Effect of Myocilin Genetic Variants on Intraocular Pressure and Pressure Variation in Sitting and Supine Positions: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Myocilin Genetic Variants on Intraocular Pressure and Pressure Variation in Sitting and Supine Positions (NCT00906087), a na phase 4 study. The primary outcome is Intraocular Pressure in Sitting and Supine Positions..

2. Clinical Question

3. Trial Design

This was a Phase 4, completed, single-group study sponsored by the University of Michigan. The registry lists an enrollment of 14 and describes the condition as glaucoma. The study started on 2009-08-04, and primary completion was recorded on 2012-07-18. The record identifies Cosopt, a combination eyedrop of dorzolamide and timolol, as the drug intervention.

The planned measurement conditions were after washout of clinical treatment, after treatment with Cosopt, and after another washout of Cosopt. This sequence indicates that the registry intended to examine measurements under different treatment conditions in the study group. It does not make the study a randomized parallel-group trial: allocation is listed as NA, the model is single group, and masking is none. The registry record does not give further details about the duration or implementation of each condition beyond the primary outcome timeframe of 10 weeks.

The primary outcome is titled “Intraocular Pressure in Sitting and Supine Positions.” It is described as the effect of Cosopt treatment on intraocular pressure changes from sitting to supine positions. The registry characterizes the measure as a mean of a continuous measure, with standard deviation as the dispersion measure and mmHg as the unit. A secondary outcome is listed for the myocilin mutation Arg272Gly in subjects.

The registry lists three outcome measures but no analyses. Numerical primary-outcome estimates, variability results, and results for the secondary outcome are not reported in the registry record. A sample-size justification, detailed statistical analysis plan, and further information about the study’s measurement schedule are also 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.

Initial Washout

Reasons for not completing this period:

Cosopt Treatment 6 Weeks

Final Washout Period 4 Weeks

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 Intraocular Pressure in Sitting and Supine Positions., measured over 10 weeks.

The primary endpoint concerns intraocular pressure measured in sitting and supine positions. The registry describes the target as the effect of Cosopt treatment on the change in intraocular pressure when moving from sitting to supine. Intraocular pressure is recorded in mmHg, and the endpoint is characterized as a continuous measure summarized by a mean, with standard deviation used to describe dispersion.

Comparing measurements across positions addresses the study’s stated interest in pressure variation associated with posture. The treatment condition matters because the study asks whether this positional change differs after Cosopt treatment compared with the washout conditions. The endpoint is therefore about a change across positions under treatment conditions, not simply a single pressure measurement at one posture. The record does not provide the exact formula used to define the positional change, the measurement protocol, or the specific analysis used to compare conditions.

In general, a mean describes the central value of a continuous measurement, while a standard deviation describes how spread out individual measurements are around that mean. Those summaries can help characterize a group’s observed measurements, but they do not by themselves show how precisely a treatment contrast has been estimated. A confidence interval or other uncertainty estimate would be needed to communicate that precision. Numerical endpoint results and confidence intervals are not reported in the registry record, so the magnitude and precision of any Cosopt-associated change cannot be assessed from the registry results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary measure as continuous, reports its unit as mmHg, and specifies a mean with standard deviation. It does not report numerical primary-outcome results or analyses. The statistical concepts below are general explanations of what these choices mean and what information would ordinarily be needed to interpret them; they are not descriptions of analyses confirmed in the registry record.

What does a mean describe?

In general, a mean is a measure of the center of a set of observations. For a continuous outcome such as intraocular pressure, it provides a way to summarize the group’s measured values under a particular condition or position. A mean alone does not show whether participants’ measurements were similar to one another or widely spread. That is why the registry’s specification of standard deviation as a dispersion measure is relevant: the standard deviation describes the spread of observations around the mean.

The primary question concerns changes from sitting to supine positions under different treatment conditions. A complete analysis would need to define how those position-specific measurements are combined into a change and how changes under different conditions are compared. The record states the general endpoint description but does not report the calculation definition or a statistical model. It is therefore not possible to infer the precise estimand, meaning the exact treatment-related quantity the analysis was intended to estimate.

What would uncertainty estimates add?

In general, a confidence interval gives a range of values compatible with the data and the analysis assumptions at a stated confidence level. It helps communicate both the estimated effect and its precision. A narrow interval indicates more precision than a wide interval, while an interval that includes values in different directions may leave the direction of an effect uncertain. A p-value addresses compatibility of the observed data with a specified null hypothesis under an analysis model; it is not a measure of effect size or clinical importance.

No confidence intervals, p-values, or numerical treatment estimates for the primary outcome are reported in the registry record. Accordingly, the precision of the study’s primary estimate and its compatibility with different possible effects cannot be assessed from the posted results. Standard deviations, even if available, would not replace an interval for the treatment contrast because they describe individual-level spread rather than the uncertainty in that contrast.

