Inhaled Corticosteroids: Effect on Intraocular Pressure in Patients With Controlled Glaucoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Inhaled Corticosteroids: Effect on Intraocular Pressure in Patients With Controlled Glaucoma (NCT02338362), a randomized phase 4 study. The primary outcome is Mean Intraocular Pressure.

2. Clinical Question

3. Trial Design

The registry describes a completed, phase 4, randomized, quadruple-masked, parallel-group trial sponsored by University Health Network, Toronto. The recorded enrollment was 22. The arm descriptions say participants were asked to use either fluticasone propionate or saline placebo for 6 weeks, with one inhaler puff twice daily in each arm. The primary outcome summaries report 10 participants in each arm. The registry record does not explain how the enrollment figure relates to the outcome-summary counts.

The study population was people with ocular hypertension or open-angle glaucoma. Its stated purpose was to determine whether inhaled corticosteroid treatment would produce a clinically meaningful elevation in intraocular pressure in this population. The primary outcome was mean intraocular pressure at week 6, assessed using Goldmann applanation tonometry. The description specifies that the recorded value was the mean of 2 measurements within 1 mmHg.

The posted primary results give the mean and standard deviation for each arm, along with a mean difference and confidence interval. The registry record lists no reported analyses. Details of the randomization sequence, allocation concealment, masking procedures, adherence to the assigned treatment beyond the posted adherence outcome, and the analysis population are not reported in the registry record. Nor are the original sample-size assumptions, any planned interim analyses, or the original statistical analysis plan reported in the registry record.

The secondary outcomes include mean visual acuity, side effects, intraocular pressure elevation greater than 20% from baseline, and adherence. Results are posted for visual acuity and adherence, while the registry record does not provide results for every listed secondary outcome. These design and reporting details matter when judging both the strength of the comparison and how broadly it can be interpreted.

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: 22 consented to participate and 20 completed the study.

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 Mean Intraocular Pressure, measured over week 6.

The primary endpoint is mean intraocular pressure at week 6, measured in mmHg. Intraocular pressure is the pressure within the eye; the registry selected it to assess whether inhaled corticosteroid exposure was accompanied by a change in pressure among people with ocular hypertension or controlled open-angle glaucoma. The endpoint therefore addresses the study’s stated question directly, rather than relying on a broader clinical outcome.

Measurements were made using Goldmann applanation tonometry. The registry description says the recorded value was the mean of 2 measurements within 1 mmHg. Averaging repeated measurements can reduce the influence of random measurement variation, while the specified device and procedure define how the outcome was assessed. The record does not report further details about assessor training, measurement reliability, or the handling of readings that did not meet the specified condition.

The endpoint is continuous: each participant can have a pressure measurement across a range of values, and the arm summaries describe the mean and standard deviation. Comparing arm means estimates the average difference between assigned groups. That average does not reveal every participant’s measurement or the range of individual responses. Nor does the registry report a threshold for a clinically meaningful difference in the primary endpoint. The study description refers to a clinically meaningful elevation, but the value defining such an elevation is not reported in the registry record.

7. Results Posted in the Registry

• Fluticasone: mean 14.70 versus 14.80 on control; difference -0.10 (95% CI -2.89 to 2.69), standardized effect d = -0.03; z-test p = 0.944.

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.

Mean Visual Acuity

• 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:
  • Fluticasone: mean 0.15 versus 0.15 on control; difference 0.00 (95% CI -0.09 to 0.09), 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 Fluticasone and the control. The interval gives the range of effects that remain compatible with the data.

Adherence

• 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:
  • Fluticasone: mean 93.60 versus 96.10 on control; difference -2.50 (95% CI -7.68 to 2.68), standardized effect d = -0.42; z-test p = 0.344.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Fluticasone and the control. The interval gives the range of effects that remain compatible with the data.

The secondary results include mean visual acuity and adherence. The registry also lists side effects and intraocular pressure elevation greater than 20% from baseline as secondary outcomes, but results for those outcomes are not reported in the registry record. The posted visual-acuity means are identical, while the adherence summaries are somewhat different; both comparisons have uncertainty intervals that include zero. Those secondary observations do not materially change the broad reading of the primary result: the primary mean difference is close to zero but imprecise.

