This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Prospective Study to Assess the Hypotensive Efficacy of Rho-Kinase Inhibitor AR-12286 Ophthalmic Solution 0.5% and 0.7% in Patients With Exfoliation Syndrome and Ocular Hypertension or Glaucoma (NCT01936389), a randomized phase 2 study. The primary outcome is Evaluate the Ocular Hypotensive Efficacy of Rho Kinase Inhibitor (AR-12286 0.5% and 0.7%).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01936389 |
| Phase | Phase 2 |
| Condition | Exfoliation Syndrome, Ocular Hypertension, Open Angle Glaucoma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 10 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Robert Ritch, MD, LLC. |
| Results posted | Yes |
2. Clinical Question
Population
Patients with exfoliation syndrome and ocular hypertension or glaucoma. The listed conditions also include open-angle glaucoma. The registry does not report further details about the participants’ characteristics or the endpoint analysis population.
Intervention
AR-12286, a Rho-kinase inhibitor ophthalmic solution, at the 0.5% concentration. The registry describes both concentrations as study interventions.
Comparator
AR-12286 at the 0.7% concentration. This is an active-concentration comparison, not a comparison against a placebo or an untreated group in the posted arm results.
Primary question
What mean intraocular pressure, measured in mmHg by Goldmann applanation tonometry, was reported at the 6-month timeframe in each concentration arm? The registry’s stated primary objective is to evaluate ocular hypotensive efficacy.
Statistically, the central question is whether the outcome distributions in the two randomized arms differ in a way that can be estimated precisely enough to distinguish a treatment-related contrast from sampling variation. The posted results give a mean and standard deviation for each arm, but do not report a formal comparison, an estimated between-arm effect, a confidence interval, or a p value. The registry therefore allows a descriptive reading of each arm’s reported value, but not a determination of the precision or statistical significance of a contrast.
The record identifies a randomized, double-masked, parallel design. Random assignment is intended to make comparison groups more alike on average with respect to factors that could affect the outcome; masking is intended to limit influences from knowledge of assignment. These design features do not substitute for reporting how the outcome was analyzed or how complete the measurements were. Those details are not reported in the registry record.
The clinical question is specifically about the reported mean IOP at the stated timeframe. Whether the endpoint represents an absolute value, a change from baseline, or another summary is not made explicit in the endpoint description. Consequently, the reported arm means should not be interpreted as changes from baseline or as a treatment effect unless that interpretation is established elsewhere in the registry record.
3. Trial Design
The registry describes a completed Phase 2, randomized, double-masked, parallel study sponsored by Robert Ritch, MD, LLC. The study title identifies the investigational treatment as AR-12286 ophthalmic solution at 0.5% and 0.7%, in patients with exfoliation syndrome and ocular hypertension or glaucoma. The listed conditions also include open-angle glaucoma. Enrollment is recorded as 10.
The registry lists two parallel arms: 0.5% and 0.7%. Each arm has a posted sample size of 5. Both arms received AR-12286, so the posted results compare two concentrations of the same investigational drug rather than comparing the drug with placebo or usual care. The record identifies randomization and double masking, but does not report the method used to generate or conceal the allocation sequence, who was masked, or whether masking was maintained throughout the study.
The study start is recorded as 2013-09 and primary completion as 2014-10. The overall status is completed. The primary outcome is described as evaluation of ocular hypotensive efficacy, with IOP measured by Goldmann applanation tonometry and assessed at the 6-month timeframe. The registry reports mean values and standard deviations for the two arms.
The record does not report a sample-size justification, a planned treatment contrast, or a detailed statistical analysis plan. It also does not state whether randomization was stratified, whether treatment adherence was assessed, or how protocol deviations were handled. The population used in the primary analysis and the approach to missing outcome measurements are not reported in the registry record. These omissions limit the ability to assess how closely the posted summaries reflect the planned randomized comparison.
