Regimen of Alfentanil in Propofol Sedative Fibro-bronchoscopy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Regimen of Alfentanil in Propofol Sedative Fibro-bronchoscopy (NCT01470170), a randomized phase 4 study. The primary outcome is Effect Site Concentration When Conscious Level Reaches OAAS-3.

2. Clinical Question

The primary outcome was a measure of propofol concentration at a specified sedation level, not a direct measure of recovery, procedural success, or a patient-centered benefit. The trial record describes a prospective randomized, double-blind, placebo-controlled study of alfentanil regimens during propofol sedation for flexible bronchoscopy. The control condition was propofol alone; the four alfentanil groups varied dose and timing.

The clinical question therefore concerns whether the recorded effect-site concentration at OAAS-3 differed across these regimens and the control. Hypoxemia and hypotension are listed as secondary outcomes. Although cough severity and propofol injection-related pain appear in the study description, they are not among the secondary outcomes posted in the record. Results for those outcomes are not reported in the registry record.

The registry record does not give detailed eligibility criteria, participant characteristics, or the clinical rationale for selecting the OAAS-3 threshold. Those omissions limit how precisely the study population and the meaning of the comparison can be characterized.

3. Trial Design

The registry describes NCT01470170 as a completed, Phase 4, randomized, double-blind, parallel-group trial sponsored by Chang Gung Memorial Hospital. Enrollment was 173. The study started in 2010-10, and primary completion was recorded as 2011-09. The registry status is completed.

The five arm descriptions distinguish propofol alone from four alfentanil regimens. Group1 received Alfentanil 2.5μg/kg before propofol; Group 2 received Alfentanil 5μg/kg before propofol. Group 3 received Alfentanil 2.5μg/kg two minutes before propofol; Group 4 received Alfentanil 5μg/kg two minutes before propofol. Group 5 /Control received propofol alone. The registry lists targeted controlled infusion as a device intervention and explains that propofol concentration was calculated by target-controlled infusion using the Schnider model.

The primary outcome was a continuous measure, reported as a mean with standard deviation. Each arm has a posted mean and standard deviation, with arm sizes ranging from 34 to 36. The primary outcome timeframe is described as the bronchoscope-room stay, expected to average 2 hours. Hypoxemia and hypotension are listed as secondary outcomes, but outcome-specific results for them are not posted in the registry record.

The record does not report the original sample-size calculation, planned allocation ratio, detailed randomization procedures, concealment method, or the full statistical analysis plan. Although the study is described as double-blind and placebo-controlled, the specific blinding procedures 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

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 Effect Site Concentration When Conscious Level Reaches OAAS-3, measured over All participants wil be follow for the duration of bronchoscope room stay, an expect average of 2 hours.

The primary endpoint is the propofol effect-site concentration when the participant’s consciousness level reaches observer assessment of alertness and sedation scale 3, abbreviated OAAS-3. The concentration is expressed in ug/ml. The record says the value was calculated by target-controlled infusion using the Schnider model; it is therefore a model-estimated concentration at the specified assessment point, rather than a direct measurement of propofol concentration in the brain.

This endpoint is used to compare the concentration associated with reaching the same stated sedation level under different alfentanil regimens and propofol alone. A lower recorded concentration at OAAS-3 would mean that the model estimated a lower propofol concentration at that point in the sedation scale. That finding, on its own, would not establish a difference in procedural quality, recovery, or the frequency of adverse outcomes.

The registry describes monitoring through the bronchoscope-room stay, expected to average 2 hours. It does not explain whether the endpoint was assessed at a single prespecified time, how OAAS-3 was assessed across the groups, or how observations were handled if a participant did not reach that level. Those details are not reported in the registry record.

7. Results Posted in the Registry

• Group1: mean 2.30 versus 2.60 on control; difference -0.30 (95% CI -0.49 to -0.11), standardized effect d = -0.75; z-test p = 0.002.
• Group 2: mean 2.20 versus 2.60 on control; difference -0.40 (95% CI -0.59 to -0.21), standardized effect d = -1.00; z-test p = <0.001.
• Group 3: mean 2.50 versus 2.60 on control; difference -0.10 (95% CI -0.29 to 0.09), standardized effect d = -0.25; z-test p = 0.303.
• Group 4: mean 2.20 versus 2.60 on control; difference -0.40 (95% CI -0.61 to -0.19), standardized effect d = -0.88; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean describe?

The primary endpoint is continuous, and the registry reports a mean and standard deviation for each arm. A mean is a measure of the central value of the observations. The standard deviation describes how spread out the individual observations are around that mean. It is not the uncertainty in the mean itself: uncertainty in an estimated group mean depends on both the spread of observations and the number of observations contributing to it.

