BEST (Burn Center Evaluation of Standard Therapies) Ventilator Mode Study-: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for BEST (Burn Center Evaluation of Standard Therapies) Ventilator Mode Study- (NCT00351741), a randomized na study. The primary outcome is Ventilator-free Days During the First 28 Days.

2. Clinical Question

The registry’s stated hypothesis was that patients assigned to high-frequency percussive ventilation would have a higher number of ventilator-free days than patients receiving conventional volume-mode ventilation. The endpoint counted days after randomization, from day 0 through day 28, when a participant was alive and free of ventilator assistance for at least 48 consecutive hours.

This question combines survival and freedom from ventilation in one outcome: a day contributes to the count only when both conditions in the definition are met. The primary comparison is therefore not simply a measure of time on a ventilator among survivors. The registry does not report a separate primary analysis of those components or identify a more restricted analysis population. The posted arm summaries describe the observed mean and standard deviation for each group; the comparison between groups is an unadjusted recalculation from those summaries.

3. Trial Design

The registry describes BEST as a prospective randomized controlled trial with parallel groups. It lists random allocation and no masking. Enrollment was 62 participants, with 31 in the high-frequency group and 31 in the conventional group. The study is listed as terminated. Its start is recorded as 2006-07 and its primary completion as 2010-02. The reason for termination is not reported in the registry record.

The intervention groups were defined by ventilation approach. The high-frequency arm used high-frequency percussive ventilation. The conventional arm used ARDSnet ventilation and was described as lung-protective, low tidal volume support. These descriptions identify the approaches being compared, but the registry record does not give further device settings, treatment duration rules, or details about how changes in ventilation were managed.

The primary endpoint was ventilator-free days during the first 28 days. The registry also lists secondary outcomes covering days free from nonpulmonary organ failure, death during hospitalization, ventilator-associated pneumonia, need for rescue ventilation, barotrauma, and ventilator-associated tracheobronchitis. Six secondary outcomes are listed, while the primary outcome brings the stated total number of outcome measures to seven.

The registry record does not report the original sample-size justification, target enrollment, planned analysis population, or a detailed statistical analysis plan. It lists no reported analyses. As a result, the posted group summaries can be described, and unadjusted comparisons can be recalculated from them, but they should not be mistaken for a reported sponsor analysis.

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 Ventilator-free Days During the First 28 Days, measured over 28 days.

Ventilator-free days during the first 28 days was the primary endpoint. Under the registry definition, a counted day occurred after randomization, between day 0 and day 28, when a participant was alive and had been without ventilator assistance for at least 48 consecutive hours. The endpoint therefore reflects both survival and time free from ventilation during the stated follow-up period.

The registry reports the endpoint as a continuous measure summarized by its mean and standard deviation. Comparing means gives a group-level description of the average number of ventilator-free days; the standard deviation describes the spread of individual values within each group. Neither statistic shows how many participants experienced a particular outcome or how values were distributed across participants.

As a general statistical point, a composite count such as ventilator-free days can be useful when the clinical question concerns both survival and freedom from support over a fixed period. Its interpretation depends on the exact counting rule. Here, the requirement to be alive and free from ventilator assistance for at least 48 consecutive hours is part of the endpoint definition, not an assumption made by the analysis. The registry record does not report separate component results or additional rules for participants who died or had incomplete follow-up.

7. Results Posted in the Registry

• Conventional: mean 11.00 versus 12.00 on control; difference -1.00 (95% CI -5.48 to 3.48), standardized effect d = -0.11; z-test p = 0.662.

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.

Days Free From Nonpulmonary Organ Failure

• 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:
  • Conventional: mean 15.00 versus 15.00 on control; difference 0.00 (95% CI -5.23 to 5.23), standardized effect d = 0.00; z-test p = 1.000.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Conventional and the control. The interval gives the range of effects that remain compatible with the data.

Death

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Conventional: 19.4% (6/31) versus 19.4% (6/31) on control; risk difference 0.0 percentage points (95% CI -19.7 to 19.7), risk ratio 1.00 (0.36–2.76); unadjusted two-proportion z-test p = 1.000.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Conventional and the control. The interval gives the range of effects that remain compatible with the data.

