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 Ocular Hypertension Treatment Study (OHTS) (NCT00000125), a randomized phase 3 study. The primary outcome is Incidence of Primary Open-Angle Glaucoma in Hypotensive Patients.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00000125 |
| Phase | Phase 3 |
| Condition | Ocular Hypertension, Glaucoma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 1636 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Washington University School of Medicine |
| Results posted | Yes |
2. Clinical Question
Population
Ocular hypertensive participants judged to be at moderate risk for developing open-angle glaucoma. The registry record reports that 1636 participants were randomized.
Intervention
Treatment with commercially available topical ocular hypotensive eye drops.
Comparator
Close observation. In June 2002, observation participants were offered treatment with topical ocular hypotensive eye drops.
Primary question
What is the cumulative proportion of participants who develop primary open-angle glaucoma in the observation and medication groups?
The study’s stated aims included determining whether medical reduction of intraocular pressure prevents or delays the onset of glaucomatous visual field loss or optic disc damage. It also aimed to produce natural history data, help identify participants at greatest risk, and quantify risk factors for developing open-angle glaucoma among ocular hypertensive individuals.
The posted primary outcome is the incidence of primary open-angle glaucoma, expressed as a percentage of participants. Its description specifies a comparison between the observation and medication groups. The registry record identifies two time frames: 5 yrs (OHTS I, June 2002) and 13.0 yrs (completion of both phases of OHTS, March 2009). It does not report a single comparison that combines or selects between those time points.
3. Trial Design
The Ocular Hypertension Treatment Study (OHTS) is recorded as a Phase 3, randomized, parallel trial with no masking. Washington University School of Medicine is listed as the sponsor. The trial is marked completed. The recorded enrollment is 1636 participants, described as ocular hypertensive.
Participants were randomized to close observation or treatment with topical ocular hypotensive eye drops. The treatment description specifies commercially available drops. The registry record states that participants were randomized from February 1994 through June 2002. In June 2002, observation participants were offered treatment with topical hypotensive eye drops. Thus, the original group assignment describes the initial comparison, while the later treatment offer is part of the stated study context for the longer follow-up.
The primary outcome is framed as a comparison of cumulative proportions developing primary open-angle glaucoma, with one time frame ending in June 2002 and another at completion of both phases in March 2009. The registry record does not describe the sequence or details of follow-up visits, how outcomes were adjudicated, or how outcomes after the offer of treatment were handled in the analysis. It also does not report a statistical analysis plan or the methods used to preserve or account for the randomized comparison over the longer time frame.
The absence of masking is recorded, but the registry record does not explain why masking was not used or whether outcome assessors were masked. No further details about allocation procedures or concealment are reported in the registry record. The enrollment number describes the trial as recorded; the registry record does not state how many participants contributed data to each reported outcome time point.
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 | Observation | Treatment |
|---|---|---|
| STARTED | 819 | 817 |
| Completed OHTS Phase I, June 2002 | 706 | 702 |
| COMPLETED | 580 | 579 |
| NOT COMPLETED | 239 | 238 |
Analysis population for the primary outcome, as defined in the registry: 1636 ocular hypertensive participants were randomized to either close observation or treatment with topical hypotensive eyedrops from February 1994 through June 2002. In June 2002 the observation participants were offered treatment with topical hypotensive eyedrops.
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.
Population: 1636 ocular hypertensive patients were randomized to either close observation or ocular hypertensive medication.
| Characteristic | Unit | Observation | Treatment | Total |
|---|---|---|---|---|
| Participants analysed | 819 | 817 | 1636 | |
| Age, Continuous | years | 55.6 (SD 9.7) | 55.2 (SD 9.5) | 55.4 (SD 9.6) |
| Sex: Female, Male: Female | Participants | 346 | 359 | 705 |
| Sex: Female, Male: Male | Participants | 473 | 458 | 931 |
| Race/Ethnicity, Customized: Native American | participants | 3 | 1 | 4 |
| Race/Ethnicity, Customized: Asian | participants | 10 | 4 | 14 |
| Race/Ethnicity, Customized: African American | participants | 205 | 203 | 408 |
| Race/Ethnicity, Customized: Hispanic | participants | 35 | 24 | 59 |
| Race/Ethnicity, Customized: White | participants | 560 | 577 | 1137 |
| Race/Ethnicity, Customized: Other | participants | 6 | 8 | 14 |
6. Primary Endpoint
The registry lists the primary outcome as Incidence of Primary Open-Angle Glaucoma in Hypotensive Patients, measured over 5 yrs (OHTS I, June 2002) and 13.0 yrs (completion of both phases of OHTS, March 2009).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percent of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint measures the cumulative proportion of participants who develop primary open-angle glaucoma in the observation and medication groups. It is recorded as a percentage of participants, and its description identifies the endpoint as a comparison between those groups. The listed time frames are 5 yrs (OHTS I, June 2002) and 13.0 yrs (completion of both phases of OHTS, March 2009).
