Self-Administered Nitrous Oxide (SANO) During Transrectal Prostate Biopsy to Reduce Patient Anxiety and Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Self-Administered Nitrous Oxide (SANO) During Transrectal Prostate Biopsy to Reduce Patient Anxiety and Pain (NCT05803096), a randomized phase 4 study. The primary outcome is Post-biopsy Pain (VAS-P).

2. Clinical Question

3. Trial Design

The registry record describes a randomized, double-masked, parallel-group Phase 4 study. Participants were assigned to self-administered nitrous oxide or oxygen during transrectal prostate biopsy. In a parallel design, each participant is assigned to one group, rather than switching between interventions. Random allocation is intended to make the groups comparable on average, including for factors that may affect outcomes, although it cannot guarantee that every characteristic is balanced in a particular trial.

The recorded enrollment is 143. The primary outcome summaries list 61.0 participants for self-administered nitrous oxide and 67.0 for oxygen. The registry record does not explain the relationship between enrollment and the numbers included in those summaries, or state whether these counts reflect all randomized participants, participants with observed endpoint data, or another analysis population.

The intervention was given during biopsy. The SANO group received nitrous oxide alongside a periprostatic bupivacaine nerve block, with nitrous oxide set to 30%. The oxygen group received 100% oxygen at 10 Liters/minute. The record says both regimens were used for the duration of the biopsy. Further procedural details, including how randomization was generated, whether assignment was concealed, and which people were masked, are not reported in the registry record. The designation “double” indicates the recorded masking category, but does not identify the masked roles.

The trial status is completed. Its recorded start date is 2021-12-12 and its primary completion date is 2022-09-02. The record lists four secondary outcomes: time of prostate biopsy and operator assessments of tolerating insertion of the rectal probe, maintaining positioning, and tolerance of the procedure. Results for these outcomes 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.

Before assignment: Of note, 143 patients were consented for procedure, but only 133 were randomized. This discrepancy was due to study staff availability or patient cancellation of procedure.

Overall Study

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 Post-biopsy Pain (VAS-P), measured over 5-minutes after prostate biopsy.

The primary endpoint is post-biopsy pain, assessed 5 minutes after prostate biopsy using a Visual Analog Scale for Pain. The scale runs from 0, meaning no pain, to 10, meaning worst pain. It targets the patient's immediate pain experience at a defined point after the procedure. A specified measurement time helps make the intended comparison clear: the endpoint concerns pain at 5 minutes, not pain at every stage of biopsy or later recovery.

The registry record summarizes this score with a median and an inter-quartile range. The median identifies the middle of the observed scores when ordered, while the inter-quartile range describes the span from the lower to the upper quartile. These summaries can be useful when scores are skewed or concentrated near one end of a scale, because the median is less influenced by extreme values than the mean. They also retain the scale's clinical meaning: scores near 0 indicate less reported pain than scores near 10.

The endpoint is relevant to the study's stated aim of assessing patients' experience during biopsy. It is distinct from anxiety, procedure duration, and operator assessments, which are separate outcomes or questions. The registry record reports a median of 1.0 and an inter-quartile range from 0.0 to 2.0 for each group. It does not report a confidence interval, a test result, or further detail about how the scale was administered.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The main statistical information posted for the primary endpoint is a median, an inter-quartile range, and the number of participants represented in each group summary. Interpreting these requires separating description from inference. Description reports features of the observed data. Inference uses an analysis model or test to quantify how uncertain a comparison may be beyond those observed participants. The registry record reports the descriptive summaries, but does not report an inferential result for the primary comparison.

What does the median describe?

When scores are arranged from lowest to highest, the median marks the center of that ordered set. It is not the arithmetic average. A median of 1.0 means the reported center of the score distribution is 1.0 on the stated 0-to-10 scale. The median is often useful for bounded or skewed outcomes, particularly when many observations may cluster near one end. It is relatively resistant to unusually high or low values, but it does not describe the full shape of the distribution.

The inter-quartile range gives the interval between the lower and upper quartiles, which mark the central half of the observed scores. For each group, the posted range is from 0.0 to 2.0. This communicates that the middle portion of the scores lies in a relatively low part of the scale. It does not reveal the exact score for every participant, the number of scores at each value, or the tails outside that interval. Equal medians and inter-quartile ranges can coexist with differences elsewhere in the score distributions.

What can a group comparison establish?

A descriptive comparison can show whether the reported summaries differ. Here, the reported median and inter-quartile range are the same for the two groups. That observation does not, on its own, quantify uncertainty or establish whether a difference in the underlying populations is absent. An inferential comparison would need to account for the study design and the distribution of observed scores. The registry record does not report the method used for such an analysis, a test statistic, a p-value, or a confidence interval.

