants at risk, respectively. These figures are event counts in the registry record, not proof that no adverse experiences occurred outside the recorded categories or observation process.

The adverse-event counts use at-risk group sizes that differ from the posted primary outcome counts. The registry record does not explain this difference, describe the safety observation period, or provide additional detail on event collection. Death counts are not reported in the registry record. The figures should therefore be read narrowly as the listed serious and other adverse-event counts and denominators, without inferring a broader safety conclusion or comparing risks beyond what is recorded.

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

The posted results describe a randomized comparison of two cue conditions delivered before virtual reality exposure therapy. At post-treatment, the observed Fear of Flying Inventory mean was lower in the Reactivation + VRE arm than in the Neutral Cue + VRE arm, while the estimated mean difference was 11.02 units in the neutral-minus-reactivation direction. The confidence interval ranges from -11.31 to 33.35, and the unadjusted p-value is 0.333. These results show an uncertain post-treatment contrast, not a precise estimate of how the cue conditions differ.

The interval includes zero and values in both directions. The data therefore do not establish that the cue conditions differ, but they also do not establish equivalence. A non-significant p-value is not evidence that the groups are identical. The registry record does not report a clinically meaningful difference threshold, so statistical estimates cannot be translated into a claim about the practical importance of a particular score difference.

The study’s stated rationale concerns reactivating fear memory before exposure and its longer-term interest includes relapse or return of fear. The posted primary result concerns a single post-treatment assessment at 9 weeks. It should not be interpreted as evidence about later relapse, durability, or outcomes beyond that measurement. Nor does the comparison evaluate exposure therapy against no treatment: both arms received exposure therapy, with different preceding cues.

The registry record does not report the original analysis plan, handling of missing data, or analysis population. Those omissions limit assessment of how closely the posted unadjusted comparison corresponds to the intended analysis. The results support a cautious description of the observed post-treatment scores and their uncertainty, rather than a conclusion that either cue strategy works or does not work.

17. Why This Trial Matters Statistically

This trial is statistically useful as an example of why an observed difference and its uncertainty need to be read together. The primary estimate is in one direction, but its confidence interval extends across zero and into the opposite direction. Reporting only the arm means or only the point estimate would conceal how imprecisely the group contrast is located. The interval makes that uncertainty visible.

The design also illustrates the importance of defining the comparison accurately. Both groups received virtual reality exposure therapy; the randomized contrast was whether exposure was preceded by a fear-related reminder or a neutral cue. That distinction prevents the results from being misdescribed as a test of exposure therapy itself. The outcome’s direction is also important: higher Fear of Flying Inventory scores indicate greater fear intensity, so the sign of the mean difference must be interpreted alongside the subtraction order.

Finally, this record highlights how much interpretation depends on reporting beyond summary outcomes. The registry does not report the original sample-size rationale, analysis plan, missing-data handling, or analysis population. Without those details, readers can describe the posted means, standard deviations, interval, and unadjusted p-value, but cannot fully assess whether all prespecified decisions are represented. These are central considerations for evaluating a pilot trial and planning future work, not grounds for overstating what the posted results establish.

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 result is limited to the post-treatment assessment at 9 weeks. Although the study’s stated aims include return of fear, later follow-up results are not reported in the registry record. The posted endpoint therefore cannot establish whether any observed score pattern persisted or whether fear later returned.

The registry lists enrollment of 89, while primary outcome summaries include 38 participants in the reactivation arm and 35 in the neutral-cue arm. The record does not explain the difference, identify the analysis population, or describe missing-data methods. Safety denominators are also different from the primary outcome counts, without an explanation in the registry record. These reporting gaps make it difficult to assess the influence of unavailable measurements or participant flow.

The posted primary comparison is an unadjusted calculation from summary statistics. The registry record does not report the sponsor’s statistical analysis plan, baseline adjustment, covariates, or prespecified criteria for interpreting the outcome. It also does not report a clinically meaningful difference threshold. As a result, the estimate cannot be fully contextualized against a prespecified clinical benchmark or compared with an original analysis approach.

The outcome is a self-report scale, and the registry record does not report masking procedures in enough detail to assess whether participants or assessors could distinguish cue conditions. It also does not report adherence to the cue procedure or treatment, or the success of masking. The record describes the study as a pilot, but does not provide pilot-specific progression criteria. These limitations qualify interpretation of the posted post-treatment contrast and do not resolve whether the two cue conditions differ.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Targeting Reconsolidation to Prevent Return of Fear — NCT01623830.
• Registry record last updated 2017-02-02; status last verified 2016-12.
• Results first posted 2017-02-02.
• 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

NCT01623830, titled Targeting Reconsolidation to Prevent Return of Fear, is a completed randomized, triple-masked, parallel-group behavioral trial sponsored by Emory University. The registry lists Fear of Flying as the condition and enrollment of 89. The two groups received virtual reality exposure therapy preceded by either a fear-related airplane reminder or a neutral living-room cue.

The primary outcome was the Fear of Flying Inventory mean at post-treatment, 9 weeks. The posted means were 65.55 for Reactivation + VRE and 76.57 for Neutral Cue + VRE. The mean difference was 11.02, with a 95% confidence interval from -11.31 to 33.35 and an unadjusted p-value of 0.333. The registry also reports three post-treatment secondary measures. The original statistical plan, missing-data handling, analysis population, and later return-of-fear results are not reported in the registry record.