POLAT-001 Compared to Latanoprost Ophthalmic Solution in Patients With Ocular Hypertension and Open-angle Glaucoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for POLAT-001 Compared to Latanoprost Ophthalmic Solution in Patients With Ocular Hypertension and Open-angle Glaucoma (NCT02466399), a randomized phase 2 study. The primary outcome is Mean Change in Intraocular Pressure Between Two Measures- Baseline and 3 Months.

2. Clinical Question

The primary endpoint is a continuous measure, reported in mmHg. The registry lists a mean change of -2.3 for POLAT-001 and -6.4 for latanoprost ophthalmic solution. The posted mean difference is -4.1 for the comparison of latanoprost solution with POLAT-001. This direction indicates that the reported mean change was more negative in the solution arm. Those values describe the trial results; they do not, by themselves, determine why the groups differed or settle the comparative clinical question.

3. Trial Design

The registry describes a randomized, open-label, multicenter, active-controlled, parallel comparison of POLAT-001 with latanoprost ophthalmic solution. The study was phase 2 and is listed as completed. Its registered enrollment is 80. The registry lists the study start as 2015-07 and primary completion as 2016-04.

Random allocation means treatment assignment was intended to use a chance-based process, but the method used to generate the allocation sequence and conceal assignments is not reported in the registry record. Open-label means the study was not masked; details about which participants or study personnel knew treatment assignments are not reported. The parallel design means the arms were compared alongside one another rather than participants being described as crossing between treatments.

The registry identifies POLAT-001 as a latanoprost liposome ophthalmic injection and the comparator as latanoprost ophthalmic solution 0.005%. The primary outcome was mean change in intraocular pressure from baseline at 3 months, assessed at 0800 hrs. The outcome population is described as per protocol. The registry reports endpoint counts of 45 for POLAT-001 and 27 for latanoprost ophthalmic solution. These endpoint counts are not the registered enrollment figure, and the record does not explain the difference.

The registry record does not report the treatment schedule, specific study locations, allocation sequence details, masking procedures beyond the unmasked designation, or reasons participants may not have contributed to the endpoint analysis. Those omissions limit how fully the study conduct can be reconstructed from the record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per protocol

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 Change in Intraocular Pressure Between Two Measures- Baseline and 3 Months, measured over 3 months.

The primary endpoint is the mean change in intraocular pressure from baseline to 3 months, measured at 0800 hrs and expressed in mmHg. It is reported for the per-protocol population. A change score compares a participant’s follow-up measurement with that participant’s baseline measurement; the arm-level mean describes the average of those changes among participants included in that analysis.

Intraocular pressure is a continuous measurement, so summarizing the mean change gives a compact description of the average direction and magnitude of change within each arm. Comparing mean changes between randomized arms addresses whether the observed average changes differed in this study. The posted arm means are -2.3 for POLAT-001 and -6.4 for latanoprost ophthalmic solution. Their standard deviations are 4.6 and 2.9, respectively, describing the spread of participant-level changes around each arm’s mean.

The specified measurement time matters because intraocular pressure may vary over time; the endpoint description fixes the assessment at 0800 hrs. The registry record does not report further details on measurement procedures, handling of repeated readings, or the clinical importance threshold for a difference. A mean change is a group summary and does not show every participant’s response. Nor does it alone establish the source of a between-arm difference.

7. Results Posted in the Registry

• Latanoprost Ophthalmic Solution: mean -6.40 versus -2.30 on control; difference -4.10 (95% CI -5.83 to -2.37), standardized effect d = -1.01; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous, and the registry describes it as a mean. The arm summaries report a mean change and a standard deviation for each treatment. The comparison is expressed as a mean difference, with a confidence interval and an unadjusted p-value. Together, these statistics describe the observed contrast and its uncertainty, but the registry record does not give the statistical analysis plan or identify the precise test used.

What does a mean change summarize?

A participant’s change score is the follow-up measurement minus the baseline measurement. The arm mean summarizes those participant-level changes. Negative values indicate that the follow-up value was lower than baseline under this subtraction convention. The registry reports mean changes of -2.3 for POLAT-001 and -6.4 for latanoprost ophthalmic solution. The standard deviations, 4.6 and 2.9, describe how dispersed the changes were around their respective means. They are not standard errors and should not be interpreted as confidence intervals.

Comparing change scores focuses on the change over time rather than simply comparing follow-up values. However, the record does not report whether an alternative model or baseline-adjusted analysis was also conducted. It also does not provide individual-level data, so the summaries cannot be used to examine distributions, outliers, or relationships between baseline measurements and follow-up changes.

How should the mean difference be read?