For this trial, the endpoint is a model-calculated propofol effect-site concentration at OAAS-3. The mean therefore describes the average recorded model estimate in an arm. It does not show the range of individual values, and it does not tell whether the groups had similar participant characteristics or similar measurement conditions. Those details are not reported in the registry record.

How should a mean difference be read?

A mean difference expresses the mean in an alfentanil arm relative to the mean in the propofol-alone control arm. A negative estimate means the alfentanil arm’s mean was lower than the control mean. For example, the posted estimate for Group1 is -0.3 ug/ml, and the estimate for Group 2 is -0.4 ug/ml. These are differences in the endpoint’s units. They are not percentages and do not represent a change in a participant’s outcome over time.

The comparisons are reported as unadjusted. In general, an unadjusted comparison estimates the difference without accounting for other variables or for the fact that several comparisons may be examined. The registry record does not report covariate adjustment or a model used for the sponsor’s analysis. The posted recalculations are simple unadjusted comparisons based on the summary statistics.

What does a confidence interval add?

In general, a confidence interval gives a range of values compatible with the data and the method used to calculate the interval. It communicates precision as well as direction: a narrow interval indicates less statistical uncertainty than a wide interval, while an interval spanning zero is compatible with no mean difference under that analysis. The posted intervals for Groups 1, 2, and 4 are below zero; the interval for Group 3 spans zero. Exact interval bounds are not repeated in this explanation.

A confidence interval is not a guarantee that the true value lies inside its endpoints, and it does not identify which values are clinically important. The registry does not report a threshold for clinical importance for this endpoint. Interpretation should therefore distinguish evidence about a mean difference from evidence about its practical significance.

What does a p-value say?

In general, a p-value describes how incompatible the observed data are with a specified null hypothesis, assuming the analysis model and its assumptions apply. Smaller p-values indicate greater incompatibility with that null hypothesis; they do not measure the size or importance of an effect, nor the probability that the null hypothesis is true. The posted unadjusted p-values are 0.002 for Group1, < 0.001 for Group 2, 0.303 for Group 3, and < 0.001 for Group 4.

Because the record does not report adjustment for multiple comparisons, these p-values should be read as unadjusted. Considering multiple comparisons can increase the chance of a false-positive finding across a family of tests. Whether and how to adjust depends on the planned analysis and the questions being asked; the trial’s multiplicity plan is not reported in the registry record.

Why can variability matter?

In general, more variable measurements make a group mean less precise when other design features are held constant. The arm standard deviations are 0.4 for Groups 1, 2, 3, and Group 5 /Control, and 0.5 for Group 4. The registry does not give individual-level data, so the posted summary statistics cannot show the shape of the observations or identify unusual values. The record describes a continuous endpoint and does not report a distributional assessment or a robust alternative analysis.

For other kinds of outcomes, such as event counts, over-dispersion can matter when variability exceeds what a simple count model assumes. In general, ignoring over-dispersion may make uncertainty estimates too small. This is general statistical context, not a description of an analysis used in this trial: the registry posts no secondary-outcome results or analysis details for hypoxemia and hypotension.

What limits interpretation?

The registry reports arm-level sample sizes and summary statistics, but does not report participant-level data, missing-data handling, the analysis population, or the original statistical plan. It also does not report whether outcome assessment was consistent across groups or whether there were deviations from the assigned regimens. These are relevant to judging the assumptions behind an analysis and the applicability of the estimates.

The trial is described as randomized and double-blind, but those labels do not supply the missing operational details. The available summary comparisons can describe the posted outcome and its statistical uncertainty; they cannot answer questions the record does not report, such as the effect of missing outcomes or the results of the secondary endpoints.

10. Confidence Intervals and Precision

The mean differences are estimates, and their confidence intervals express uncertainty around those estimates. For Group1, Group 2, and Group 4, the posted intervals lie below zero, consistent with lower mean concentrations than control under the unadjusted comparisons. For Group 3, the interval includes zero, so the posted data are compatible with both a lower mean and no mean difference under that comparison.

Precision is not the same as clinical importance. An interval may indicate a statistically distinguishable difference without showing whether the difference matters in practice. The registry record does not report a clinically important difference threshold for the modeled concentration. It also does not report how the endpoint’s variability or measurement process was evaluated.

The arm standard deviations range from 0.4 to 0.5, and the posted arm sizes range from 34 to 36. The confidence intervals differ in width across comparisons, reflecting the estimated uncertainty in each comparison. Exact interval bounds are available in the posted results, but are not repeated in this explanation because they are reported with more than three decimal places.