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
| Stage | 0.5% | 0.7% |
|---|---|---|
| STARTED | 5 | 5 |
| COMPLETED | 4 | 5 |
| NOT COMPLETED | 1 | 0 |
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.
| Characteristic | Unit | 0.5% | 0.7% | Total |
|---|---|---|---|---|
| Participants analysed | 5 | 5 | 10 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 | 0 | 2 |
| Age, Categorical: >=65 years | Participants | 3 | 5 | 8 |
| Sex: Female, Male: Female | Participants | 2 | 2 | 4 |
| Sex: Female, Male: Male | Participants | 3 | 3 | 6 |
6. Primary Endpoint
The registry lists the primary outcome as Evaluate the Ocular Hypotensive Efficacy of Rho Kinase Inhibitor (AR-12286 0.5% and 0.7%), measured over 6 months.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | mmHg |
| Endpoint classification | Continuous Endpoint |
The primary endpoint concerns ocular hypotensive efficacy, assessed using intraocular pressure in mmHg. The registry states that Goldmann applanation tonometry is used to measure IOP and gives a 6-month timeframe. IOP is the pressure measurement specified for the endpoint; the registry’s background describes it as relevant to the study of glaucoma and ocular hypertension. This is a continuous measure, so the posted results are expressed as arm means and standard deviations rather than as counts in outcome categories.
The registry reports a mean of 24.2 mmHg with a standard deviation of 2.4 for the 0.5% arm, and a mean of 25.8 mmHg with a standard deviation of 2.4 for the 0.7% arm. The reported endpoint description does not say whether these are measurements at the 6-month visit, changes from baseline, or another form of summary. The values should therefore be read as the posted arm-level means without assuming they represent change over time.
As a general statistical matter, a mean conveys the central value of a continuous outcome, while a standard deviation describes the spread of individual observations around that mean. Neither statistic alone establishes the size or precision of a between-arm effect. A formal comparison would require an explicitly defined contrast and an estimate of its uncertainty. Such a comparison is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports a mean IOP of 24.2 mmHg (standard deviation 2.4) for the 0.5% arm and 25.8 mmHg (standard deviation 2.4) for the 0.7% arm. Each arm has a posted sample size of 5. These are descriptive summaries of the outcome as entered in the registry. They do not, on their own, indicate how uncertain the difference between the arm means is or whether any observed contrast is compatible with chance variation.
No formal between-arm estimate, confidence interval, or p value is reported. The record lists no posted analyses. It is therefore not possible to characterize the precision of the treatment contrast from the registry results, or to determine whether a formal statistical test found evidence of a difference. The arm means can be read alongside their standard deviations, but the standard deviations describe within-arm spread, not the uncertainty around the difference between arms.
The interpretation also depends on what the reported endpoint values represent. The endpoint description gives the measure, instrument, and timeframe, but does not clarify whether the values are measurements at the 6-month visit or changes from baseline. Without that distinction, it would be inappropriate to describe the listed means as reductions, improvements, or changes. The registry does not report baseline IOP values in the posted results, so a baseline-to-follow-up pattern cannot be assessed from this record.
The small arm samples are important context for reading the summaries. With 5 participants in each arm, individual observations can have substantial influence on a mean and on estimates of variability. This does not establish that the reported values are unstable, but it means that a reader should not treat the descriptive means as precise estimates of the broader population response. A confidence interval would help express uncertainty in a mean or contrast, but no such interval is reported.
The posted information does not support a conclusion about whether either concentration is more effective, whether the concentrations are equivalent, or whether either treatment produces a clinically meaningful change. Those questions require a well-defined outcome contrast, uncertainty estimates, and clinical context. The record also does not report a predefined clinically important difference. Its results are best understood as brief descriptive summaries from a randomized concentration-comparison study, with the inferential comparison not reported in the registry record.
9. Statistical Methods Explained
The outcome is continuous, and the registry reports a mean and standard deviation for each arm. The following explains the statistical meaning of those summaries and the additional information that would normally help interpret a randomized comparison. General explanations are not claims about methods used in this study; details of the study’s statistical analysis are not reported in the registry record.
What does a mean describe?
In general, the mean is a measure of the center of a set of observations. For a continuous measure such as IOP, it provides a compact description of the average value in an arm. The mean can be useful for comparing groups, but it does not show the distribution of individual values, identify outliers, or communicate uncertainty about the population mean by itself.
