Effectiveness Study of Different Local Anesthetic Mixtures: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effectiveness Study of Different Local Anesthetic Mixtures (NCT01243112), a non-randomized phase 4 study. The primary outcome is Length of Action.

2. Clinical Question

The study asks how the onset and duration of local anesthesia vary across formulations containing lidocaine, bupivacaine, or both, with epinephrine. Its primary endpoint is Length of Action: the time from onset of local anesthesia until sensation of sharp returns, measured in 15 minute increments for up to 12 hours. The registry describes injections at 4 forearm sites in healthy volunteers and an enrollment of 25.

This is a question about a measured effect in healthy volunteers under the study conditions. It is not, on the information in the record, a comparison of clinical outcomes among patients undergoing procedures. The study purpose also refers to onset, but the primary endpoint described in detail is duration; a separate onset result is not reported in the registry record.

3. Trial Design

The registry identifies NCT01243112 as a completed phase 4 study titled Effectiveness Study of Different Local Anesthetic Mixtures. The study started in 2010-05, had primary completion in 2010-09, and lists enrollment of 25. Scott and White Hospital & Clinic is named as sponsor. The condition listed is Pain.

The design is described as non-randomized, triple-masked, and single-group. Those labels need to be read together: the record does not describe a randomized allocation, and it explicitly cautions that the arms are not a like-for-like control comparison. It does not explain which parties were masked, how masking was maintained, or how the single-group designation relates to the four listed formulations and four forearm sites. Those operational details are not reported in the registry record.

The formulations include lidocaine alone with epinephrine, bupivacaine alone with epinephrine, and two mixtures of lidocaine and bupivacaine with epinephrine. The concentrations and epinephrine dilutions differ among the listed formulations. Therefore, the design does not isolate a single ingredient change across otherwise identical conditions. Any comparison would need to be interpreted in light of the complete formulation differences, as well as the non-randomized design.

The registry summary describes healthy volunteers receiving injections at 4 forearm sites. It does not report how participants or sites were assigned to each formulation, whether every participant received every formulation, the sequence of administration, or whether measurements were paired within participants. These details matter for deciding which statistical comparisons are appropriate, and should not be inferred from the single-group label alone.

The registry record identifies 2 outcome measures and 2 analyses, but does not provide numerical results for the primary endpoint. It also does not report a detailed statistical analysis plan, an account of interim analyses, or the handling of deviations from the intended design. The status is completed, but completion status by itself does not establish that all planned results were posted.

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

Analysis population for the primary outcome, as defined in the registry: A calculation was made to power the study appropriately to determine a difference of 5 minutes based on previous studies which did not include the use of epinephrine.

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 Length of Action, measured over Up to 12 hours.

Length of Action is defined as the time from onset of local anesthesia until cessation of effect, assessed by sensation of sharp. The registry specifies measurement in 15 minute increments and a timeframe of up to 12 hours. The endpoint is expressed in minutes, with the mean as the listed summary parameter and the standard deviation as the listed measure of dispersion.

The endpoint is intended to quantify duration of sensory effect. In general, a duration measure can describe how long an effect persists, while an onset measure describes how quickly it begins; the registry summary distinguishes these concepts but gives detailed primary-endpoint information only for duration. The record does not report a separate numerical onset result.

Because observations are recorded in 15 minute increments, the endpoint has a measurement granularity that should inform interpretation: a reported value cannot necessarily distinguish changes finer than the measurement schedule. This is a general point about the stated measurement approach, not a claim about the observed values, which are not reported in the registry record.

The record says a calculation was made to power the study to determine a difference of 5 minutes, based on previous studies without epinephrine. It does not report a detailed rationale for choosing that target, or the sample-size assumptions and calculation used for the trial’s own design. The target should therefore be read as a stated planning objective, not as an observed effect or a result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry lists Length of Action as a continuous measure summarized by a mean and standard deviation. The endpoint is measured in minutes, from onset of local anesthesia until cessation of effect by sensation of sharp. Measurement occurs in 15 minute increments over a timeframe of up to 12 hours. The record does not report the observed values or the statistical procedures used to analyze them.

What does a mean describe?

General explanation: a mean is the arithmetic average of the observations included in an analysis. It gives a central summary on the original measurement scale, so a mean duration expressed in minutes can be interpreted as an average time. A mean alone does not reveal whether observations cluster closely together or vary considerably; the standard deviation gives a descriptive measure of that variability. Neither summary, by itself, establishes the uncertainty of a difference between formulations.

The endpoint has a fixed measurement schedule in 15 minute increments. General explanation: when a value is recorded at set intervals, the measurement may not capture the exact instant at which a sensation changes. The implications depend on how the endpoint was operationalized and analyzed. The registry defines the interval but does not describe any rounding, interpolation, or other treatment of the recorded times. Those procedures are not reported in the registry record.

What would a comparison estimate?

General explanation: a comparison of means estimates the average difference between the groups or conditions included in that comparison. Its interpretation depends on how observations were assigned and whether measurements from the same participant are related. If observations are paired, a method that accounts for the pairing may be appropriate; if they are independent, a different method may be needed. This is a general distinction, not a description of the analysis used in this study. The registry record does not state whether the formulations were compared within participants, how sites were allocated, or which statistical test was used.