The posted contrast is latanoprost ophthalmic solution compared with POLAT-001. Its estimate is -4.1, calculated as the solution-arm mean change relative to the POLAT-001 mean change. Thus, its sign indicates that the solution-arm mean change was more negative. The confidence interval runs from -5.833 to -2.367. The direction and scale of a contrast depend on which arm is subtracted from which; reversing the comparison would reverse the signs, without changing the underlying separation described by the data.

A mean difference is a group-level contrast. It does not say that every participant in one arm had a larger or smaller change than every participant in the other arm. The amount of overlap between individual responses cannot be determined from the means and standard deviations alone. The record does not provide a clinical threshold for interpreting the magnitude of the contrast.

What does the p-value contribute?

The reported unadjusted p-value is <0.001. In general, a p-value measures how unusual data at least as inconsistent with a specified null model would be if that model and the test assumptions held. It is not a measure of the probability that the null hypothesis is correct, and it does not quantify the probability that the observed estimate arose by chance in an everyday sense. The word “unadjusted” indicates that the reported value is not presented as adjusted for multiple comparisons. The registry does not report the test statistic, degrees of freedom, sidedness of the primary endpoint test, or adjustment procedures.

The registry’s planning assumptions separately state a two-sided significance level of 0.05 for the sample-size illustrations. That stated planning assumption does not establish the test used for the trial’s primary result. The record lists no analysis entries, and does not identify who calculated the displayed comparison statistics or whether they were part of a sponsor analysis.

Why can variation affect the comparison?

Standard deviation represents participant-to-participant variability in observed change. When outcomes are more variable, an estimated mean difference is generally less precise for a given amount of information. In this record, the reported variability differs between arms. General statistical methods may account for unequal variability in different ways, but the registry record does not say which variance assumption or estimation procedure was used. It would therefore be inappropriate to infer a particular test solely from the summaries.

Over-dispersion is a concern when observed variation is greater than a model expects. In general, a model that understates variability can produce uncertainty estimates that are too narrow. For a continuous outcome, the specific concern is whether the assumed distribution and variance structure adequately represent the data. The registry does not report diagnostics, distributional checks, or alternative analyses, so the adequacy of any such assumptions cannot be assessed from this record.

What does the analysis population imply?

The primary endpoint population is per protocol. In general, this refers to participants considered to have met specified protocol requirements, but the particular requirements and exclusions are not reported in the registry record. A per-protocol analysis is not interchangeable with an analysis that retains participants according to randomized assignment regardless of adherence or protocol deviations. Because the registry does not report an intention-to-treat analysis, the results cannot be compared across those analysis populations.

The endpoint counts differ from the registered enrollment figure. The record does not report the reasons for this, the amount or pattern of missing outcome data, or how missing measurements were handled. These details matter because a comparison can be affected if inclusion in the analysis is related to treatment assignment or outcome. Without participant flow and missing-data methods, the possible direction or size of such effects is unknown.

10. Confidence Intervals and Precision

The reported mean difference is -4.1 mmHg, with a confidence interval from -5.833 to -2.367. A confidence interval gives a range of values compatible with the observed data under the statistical procedure and its assumptions. It conveys uncertainty about the estimated mean contrast; it is not a range containing a fixed share of individual participant changes, nor is it a guarantee that the true value lies within the interval.

The interval is entirely on the negative side of zero, matching the negative estimated contrast and indicating that the reported data are more compatible with a negative rather than a zero contrast under the interval procedure. The p-value is reported as <0.001, but the registry record does not report the confidence-interval method or enough analysis detail to independently assess its assumptions. The interval should therefore be interpreted as a posted statistical summary, not as a substitute for a complete analysis report.

Precision is distinct from the size of an estimate. The point estimate describes the observed mean difference; the interval shows uncertainty around that estimate. The arm standard deviations, 4.6 and 2.9, describe variability among observed changes and are different from uncertainty around the contrast. No confidence intervals are reported for the separate arm means.

The endpoint is restricted to the per-protocol population, and its reported counts are 45 for POLAT-001 and 27 for latanoprost ophthalmic solution. The registry record does not describe missing outcomes, participant flow, or reasons for exclusion from this analysis. Statistical precision conditional on the analyzed data does not address possible selection or missing-data concerns. Nor does it establish how precisely the result would apply beyond the participants and setting represented in the trial.

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 event counts. They are illustrative calculations based on the observed mean difference, not the trial’s original design assumptions. The registry’s stated assumptions are a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. Each planning scenario uses a stated fraction of the observed effect. The trial’s own sample-size justification and original design assumptions are not reported in the registry record.