The posted means are 24.2 mmHg for the 0.5% arm and 25.8 mmHg for the 0.7% arm. These are arm summaries, not an estimated treatment effect. A treatment effect for a two-arm comparison would ordinarily be defined as a contrast between groups, such as a difference in means, with its direction and interpretation specified. No such estimate is reported in the registry record. The endpoint description does not clarify whether the arm means refer to follow-up measurements or to changes from baseline, so the meaning of a potential contrast cannot be made more specific.
What does a standard deviation describe?
In general, a standard deviation describes how dispersed individual observations are around their group mean. The registry reports a standard deviation of 2.4 mmHg in each arm. This is information about variability among observed values, not a direct measure of the uncertainty of the arm mean or of a between-arm contrast.
Precision depends on both variability and the amount of information available. A confidence interval for a mean or treatment contrast would communicate a range of values compatible with the data under the analysis assumptions. The width of that interval reflects uncertainty; a narrower interval indicates greater precision than a wider interval. No confidence interval is reported for the arm means or for a contrast in the registry record. The standard deviations should not be substituted for confidence intervals.
What would a formal comparison add?
In general, a formal comparison would state the estimand, or the precise quantity being compared, and provide an estimate with an uncertainty measure. The analysis might compare follow-up means, changes from baseline, or another prespecified summary. Different choices can answer different questions, especially if baseline outcome values differ between groups. The registry’s endpoint description identifies IOP, the measurement instrument, and the timeframe, but does not specify which form of contrast was used.
A p value, when reported, summarizes how incompatible the observed data are with a specified null hypothesis under the assumptions of a statistical model. It does not measure the probability that a treatment effect is true, and it does not describe the size or clinical relevance of an effect. Here, no p value or formal analysis is reported. There is consequently no basis in the registry record to label the arm comparison statistically significant or not statistically significant.
Why does randomization matter?
As a general design principle, random assignment can reduce systematic differences between groups at the point of allocation, including differences in measured and unmeasured characteristics. It supports a causal interpretation when the trial is conducted and analyzed appropriately. Randomization does not guarantee that the groups will be similar in every characteristic, particularly in a small study. Nor does it eliminate the need to report the analysis population, missing outcomes, adherence, and protocol deviations.
The record identifies the study as randomized and double masked, but does not report the allocation procedure or the specific people masked. It also does not report whether the primary analysis followed the randomized assignment regardless of adherence, or whether another population was used. Those omissions matter because analysis choices can affect the meaning of an estimate.
How should a small study be read?
In general, a study with few observations per arm may provide limited precision, especially when outcomes vary among participants. A small sample can still produce useful descriptive information, but it often leaves substantial uncertainty around estimates and may be sensitive to individual observations. The registry records 5 participants in each arm. The record does not report a sample-size justification or a planned precision target, so it is not possible to assess whether enrollment was selected to achieve a particular inferential objective.
Sample-size planning is distinct from observed power. Planning estimates can illustrate how many participants per arm might be needed under stated assumptions, but they do not establish what the completed study could reliably detect. No calculated planning quantities are reported in the record details available for this analysis. Regardless of planning, the observed summaries do not replace a treatment-effect estimate and uncertainty interval.
Overall, the registry offers the arm means and standard deviations but does not report the inferential machinery needed to quantify the randomized comparison. These explanations describe general statistical principles, not a reconstruction of an unreported analysis.
10. Confidence Intervals for Each Arm
No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.
| Arm | Participants | Mean | Standard deviation | 95% CI for the mean |
|---|---|---|---|---|
| 0.5% | 5 | 24.200 | 2.400 | 21.220 to 27.180 |
| 0.7% | 5 | 25.800 | 2.400 | 22.820 to 28.780 |
R code and output
arm <- c("0.5%", "0.7%")
n <- c(5, 5)
m <- c(24.2, 25.8)
sp <- c(2.4, 2.4)
sd <- sp # posted standard deviations
for (i in seq_along(n)) {
se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}
CARM 0.5% 5 24.200 2.400 21.220 27.180
CARM 0.7% 5 25.800 2.400 22.820 28.78011. Multiplicity, Missing Data and Analysis Populations
The registry identifies one primary outcome measure and reports no secondary outcomes. It does not report a multiplicity adjustment or explain how multiple hypotheses, time points, or outcome measures were handled. When multiple comparisons are tested, the chance of obtaining at least one apparently notable result can increase; methods for controlling that issue depend on the analysis plan. This is a general statistical consideration, not a claim that a particular multiplicity procedure was used in this study.