The record identifies non-randomized allocation, a single-group model, and a warning that the arms are not a like-for-like control comparison. General explanation: without random assignment, measured differences can reflect the treatment conditions, differences in who or what receives each condition, or both. That concern cannot be quantified from the design labels alone. The details of assignment, sequence, and analysis are not reported in the registry record, so the specific risks of bias cannot be determined.

Why report uncertainty as well as an estimate?

General explanation: an estimate is a best summary of the observed data under a chosen method, while a confidence interval communicates its precision. A relatively narrow interval indicates greater precision than a wide interval, though precision is not the same as freedom from bias. A p-value, when used, describes how compatible the data are with a specified null model under the method’s assumptions; it does not measure the size or clinical importance of an effect. The registry record does not report an estimate, confidence interval, or p-value for Length of Action.

The listed standard deviation describes variability among observations, whereas a confidence interval would address uncertainty in an estimate. These quantities answer different questions. A mean and standard deviation may be useful descriptive statistics, but a reader would still need an appropriate comparative estimate and uncertainty measure to evaluate how well the data distinguish among the formulations. Those results are not reported in the registry record.

What are the planning assumptions?

The registry states that a calculation was made to power the study to determine a difference of 5 minutes, based on previous studies that did not include epinephrine. It does not report the detailed assumptions or calculation for the trial’s own design. Separately, a planning illustration associated with the analyses uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Such an illustration is a planning exercise rather than an observed result. Any sample sizes derived from it are planning illustrations, not observed power. The registry’s sample-size justification and the relationship between the stated 5-minute target and the design assumptions are not reported in the registry record.

General explanation: power is the probability, under a specified statistical model and assumed effect, of detecting that effect according to a chosen decision rule. It depends on the assumed effect, variability, sample size, allocation, and analysis. It cannot establish that a study has detected an effect, and a post hoc power calculation based on an observed estimate does not replace a confidence interval. The record does not provide enough trial-specific planning detail to assess the original power calculation.

How might distributional features matter?

General explanation: analyses based on means often rely on assumptions about the distribution of observations or the behavior of estimates. Duration outcomes can sometimes be asymmetric, and observations may be limited by the measurement window. Whether those issues affected this study cannot be determined without the outcome data and analysis details. The registry does not report a distributional assessment, a transformation, a model for censored observations, or an approach to observations that reached the end of the measurement timeframe.

General explanation: over-dispersion means that variation is greater than a model assumes. When it occurs, standard errors can be too small if the model does not account for it, making uncertainty appear lower than it is. This concept is relevant only if the chosen analysis has a variance assumption that could be violated; the registry does not identify the statistical model used. It is therefore not possible to say whether over-dispersion was present or how it was handled.

In summary, the record gives the endpoint’s definition, scale, planned summary parameter, and a stated target difference. It does not report the numerical outcome results or enough analysis detail to reproduce or evaluate a comparison. Statistical interpretation must remain at the level of the stated design and measurement rather than claims about observed formulation effects.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies 2 outcome measures and 2 analyses. The detailed primary endpoint available in the record is Length of Action. The identity and definitions of the other outcome measure and analysis are not reported in the registry record. The record also does not state which outcomes were primary or secondary beyond the listed primary endpoint, how many comparisons were planned, or whether a multiplicity adjustment was used.

General explanation: when several outcomes or comparisons are tested, the chance of at least one apparently unusual result can increase. A multiplicity strategy may define a primary comparison, adjust significance thresholds, or otherwise account for the set of planned analyses. Whether such a strategy is needed depends on the analysis plan and inferential aims. No multiplicity procedure is reported in the registry record, so it is not possible to assess how multiple testing was handled.

Missing-data procedures are also not reported. The record does not state whether all enrolled participants contributed endpoint measurements, how incomplete measurements were handled, or whether any observations were excluded. It does not report reasons for missingness or a sensitivity analysis. General explanation: missing-data methods can affect an estimate when the chance of missingness is related to the outcome or participant characteristics. Without counts and methods, the impact cannot be evaluated.

The analysis populations are not described. The record does not say whether analyses included all enrolled volunteers, only those who received a formulation, or a different defined set. It also does not report a participant flow account or protocol deviations. These omissions prevent assessment of how the analyzed observations relate to the enrollment of 25.

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 1% reporting threshold.

The registry lists a Study Group with 25 participants at risk for serious adverse events and 0 affected. It also lists 25 at risk for other adverse events and 0 affected. The deaths field is null, which means that a death count is not reported in the registry record; it should not be interpreted as a reported count of zero. The record lists no top serious adverse event terms.

These figures describe what is entered in the registry safety fields. A reported zero affected means no affected participants are listed for that category in this record. It does not establish that no event occurred outside the reported collection or reporting process, and it does not by itself quantify how precisely the study could detect uncommon events. The record does not provide event definitions, surveillance procedures, follow-up completeness, or a narrative explaining the safety entries.