A cumulative proportion describes how many participants in a group have experienced the outcome by a specified follow-up point. General statistical context: this type of endpoint can summarize the occurrence of an outcome across a defined period, rather than describing only a measurement at one visit. Interpreting it depends on knowing the outcome definition, the follow-up period, the participants included in the analysis, and how incomplete follow-up was handled.
The endpoint is relevant to the study’s stated question because the stated aims concern preventing or delaying glaucoma onset in people with ocular hypertension. However, the registry record does not report the outcome values or a single comparison at either listed time point. It also does not provide an operational definition of glaucoma onset, adjudication procedures, or a method for accounting for censoring or missing outcome information. Those details are not reported in the registry record, so the endpoint’s numerical results and precision cannot be assessed from the posted results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the trial’s central comparison and the outcome it intended to assess: cumulative development of primary open-angle glaucoma among participants assigned to close observation or topical ocular hypotensive treatment. It also states that observation participants were offered treatment in June 2002, an important feature when interpreting the longer follow-up time frame.
However, the posted primary outcome is not reduced to one comparison because it has multiple categories or time points. No primary outcome values, effect estimate, confidence interval, or p-value are reported in the registry record. The record lists one outcome measure and zero analyses. As a result, it is not possible to describe the magnitude, direction, or statistical precision of the primary outcome contrast from these registry data. The listed follow-up times alone do not indicate whether the groups differed.
The two stated time frames represent distinct points in the study’s history: 5 yrs (OHTS I, June 2002) and 13.0 yrs (completion of both phases of OHTS, March 2009). Because the observation group was offered treatment in June 2002, the longer-term comparison may involve a different treatment history from the initial randomized comparison. The registry record does not report how this transition was incorporated into any analysis, or whether group comparisons were adjusted or otherwise defined for the later period. No interpretation of the longer-term contrast can therefore be made from the time-frame label alone.
General statistical context: an effect estimate describes the observed contrast between groups, while a confidence interval describes the uncertainty around that estimate under the analysis assumptions. A p-value addresses how compatible the observed data are with a specified null model; it does not measure the size or clinical importance of an effect. None of these quantities is reported for the primary outcome in the registry record, so precision and statistical evidence cannot be evaluated.
The serious adverse event listings contain group-specific counts, but these are safety data and do not substitute for the primary glaucoma outcome. The registry lists 12 affected participants among 819 at risk in Observation and 13 among 817 at risk in Treatment. It also lists Ocular Serious Adverse Events (OHTS I, June 2002) at 1.6%, without a group assignment for that summary term. These figures should be read as registry-reported safety information, not as an estimate of the primary outcome or proof of a treatment effect.
9. Statistical Methods Explained
The main statistical quantity named in the registry record is a cumulative proportion: the percentage of participants who develop primary open-angle glaucoma in each group by a stated follow-up time. The record identifies a randomized comparison, but does not give the outcome counts or percentages needed to describe the observed contrast. It also does not report an analysis result, confidence interval, or p-value.
What does a cumulative proportion describe?
In general, a cumulative proportion summarizes the fraction of a defined group that has experienced an event by a particular point in follow-up. It is interpretable only alongside the event definition, the time frame, and the population included in the calculation. In a trial with differing follow-up or incomplete observations, the method used to account for those circumstances can affect the estimate. The registry record does not report whether the posted endpoint was calculated as a simple proportion or by a time-to-event method, nor does it describe how incomplete follow-up was handled.
The listed outcome time frames are 5 yrs (OHTS I, June 2002) and 13.0 yrs (completion of both phases of OHTS, March 2009). These are not interchangeable summaries. General statistical context: estimates at different follow-up points can reflect different amounts of time at risk and, where treatment changes over time, different treatment histories. The registry record notes that observation participants were offered treatment in June 2002, but does not explain how that later treatment was incorporated into the long-term analysis.
How does randomization inform interpretation?
Random assignment is intended, in general, to create groups that are comparable at the start of a trial with respect to both measured and unmeasured characteristics. A comparison based on the assigned groups can therefore support an assessment of the effect of assignment, provided the analysis and follow-up preserve that comparison appropriately. The registry record identifies randomization and parallel groups, but does not report the analysis population, the handling of participants who changed treatment, or whether all randomized participants were included in the primary analysis. It is not possible to label the analysis as intention-to-treat or to infer another analysis population.
The trial is recorded as having no masking. General statistical context: knowledge of group assignment can sometimes influence reporting, assessment, or decisions about follow-up, depending on the outcome and procedures. For an outcome such as glaucoma onset, interpretation can depend on how the outcome was assessed and whether assessors were masked. The registry record does not report outcome-adjudication procedures or whether assessors were masked, so the influence of masking cannot be evaluated from the record.