The p-values provide another view of evidence against a zero mean difference, but they do not replace interval estimates. All reported p-values are unadjusted. Since the registry record does not describe a multiplicity plan, the intervals and p-values should not be read as adjusted for examining multiple alfentanil regimens.

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. The record’s stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set as a stated fraction of the observed effect. These are planning illustrations based on the observed comparisons, not the original trial design assumptions; the trial’s own sample-size justification is not reported in the registry record. This is not observed power.

The 80% power column gives the estimated participants per arm for a planning scenario designed to have an 80% chance of detecting the stated effect under those assumptions. The 90% power column gives the corresponding estimate for a 90% chance. These are not guarantees about the result of a future study. They are conditional planning values and depend on the assumptions and effect size used.

The planning rows consider 100%, 75%, and 50% of the observed effect. Smaller effects need more participants to detect under the stated assumptions. The figures illustrate how strongly planning requirements depend on the effect chosen: for Group 2, the estimate for 80% power is 16 participants per arm when planning for 100% of the observed effect, 28 when planning for 75%, and 63 when planning for 50%. For Group 3, the corresponding estimates are 252, 447, and 1,005 participants per arm.

These differences also reflect that the observed Group 3 comparison was closer to zero than the other posted comparisons. Such calculations should not be interpreted as evidence that the trial had adequate or inadequate power for its original question. The record does not report the original target effect, planned power, or original sample-size calculation.

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 = -0.300; pooled standard deviation σ = 0.400.
2. n = 2 × (1.96 + 0.842)² × 0.400² / -0.300² = 27.9, rounded up to 28 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 <- -0.3                      # observed difference in means
sigma <- 0.4                     # 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(1470170)
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 = 28 (80% power), 38 (90% power)
 75% of observed effect: n per arm = 50 (80% power), 67 (90% power)
 50% of observed effect: n per arm = 112 (80% power), 150 (90% power)
power.t.test: 28.9 
Simulated power at n = 28 per arm: 0.785 (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. Multiplicity, Missing Data and Analysis Populations

The trial compares each alfentanil regimen with propofol alone, and the posted comparison p-values are unadjusted. The registry record does not report whether the trial protocol specified a primary comparison, a hierarchy among comparisons, or a correction for multiple testing. When several comparisons are examined, the chance of at least one apparently unusual result can increase; statistical procedures and interpretation plans can address that issue, but the plan used in this trial is not reported.

The registry lists hypoxemia and hypotension as secondary outcomes, but does not post their results. The study description also mentions cough severity and propofol injection-related pain, for which results are not reported in the registry record. The number of outcome measures is listed as 5, while no statistical analyses are listed. The record does not explain which outcomes were measured, analyzed, or omitted from the posted results beyond the information in the outcome listings.

Missing-data methods are not reported in the registry record. It is therefore unclear whether every randomized participant contributed primary-outcome data, how missing observations were handled, or whether any sensitivity analyses were performed. The posted arm sizes for the primary endpoint do not by themselves establish how missing outcomes were treated.

The analysis population is also not reported. The record does not say whether the primary comparison followed an intention-to-treat approach, included participants according to treatment received, or used another population definition. It does not report protocol deviations, exclusions from analysis, or analysis-specific denominators beyond the arm summaries.

These omissions do not establish that a particular method was or was not used. They mean that the registry record does not permit assessment of the multiplicity, missing-data, and analysis-population decisions behind the posted results. Those details would be important when interpreting the reported comparisons.

14. 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.

The registry’s adverse-event figures list zero serious adverse events and zero other adverse events for each arm. The numbers at risk are 34 for Group1, 35 for Group 2, 34 for Group 3, 36 for Group 4, and 34 for Group 5 /Control. No serious adverse-event terms are listed. Deaths are not reported in the registry record.

These entries describe the event counts posted in the registry; they should not be taken as proof that no adverse events occurred outside the registry’s reporting definitions or observation procedures. The record does not provide event definitions, severity criteria, collection methods, or a detailed safety follow-up description. The primary outcome timeframe is described as the bronchoscope-room stay, expected to average 2 hours, but the adverse-event reporting timeframe is not reported in the registry record.

Hypoxemia and hypotension are listed as secondary outcomes, but their results are not posted. Their absence from the results does not mean the outcomes were absent. The zero adverse-event counts therefore cannot substitute for outcome-specific results on hypoxemia or hypotension, nor for results on cough or injection-related pain.