Secondary endpoints can add context by showing whether related measurements or study conduct followed a similar pattern. Visual acuity is a distinct outcome from intraocular pressure, so a similar or different pattern does not substitute for the primary pressure comparison. Adherence helps describe use of the assigned inhalers, but it does not establish the biological effect of treatment. The record’s listed threshold outcome could have provided a complementary view of participants with larger pressure increases, but its result is not reported in the registry record.

The secondary comparisons carry less weight than the primary result for several reasons. They are not the stated primary endpoint, the registry record does not report a complete analysis plan, and multiple outcomes create more opportunities for chance findings when each is examined separately. The posted p-values are unadjusted. Without a reported multiplicity strategy, an isolated secondary difference would require cautious interpretation rather than being treated as confirmatory evidence.

The record lists 4 secondary outcomes, while outcome summaries are posted for only some of them. Reasons for the unavailable secondary results, and any procedures for handling missing measurements, are not reported in the registry record. The overall secondary pattern can therefore provide descriptive context, but it cannot establish a comprehensive safety or efficacy profile or resolve the uncertainty around the primary estimate.

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

• Mean Visual Acuity
• Side Effects
• Intraocular Pressure Elevation >20% From Baseline
• Adherence

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is a continuous measurement, and the registry reports its mean and standard deviation in each treatment arm. A mean gives the arithmetic average of the observed measurements. A standard deviation describes how spread out those measurements are around the mean. These summaries answer different questions: the mean locates the group average, while the standard deviation describes within-arm variability. Neither one alone describes the uncertainty in the comparison between arms.

What does the mean difference represent?

The posted mean difference is fluticasone minus saline placebo. Its estimate is -0.1 mmHg, based on means of 14.7 mmHg and 14.8 mmHg, respectively. A negative value indicates that the observed mean was lower in the fluticasone arm. The sign is a matter of the chosen subtraction order; it does not by itself indicate benefit, harm, or clinical importance. The estimate concerns an average group difference, not the pressure change for every participant.

For a continuous outcome, comparing arm means is a straightforward way to express the difference in the original measurement units. That makes the result interpretable in mmHg. The registry record does not report an adjusted analysis, such as one accounting for baseline pressure, and does not describe the original statistical model. The posted result should therefore be read as the arm-level comparison recorded, without assuming that baseline adjustment or other covariate adjustment was used.

What does the confidence interval add?

A confidence interval gives a range of values reasonably compatible with the observed data under the statistical method used. The primary interval runs from -2.886 to 2.686 mmHg. It includes zero, the value corresponding to no difference in means, but it also includes values on both sides of zero. The interval communicates uncertainty in the estimated mean difference more directly than the point estimate alone.

General statistical explanation: an interval that includes zero does not prove that there is no underlying difference. It indicates that the data do not sharply distinguish zero from other values included in the interval under the method’s assumptions. An interval can include differences that would matter clinically, depending on the clinical threshold. No threshold for a clinically meaningful primary-outcome difference is reported in the registry record, so the interval cannot be classified against such a benchmark.

How should the p-value be read?

The unadjusted p-value is 0.944. A p-value measures how unusual data at least as incompatible with a specified null model would be if that model and its assumptions held. It is not the probability that the null hypothesis is true, nor is it a measure of the size or clinical importance of an effect. A large p-value does not establish equivalence or rule out an important difference. The registry record does not report a multiplicity adjustment or a full prespecified testing strategy, so the p-value should be understood as unadjusted.

General statistical explanation: a p-value is most informative when considered alongside the effect estimate, confidence interval, design, and analysis plan. For this trial, the small observed mean difference and broad interval together convey more about the result’s precision than the p-value alone.

Why does variation matter?