What can be said about precision and testing?
A confidence interval is a range of estimates compatible with the data under the model and assumptions used; a narrower interval generally represents greater precision. A hypothesis test and its p-value address compatibility with a null hypothesis under specified assumptions. Neither a confidence interval nor a p-value for the primary outcome is reported in the registry record. Without an effect estimate and its uncertainty, the observed result’s precision cannot be assessed.
The registry record also does not report whether an adjusted model was used, which covariates might have been included, or whether assumptions were checked. General statistical context: adjustment can account for specified baseline variables, but it does not replace clear reporting of the comparison, analysis population, and model. No particular modeling strategy should be inferred.
A sample-size illustration based on an observed effect is a planning calculation, not an observed trial result and not evidence of observed power. The registry record describes such illustrations as using a two-sided significance level of 0.05, equal allocation, a normal approximation, and a stated fraction of the observed effect. It does not report that these illustrations were the trial’s original design justification. The actual planning estimates are not stated in the registry record, and no sample-size rationale for the original trial is reported.
10. Multiplicity, Missing Data and Analysis Populations
The registry record identifies one primary outcome measure, but its time frame includes 5 yrs (OHTS I, June 2002) and 13.0 yrs (completion of both phases of OHTS, March 2009). The outcome is not reduced to one comparison because it has multiple categories or time points. The record does not identify one time point as the sole primary analysis for interpretation, explain how the time points were prioritized, or report whether any multiplicity procedure was used. These details are not reported in the registry record.
Multiplicity matters in general when several outcomes, time points, or comparisons are tested: repeated testing can increase the chance of a nominally notable finding even when no true difference exists. The appropriate interpretation depends on the planned testing strategy and which results were designated as primary. No such strategy or family of tests is described in the registry record, so it is not possible to assess how multiplicity was handled.
The record lists zero analyses and gives no primary outcome values, effect estimates, confidence intervals, or p-values. It also does not report the analysis population, the number of participants with outcome data at each time point, or how missing data and loss to follow-up were addressed. No imputation method, censoring approach, or sensitivity analysis is described. These omissions limit assessment of both the validity and precision of the reported endpoint.
General statistical context: missing outcome information can affect a group comparison if the likelihood of missingness differs between groups or relates to the outcome. The direction and extent of any resulting bias depend on the reasons for missingness and the analytical approach. The registry record does not provide those details, so the impact of missing data cannot be determined.
11. 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 |
|---|---|---|---|
| Observation | 12 | 819 | 1.5% |
| Treatment | 13 | 817 | 1.6% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Observation | 481 of 819 |
| Treatment | 570 of 817 |
Most frequent serious adverse event terms
| Event term | Organ system | Observation | Treatment |
|---|---|---|---|
| Ocular Serious Adverse Events (OHTS I, June 2002) | Eye disorders | 12 of 819 | 13 of 817 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Observation | Treatment |
|---|---|---|---|
| Ocular Adverse Event (Not Serious) | Eye disorders | 481 of 819 | 570 of 817 |
Serious events with the highest arm-level rate: ocular serious adverse events (ohts i, june 2002) (1.6%).
The registry lists serious adverse event figures by group. For Observation, 12 affected participants are listed among 819 at risk. For Treatment, 13 affected participants are listed among 817 at risk. The record also lists Ocular Serious Adverse Events (OHTS I, June 2002) at 1.6%. That summary term is not assigned to a specific group in the listing, so it should not be treated as a group-specific percentage.
These figures describe the registry’s serious adverse event reporting, not the primary outcome of glaucoma onset. The record does not explain whether the group counts refer to participants with at least one event, how events were coded, how long the safety observation period covered, or whether the event was considered related to treatment. Those details are not reported in the registry record. The deaths fields are null; deaths therefore are not reported in the registry record, rather than being documented as zero.
General statistical context: safety counts are most informative when their observation periods, event definitions, and denominators are clear and comparable across groups. The at-risk counts and affected counts should be read as listed, without deriving additional rates from them. The registry record does not report a statistical comparison of serious adverse events, so these figures do not establish whether groups differed in safety outcomes.
12. What the Result Does, and Does Not, Mean
The registry record describes a randomized comparison of close observation and topical ocular hypotensive eye drops among ocular hypertensive participants. Its stated primary question concerns the cumulative proportion developing primary open-angle glaucoma. It identifies two follow-up time frames and notes that the observation group was offered treatment in June 2002. These design details define the question the trial set out to address, but they do not provide an answer to it.
