Reducing Pain of Lidocaine Injection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Reducing Pain of Lidocaine Injection (NCT02288364), a randomized phase 4 study. The primary outcome is Pain.

2. Clinical Question

The clinical question concerns discomfort at the start of the anesthetic injection, rather than pain during the biopsy as a whole or pain after the procedure. The registry background explains that lidocaine injection can cause brief pain before its numbing effect begins, and that some physicians believe the acidity of lidocaine may contribute to that discomfort. The comparison therefore tests whether buffering the lidocaine is associated with a different reported pain score at the specified time.

Both approaches are described in the registry as routine standard of care. This is an active comparison between two anesthetic preparations, not a comparison with no local anesthetic. The registry record does not establish which approach is preferable for individual patients; the results describe the measured scores in the participants enrolled in this trial.

3. Trial Design

The registry identifies this as a Phase 4, randomized, double-masked, parallel-group trial. Participants were assigned to one of two groups: 1% lidocaine alone or 1% lidocaine plus sodium bicarbonate. The record reports enrollment of 88 participants and a completed status. The sponsor is Duke University. The registry dates are 2014-12 for study start and 2015-08 for primary completion.

A randomized design is intended to make the groups comparable, on average, with respect to factors that could affect the outcome. Double masking means the record describes masking at two levels, but it does not state which people were masked or how masking was maintained. Details of random sequence generation, allocation concealment, and masking procedures are not reported in the registry record. These omissions mean the design label alone cannot answer how those procedures were carried out.

The parallel-group structure means the comparison is between participants assigned to different preparations, rather than a within-participant comparison of both preparations. The primary outcome is a continuous pain score summarized by a mean and standard deviation in each arm. The registry reports 42 participants in the lidocaine-alone arm and 44 in the lidocaine-plus-bicarbonate arm for this outcome.

The record lists 10 outcome measures and 3 analyses, and the overall status is completed. It does not describe the trial's original sample-size justification, the prespecified statistical analysis plan, or whether analyses were interim or final. The registry record also does not report the number screened, the number excluded, the number analyzed under each intended analysis population, or reasons for any missing outcome measurements. Enrollment and the outcome-specific arm counts should therefore not be treated as a full account of participant flow.

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 Pain, measured over immediately prior to anesthetizing, within approximately 1 minute of starting.

The primary endpoint is pain measured immediately before anesthetizing, within approximately 1 minute of starting. The registry describes a 0-to-10 scale: zero represents no pain, and 10 represents the worst pain possible. The arm results are reported as means with standard deviations.

This timing targets the initial discomfort that motivates the study question: the pain associated with injecting lidocaine before its numbing effect begins. It is distinct from the separate secondary pain measurement taken immediately on completion of anesthetizing the skin, also within approximately 1 minute of starting. Keeping the timing explicit matters because pain at different stages of a procedure can represent different experiences and should not be treated as interchangeable measurements.

As a continuous measure, the endpoint can be summarized by the average score in each randomized group and by a mean difference between groups. A mean difference retains the scale's units, so its interpretation is in pain-score units. The registry does not report additional details about the instrument's validation, how participants entered their scores, or how the scale was administered. Those measurement details are not reported in the registry record.

The endpoint provides a group-level description of reported pain at the specified time. It does not, by itself, describe every participant's experience, later pain, or other aspects of the biopsy procedure.

7. Results Posted in the Registry

• 1% Lidocaine Plus Sodium Bicarbonate: mean 0.56 versus 1.19 on control; difference -0.63 (95% CI -1.33 to 0.07), standardized effect d = -0.39; z-test p = 0.076.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Pain

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • 1% Lidocaine Plus Sodium Bicarbonate: mean 1.61 versus 2.07 on control; difference -0.46 (95% CI -1.31 to 0.39), standardized effect d = -0.23; z-test p = 0.291.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 1% Lidocaine Plus Sodium Bicarbonate and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists nine secondary outcomes as posted and identifies pain among the secondary outcome labels. The numerical secondary information in the record includes a pain measurement taken immediately on completion of anesthetizing the skin, within approximately 1 minute of starting. Its group means follow the same directional pattern as the primary outcome: the bicarbonate group has the lower average score. The secondary comparison's interval includes zero, and the posted unadjusted p-value does not indicate a clear difference. The record also lists a chi-squared result for this outcome, but does not explain how that test was applied to the continuous pain measure.

The similarity in direction between the available secondary comparison and the primary estimate can be considered descriptive, but it does not establish that the treatment contrast is consistent across all secondary outcomes. The registry record does not provide detailed numerical results for every listed secondary outcome in the registry record for this analysis. It is therefore not possible to characterize a complete pattern across all nine as if each had been evaluated and reported in the same way.