The safety figures should also be read in the context of the study population and enrollment. The registry summary describes healthy volunteers and an enrollment of 25. These registry entries are not a substitute for detailed event-level reporting, and they do not provide a comparative safety estimate among the four formulations. The record does not report such a comparison.

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

The registry record establishes that a completed phase 4 study was designed to examine onset and duration across local anesthetic formulations containing lidocaine, bupivacaine, and epinephrine. It specifies Length of Action as the primary endpoint and describes its measurement through return of sensation of sharp. It also reports an enrollment of 25 healthy volunteers and the study’s non-randomized, triple-masked, single-group design labels.

What the record does not establish is the observed duration for any formulation, the size or direction of a difference, or the precision of a comparison. Numerical endpoint results are not reported in the registry record. The stated target difference of 5 minutes is a planning objective, not an observed treatment effect. Without estimates and uncertainty measures, a reader cannot determine whether the formulations produced similar or different durations in the measured observations.

Even if numerical contrasts were available, interpretation would need to account for the design. The registry cautions that the arms are not like-for-like controls, and allocation is non-randomized. The formulations also differ in their ingredient concentrations and epinephrine dilutions. A contrast would therefore describe the conditions as administered, not necessarily the isolated effect of lidocaine, bupivacaine, or epinephrine individually.

The healthy-volunteer setting and forearm measurements define the context of the question. The record does not report how those measurements relate to outcomes during clinical procedures or how broadly the findings might apply beyond the study conditions. No clinical conclusion should be inferred from the design description alone.

In short, the posted registry information allows a reader to understand the endpoint and important design constraints, but not to judge the observed result. The missing numerical endpoint findings and analysis details are central to evaluating the study’s statistical evidence.

13. Why This Trial Matters Statistically

This study raises several useful statistical issues in a compact design. First, the outcome is a duration measured over time, but the registry describes it using a mean and standard deviation. Readers need to distinguish the endpoint’s time-based meaning from the summary statistics used to characterize it. The 15 minute measurement increments and the stated timeframe of up to 12 hours also make measurement resolution and the handling of observations at the end of follow-up relevant questions.

Second, the design labels require careful reading. Non-randomized allocation and a single-group model do not describe a conventional randomized parallel-group comparison, while the record explicitly cautions that the arms are not like-for-like controls. Understanding the assignment of formulations and sites would be essential for choosing an analysis and interpreting any contrast. Those details are not reported in the registry record.

Third, the formulations differ in more than one feature. A statistical contrast between complete formulations would not automatically identify which ingredient or concentration accounts for any observed difference. This illustrates the distinction between estimating differences among treatment packages and isolating the effect of a specific component.

Finally, the record gives a planned target difference but not numerical endpoint findings. This illustrates why a design target, a sample-size calculation, an observed estimate, and the precision of that estimate are separate pieces of evidence. A planning objective cannot substitute for results. Here, the absence of posted outcome estimates and analysis details prevents evaluation of the measured differences, regardless of the completion status.

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 the study is that numerical primary-endpoint results are not reported in the registry record. The means, standard deviations, contrasts, confidence intervals, and p-values needed to describe the observed duration and its precision are not available. The stated target difference of 5 minutes does not fill this gap.

The design is listed as non-randomized and single-group, and the record cautions that the arms are not a like-for-like control comparison. The assignment process, sequence of formulations, and relationship between participant and site observations are not reported. As a result, the appropriate comparison structure and the potential for assignment-related differences cannot be assessed.

The four formulations vary in ingredients and concentrations, including epinephrine dilution. This limits the interpretation of any formulation contrast as an isolated component effect. The registry also does not explain which parties were masked despite listing triple masking.

The registry describes 25 healthy volunteers and forearm injections. It does not report participant characteristics, the completeness of endpoint follow-up, or how the study measurements relate to clinical procedure settings. The endpoint was measured in 15 minute increments for up to 12 hours, but handling of incomplete or end-of-window observations is not reported.

Finally, the record does not specify the analysis methods, multiplicity approach, missing-data procedures, analysis populations, or detailed sample-size assumptions. These gaps restrict assessment of bias, uncertainty, and reproducibility. They do not prove that a particular method was absent from the study; they mean that the method is not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effectiveness Study of Different Local Anesthetic Mixtures — NCT01243112.
• Registry record last updated 2011-12-02; status last verified 2011-10.
• Results first posted 2011-12-02.
• 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

NCT01243112 is a completed phase 4 study sponsored by Scott and White Hospital & Clinic, with enrollment of 25. The registry lists a start in 2010-05 and primary completion in 2010-09. It describes healthy volunteers receiving local anesthetic at 4 forearm sites and lists four lidocaine, bupivacaine, and combination formulations with epinephrine.

The primary endpoint is Length of Action, measured in minutes from onset of anesthesia until sensation of sharp returns, in 15 minute increments for up to 12 hours. The endpoint is listed as a mean with standard deviation. The record describes non-randomized allocation, triple masking, and a single-group model, and cautions that the arms are not like-for-like control comparisons.

Numerical primary-endpoint results and detailed analysis procedures are not reported in the registry record. The safety fields list 0 affected for serious and other adverse events among 25 at risk in each category; deaths are not reported.