Effect of Nitrous Oxide (N2O) on Intraocular Pressure in Healthy Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Nitrous Oxide (N2O) on Intraocular Pressure in Healthy Volunteers (NCT00967694), a na phase 4 study. The primary outcome is Change in Intraocular Pressure During Nitrous Oxide Sedation.

2. Clinical Question

The clinical motivation described in the record is that some patients need medication to complete eye examinations that measure intraocular pressure, while some medicines may affect that pressure. The study therefore asks about nitrous oxide in healthy volunteers, rather than directly testing an examination or treatment strategy in patients with glaucoma. Its within-person measurements can describe how pressure readings vary around nitrous oxide administration in the studied volunteers. They do not, on their own, establish what would happen in a different patient population or under a separate treatment comparison.

3. Trial Design

The registry describes a Phase 4, single-group study with an enrollment of 20 healthy volunteers. Allocation is listed as NA, and the study model is single group. The masking field is listed as single, but the record does not specify who was masked or how masking was implemented. The study is marked completed. Its recorded start is 2009-08 and its primary completion is 2011-10.

All participants in the described arm had intraocular pressure measured at baseline, then after 3, 6, 9 and 12 minutes of nitrous oxide administration. Further measurements were taken after 5, 10 and 15 minutes of breathing room air. The record says each individual served as their own control. That means the principal comparison is across measurement times within the same participants, rather than between randomized treatment groups. The baseline and room-air observations provide reference measurements, but they are not a separate concurrent control arm.

The registered primary outcome is titled “Change in Intraocular Pressure During Nitrous Oxide Sedation.” It is a continuous measure expressed as a difference in intraocular pressure in mmHg, with the mean and a 95% confidence interval specified as the summary. Its timeframe is described as before, during and after nitrous oxide administration, 45 minutes total. The record does not supply a numerical estimate for this outcome.

The record states that investigators also intended to assess whether gender had a role in the effect. It does not report a gender-specific result or describe the method for that assessment. The intervention entry names nitrous oxide but does not report a dose or concentration. Further details of the administration procedure, beyond the recorded measurement schedule, are 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.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Volunteers recruited via locally placed posters, research opportunities website and email servers. Power calculations estimated 20 subjects would be needed to detect a 2.8mmHg difference in IOP. 26 subjects began nitrous oxide administration, with 6 choosing to withdraw. Baseline analysis based on the 20 participants completing the study.

6. Primary Endpoint

The registry lists the primary outcome as Change in Intraocular Pressure During Nitrous Oxide Sedation, measured over Before, during and after administration of nitrous oxide (45 minutes total).

The primary endpoint concerns change in intraocular pressure (IOP), a continuous measurement of pressure inside the eye. The registry expresses the outcome as a difference in IOP in mmHg and specifies the mean with a 95% confidence interval. Measurements were scheduled before, during and after nitrous oxide administration.

Repeated readings over these periods are intended to address more than whether a pressure measurement differs from baseline. They also relate to the investigators’ stated interest in the magnitude and duration of any change. Measurements during nitrous oxide administration can describe the pattern while the gas is being administered; measurements during room-air breathing can describe subsequent readings. The registry record does not define a single time point or aggregation rule as the primary contrast, so it is not possible to tell from the record how the repeated measurements were combined into the endpoint estimate.

IOP is relevant to the clinical context described by the investigators because eye-pressure readings may inform decisions about treatment and surgery options. A continuous endpoint retains information about the measured scale, rather than reducing each reading to a category. But interpretation still depends on the estimate, its uncertainty, the measurement schedule and the analysis used. The posted results do not report the mean change or its confidence interval. Consequently, the record does not allow readers to determine the observed direction, size or precision of the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies IOP change as a continuous outcome, specifies a mean as the summary measure and names a 95% confidence interval as the dispersion measure. It also describes one analysis for the registered outcome. These entries identify the intended form of the result, but the analysis method itself and its numerical output are not reported in the registry record.

What does a mean change describe?

For a continuous measure, a mean summarizes the average value or average change across the observations included in an analysis. In this study, the endpoint is framed as a difference in IOP, in mmHg. A mean difference can make the direction and scale of an average change interpretable, provided the comparison being averaged is clearly defined. With repeated measurements, that definition matters: an average could refer to a particular time point, a collection of time points, or another specified contrast. The record lists the measurement schedule but does not explain how it was translated into the primary mean estimate.

General statistical explanation: a confidence interval expresses uncertainty around an estimate, under the assumptions of the statistical method used. A narrower interval indicates greater precision than a wider interval, while the interval’s location indicates which values are compatible with the estimate and method. A 95% confidence interval is not a guarantee that the true value lies within a particular calculated interval. The registered record names this interval type but gives no endpoints, so its precision cannot be interpreted for this study.

Why does the repeated-measure structure matter?

The same participants were measured at baseline, during nitrous oxide administration and while breathing room air. Repeated observations from one person are generally related: measurements from that person share characteristics and conditions. General statistical explanation: an analysis that treats related observations as if they were independent can misstate uncertainty. Methods for repeated measurements account for the within-person relationship in some way, but the appropriate method depends on the design, outcome and target comparison. The specific approach used for this study is not reported in the registry record.