How does the single-group structure matter?

The registry identifies a single-group model and describes measurements after clinical-treatment washout, after Cosopt, and after another washout. It does not describe randomized assignment to separate treatment and control groups. General statistical reasoning therefore distinguishes this design from a parallel-group randomized comparison. Measurements across conditions may be related because they arise from the same study group, and analysis should reflect that structure. The particular method used to account for this relationship is not reported in the registry record.

In general, measurements taken repeatedly from the same participants are not necessarily statistically independent. Treating related measurements as if they were unrelated can misrepresent uncertainty. A paired analysis or a repeated-measures model may be appropriate in some settings, but the registry record does not identify which approach, if any, was used. The order of the described conditions also makes timing relevant: the record gives the sequence of washout, Cosopt, and another washout, but does not report how period effects or changes over time were evaluated.

What does the planning illustration represent?

In general, a sample-size planning calculation uses assumptions about the effect to detect, variability, significance level, allocation, and analysis method to illustrate the amount of information a study might require. Such a calculation is not a result observed in participants and is not observed power. The planning assumptions associated with this study specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe the effect to detect as a stated fraction of the observed effect. For non-time-to-event outcomes, planning quantities are expressed as participants per arm.

Those assumptions describe a planning illustration, not the trial’s own design rationale. The study itself is listed as single group, with allocation NA; equal allocation between two arms should not be mistaken for the study’s actual allocation. A trial-specific sample-size justification and the original assumptions used when planning enrollment are not reported in the registry record. The planning illustration should not be read as evidence that the study had a particular probability of detecting an effect.

What cannot be assessed from the registry results?

Because numerical primary-outcome results and analyses are not reported, it is not possible to check model assumptions, reproduce an estimate, or compare an analysis with its stated plan. The registry also does not report the handling of missing measurements, the analysis population, or whether any interim analyses were undertaken. Those omissions leave important aspects of the statistical analysis unknown. General methods can explain what information would matter, but they cannot supply results or resolve the study’s unreported analytic choices.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and identifies intraocular pressure in sitting and supine positions as the primary outcome. A secondary outcome is listed for myocilin mutation Arg272Gly in subjects. The registry record does not report a multiplicity plan describing how interpretation would account for examining multiple outcomes or comparisons. It also reports no analyses, so there are no posted outcome tests from which to assess whether any adjustment was made.

In general, multiplicity matters when several hypotheses are tested: the chance of at least one apparently notable result can increase as more tests are considered. A prespecified hierarchy or other adjustment can help control that issue, but whether such a strategy was planned or used is not reported in the registry record. The outcome listing alone does not establish how confirmatory or exploratory analyses were distinguished.

Missing-data methods and the analysis population are also not reported in the registry record. The record does not state how many participants contributed primary-outcome measurements, whether any measurements were unavailable, how missing measurements would be handled, or whether the analysis used all enrolled participants or a defined subset. The enrollment count of 14 should therefore not be treated as proof that 14 participants contributed to every endpoint or condition.

In general, missing measurements can affect both the estimate and its uncertainty, particularly when their absence is related to participant characteristics or outcomes. Without information about completeness and handling, the impact cannot be evaluated. The registry record also does not report interim analyses or a detailed statistical analysis plan. These details should be regarded as unreported rather than inferred from the study’s completed status.

11. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse event counts for two named conditions. In the Cosopt group, 0 serious adverse events were recorded among 12 participants at risk. In the washout (no Glaucoma Medication) group, 0 serious adverse events were recorded among 14 participants at risk. The record lists 0 deaths for both groups.

For other adverse events, the registry lists 0 affected participants among 12 at risk in the Cosopt group, and 1 affected participant among 14 at risk in the washout group. These are counts and denominators as recorded; they are not percentages or estimates of comparative risk. The registry does not list any top serious adverse event terms.

In general, a zero count means that no event was recorded in that category among the participants represented by the stated denominator. It does not establish that an event is impossible or that all potential harms have been ruled out. The denominators differ, and the study is described as a single-group study rather than a randomized safety comparison. The record does not provide further detail about safety ascertainment, duration of safety follow-up, or the specific event underlying the other adverse event count. These figures should therefore be read as limited descriptive registry counts, not as a basis for a definitive comparative safety conclusion.

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

The registry establishes that a completed study enrolled 14 participants and was designed to examine intraocular pressure changes between sitting and supine positions under washout and Cosopt conditions. Its broader stated purpose concerned whether myocilin genetic variants were associated with larger changes in intraocular pressure and blood pressure. These aims are informative about the questions researchers intended to study.