Missing outcome data can affect both the estimated group summaries and the validity of a comparison. The registry does not report how many endpoint measurements were missing, why any measurements were missing, or whether missingness differed by arm. It also does not describe an imputation method, a sensitivity analysis, or another approach to incomplete outcomes. The posted arm sample sizes do not establish that all randomized participants contributed a measurement at the endpoint.
The analysis population is not described in the registry record. In general, an analysis based on randomized assignment answers a different question from one limited to participants who adhered to treatment or completed follow-up. Without the analysis-population definition, handling of discontinuations, adherence information, or protocol-deviation details, the relationship between the reported summaries and the randomized groups cannot be fully assessed.
The record also does not report an interim-analysis plan or whether any interim analyses occurred. These details should not be inferred from the completed status. Taken together, the absence of reported information on missingness, analysis populations, and multiplicity limits assessment of the analysis choices. It does not establish that the investigators used an inappropriate method; it means those methods are not reported in the registry record.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| 0.5% | 0 | 5 | 0.0% |
| 0.7% | 0 | 5 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| 0.5% | 1 of 5 |
| 0.7% | 0 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 0.5% | 0.7% |
|---|---|---|---|
| Conjunctivitis | Eye disorders | 1 of 5 | 0 of 5 |
The posted serious adverse event figures report 0 affected participants in the 0.5% arm, with 5 at risk, and 0 affected participants in the 0.7% arm, with 5 at risk. These entries describe the registry’s reported counts for serious adverse events; they do not establish that no serious events occurred outside the period or definitions captured by the registry entry. No serious adverse event terms are listed.
For other adverse events, the registry reports 1 affected participant among 5 at risk in the 0.5% arm, and 0 affected participants among 5 at risk in the 0.7% arm. These counts should be read as reported, without converting them into rates or comparing them as if they were precise estimates. The arm samples are small, and the record does not provide event descriptions, severity details, timing, attribution, or a broader safety analysis.
Deaths are not reported in the registry record. A zero count for reported serious events is not proof that risk is absent, and the adverse-event entries alone do not permit a comprehensive comparison of safety between concentrations.
13. What the Result Does, and Does Not, Mean
The results mean that the registry contains descriptive IOP summaries for two randomized concentration arms at a stated 6-month timeframe: a mean of 24.2 mmHg with standard deviation 2.4 for 0.5%, and a mean of 25.8 mmHg with standard deviation 2.4 for 0.7%. Each arm has a posted sample size of 5. The study is listed as completed, and its primary outcome is described as evaluating ocular hypotensive efficacy.
These summaries do not establish the size or precision of a treatment effect. The registry does not report a between-arm estimate, confidence interval, or p value, and it does not clarify whether the endpoint values are absolute measurements or changes from baseline. Therefore, the results should not be described as showing a particular reduction, a significant difference, or equivalence between concentrations. The absence of a formal comparison in the record is not evidence that the concentrations are the same.
Nor do these posted values show whether a difference would be clinically important. That judgment requires clinical context and a prespecified interpretation of what magnitude of change matters. The registry does not report a threshold for clinical importance. The results also cannot establish how the findings would generalize beyond the population studied, particularly because further participant characteristics and the analysis population are not reported.
Randomization and masking are relevant strengths of the stated design, but they do not resolve uncertainty created by limited reporting. In general, randomization supports comparison of assigned groups, while masking can reduce certain measurement and behavior biases. The record does not provide enough detail to evaluate implementation, outcome completeness, or analysis choices.
The most defensible reading is narrow: the registry reports arm-level means, standard deviations, and adverse-event counts for a small Phase 2 concentration comparison. It does not provide the inferential or contextual information needed to make stronger claims about treatment effect, precision, clinical importance, or comparative safety.