Ventilator Associated Pneumonia

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Conventional: 51.6% (16/31) versus 32.3% (10/31) on control; risk difference 19.4 percentage points (95% CI -4.7 to 43.4), risk ratio 1.60 (0.87–2.96); unadjusted two-proportion z-test p = 0.123.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Conventional and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes extend the clinical picture beyond the primary count of ventilator-free days. They cover organ-failure-free days, death, ventilator-associated pneumonia, and additional complications or rescue interventions. Across the outcomes with posted numerical results, the pattern is not a consistent separation across all measures: the continuous organ-failure measure and death counts are alike between groups, while the pneumonia counts are higher in the conventional group. The registry also lists outcomes without posted numerical results, so the available pattern is incomplete.

These measures relate to the primary endpoint but are not interchangeable with it. The primary endpoint combines survival and time without ventilator assistance under its stated definition. Death and pneumonia address specific events, while organ-failure-free days describe another clinical dimension. Similarity or difference in one secondary measure does not establish what would have happened on the primary endpoint, and the primary result cannot substitute for missing secondary results.

Secondary comparisons carry less weight as confirmatory evidence when their status in the analysis plan is unclear. The registry lists multiple outcomes but no reported analyses, no stated testing hierarchy, and no multiplicity adjustment. As a general statistical matter, examining multiple outcomes increases the opportunity for apparently notable findings to arise by chance if each is tested separately. Without a reported plan, the secondary results are best treated as descriptive and hypothesis-generating, not as a basis for a definitive conclusion about any single outcome.

The posted secondary calculations are unadjusted and have uncertainty that should be considered alongside the observed counts. They do not correct for baseline differences, missing data, or multiple comparisons. The registry record does not report whether all listed secondary outcomes were assessed in the same participants or how incomplete observations were handled. The overall pattern can therefore describe the results that are posted, but it cannot establish a comprehensive comparison across all the outcomes originally listed.

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

• Days Free From Nonpulmonary Organ Failure
• Death
• Ventilator Associated Pneumonia
• Need for Rescue Ventilator
• Barotrauma
• Ventilator Associated Tracheobronchitis (VATB)

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports means and standard deviations for the continuous primary outcome. A mean is the arithmetic average of the observed values in a group. A standard deviation describes how dispersed those values are around the group mean; it is not the uncertainty in the mean itself. The posted primary summaries are 12.0 days with a standard deviation of 9.0 in the high-frequency group, and 11.0 days with a standard deviation of 9.0 in the conventional group.

The mean difference compares the two group averages. In the posted comparison, conventional ventilation is contrasted with high-frequency ventilation, yielding a recalculated difference of -1.0 days. The direction depends on the order of the groups: a negative value means the conventional-group mean is lower under this ordering. This is a simple unadjusted recalculation from posted summary statistics. It is not a regression-adjusted estimate or a reported sponsor analysis.

A confidence interval describes a range of effect estimates that are reasonably compatible with the observed data and the assumptions used to calculate it. It reflects sampling uncertainty, not the full range of possible uncertainty from study conduct, outcome measurement, or unreported analysis decisions. The primary interval extends from -5.48 to 3.48 days. Because it includes zero, the summaries do not distinguish the observed comparison from no mean difference at the conventional confidence-interval level. The breadth of the interval is also important: it allows for group differences in either direction.

The unadjusted p-value for the primary comparison is 0.662. In general, a p-value measures how unusual the observed data, or data more extreme, would be under a specified null model. It is not a measure of effect size, precision, clinical importance, or the probability that the null model is true. The registry record reports no analyses; this p-value is therefore best understood as part of the unadjusted recalculation rather than a registry-reported test.