The observed standard deviations were 2.4 mmHg for fluticasone and 3.8 mmHg for saline placebo. Within-arm variation affects how precisely a mean and the between-arm difference can be estimated. When observations vary more, a similar amount of participant information generally produces less precise estimates. This is a general statistical principle; it does not identify why measurements varied in this trial.

General statistical explanation: standard deviations are not standard errors. A standard deviation describes variation among individual measurements; a standard error describes uncertainty in an estimate such as a mean. The registry also posts standard errors for the arm means, but the primary interpretation is supported by the mean difference and its confidence interval. The registry record does not detail the exact procedure used to construct the posted interval.

What is not documented?

The registry record lists no reported analyses. It does not report the original statistical analysis plan, the method for handling missing outcome data, the analysis population, or whether any outcome data were excluded. It also does not report baseline outcome summaries or an adjusted primary analysis. These omissions prevent a reader from checking whether the posted comparison followed a prespecified plan or from assessing the possible influence of missing data and baseline imbalance.

General statistical explanation: randomization supports a comparison by making treatment groups comparable on average, but the actual quality of inference still depends on implementation, follow-up, outcome measurement, and analysis. Masking can help limit some forms of bias, but the registry’s quadruple-masking label does not itself establish how masking was maintained. The posted numerical results should therefore be interpreted in light of both the trial’s randomized design and the analysis details that are not reported in the registry record.

11. Confidence Intervals and Precision

The primary mean difference is -0.1 mmHg, with a confidence interval from -2.886 to 2.686 mmHg. This range is wide around the point estimate and crosses zero. It is compatible with a lower mean pressure in the fluticasone arm, little difference, or a higher mean pressure in that arm. The interval therefore conveys appreciable uncertainty about both the direction and size of the underlying difference.

Precision is not the same as whether a result is statistically significant. The p-value is 0.944, but the central issue for interpretation is that the interval includes a range of effects rather than concentrating closely around the estimate. The registry record does not provide a threshold for a clinically meaningful change in the primary endpoint. Without that benchmark, the range cannot be formally classified as excluding or including only clinically unimportant differences.

The primary outcome summaries list 10 participants per arm, and the standard deviations are 2.4 mmHg and 3.8 mmHg. These summaries give context for the variability underlying the comparison. They do not resolve the uncertainty represented by the interval. The estimate is best read as a near-zero observed difference accompanied by limited precision, rather than as evidence that the groups’ underlying mean pressures were exactly the same.

Confidence intervals also depend on the statistical method and its assumptions. The registry record does not describe the interval-construction method in detail, and it lists no reported analyses. Accordingly, the interval is useful as the posted measure of uncertainty, but the record does not allow a full audit of its analytical derivation.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. They are illustrations based on the observed effect rather than the trial’s original design assumptions. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The trial’s own sample-size assumptions are not reported in the registry record.

The 80% power column describes the number of participants per arm an illustrative future study would need, under those assumptions, to have an 80% chance of detecting the specified effect if that effect were the true one. The 90% power column uses a higher target chance of detection, and consequently lists a larger required number of participants per arm for each effect scenario. The scenarios describe planning for 100%, 75%, or 50% of the observed effect. Smaller effects require more participants because they are harder to distinguish from random variation.

For the primary outcome, the planning figures are 15,855 participants per arm for 80% power and 21,225 participants per arm for 90% power when planning for 100% of the observed effect. For 75% of the observed effect, the corresponding figures are 28,187 and 37,734 participants per arm. For 50% of the observed effect, they are 63,419 and 84,900 participants per arm. These large estimates reflect the very small observed mean difference used as the planning basis; they are not a recommendation or a claim about the appropriate design for a future study.

