Comparison of Intravascular Uptake and Pain Perception During Epidural Injection Using 22 Gauge vs 25 Gauge Needle: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of Intravascular Uptake and Pain Perception During Epidural Injection Using 22 Gauge vs 25 Gauge Needle (NCT04350307), a randomized na study. The primary outcome is Intravascular Uptake.

2. Clinical Question

3. Trial Design

This completed study, registered as NCT04350307, was a randomized, single-masked, parallel-group trial sponsored by Yale University. The registry lists an enrollment of 162. The study began on 2018-02-01, had a primary completion date of 2019-06-30, and is marked completed. Phase is listed as not applicable.

The intervention was the needle used during lumbosacral transforaminal epidural steroid injection. One arm used a 22-gauge Quincke needle and the other used a 25-gauge Quincke needle. The registry calls the interventions devices. Random allocation means assignment was intended to occur by chance, but the method used to generate and conceal the allocation sequence is not reported in the registry record. The meaning and implementation of single masking are also not described.

The primary outcome was intravascular uptake during the procedure. The registry describes observations made after the needle reached its target: contrast was injected and assessed with live fluoroscopy, and/or blood aspiration was attempted using a syringe. The outcome for a needle was marked present if contrast suggested that the needle was in a vessel or blood was aspirated; it was marked absent if neither indication was present. Although the event at the needle level was binary, the posted arm summaries are means of percentages averaged across participants.

Patient Reported Pain is listed as a secondary outcome. Its results, measurement details, and timing are not reported in the registry record. The record lists zero analyses. It does not describe the protocol, allocation procedures, sample-size justification, interim analyses, or a statistical analysis plan. The listed enrollment is a trial-record fact, not evidence by itself about how the study was designed to detect a particular effect.

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

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 Intravascular Uptake, measured over During the procedure.

The primary endpoint is intravascular uptake assessed during the procedure. For each needle, the registry describes a present-or-absent classification based on live fluoroscopy and/or attempted blood aspiration. A contrast pattern suggesting that the needle was in a vessel, or blood aspirated using a syringe, counted as present. A pattern not suggesting a vessel, together with no aspirated blood, counted as absent.

The registry reports the endpoint as a percentage of needles showing uptake, with participant-level percentages averaged within each arm. Thus, the posted values are mean percentages, not counts of participants with an event and not a single pooled percentage across all needles. The record's unit wording is “percentage of total number of needle.” It does not report the number of needles contributed by each participant or further details about how participant-level percentages were formed.

This outcome is used to describe how often uptake was observed during the procedure under the trial's stated assessment approach. Because the underlying needle-level classification is binary, the percentage expresses the share of assessed needles meeting the event definition. A higher percentage is explicitly described in the registry as a worse outcome. The endpoint captures this procedural observation; by itself, it does not describe other clinical outcomes or establish the consequences of an uptake observation.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary results are reported as means for a continuous summary measure, with 95% confidence intervals. The underlying event—whether uptake was present for a needle—is binary. The reported statistic is not a simple event count: the registry says percentages were averaged across participants. Understanding the distinction between the observation and the summary is important when interpreting the numbers.

What does a confidence interval describe?

In general, a confidence interval expresses uncertainty around an estimate, according to a statistical method and its assumptions. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. The intervals reported for this trial are attached to each arm's mean. They describe uncertainty in those separate means, not uncertainty in a contrast between the two arms. To quantify the comparative result directly, a reader would need an estimate of the between-arm contrast and its uncertainty, or a reported test. These are not reported in the registry record.

In general, comparing whether two arm-specific confidence intervals overlap is not equivalent to testing the difference between the arms. The precision of a difference depends on the uncertainty in both arm estimates and on the comparison method. The posted intervals therefore give context for the arm means but do not supply a formal conclusion about a group difference.

Why does the outcome's structure matter?

The registry describes a binary classification for each needle: uptake present or absent. It then describes calculating percentages and averaging those percentages across participants. This makes the analysis unit and the reporting unit distinct. A percentage calculated within a participant summarizes that participant's observed needles; an arm mean then summarizes those participant-level percentages. This approach can give each participant a role in the mean that differs from pooling every needle into one overall event percentage.

In general, observations from the same participant may be related rather than independent. If a participant contributes multiple needles, those observations may share procedural or participant characteristics. Methods that treat all needle observations as independent can understate uncertainty when within-participant correlation is present. Conversely, calculating participant-level percentages can address some features of repeated observations, but the registry does not provide enough detail to assess the exact construction, weighting, or variance method used. It does not report how many needles each participant contributed or whether that number varied.