For binary outcomes, the registry posts participant counts by arm and the comparison is expressed as a risk difference. A risk difference subtracts one group’s event proportion from the other’s. It is an absolute contrast, so it is expressed on the probability scale. The secondary outcome calculations also include relative measures, such as risk ratios and odds ratios. As a general statistical distinction, a risk ratio compares probabilities, while an odds ratio compares odds; neither is interchangeable with an absolute risk difference. These calculations are unadjusted and should be interpreted with their confidence intervals and the limited group sizes in mind.

For the continuous secondary outcome, days free from nonpulmonary organ failure, the registry also posts means and standard deviations. The binary secondary outcomes include death during hospitalization and ventilator-associated pneumonia. The registry lists additional secondary outcomes, but not all have posted numerical results. A listed outcome should not be assumed to have been measured successfully or analyzed simply because it appears in the registry.

General statistical context: an unadjusted comparison treats the posted group summaries as the basis for estimating the contrast and does not account for covariates or other features of the study design. Adjustment can be useful when specified in advance and carried out with suitable data, but the registry record does not report an adjusted analysis or state that one was planned. The record also does not describe randomization procedures beyond identifying allocation as randomized, or provide information about stratification, concealment, or balance on baseline characteristics.

General statistical context: for a continuous outcome, a mean-based comparison summarizes location, while the standard deviation gives information about variability. If data are strongly skewed or contain influential extreme values, a mean can be sensitive to those features. The registry record does not give the outcome distribution, participant-level observations, or diagnostic checks, so those features cannot be assessed from the posted summaries. No alternative summary or analysis is reported.

Likewise, the registry record does not report how missing primary outcome values were handled, whether all randomized participants were included in the posted summaries, or how deaths and incomplete follow-up were represented beyond the endpoint definition. These details matter because analysis choices can affect both estimates and their uncertainty. No specific method should be attributed to the trial when it is not reported.

Finally, the registry record lists seven outcome measures and no reported analyses. A statistical analysis plan, prespecified hierarchy among outcomes, and multiplicity procedure are not reported in the registry record. The reported secondary comparisons should therefore be viewed as exploratory, unadjusted summaries rather than as a set of confirmatory tests with controlled error rates.

11. Confidence Intervals and Precision

Precision concerns how narrowly the data locate an effect estimate. For ventilator-free days, the recalculated mean difference is -1.0 days and its 95% confidence interval ranges from -5.48 to 3.48. This interval spans zero and includes differences in both directions. It therefore does not identify a precise direction or size of the mean contrast.

The confidence interval is not a range containing a fixed proportion of individual participants’ outcomes. It describes uncertainty about the estimated group difference under the calculation’s assumptions. The standard deviation of 9.0 days in both groups describes participant-level spread; it serves a different purpose from the confidence interval. A wide interval can coexist with a clear point estimate because the estimate’s uncertainty depends on the amount of information and variability, not just the point estimate.

With 31 participants in each arm, the posted sample is limited for estimating differences in an outcome with the reported spread. The interval’s breadth makes clear that a small observed mean difference does not tightly rule out larger differences in either direction. It is not appropriate to use the p-value alone as a measure of precision; the interval conveys both direction and plausible magnitude more directly.

For binary secondary outcomes, confidence intervals similarly show uncertainty in the corresponding unadjusted contrasts. With group sizes of 31, such estimates can be imprecise, especially when event counts are limited. The registry record does not report adjusted intervals, a sponsor analysis, or a prespecified clinically important margin. Statistical precision should therefore be described from the posted unadjusted calculations, without treating the interval as a judgment about clinical importance.

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 sample-size planning figures are participants per arm, not total event counts. The same interpretation applies to the listed planning estimates for the continuous primary outcome and the binary secondary outcome: each number is the planned size of one arm under the stated illustration, not the total for both arms. The registry’s sample-size assumptions describe a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect.

The 80% power column gives the number of participants per arm required, under those assumptions, for an 80% chance of detecting the chosen effect if that effect were the true one. The 90% column gives the corresponding number per arm for a 90% chance. These are planning probabilities under a model, not guarantees for a future study. For the primary endpoint, the listed requirements are 1,272 per arm for 100% of the observed effect, 2,261 per arm for 75% of the observed effect, and 5,087 per arm for 50% of the observed effect at 80% power. The corresponding 90% figures are 1,703, 3,027, and 6,809 per arm.