These figures are not observed power. They are planning illustrations derived from the observed effect, and they should not be treated as a retrospective measure of the trial’s success. A planning curve represents the same relationship: as the target effect becomes smaller, the required sample size rises under the stated assumptions.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.100; pooled standard deviation σ = 3.178.
2. n = 2 × (1.96 + 0.842)² × 3.178² / -0.100² = 15,854.7, rounded up to 15,855 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 <- -0.100000000000001                      # observed difference in means
sigma <- 3.17804971641414                     # 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(2338362)
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 = 15,855 (80% power), 21,225 (90% power)
 75% of observed effect: n per arm = 28,187 (80% power), 37,734 (90% power)
 50% of observed effect: n per arm = 63,419 (80% power), 84,900 (90% power)
power.t.test: 15855.7 
Simulated power at n = 15,855 per arm: 0.799 (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 one primary outcome and 4 secondary outcomes. Testing or examining several outcomes can raise the chance of seeing an apparently unusual result by chance, particularly when each comparison is considered independently. The posted p-values are unadjusted. A multiplicity adjustment, hierarchy for interpreting outcomes, or other prespecified strategy is not reported in the registry record. Accordingly, secondary findings should be treated as exploratory or descriptive unless an analysis plan elsewhere establishes a different status.

The record reports no analyses and does not provide a statistical analysis plan. It does not say whether the primary comparison was prespecified in the form posted, whether any subgroup or sensitivity analyses were planned, or whether there were interim analyses. Those details are not reported in the registry record. Their absence does not show that such procedures did or did not occur; it limits what can be verified from the registry entry.

Missing-data handling and the analysis population are also not reported in the registry record. The primary outcome summaries list 10 participants in each arm, while recorded enrollment is 22. The record does not explain this relationship or state whether all randomized participants contributed to the primary analysis. It does not report the amount, reasons, or treatment-arm distribution of missing outcome data, nor whether imputation or another method was used.

General statistical explanation: missing outcomes can affect a comparison when the chance of being observed is related to treatment or outcome. The direction and size of any effect cannot be inferred without information about who was missing and why. Likewise, an intention-to-treat analysis and a per-protocol analysis answer related but distinct questions; the registry record does not identify which analysis population was used.

These reporting gaps matter because randomization alone does not describe how outcome data were handled after assignment. The posted estimates remain useful summaries of the results in the record, but the missing analysis details limit assessment of robustness, selective reporting, and the scope of conclusions.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event record lists 0 serious adverse events among 10 participants at risk in the fluticasone arm and 0 among 10 at risk in the saline placebo arm. It lists 2 participants affected by other, non-serious adverse events in each arm, with 10 participants at risk in each. These are the counts recorded; they do not establish that all possible adverse events were captured or that the groups had identical safety experiences.

No deaths are listed in the posted adverse-event summaries; the death counts are not reported in the registry record. The record also provides no serious adverse event terms, and it does not give descriptions, severity, timing, or attribution for the other adverse events. A count of affected participants is not a full description of event type or clinical course.

Because the outcome summaries are limited in size and follow-up was described as 6 weeks, the adverse-event counts should be read descriptively. They do not determine whether uncommon events could occur, and they do not provide a comprehensive comparison of safety. No treatment recommendation follows from these figures.

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

The registry reports a randomized comparison of inhaled fluticasone propionate with saline placebo in people with ocular hypertension or controlled open-angle glaucoma. At week 6, the observed mean intraocular pressures were 14.7 mmHg and 14.8 mmHg, respectively. The estimated mean difference was -0.1 mmHg, with a confidence interval from -2.886 to 2.686 mmHg. This describes a small observed difference, with uncertainty that includes effects in either direction.

The result does not establish that the treatments are equivalent, nor does it rule out a clinically meaningful pressure change. The registry record does not report a clinical-importance threshold for the primary endpoint. It also does not report the result for the listed secondary outcome of intraocular pressure elevation greater than 20% from baseline. Therefore, the mean comparison should not be interpreted as a direct evaluation of that threshold outcome.

The study’s population and duration define the scope of the posted evidence. The intervention was used for 6 weeks in a population with ocular hypertension or open-angle glaucoma. The registry record does not support extending the result to other populations, other corticosteroids, other dosing schedules, or longer durations. Nor does the record provide enough information to determine how missing outcomes or deviations from assigned treatment were handled.

The trial’s small outcome summaries and broad interval mean that the estimated difference is not precise. The p-value of 0.944 does not change that interpretation and is not evidence that no effect exists. The registry also does not report the original statistical analysis plan, a multiplicity strategy, or the original sample-size rationale, which limits assessment of the full analytical context.