What can the arm means support?

The values support a descriptive statement about the posted average percentages in each randomized arm. They do not show the full distribution of participant-level outcomes, including how many participants had no uptake or how widely percentages varied between participants. The registry reports no dispersion statistic apart from the confidence intervals. It also does not report a direct model, adjustment variables, an analysis population, or a test statistic. No particular statistical model or assumption should be inferred from the means alone.

In general, a randomized comparison can use an unadjusted contrast or a model-based analysis, depending on the outcome and the prespecified plan. The registry record does not report which comparative method was intended or used. It also does not report whether any assumptions were checked. Since the endpoint is formed from binary observations and summarized as percentages, the details of the analysis matter for standard errors and for the interpretation of the confidence intervals.

How should planning illustrations be understood?

The record describes planning illustrations based on an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is described as a fraction of the observed effect. Such calculations are general planning exercises, not findings from the randomized trial and not observed power. They do not establish the original design rationale. The trial's own sample-size justification is not reported in the registry record. No numerical planning results are stated in the record, so no target sample size beyond the reported enrollment should be inferred.

In general, planning calculations depend on assumptions about the effect to detect, variability, allocation, and the analysis method. If those assumptions differ from the trial's actual design or outcome structure, the calculation may not describe the study's operating characteristics. In particular, the record's endpoint description raises questions about participant-level percentages and potentially repeated needle observations, while the planning note specifies a normal approximation. Without the underlying calculation details or statistical plan, the fit between those assumptions and the trial analysis cannot be evaluated.

Overall, the appropriate reading is descriptive and cautious: the registry gives two arm means and their confidence intervals for the primary measure, but does not report the comparative estimate or analysis details needed to reconstruct a full inferential result.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, comparisons, or analyses are examined: the chance of at least one apparently notable result can increase when many tests are conducted. The registry lists intravascular uptake as the primary outcome and Patient Reported Pain as a secondary outcome. It does not report a multiplicity adjustment, a hierarchy for interpreting outcomes, or a prespecified statistical analysis plan. The pain outcome's results are not reported in the registry record, so no conclusion about that outcome or its relation to the primary result is possible.

The record lists zero analyses. This means it does not present a set of analysis records describing statistical comparisons; it does not demonstrate that no analysis was conducted. A between-arm test, p-value, or adjusted effect estimate is not reported. The available arm means and confidence intervals should therefore not be treated as a complete account of the planned or conducted inferential analyses.

Missing-data methods and analysis populations are not reported in the registry record. There is no description of how missing endpoint observations were handled, whether participants were analyzed according to randomized assignment, or whether exclusions occurred after randomization. The arm-level participant counts are reported, but the record does not explain whether those counts represent all randomized participants, all participants with endpoint data, or another analysis set. It also does not report reasons for missing or excluded observations.

These omissions limit assessment of potential bias from missing outcomes, deviations from assigned treatment, or selective reporting. They do not prove that such issues occurred; they mean that the registry information is insufficient to evaluate them. The registry record also does not report interim analyses or stopping rules. No assumptions about these procedures can be made from the completed status alone.

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.

The serious adverse event entries report zero affected participants in the 22-gauge arm, with 84 at risk, and zero in the 25-gauge arm, with 78 at risk. The record also reports zero participants with other adverse events in each arm and zero deaths in each arm. These are the registry's posted counts for the groups and categories recorded.

A zero count means no events were recorded in that category for the listed group; it does not establish that the risk is absent. Counts from a trial also depend on the duration and completeness of observation, the definitions used, and how events were collected. The registry record does not provide detailed adverse-event definitions, a fuller collection procedure, or additional context for interpreting the observation period.

The serious adverse event entries should not be confused with the primary endpoint. Intravascular uptake was recorded as a procedural outcome, whereas the adverse-event entries are separate safety summaries. The registry lists no serious adverse event terms among the top serious terms. The posted figures describe recorded events in this trial and should not be extended beyond those observations.

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

The registry reports mean intravascular uptake percentages of 5.9 for the 22-gauge arm and 7.1 for the 25-gauge arm. Each mean is accompanied by a 95% confidence interval: 1.9 to 9.8 for the 22-gauge arm and 2.4 to 11.8 for the 25-gauge arm. Since the registry defines higher percentages as worse, the reported arm means are descriptive of the observed direction in these summaries.

These figures do not by themselves establish a statistically reliable difference between needle groups. The registry does not report a direct estimate of the between-arm contrast, an interval for that contrast, or a p-value. The arm-specific intervals overlap, but that fact alone is not a formal test. The record also does not give enough detail about the analysis to determine how uncertainty was calculated or how multiple needles from a participant were handled.