In general, a confidence interval is a way to express the uncertainty associated with an estimate under a specified statistical procedure. It is not a range containing a fixed proportion of individual participant scores. A narrow interval would indicate greater precision than a wide one, under the procedure's assumptions. No interval for the primary comparison is reported in the registry record, so the precision of a between-group effect estimate cannot be assessed from the posted endpoint summaries.

How does randomization affect interpretation?

Random assignment is intended to reduce systematic differences between groups at the start of a trial, including differences in measured and unmeasured factors. It supports a comparison of the assigned regimens, provided the analysis and follow-up preserve the randomized comparison appropriately. Randomization does not ensure that groups will be exactly alike, and it does not resolve issues such as missing outcome data or departures from assigned treatment. The record labels the study randomized but does not report the allocation sequence, concealment method, or analysis population.

The parallel-group structure means the assigned regimens are compared between groups. The trial is also recorded as double masked. Masking can reduce the potential for expectations to influence care, reporting, or assessment, depending on which people are masked and how masking is maintained. The registry record does not identify the masked roles or report whether masking was assessed. Those details should not be inferred from the category alone.

How should planning illustrations be read?

The registry record describes planning illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. Such illustrations address hypothetical future planning under stated assumptions; they do not describe the design justification for this completed trial. The record does not report the trial's own sample-size justification. Planning calculations are not observed power and cannot substitute for an estimate and uncertainty interval from the trial. The effect assumed for planning is also not evidence that the corresponding effect is clinically important.

For count outcomes, general statistical methods may need to account for over-dispersion, which occurs when variation is greater than a simple model assumes. That concept is not a reported feature of this primary endpoint, which is a bounded pain score summarized by median and inter-quartile range. The registry record does not describe a model for the primary endpoint, so no specific distributional assumptions or adjustment methods can be attributed to the trial.

Finally, statistical interpretation depends on how the recorded endpoint was collected, which participants contributed data, and how missing observations were handled. Those details can affect both the estimate and its uncertainty. The registry record does not report those analysis details. The posted median and inter-quartile range are therefore best read as concise descriptive summaries, not as a complete account of the statistical analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists four secondary outcomes: time of prostate biopsy and operator assessments of tolerating insertion of the rectal probe, maintaining positioning, and tolerance of the procedure. It also records seven outcome measures overall. The posted primary endpoint is post-biopsy pain. Results for the listed secondary outcomes are not reported in the registry record, so their direction, magnitude, and uncertainty cannot be assessed.

When a trial evaluates multiple outcomes, the chance of obtaining an apparently notable result by chance can increase if each outcome is tested separately. Statistical plans sometimes address this multiplicity through a prespecified hierarchy or an adjustment to the inference procedure. The registry record does not report whether any multiplicity strategy was planned or used, nor does it identify which outcomes, if any, were treated as confirmatory. No adjustment should be assumed.

The record does not list analysis entries. It does not report how missing primary or secondary outcome data were handled, whether imputation was used, or how participants were included in the analysis. It also does not report an intention-to-treat population, a per-protocol population, or another defined analysis set. These omissions matter because the number contributing to a result and the method for handling missing observations can affect its interpretation. The primary outcome summaries list 61.0 and 67.0 participants, while enrollment is recorded as 143; the record does not explain that relationship.

The registry record also does not report a prespecified statistical analysis plan or the methods used to address deviations from assigned treatment. These items should be treated as not reported in the registry record, rather than inferred from the randomized and double-masked design labels.

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 record reports no serious adverse events among the 61 participants at risk in the self-administered nitrous oxide group and none among the 67 at risk in the oxygen group. It reports no deaths in either group. For other adverse events, it records 1 affected participant among 61 at risk in the nitrous oxide group and 2 among 67 at risk in the oxygen group.

These are event counts, not estimates of comparative risk. The registry record does not provide a confidence interval, a statistical comparison, or further details about the definitions and collection of “other” adverse events. It also does not identify the specific non-serious events in these summaries. The empty list of top serious event terms does not add detail about event types.

Zero recorded serious events does not establish that serious events are impossible or that the groups have identical safety profiles. The counts should be read in the context of the participants represented and the way events were collected, details that are not fully reported in the registry record. The available figures describe what was posted, not a definitive comparison of safety.

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

The primary endpoint provides a focused description of pain 5 minutes after transrectal prostate biopsy. In the posted results, the median score is 1.0 in each group, and each inter-quartile range extends from 0.0 to 2.0. These statistics indicate that the reported central summaries are alike at the precision shown. They do not show that each participant experienced the same pain, or that the full distributions of scores were the same.