In statistical terms, the posted result is an uncertain estimate of the between-arm difference at the stated assessment time. It can inform understanding of what was observed in this randomized study, but it cannot settle the possibility of smaller, larger, or subgroup-specific effects. These are descriptions of the registry results, not medical advice.

17. Why This Trial Matters Statistically

This trial raises a focused statistical question: whether a short course of inhaled corticosteroid is associated with a difference in mean intraocular pressure in people with ocular hypertension or controlled open-angle glaucoma. The randomized, masked, parallel-group design is relevant because it compares assigned treatments while aiming to reduce some sources of bias. The primary endpoint is a direct continuous measurement, expressed in clinically interpretable units.

The main statistical lesson is the distinction between a small point estimate and a precise conclusion. The observed mean difference is -0.1 mmHg, but its confidence interval extends from -2.886 to 2.686 mmHg. A near-zero estimate does not mean the true difference is known to be near zero; the interval shows that the data remain compatible with a wider range of values. This is why uncertainty should be interpreted alongside the point estimate and not replaced by the p-value alone.

The record also illustrates the value of transparent reporting. It posts group summaries and a confidence interval, but does not report the analysis plan, handling of missing data, analysis population, original sample-size assumptions, or multiplicity strategy. These omissions make it harder to evaluate how the analysis was specified and whether the posted results represent all intended outcomes.

Finally, the planning illustrations show how sample-size requirements depend on the effect chosen for detection. Because the observed primary difference is small, illustrations based on fractions of that difference produce large per-arm requirements. These are not observed power and do not reveal the original rationale for this trial. They instead demonstrate why planning should be based on a clinically meaningful target and explicit assumptions, which are not reported in the registry record.

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 based on outcome summaries listing 10 participants per arm, and its confidence interval is broad. This limits precision. The registry’s recorded enrollment is 22, but the relationship between enrollment and the primary outcome counts is not explained. The record does not report whether participants were excluded from analysis, whether outcomes were missing, or why the summary counts differ from the enrollment figure.

The assessment is reported at week 6, following the described 6-week inhaler course. The registry record does not provide later follow-up results, so the posted information does not address persistence or change after this assessment. It also does not report a threshold for a clinically meaningful difference in mean intraocular pressure. Although a greater-than-20% elevation from baseline is listed as a secondary outcome, its results are not reported in the registry record.

The registry does not report baseline intraocular pressure by arm, an adjusted primary analysis, or the original statistical analysis plan. It also does not explain the method used to construct the confidence interval or describe how missing data were handled. These gaps restrict assessment of baseline comparability, analytic choices, and robustness to alternative assumptions.

The record lists 4 secondary outcomes but does not post results for every listed outcome. No multiplicity strategy is reported, and the posted p-values are unadjusted. The adverse-event record provides counts but not descriptions or timing of events; death counts are not reported in the registry record. Finally, findings from this population and treatment duration should not be assumed to apply to other populations, corticosteroids, regimens, or durations.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Inhaled Corticosteroids: Effect on Intraocular Pressure in Patients With Controlled Glaucoma — NCT02338362.
• Registry record last updated 2019-05-03; status last verified 2019-04.
• Results first posted 2019-05-03.
• 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

NCT02338362 is a completed, phase 4, randomized, quadruple-masked, parallel-group trial comparing fluticasone propionate inhaler with saline placebo in people with ocular hypertension or open-angle glaucoma. The described inhaler schedule was one puff twice daily for 6 weeks. The primary endpoint was mean intraocular pressure at week 6, assessed by Goldmann applanation tonometry.

The posted primary means were 14.7 mmHg for fluticasone and 14.8 mmHg for placebo. The mean difference was -0.1 mmHg, with a confidence interval from -2.886 to 2.686 mmHg and an unadjusted p-value of 0.944. The estimate is close to zero but imprecise. The registry record does not report the original analysis plan, missing-data methods, analysis population, or sample-size assumptions.