The registry does not report numerical results for the primary endpoint, and it lists no analyses. As a result, the posted information does not establish the size or direction of any change in intraocular pressure, how variable measurements were, or how precisely a treatment contrast was estimated. Nor does it establish whether myocilin variants were associated with the pressure changes. The secondary outcome listing for Arg272Gly is not itself a result.

The design description is also important to the scope of interpretation. This is a single-group study with measurements under successive conditions, not a randomized comparison between separate treatment arms. If a contrast across conditions was estimated, its interpretation would depend on the measurement and analysis details, which are not reported in the registry record. The registry therefore does not support attributing a difference to Cosopt while excluding other explanations based on the posted information alone.

In general, an observed association does not by itself establish causation, and an absence of reported results is not evidence that no effect occurred. Likewise, a completed status does not show that an endpoint was measured successfully or that the study answered its research question. The safety counts describe the events recorded for the stated denominators, but they do not provide a complete account of possible safety outcomes.

The appropriate reading is narrow: the registry documents the study’s purpose, broad design, listed outcomes, and limited safety counts. It does not provide the statistical evidence required to judge the primary endpoint or genetic association question. No conclusion about treatment benefit or lack of benefit follows from the registry record.

13. Why This Trial Matters Statistically

This study illustrates why a clearly stated research question and a report of numerical results are both needed for statistical interpretation. The primary question is about a continuous pressure measure across two positions and treatment conditions. The registry identifies the outcome unit, mean, and standard deviation, which indicate the type of summary intended. Yet without outcome estimates and uncertainty measures, readers cannot judge the magnitude, direction, or precision of the result.

The single-group structure is also statistically consequential. The registry describes measurements under washout and treatment conditions, rather than randomized allocation to separate groups. This makes it important to know how repeated measurements were handled and how the comparison was defined. The record does not report those analytic details. A study can be completed and have a clearly named endpoint while still leaving the statistical evidence needed for interpretation unavailable in its registry entry.

The genetic question highlights the difference between listing an outcome and reporting a finding. Arg272Gly is named as a secondary outcome, while the broader aim mentions myocilin variants. Neither the listing nor the stated aim indicates whether a variant was present, how many participants carried it, or whether variant status was associated with pressure variation. Those results are not reported in the registry record.

Finally, the planning assumptions are distinct from the study design and from observed evidence. An illustration using two-arm equal allocation does not describe this single-group study’s actual allocation, and planning quantities are not observed power. Together, these features make the record useful for understanding the intended question and design, while emphasizing the need for outcome reporting, analysis details, and uncertainty estimates before drawing statistical conclusions.

14. 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 most consequential limitation for interpretation is that numerical primary-outcome results are not reported in the registry record. The record lists no analyses, so there is no reported estimate to assess for direction, magnitude, or precision. Results for the listed secondary outcome concerning myocilin mutation Arg272Gly are also not reported.

The enrollment was 14, but the registry does not report the number of participants contributing measurements to each condition or outcome. Safety denominators are listed as 12 for Cosopt and 14 for washout, but those counts do not specify the analysis population for the primary endpoint. The handling of missing measurements is not reported in the registry record.

The single-group design and lack of masking are recorded, while allocation is NA. The registry describes a sequence of washout, Cosopt treatment, and another washout, but does not report additional protocol details about measurement timing, implementation, or analysis. The specific method for comparing repeated measurements and accounting for time or condition order is not reported. A randomized control comparison should not be inferred.

The record identifies three outcome measures but does not provide a detailed statistical analysis plan, multiplicity approach, interim-analysis information, or sample-size justification. It also does not report confidence intervals or other uncertainty estimates. The single-group design, limited enrollment, and missing analytic detail constrain what could be learned even if numerical findings were available; without the primary results, the registry cannot support a quantitative assessment of the endpoint.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of Myocilin Genetic Variants on Intraocular Pressure and Pressure Variation in Sitting and Supine Positions — NCT00906087.
• Registry record last updated 2017-06-02; status last verified 2017-05.
• Results first posted 2017-06-02.
• 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.

18. Record Summary

NCT00906087 is a completed Phase 4, single-group study sponsored by the University of Michigan. The registry lists 14 participants with glaucoma and describes Cosopt, a combination of dorzolamide and timolol, as the intervention. The planned conditions were measurement after clinical-treatment washout, after Cosopt treatment, and after another washout of Cosopt.

The primary outcome concerns intraocular pressure changes from sitting to supine positions, with a 10 weeks timeframe. It is specified as a continuous mean in mmHg with standard deviation as the dispersion measure. A secondary outcome concerning myocilin mutation Arg272Gly is listed. The record reports no analyses, and numerical results for the primary and secondary outcomes are not reported in the registry record.

Safety entries list zero serious adverse events in both conditions, zero deaths, and one other adverse event in the washout group. The study’s detailed statistical analysis plan, missing-data approach, analysis populations, and sample-size justification are not reported in the registry record.