The pattern reflects a general principle: smaller effects are harder to distinguish from random variation, so detecting a smaller fraction of the observed effect requires more participants. These estimates are illustrations based on the observed effect, rather than the trial’s original design. The trial’s own sample-size justification and original design assumptions are not reported in the registry record. These planning figures are not observed power.

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 = -1.000; pooled standard deviation σ = 9.000.
2. n = 2 × (1.96 + 0.842)² × 9.000² / -1.000² = 1,271.5, rounded up to 1,272 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 <- -1                      # observed difference in means
sigma <- 9                     # 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(351741)
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 = 1,272 (80% power), 1,703 (90% power)
 75% of observed effect: n per arm = 2,261 (80% power), 3,027 (90% power)
 50% of observed effect: n per arm = 5,087 (80% power), 6,809 (90% power)
power.t.test: 1272.5 
Simulated power at n = 1,272 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 seven outcome measures in total: the primary ventilator-free-days endpoint and six secondary outcomes. It reports no analyses. The registry record does not state whether the primary endpoint was designated as the sole confirmatory outcome in a statistical analysis plan, whether secondary outcomes were ordered hierarchically, or whether any correction for multiple comparisons was planned or applied.

Multiplicity is the general issue that arises when several hypotheses are examined. If each result is interpreted independently, the chance of encountering at least one apparently notable result can increase across a collection of tests. Prespecified procedures can address that concern, but the registry record does not report a procedure. Consequently, the unadjusted secondary p-values should not be treated as if they controlled the overall error rate across all outcomes. This is a limitation on interpretation, not evidence that any individual calculation is incorrect.

Important analysis details are also not reported in the registry record. These include the analysis population, whether the primary analysis followed the randomized assignment regardless of treatment received, and how protocol deviations or changes in ventilation were handled. The record does not describe missing-data rules, the number of missing endpoint observations, or sensitivity analyses. It does not report whether the displayed summaries include every randomized participant.

These omissions matter because a statistical comparison depends not only on the chosen formula but also on which participants and observations enter it. Missing outcomes can affect group summaries, and different assumptions about those missing values can affect estimates and uncertainty. No particular missing-data method or analysis population should be inferred from the available record. The posted comparisons are unadjusted recalculations from summary statistics and cannot fill these reporting gaps.

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 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: ventilator associtated pneumonia (51.6%), barotrauma (12.9%).

The registry’s adverse-event summary lists 10 participants with serious events in the high-frequency group and 16 in the conventional group, with 31 at risk in each. It lists other affected participants as 2 and 0, respectively. These are posted group counts; they do not by themselves explain event severity, timing, duration, or whether an event was considered related to ventilation.

The listed top serious-event terms are “Ventilator Associtated Pneumonia” at 51.6% and “Barotrauma” at 12.9%. The registry record does not provide enough information in these summary fields to interpret those percentages as participant-level risks for a particular arm or to establish how events were counted. The adverse-event summary does not report deaths in its death field. Separately, the secondary outcome for death during hospitalization lists six participants in each group; that outcome should not be conflated with the adverse-event field.

These counts are descriptive, not proof of a causal safety difference. The record does not report a statistical safety analysis, event-level narratives, or an attribution assessment. The comparisons should be read in light of the group sizes and the limited detail available in the registry record.

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

The posted results describe a randomized, parallel-group comparison in which the mean number of ventilator-free days was 12.0 for high-frequency ventilation and 11.0 for conventional ventilation. The unadjusted recalculated mean difference is -1.0 days for conventional relative to high-frequency ventilation, with a 95% confidence interval from -5.48 to 3.48. The estimate is imprecise enough to leave uncertainty about both the direction and magnitude of the group difference.

This result does not establish that the two ventilation approaches are equivalent. A failure to distinguish a difference in an unadjusted comparison is not the same as showing that any difference is small enough to be unimportant. The registry record does not report an equivalence or noninferiority design, a prespecified margin, or a sponsor-reported primary analysis.