At 100% of the observed effect, the illustration gives 16 participants per arm for 80% power and 21 participants per arm for 90% power. At 75% of the observed effect, it gives 28 participants per arm for 80% power and 37 participants per arm for 90% power. At 50% of the observed effect, it gives 62 participants per arm for 80% power and 83 participants per arm for 90% power. The 80% and 90% columns describe the probability, under the planning model and its assumptions, of detecting the specified effect at the stated significance level. They are not guarantees about a future study.

For a fixed planning framework, smaller effects generally require more participants to detect. The displayed scenarios illustrate that relationship by reducing the effect fraction while increasing the required per-arm sample sizes. The calculations use the observed effect as their starting point, so they should not be treated as evidence that the original trial was designed around those values. This is a planning illustration, not observed power.

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 = -4.100; pooled standard deviation σ = 4.053.
2. n = 2 × (1.96 + 0.842)² × 4.053² / -4.100² = 15.3, rounded up to 16 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 <- -4.1                      # observed difference in means
sigma <- 4.05268870187259                     # 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(2466399)
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 = 16 (80% power), 21 (90% power)
 75% of observed effect: n per arm = 28 (80% power), 37 (90% power)
 50% of observed effect: n per arm = 62 (80% power), 83 (90% power)
power.t.test: 16.4 
Simulated power at n = 16 per arm: 0.787 (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 registry record lists one primary outcome measure and no posted secondary outcomes. It lists no analysis entries. The available comparison includes an unadjusted p-value, but the record does not report a complete analysis plan, any prespecified hierarchy of outcomes, or a multiplicity-adjustment method. The presence of an unadjusted p-value does not establish how many analyses were considered during the study or whether additional analyses were conducted but not registered.

Multiplicity arises when several hypotheses or outcomes are tested: with repeated testing, the chance of at least one apparently notable result can increase. In general, prespecifying primary analyses and explaining any adjustment helps readers understand the evidential role of each result. Here, the registry record does not report enough detail to determine whether the primary outcome was the only outcome analyzed or whether multiple comparisons were considered. No adjusted p-value is reported.

The primary outcome is described for the per-protocol population. The record does not report an intention-to-treat analysis, the criteria defining per-protocol status, or whether those criteria were set before outcome data were examined. It also does not describe participant flow from enrollment to endpoint analysis. The endpoint counts are 45 for POLAT-001 and 27 for latanoprost ophthalmic solution, while registered enrollment is 80; the reasons those counts differ are not reported.

Missing-data handling is also not reported in the registry record. It does not state how absent measurements were treated, whether any imputation was used, or whether sensitivity analyses assessed alternative assumptions. In general, missing outcomes can affect a treatment comparison when the likelihood of having an observed outcome is related to treatment assignment or the outcome itself. Without details about who was missing and why, the potential impact cannot be assessed from the summary statistics.

These gaps do not show that a particular bias occurred. They mean that the robustness of the comparison to analysis-population choices, missing data, or multiple testing cannot be evaluated from the registry record alone.

14. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: bone and bladder cancer (1.9%).

The serious adverse event figures use the registry’s reported at-risk groups: 53 for POLAT-001 and 27 for latanoprost ophthalmic solution. The registry reports 1 serious adverse event affecting participants in the POLAT-001 group and 0 in the solution group. Deaths are reported as 0 in each group. The record lists “bone and bladder cancer” at 1.9% among the top serious adverse event terms. It does not provide additional detail about that term in the listed results.

These counts are descriptive safety summaries. A count of zero in a group does not demonstrate that an event cannot occur, and a count of one does not by itself establish that treatment caused the event. The record does not report event-level timing, seriousness criteria, relatedness assessments, or participant-level narratives. It also does not provide enough information to determine whether the listed term corresponds to the serious event count in a specific arm.

For other adverse events, the registry reports 14 affected participants among 53 at risk in the POLAT-001 group and 1 among 27 at risk in the solution group. These figures describe reported events in this trial and should not be interpreted as a controlled estimate of comparative risk without further information about ascertainment and follow-up. The registry record does not report a detailed safety analysis plan.

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

The posted results describe a difference in mean intraocular-pressure change at 3 months between the per-protocol groups. Mean change was -2.3 mmHg for POLAT-001 and -6.4 mmHg for latanoprost ophthalmic solution. The reported contrast, defined as solution compared with POLAT-001, was -4.1 mmHg, with a confidence interval from -5.833 to -2.367 and an unadjusted p-value of <0.001. These statistics summarize the observed comparison under the reported analysis population.