The within-person structure can be useful because each participant contributes measurements at multiple stages. It also means that the timing and definition of the contrast are important. A change from baseline at one time point is not automatically the same estimand as an average change across several time points. The record gives scheduled measurement times but does not report which contrast generated the primary result, how missing readings were handled, or whether the primary analysis used all scheduled measurements.

What does the single-group comparison establish?

There is one study arm, and the record describes each individual as their own control. This supports a descriptive comparison of measurements across phases within the study. It does not create an independent, untreated group. General statistical explanation: when time and intervention occur in sequence, a difference across measurement times can reflect the intervention, but it may also reflect time-related changes, measurement conditions or other influences. A separate randomized comparison can help address some of these concerns; this record does not describe such a comparison.

The arm schedule includes baseline observations, readings after 3, 6, 9 and 12 minutes of nitrous oxide administration, and readings after 5, 10 and 15 minutes of room-air breathing. Those intervals allow the investigators’ stated interest in duration to be considered in principle. But the schedule alone does not show the pattern of values or establish when any change began or ended. No numerical readings or time-specific results are reported in the registry record.

What can a p-value or significance test add?

A significance test, when used, evaluates how compatible the data are with a specified statistical model and a null hypothesis. A p-value does not measure the size or clinical importance of an effect, and it does not substitute for an estimate with an uncertainty interval. The registry record does not report a p-value, the null hypothesis used for testing, or the statistical test. It is therefore not possible to evaluate statistical significance from the posted record. Nor can a significance result be inferred from the investigators’ hypothesis or from the fact that one outcome is registered.

What is over-dispersion, and is it relevant?

General statistical explanation: over-dispersion refers to variability greater than a model assumes, particularly in settings where outcomes are counts and a simple model expects a particular relationship between the mean and variance. Accounting for over-dispersion can prevent uncertainty from being understated. The registered primary outcome in this study is continuous IOP change, not a count outcome. The registry record does not report an over-dispersion assessment or a model that would make it relevant to the primary endpoint. This general concept should not be mistaken for a method documented in this study.

Can a planning calculation reconstruct the study’s power?

No. The registry describes a sample-size illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. It also says that the effect to detect is a stated fraction of the observed effect. Such illustrations are planning scenarios, not observed power, and the record does not give the numerical illustration values in the information available for this interpretation. More importantly, the trial is described as a single-group repeated-measure study, not an equal-allocation two-arm comparison. The illustration’s assumptions therefore do not describe the actual study design. The registry does not report the trial’s own sample-size justification.

In summary, the listed outcome format and measurement schedule suggest what investigators intended to summarize. The missing numerical result and unspecified analysis details prevent independent assessment of the estimate, its uncertainty, the handling of within-person dependence, or the statistical test.

10. Multiplicity, Missing Data and Analysis Populations

The record lists one primary outcome measure and one analysis. It does not report a strategy for controlling multiplicity, such as how conclusions would be managed if several outcomes, time points or subgroup comparisons were examined. This matters because the measurement schedule contains repeated readings during administration and room-air breathing, and the study description also mentions a gender-related question. The registry does not specify which analyses were confirmatory or how any additional comparisons were treated.

The primary outcome population field is blank. The record does not describe an analysis population, such as which participants or measurements were eligible for the primary analysis. It also does not report how missing observations, incomplete measurement sequences, withdrawals or protocol deviations were handled. No missing-data method, imputation approach or sensitivity analysis is reported in the registry record. This does not establish that data were missing; it means the record does not explain the analysis rules for that possibility.

The registry does not report whether interim analyses were planned or conducted, or whether stopping rules applied. It also does not give a detailed statistical analysis plan. As a result, readers cannot assess how the primary contrast was selected, how repeated measurements were modeled, whether assumptions were checked, or how secondary and gender-related analyses were distinguished from the primary analysis. These omissions limit the ability to assess the analysis process independently; they do not establish that any particular method was or was not used outside the registry record.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event entry lists 26 at risk for serious adverse events and 0 affected. For other adverse events, it lists 26 at risk and 6 affected. The deaths field is null, which means deaths are not reported in the registry record; it should not be read as a reported count of zero.

The adverse-event group is titled Nitrous Oxide Administration. These figures describe the registry’s reported event counts and denominators; they do not by themselves establish whether an event was caused by nitrous oxide. The record does not give the event terms for the reported other adverse events, and the list of top serious terms is empty. It also does not explain how events were collected, classified or followed over time.

The adverse-event denominators do not match the enrollment entry, which is 20. The record does not explain why 26 are listed as at risk, so the discrepancy should be noted rather than resolved by assumption. The figures cannot be used to infer the number of unique participants or to calculate a rate. They also do not provide a comparison with another study group, because the design has a single group. These safety entries are limited descriptions in the registry record, not a complete account of the nature, timing or cause of events.