The result does not establish whether a clinically meaningful difference exists. The registry record does not report a between-group effect estimate, confidence interval, p-value, or a threshold for an important change in pain. A conclusion about the presence, absence, or precision of a difference cannot be made from the matching medians and inter-quartile ranges alone.

The finding is limited to the specific treatment regimens and measurement time described. The SANO group received nitrous oxide alongside a periprostatic bupivacaine nerve block; the oxygen group received oxygen. The endpoint addresses pain 5 minutes after biopsy, not anxiety, pain at other times, procedure duration, or operator assessments. Although the registry lists secondary outcomes addressing procedure time and operator ratings, results for them are not reported in the registry record.

The study's randomized and double-masked design labels are relevant to understanding how a treatment comparison was intended to be conducted. They do not supply missing information about the randomization procedure, masking roles, analysis population, or handling of missing data. Nor does the completion status alone establish that every planned outcome was reported.

Accordingly, the posted primary statistics are descriptive evidence about the recorded endpoint summaries. They neither demonstrate that nitrous oxide improves the biopsy experience nor establish that it has no effect. The record leaves uncertainty about the comparative estimate, the precision of that estimate, the secondary outcomes, and the analysis choices.

13. Why This Trial Matters Statistically

This trial illustrates why an endpoint summary and an inferential result are not interchangeable. The median and inter-quartile range concisely describe the center and spread of pain scores, and the reported values are the same in both groups. Yet those summaries alone do not provide an estimate of the between-group difference or the uncertainty around it. Readers need both the observed data description and appropriate inferential information to judge what a comparison can support.

It also highlights the importance of defining the outcome in time and concept. Pain at 5 minutes after biopsy is a specific patient-reported endpoint. It does not represent anxiety, the whole procedure experience, or later pain. The registry's additional outcomes address procedure time and operator assessments, but the record does not report their results. A broad study aim should not be mistaken for evidence on every aspect of experience it mentions.

The randomized, double-masked, parallel-group labels provide useful design context, while leaving important implementation details unreported. This distinction is central to registry interpretation: a design label communicates the stated category, not every procedure needed to evaluate potential bias or applicability.

Finally, comparing recorded enrollment with the participants included in the endpoint summaries raises a transparency question that the registry record does not resolve. The record lists enrollment of 143 and primary summary counts of 61.0 and 67.0. Without an explanation of participant flow and analysis populations, readers cannot determine from these figures alone why the counts differ. Clear reporting of analysis sets, missing data, outcome results, and uncertainty would make the statistical evidence easier to evaluate.

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 primary result is reported with descriptive summaries but no comparative estimate, confidence interval, or p-value. The identical median and inter-quartile range in the two groups do not reveal whether the full distributions differ or how precisely any between-group contrast is estimated. The registry record does not state a threshold for a clinically important difference on the pain scale.

There is also an unexplained relationship between enrollment and the endpoint summaries. Enrollment is recorded as 143, while the primary outcome summaries list 61.0 participants in the self-administered nitrous oxide group and 67.0 in the oxygen group. The registry record does not explain whether these are participants with observed scores, a defined analysis population, or another set of counts. Participant flow, missing-data handling, and inclusion criteria for the analysis are not reported.

The record does not report the randomization procedure, allocation concealment, or which people were masked. It also does not provide the statistical method used for the primary comparison or indicate how multiple outcomes were handled. These omissions limit evaluation of bias and of the inferential approach.

The posted primary endpoint addresses pain at one time point. Results for the four named secondary outcomes are not reported in the registry record. The adverse event information gives counts but limited detail about event types, definitions, and collection. Eligibility criteria, participant characteristics, and further procedural details are also not reported, limiting assessment of how well the results may apply to other settings or patient groups.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Self-Administered Nitrous Oxide (SANO) During Transrectal Prostate Biopsy to Reduce Patient Anxiety and Pain — NCT05803096.
• Registry record last updated 2024-01-30; status last verified 2024-01.
• Results first posted 2024-01-30.
• 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

This is a completed, randomized, double-masked, parallel-group Phase 4 trial of self-administered nitrous oxide during transrectal prostate biopsy. The recorded enrollment is 143, with a start date of 2021-12-12 and a primary completion date of 2022-09-02. The intervention group received SANO alongside a periprostatic bupivacaine nerve block; the comparator group received oxygen.

The primary endpoint was pain 5 minutes after biopsy on a Visual Analog Scale for Pain ranging from 0 to 10. Each group has a reported median of 1.0 and an inter-quartile range from 0.0 to 2.0. The registry record does not report a primary comparison test or confidence interval. It lists four secondary outcomes but does not report their results. Serious adverse events and deaths are recorded as 0 in both groups; other adverse events are recorded as 1 in the nitrous oxide group and 2 in the oxygen group.