The results do not establish that the observed difference was caused solely by treatment assignment. Randomization is a strength of the design, but the registry does not report allocation details, participant flow, missing-data handling, or the full statistical analysis plan. The trial was open-label, and the outcome population was per protocol. The record does not provide an intention-to-treat result or an analysis addressing the effects of missing endpoint data.

Nor do the means show how individual participants changed, how much their responses overlapped, or whether the contrast meets a clinical importance threshold. The registry record does not report such a threshold. The posted comparison does not establish results for populations beyond those represented in this trial, or for treatment schedules and settings not described in the record.

The safety figures are similarly descriptive. The registry reports one serious adverse event in the POLAT-001 at-risk group and none in the solution group, with no deaths reported in either group. Sparse counts and limited event detail do not establish comparative safety. The listed other-adverse-event counts also require caution because event collection and adjudication methods are not reported.

Overall, the registry supports a precise description of the posted mean contrast and its statistical uncertainty, but gaps in methods and participant accounting limit a broader interpretation. The findings should not be turned into medical advice or a conclusion about which treatment to use.

16. Why This Trial Matters Statistically

This trial illustrates why a reported effect estimate needs to be read alongside its uncertainty, analysis population, and study conduct. The mean difference of -4.1 is informative about the observed average contrast, while its confidence interval from -5.833 to -2.367 gives a separate view of statistical precision. Neither statistic reveals individual response patterns or clinical importance by itself.

The endpoint counts and registered enrollment also show why participant accounting matters. The endpoint was reported for a per-protocol population, and the registry does not explain why the endpoint counts differ from the registered enrollment of 80. Without participant flow, criteria for per-protocol inclusion, and missing-data methods, readers cannot determine whether the analyzed participants fully represent those enrolled or randomized.

The open-label design and incomplete analysis documentation are relevant to interpretation. The registry identifies randomization, but does not report how assignment was generated or concealed, which analysis procedure produced the comparison, or whether sensitivity analyses were done. These omissions do not prove that the result is biased; they limit the ability to assess robustness.

The trial also provides a useful distinction between observed results and planning illustrations. The sample-size scenarios are calculated from the observed effect under stated assumptions. They do not establish the study’s original design rationale, and they are not observed power. Interpreting such calculations as if they documented prospective planning would confuse a later illustration with the trial’s design process.

Statistically, the registry is most informative when its numerical results are presented with these boundaries: what was measured, in whom it was analyzed, and what remains undocumented. That approach preserves the value of the reported comparison without claiming more than the record can support.

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 provides only limited detail about trial conduct and analysis. It identifies the study as randomized and open-label, but does not report the allocation sequence method, concealment procedures, treatment schedule, measurement procedures, or protocol criteria for the per-protocol population. As a result, those features cannot be evaluated from the registry description.

The primary endpoint counts are 45 for POLAT-001 and 27 for latanoprost ophthalmic solution, while registered enrollment is 80. The record does not explain this difference or provide a participant-flow account. It also does not report missing-data handling, reasons for exclusion from the per-protocol analysis, or results from an analysis of all participants according to assignment.

The registry does not report the precise statistical test, model specification, confidence-interval method, distributional checks, or sensitivity analyses. The comparison includes an unadjusted p-value, but no full analysis plan or multiplicity procedure is reported. The record also lists no secondary outcomes and no analysis entries, limiting the context available for understanding whether other analyses were considered.

Safety information is summarized with event counts and at-risk group counts, but details about timing, event adjudication, relationship to treatment, and methods of collection are not reported. The reported serious-event and other-event counts therefore cannot provide a complete account of safety assessment. These are limitations of the registry record; they do not establish that the underlying trial lacked procedures that are not described there.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: POLAT-001 Compared to Latanoprost Ophthalmic Solution in Patients With Ocular Hypertension and Open-angle Glaucoma — NCT02466399.
• Registry record last updated 2020-11-16; status last verified 2020-09.
• Results first posted 2020-11-16.
• 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

NCT02466399 is a completed phase 2 randomized, open-label, multicenter, active-controlled parallel comparison of POLAT-001 and latanoprost ophthalmic solution. Registered enrollment is 80. The registry lists the start as 2015-07 and primary completion as 2016-04.

The primary outcome is mean change in intraocular pressure from baseline at 3 months, measured at 0800 hrs in the per-protocol population. The posted arm means are -2.3 for POLAT-001 and -6.4 for latanoprost ophthalmic solution. The reported solution-versus-POLAT-001 mean difference is -4.1, with a confidence interval from -5.833 to -2.367 and an unadjusted p-value of <0.001.

The registry also reports serious and other adverse-event counts. Further information about participant flow, missing data, analysis methods, and safety assessment is not reported in the registry record.