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

The record establishes the question the investigators set out to examine: whether IOP changed during nitrous oxide administration, how long any change lasted, and whether gender played a role. It also describes repeated measurements in healthy volunteers, with baseline, administration-period and room-air readings. These are design details and stated aims, not evidence of a particular outcome.

The posted results do not report the primary mean change or its 95% confidence interval. They therefore do not show whether the average pressure reading increased, decreased or remained similar across the specified periods. They also do not show how large any change was, how variable it was, or how precisely it was estimated. The stated hypothesis of a decrease cannot be treated as a finding. The record likewise does not report a gender-specific result or a numerical assessment of duration.

Even if the outcome estimate were available, a single-group repeated-measure study would support a different interpretation from a randomized comparison of nitrous oxide with a concurrent control. The measurements can describe what occurred across the observed sequence in the enrolled volunteers, but changes over time cannot automatically be attributed solely to the intervention. No separate control arm is described in the registry record.

The study concerns healthy volunteers. Its findings, if available, would not automatically describe responses in people undergoing eye examinations or in people with glaucoma. The record’s clinical motivation explains why IOP measurement and sedative medication are of interest, but the study design does not itself establish effects on examination decisions, treatment choices or surgery options.

The safest reading is therefore limited: the registry records a completed study with a specified repeated-measure design and primary outcome, but the numerical primary result is not reported in the registry record. No conclusion about the direction, size, clinical relevance or statistical significance of the IOP response can be drawn from the information recorded.

13. Why This Trial Matters Statistically

This study raises a statistical issue that arises whenever the same continuous outcome is measured repeatedly around an intervention. The analysis must distinguish a change at a particular time from an overall pattern across time, and it must account for the relationship among measurements from the same person. The registry’s schedule makes those questions relevant, while its single-group design makes the interpretation of changes over time especially important.

The clinical context also gives the measurement a practical role: the investigators describe IOP readings as informing treatment and surgery decisions. That makes it important to report not only a direction of change, but also its size and uncertainty. A mean with a confidence interval is a useful reporting framework for a continuous endpoint, but the record does not include the numerical values needed to judge either. Without the estimate, an intended clinical question remains statistically unanswered in the posted record.

The study also illustrates why a participant serving as their own control should be described precisely. Repeated measurements can offer a direct view of within-person patterns, but this approach is not interchangeable with a randomized parallel-group comparison. Time-related changes and measurement conditions remain possible explanations for observed differences. Statistical interpretation depends on the design as well as on the outcome summary.

Finally, the record includes an intended gender question and adverse-event counts, but lacks the analysis details and result information needed to interpret those entries fully. The mismatch between enrollment and adverse-event denominators is another reason to keep registry summaries distinct from a complete analysis report. The study is statistically relevant because it connects measurement timing, repeated-data methods, uncertainty and design limitations in a focused clinical question. The posted record, however, does not report the primary estimate that would allow those issues to be evaluated against the observed result.

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 interpreting this registry record is that it does not report the numerical primary outcome. The mean IOP change and 95% confidence interval are not present, and no p-value or time-specific outcome values are reported. Without them, the result’s direction, magnitude and precision cannot be evaluated. The record’s stated hypothesis should not be mistaken for an observed result.

The single-group design has no separate concurrent control arm. Each participant is described as their own control, which supports within-person comparisons but does not isolate nitrous oxide from all other changes that may occur over time or across measurement conditions. The record does not describe random allocation. It lists single masking but does not specify who was masked or how masking was carried out.

The population is described as healthy volunteers, limiting direct applicability to patients with glaucoma or to people undergoing the examinations discussed in the study rationale. The record does not report participant characteristics or a gender-specific result, despite naming gender as an aim. It also does not report the dose or concentration of nitrous oxide, the statistical model, the exact primary contrast, handling of missing readings, or a detailed analysis plan. Those details are not reported in the registry record.

There is also a denominator discrepancy: enrollment is 20, while the adverse-event group lists 26 at risk. The record does not explain it. Other adverse events are reported without event terms, and deaths are not reported. These limitations prevent fuller interpretation of both the efficacy-oriented outcome and the safety entries, without establishing that unreported methods or events did not exist.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of Nitrous Oxide (N2O) on Intraocular Pressure in Healthy Volunteers — NCT00967694.
• Registry record last updated 2014-09-23; status last verified 2014-09.
• Results first posted 2014-09-23.
• 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

NCT00967694 is a completed Phase 4, single-group study sponsored by Oregon Health and Science University. The registry lists an enrollment of 20 healthy volunteers and describes repeated IOP measurements before, during and after nitrous oxide administration. Readings were scheduled at baseline, after 3, 6, 9 and 12 minutes of administration, and after 5, 10 and 15 minutes of room-air breathing.

The primary outcome is mean change in IOP, expressed in mmHg, with a 95% confidence interval specified. Investigators aimed to assess the magnitude and duration of change and the possible role of gender. The numerical primary result and its confidence interval are not reported in the registry record. The record lists 0 serious adverse events affected, 6 other adverse events affected and 26 at risk for each category; the deaths field is not reported. The adverse-event denominator differs from enrollment, and the record does not explain the difference.