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

The posted primary-outcome results show lower mean propofol effect-site concentrations at OAAS-3 in Groups 1, 2, and 4 than in the propofol-alone control group. The Group 3 mean was also lower than control, but its unadjusted interval includes zero and its p-value is 0.303. The estimates quantify differences in a model-calculated concentration, not direct differences in patient benefit, safety, or procedure quality.

The findings do not show which alfentanil regimen is preferable. The posted comparisons are against control rather than direct comparisons among the alfentanil groups. The registry record does not define a clinically important threshold for the primary outcome, so the practical importance of the observed differences cannot be determined from these results alone. The unadjusted p-values also do not account for any multiplicity plan, which is not reported.

The results do not answer whether the regimens changed hypoxemia, hypotension, cough severity, or propofol injection-related pain. Hypoxemia and hypotension are listed as secondary outcomes without posted results; cough and pain results are not reported in the registry record. Zero adverse-event entries do not resolve those unanswered outcome questions.

More broadly, the record does not report detailed eligibility criteria, participant characteristics, missing-data handling, analysis-population definitions, or the original sample-size justification. Those omissions restrict assessment of generalizability and analytic robustness. The findings should therefore be understood as a comparison of the posted means and unadjusted estimates for this trial, not as a complete evaluation of the regimens’ clinical effects.

16. Why This Trial Matters Statistically

This trial is statistically interesting because it compares several combinations of dose and timing against a propofol-alone control while measuring a continuous, model-calculated concentration at a stated sedation level. That design makes the primary outcome interpretable as a difference in concentration at a common scale point, while also requiring care not to equate the concentration outcome with broader clinical effects.

The pattern of estimates also illustrates why effect size and uncertainty should be read together. The Group 3 estimate is closer to zero than the other posted differences, and its interval includes zero. The estimates for Groups 1, 2, and 4 are below zero with intervals that do not include zero. These distinctions describe the posted unadjusted comparisons; they do not establish differences among the alfentanil regimens.

The study also highlights questions that cannot be answered from a results summary alone. The multiplicity plan, analysis populations, missing-data methods, original sample-size justification, and results for the listed secondary outcomes are not reported in the registry record. Those details matter because they shape how comparisons are interpreted, how uncertainty is assessed, and whether findings apply beyond the measured endpoint.

Finally, the planning illustrations show how sample-size requirements depend on the effect assumed for a future study. Smaller target effects require more participants per arm under the stated assumptions. Those illustrations are separate from the trial’s original design and should not be used to infer its original planning rationale.

17. 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 registry record gives limited information about the population. Detailed inclusion and exclusion criteria, participant characteristics, and recruitment procedures are not reported. As a result, the applicability of the findings to other bronchoscopy settings or patient groups cannot be assessed from the record alone.

The primary outcome is calculated from target-controlled infusion using the Schnider model, rather than directly measured. The record does not report details about calibration, assessment procedures, or how the OAAS-3 threshold was determined. It also does not report how observations were handled for participants who may not have reached that level.

Only the primary outcome’s arm summaries and unadjusted comparisons are posted. The registry does not report results for hypoxemia or hypotension, despite listing them as secondary outcomes. Results for cough severity and propofol injection-related pain are also not reported. This prevents a broader assessment of the outcomes described in the study rationale.

The record does not report multiplicity procedures, missing-data methods, analysis populations, protocol deviations, or a full statistical analysis plan. It does not provide the original sample-size justification. The safety entries list zero serious and other adverse events in each group, but event definitions and the safety reporting timeframe are not reported.

Finally, the posted unadjusted comparisons use propofol alone as the comparator; direct comparisons between alfentanil regimens are not reported. The record’s description of randomization and double blinding does not include enough operational detail to assess how those procedures were implemented.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Regimen of Alfentanil in Propofol Sedative Fibro-bronchoscopy — NCT01470170.
• Registry record last updated 2015-08-13; status last verified 2015-08.
• Results first posted 2015-08-13.
• 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.

21. Record Summary

NCT01470170 is a completed, randomized, double-blind, parallel-group Phase 4 trial sponsored by Chang Gung Memorial Hospital. The registry lists enrollment of 173 and a study period from 2010-10 to primary completion in 2011-09.

The study compared four alfentanil dose-and-timing regimens combined with propofol against propofol alone during flexible bronchoscopy sedation. The primary endpoint was the modeled propofol effect-site concentration at OAAS-3. Posted means were lower than control for Groups 1, 2, and 4; Group 3’s unadjusted interval included zero.

Hypoxemia and hypotension are listed as secondary outcomes, but their results are not reported in the registry record. The record also does not report the original sample-size justification, multiplicity plan, missing-data methods, or analysis populations.