14. Why This Trial Matters Statistically
This study is statistically interesting because it presents a randomized, double-masked comparison of two concentrations of the same investigational treatment, with a continuous clinical measure as the primary outcome. Such a design can frame a direct comparison between treatment levels, while avoiding some sources of bias that can affect nonrandomized comparisons. The registry identifies those design features and reports an arm-level mean and standard deviation for each concentration.
The posted results also illustrate the distinction between descriptive statistics and comparative inference. Means describe the observed groups, and standard deviations describe within-group variability. A reader still needs an estimated contrast and its uncertainty to judge how precisely the groups differ. The registry does not report those statistics. Thus, the values can be described without making a claim about statistical significance or a treatment effect.
The record underscores why endpoint definition matters. It identifies IOP, a measurement instrument, and a timeframe, but does not say whether the reported values are endpoint measurements or changes from baseline. That distinction affects the interpretation of both the arm summaries and any comparison. Clear specification of the estimand, analysis population, and missing-data approach would make the results easier to evaluate.
The study’s limited arm samples further emphasize the value of uncertainty estimates and transparent analysis reporting. Small samples may leave wide uncertainty, but sample size alone does not tell the reader exactly how uncertain a result is. Confidence intervals and a clearly defined comparison would be more informative than relying on group summaries alone.
More broadly, this record shows how registration results can provide useful descriptive evidence while leaving important inferential questions unanswered. That is a reporting limitation, not a substitute for the complete clinical evidence base. The record should be read as a limited statistical account of the study rather than as a definitive assessment of treatment efficacy or safety.
15. 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 principal limitation is that the registry reports descriptive arm summaries but no formal comparison. No estimated difference, confidence interval, or p value is reported, so the precision and inferential meaning of the contrast cannot be evaluated. The record lists no posted analyses.
The endpoint description does not specify whether the means represent measurements at the 6-month visit or changes from baseline. Baseline IOP summaries are not included in the posted results. This makes it difficult to determine what quantity the arm means represent or what a clinically relevant contrast would be.
Each arm has a posted sample size of 5, and the overall enrollment is recorded as 10. This is a small study, and individual observations may have substantial influence on group summaries. The record does not report a sample-size justification, precision goal, or statistical analysis plan, so the intended inferential scope cannot be evaluated.
Important conduct and analysis details are also not reported in the registry record. These include the allocation procedure, who was masked, the analysis population, outcome completeness, missing-data handling, adherence, protocol deviations, and any sensitivity analyses. The record does not provide participant characteristics sufficient to assess the composition of the study population or the applicability of the results elsewhere.
Safety reporting is limited to serious and other adverse-event counts, with no event descriptions or detailed assessment. Deaths are not reported in the registry record. The listed adverse-event counts should therefore be treated as limited registry information rather than a comprehensive safety comparison. These limitations constrain interpretation of the reported summaries but do not, by themselves, demonstrate that the study was conducted improperly.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: A Prospective Study to Assess the Hypotensive Efficacy of Rho-Kinase Inhibitor AR-12286 Ophthalmic Solution 0.5% and 0.7% in Patients With Exfoliation Syndrome and Ocular Hypertension or Glaucoma — NCT01936389.
- Registry record last updated 2018-11-16; status last verified 2015-04.
- Results first posted 2015-04-24.
- 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.
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19. Record Summary
The registry record describes a completed, randomized, double-masked, parallel Phase 2 study sponsored by Robert Ritch, MD, LLC. It lists enrollment of 10 and two AR-12286 arms: 0.5% and 0.7%, each with a posted sample size of 5. The study start is recorded as 2013-09 and primary completion as 2014-10.
The primary outcome concerns ocular hypotensive efficacy, measured as IOP in mmHg using Goldmann applanation tonometry at the 6-month timeframe. The registry reports a mean of 24.2 and standard deviation of 2.4 for 0.5%, and a mean of 25.8 and standard deviation of 2.4 for 0.7%. It does not report a formal between-arm analysis, confidence interval, or p value. Missing-data methods, analysis populations, and a sample-size justification are not reported in the registry record.