The results do not answer the stated secondary question about patient-reported pain. Although Patient Reported Pain is listed as a secondary outcome, its results are not reported in the registry record. It would therefore be inappropriate to infer a pain comparison from the intravascular uptake outcome.

The posted results also do not establish how the findings would apply to populations or procedural settings beyond those represented in the trial. Detailed eligibility criteria and participant characteristics are not reported. Nor do the posted arm summaries describe individual participant outcomes, the number of needle observations per participant, or the clinical consequences associated with an uptake classification.

In statistical terms, the record offers arm-level descriptive summaries for the primary measure and sparse safety counts. It leaves important inferential and reporting questions unanswered. Interpretation should remain limited to these registered observations rather than treating them as proof for or against a treatment effect.

13. Why This Trial Matters Statistically

This trial illustrates why the definition of an endpoint and the unit of analysis matter. The event was classified for each needle as present or absent, while the reported outcome was a percentage averaged across participants. Those are different levels of measurement. Knowing whether a summary is based on participants, needles, or pooled observations is essential for understanding what an average represents and how its uncertainty should be calculated.

It also illustrates the distinction between arm-specific summaries and a comparative effect. Reporting a mean and confidence interval for each arm communicates the estimated level and precision within each group. A randomized comparison, however, is fundamentally about the contrast between groups. Without a reported contrast and its uncertainty, the reader cannot assess the comparative estimate directly from the registry record.

The trial's stated interest in both intravascular uptake and pain perception also highlights the importance of outcome reporting. The primary outcome has posted results, while the listed secondary pain outcome does not. When multiple outcomes are of interest, a statistical plan and transparent reporting help readers distinguish primary questions from secondary or exploratory ones and understand how multiplicity was addressed.

Finally, the registry provides sparse information about allocation, masking, missing data, and analysis methods. These details are not merely administrative: they help readers judge the risk of bias and the reliability of statistical uncertainty. The posted record offers useful descriptive information, but the missing methodological detail limits how far a statistical interpretation can go.

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.

Several trial-specific limitations arise from the registry information. The participant population is not described in detail, and eligibility criteria and participant characteristics are not reported in the registry record. The record therefore gives limited context for judging which patients or procedural settings the results represent.

The primary endpoint has a two-level structure: uptake was classified for each needle, while the reported result is the average of participant-level percentages. The record does not report how many needles each participant contributed, whether participants contributed different numbers of needles, or the precise calculation of each percentage. These details can affect both the estimand and the uncertainty calculation.

The registry reports the two arm means and their confidence intervals but does not report a direct between-arm estimate, a statistical test, a p-value, or an adjusted analysis. It also does not describe the confidence-interval method. Without these details, the comparative result cannot be independently assessed from the posted summaries.

Important trial procedures are not fully documented in the registry record. The method of random sequence generation and allocation concealment is not reported, and the meaning of single masking is not specified. The statistical analysis plan, sample-size justification, analysis populations, missing-data handling, interim analyses, and stopping rules are also not reported. These absences limit evaluation; they do not establish that the procedures were inadequate.

Patient Reported Pain is listed as a secondary outcome, but its results are not reported. The adverse-event record gives zero counts in the listed categories, but detailed definitions and collection procedures are not reported. These limitations restrict interpretation of both the secondary outcome and the safety summaries.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Comparison of Intravascular Uptake and Pain Perception During Epidural Injection Using 22 Gauge vs 25 Gauge Needle — NCT04350307.
• Registry record last updated 2020-07-20; status last verified 2020-07.
• Results first posted 2020-07-20.
• 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

NCT04350307 is a completed randomized, single-masked, parallel-group study sponsored by Yale University. It compared 22-gauge and 25-gauge Quincke needles during lumbosacral transforaminal epidural steroid injection. The registry reports an enrollment of 162, a start date of 2018-02-01, and a primary completion date of 2019-06-30.

The primary outcome was intravascular uptake during the procedure, classified as present or absent for each needle and reported as mean participant-level percentages. The 22-gauge arm mean was 5.9, with a 95% confidence interval of 1.9 to 9.8; the 25-gauge arm mean was 7.1, with a 95% confidence interval of 2.4 to 11.8. Patient Reported Pain is listed as a secondary outcome, but its results are not reported in the registry record.

The registry does not report a direct statistical comparison between arms, the analysis plan, missing-data methods, or detailed allocation and masking procedures. Serious adverse events, other adverse events, and deaths are recorded as zero in both arms.