The posted results do not give the primary outcome counts or percentages, a contrast between groups, or a measure of uncertainty. The outcome is not reduced to one comparison because it has multiple time points. Consequently, the registry record does not establish the direction or size of any difference in glaucoma incidence, or how precisely such a difference was estimated. No treatment conclusion can be drawn from the outcome information recorded.
The longer follow-up time frame also needs careful interpretation because the observation participants were offered active treatment after the initial period. The registry record does not explain how this transition was handled in the long-term analysis. General statistical context: a comparison based on initial assignment and a comparison based on treatment actually received answer different questions. Without the analysis definition, it is not possible to determine which question the long-term results were intended to address.
The safety listing reports affected-participant counts by group and a 1.6% summary for Ocular Serious Adverse Events (OHTS I, June 2002). These figures do not replace the primary endpoint and, without further details or a statistical comparison, do not establish a difference in safety between groups. Overall, the record conveys the trial’s aims, design, follow-up time frames, and limited safety information, while leaving the primary outcome result and its precision not reported in the registry record.
13. Why This Trial Matters Statistically
The trial addresses a statistical question that depends on both group assignment and follow-up time: whether the cumulative occurrence of primary open-angle glaucoma differs between ocular hypertensive participants assigned to close observation and those assigned to topical ocular hypotensive eye drops. The registry record identifies randomization, a parallel design, and the outcome of interest, making the intended comparison clear at a broad level.
The record also illustrates why a stated endpoint is not the same as a reported result. The primary outcome has two time frames, 5 yrs (OHTS I, June 2002) and 13.0 yrs (completion of both phases of OHTS, March 2009), but no single comparison is reported. Without the group values and uncertainty estimates, the outcome cannot be interpreted for magnitude or precision. A result’s clinical topic and study design do not fill that statistical gap.
The offer of treatment to observation participants in June 2002 is particularly relevant to long-term interpretation. General statistical context: changes in treatment exposure during follow-up can complicate the distinction between the effect of initial assignment and the effect of continued treatment. Clear reporting of the analysis question and handling of treatment changes is important for interpreting longer-term comparisons. Those analytical details are not reported in the registry record.
Finally, the record demonstrates the value of separating efficacy endpoints from safety listings and design information. The serious adverse event counts provide some descriptive information, but they do not answer the primary glaucoma question. Statistical interpretation depends not only on a trial’s aims and design, but also on transparent outcome definitions, analysis populations, missing-data methods, and estimates of uncertainty. Several of those elements are not reported in the registry record.
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 principal limitation for interpretation is that the registry record does not report primary outcome values or analyses. Although it specifies cumulative glaucoma incidence as the primary endpoint, the outcome is not reduced to one comparison because it has multiple time points. No effect estimate, confidence interval, or p-value is listed. The direction, magnitude, and precision of the primary comparison therefore cannot be assessed.
The registry record gives two follow-up frames and states that observation participants were offered treatment in June 2002. It does not explain how this offer affected the treatment contrast during the longer follow-up, or how participants’ later treatment was addressed analytically. The analysis population, outcome ascertainment procedures, handling of missing data, and approach to loss to follow-up are also not reported in the registry record.
The trial is recorded as randomized and unmasked, but details of allocation procedures and outcome assessment are not described. The record does not state whether outcome assessors were masked or how glaucoma onset was defined and confirmed. These omissions make it difficult to evaluate potential sources of bias or determine how consistently the endpoint was assessed.
Safety reporting is limited to the listed affected-participant counts and a 1.6% summary for Ocular Serious Adverse Events (OHTS I, June 2002). Event definitions, follow-up duration for those figures, relatedness to treatment, and a group comparison are not reported in the registry record. These limitations concern what can be concluded from the registry record; they do not by themselves establish that the underlying trial lacked additional procedures or analyses.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Ocular Hypertension Treatment Study (OHTS) — NCT00000125.
- Registry record last updated 2020-06-02; status last verified 2020-05.
- Results first posted 2015-03-19.
- 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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18. Record Summary
The Ocular Hypertension Treatment Study is recorded as a completed Phase 3 randomized parallel trial with no masking and enrollment of 1636 ocular hypertensive participants. Washington University School of Medicine is listed as sponsor. Participants were assigned to close observation or commercially available topical ocular hypotensive eye drops. Observation participants were offered treatment in June 2002.
The primary endpoint is the cumulative proportion developing primary open-angle glaucoma, with time frames of 5 yrs (OHTS I, June 2002) and 13.0 yrs (completion of both phases of OHTS, March 2009). The registry record does not report a single outcome comparison, outcome values, or analyses. Serious adverse event listings include 12 affected participants among 819 at risk in Observation and 13 among 817 in Treatment, plus Ocular Serious Adverse Events (OHTS I, June 2002) at 1.6%. The record does not report the primary outcome’s statistical precision or how missing data and the later treatment offer were handled.