Nor does the posted comparison show what caused the observed group summaries. Random allocation is reported, but the record does not provide details about the allocation process, baseline characteristics, adherence, crossover, missing data, or adjusted analyses. The recalculation uses only the posted summary statistics and cannot account for unreported information.

The secondary outcomes provide additional descriptive information, but their multiplicity and analysis status are not reported. The record does not include numerical results for every listed outcome, nor does it report how missing observations were handled. These limitations prevent a complete interpretation of the whole outcome set.

Finally, the registry lists the study as terminated, without reporting the reason. That status alone does not explain whether termination affected enrollment, follow-up, analysis, or the interpretation of results. The statistical meaning is therefore limited to the posted summaries and their unadjusted precision; it is not a recommendation about ventilation or a conclusion that one approach should be used.

17. Why This Trial Matters Statistically

This trial illustrates why a point estimate should be read together with its uncertainty. The observed difference in average ventilator-free days is small in relation to the interval around it, and the interval includes values on both sides of zero. The estimate alone could invite an overly simple reading, whereas the confidence interval shows that the posted data do not locate the group difference precisely.

It also illustrates the distinction between a registry-reported analysis and a recalculation from summary statistics. The record contains arm-level means, standard deviations, and counts, but lists no reported analyses. The unadjusted comparisons can make the descriptive contrasts easier to interpret, yet they do not recover any sponsor analysis plan, adjustment, or missing-data approach that is not reported.

Planning illustrations also need careful interpretation. The sample-size estimates use the observed effect as a planning reference and show how requirements change when the target effect is reduced. They are not evidence that the completed trial had a particular probability of success, nor do they substitute for the trial’s original design justification, which is not reported in the registry record.

Finally, the combination of multiple listed outcomes and no reported multiplicity plan demonstrates why secondary findings need cautious interpretation. A coherent reading distinguishes the primary endpoint, exploratory secondary summaries, and safety counts rather than treating every posted comparison as equally confirmatory. That distinction is useful whenever registry results are considered without a complete analysis plan.

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 enrollment was 62 participants, with 31 in each group. This is a limited basis for estimating a mean difference when the primary endpoint has a standard deviation of 9.0 days in both arms, and the resulting confidence interval is broad. The registry record does not report the original target enrollment or the rationale used to choose the planned sample size.

The study is listed as terminated, but the reason is not reported in the registry record. It is therefore not possible to determine from the record whether termination affected enrollment, outcome collection, or analysis. The record also does not give further eligibility criteria, participant characteristics, baseline comparability, ventilation settings, adherence, treatment changes, or follow-up completeness.

No reported analysis is listed. The record does not specify the analysis population, handling of missing data, adjustment for baseline factors, or sensitivity analyses. The group comparisons described in the results are unadjusted recalculations from posted summaries and cannot address those unreported details.

The registry lists several secondary outcomes, but numerical results are not posted for all of them. It does not report a multiplicity procedure or clarify which secondary outcomes, if any, were intended as confirmatory. The adverse-event summary also provides limited detail about event definitions, attribution, timing, and participant-level denominators for the listed terms. These are reporting limitations; they do not establish that the study did or did not collect the information.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: BEST (Burn Center Evaluation of Standard Therapies) Ventilator Mode Study- — NCT00351741.
• Registry record last updated 2015-09-21; status last verified 2015-09.
• Results first posted 2010-12-28.
• 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

The registry describes BEST as a prospective randomized controlled trial comparing high-frequency percussive ventilation with conventional ARDSnet ventilation in burn patients. It used a parallel-group design with no masking, enrolled 62 participants, and is listed as terminated. The primary endpoint was ventilator-free days during the first 28 days.

The posted means were 12.0 days in the high-frequency group and 11.0 days in the conventional group. Their unadjusted recalculated mean difference was -1.0 days, with a 95% confidence interval from -5.48 to 3.48. The registry record lists no reported analyses, does not report the reason for termination, and leaves key details about the original design, analysis population, and missing-data handling unspecified.