Secondary outcomes generally carry less evidential weight when many outcomes or analyses are considered. Each additional comparison creates more opportunities for a result to appear noteworthy by chance, especially when no adjustment or prespecified hierarchy is documented. The registry record does not report a multiplicity strategy, such as an adjustment for multiple testing or a designated order for interpreting outcomes. The secondary results should consequently be treated as supportive description, not as independent confirmation of the primary result.

The distinction between outcome timing also matters. A pain score immediately before anesthetizing and a score immediately on completion of anesthetizing the skin refer to different moments. Even if both are labeled pain and use the same scale, they answer related but nonidentical questions. The secondary result can add context about the pattern of reported discomfort, but it cannot replace the primary endpoint or resolve uncertainty in the primary comparison.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Pain
• Pain
• Pain
• Pain
• Pain
• Pain
• Pain
• Pain

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: each participant contributes a pain score, and the registry summarizes scores using a mean and standard deviation. The comparison of interest is the difference between the average score in the bicarbonate group and the average score in the lidocaine-alone group. A negative mean difference indicates a lower group average in the bicarbonate arm for the direction used in the posted comparison. This direction describes the arithmetic contrast, not a conclusion about clinical importance.

What does a mean difference tell us?

A mean difference expresses the gap between two group averages in the original measurement units. Here, those units are pain-scale units. It is directly interpretable in relation to the 0-to-10 scale, unlike a standardized effect measure, which rescales a difference using variability. A mean difference summarizes the average contrast; it does not imply that every participant's score changes by that amount or that scores are distributed similarly in both groups.

What do the standard deviations describe?

A standard deviation describes the spread of participant scores around the group mean. It is not the uncertainty in the mean itself and is not a confidence interval. The primary arm standard deviations are 1.92 and 1.3. A spread measure helps readers understand that people within an arm did not all report the same score. It also contributes to the precision of a comparison of group means. The registry does not provide participant-level scores or a detailed description of the score distributions, so distributional features such as skewness or concentrations at particular scale values cannot be assessed from these summaries alone.

How should the confidence interval and p-value be read?

A confidence interval represents uncertainty around an estimated effect under the method used to construct it. In general, a wider interval indicates less precision, while a narrower interval indicates more precision. For the primary outcome, the interval extends across zero. Zero represents no mean difference. Because zero is within the reported interval, the result does not rule out no average difference at the confidence level used for the interval. The interval also includes effects on either side of zero, so the direction and magnitude are not settled by the estimate alone.

A p-value measures how incompatible the observed data are with a specified null model, given the assumptions of the test. It is not the probability that the null hypothesis is true, nor the probability that the result occurred by chance. The primary comparison's unadjusted p-value is 0.076. Its interpretation depends on the analysis method, assumptions, and the context of other planned outcomes and analyses. The registry record does not report a detailed primary test specification, so the p-value should be read as the posted unadjusted recalculation rather than as a fully documented sponsor analysis.

Why can over-dispersion matter?

General statistical explanation: over-dispersion occurs when observed variability is greater than a model assumes. If a model treats observations as less variable or more independent than they really are, its standard errors can be too small and its intervals too narrow. If a model accounts for more variability, uncertainty estimates can widen. This is a general consideration for statistical modeling, not a claim that over-dispersion was present in this trial. The registry record does not report an over-dispersion assessment or a model-based primary analysis.

What is known about the analysis?

The comparison statistics shown for the primary outcome are simple unadjusted recalculations from the posted summary statistics. The registry record reports the arm means, standard deviations, and group sizes, along with the recalculated mean difference and interval. It does not report covariate adjustment, a method for handling missing outcome values, an analysis population definition, or a detailed primary analysis plan. Consequently, the recalculation should not be represented as proof of the precise analysis that the investigators planned or performed.

The record lists a chi-squared analysis with p = 0.30 for the secondary pain outcome, while the outcome is also presented as a continuous mean and standard deviation. A chi-squared test is generally used for categorical data, so the record's entry does not by itself explain which values or categorization were tested. The method's exact application is not reported in the registry record. It should not be assumed to be interchangeable with the unadjusted continuous-outcome comparison.

The registry reports that the trial was randomized, double-masked, and parallel-group, which describes important features of its design. Those labels do not provide all details needed to assess analysis validity. In particular, allocation procedures, protocol deviations, missing data, and analysis populations are not described. Statistical interpretation therefore combines the posted numerical summaries with a clear distinction between what is reported and what remains unspecified.

11. Confidence Intervals and Precision

The primary mean-difference estimate is -0.63 pain-scale units, with a 95% confidence interval from -1.326 to 0.066. The interval crosses zero, the value representing no average difference. It therefore includes both a possible lower mean score with bicarbonate and a possible higher mean score with bicarbonate, as well as no mean difference. The point estimate alone gives a single value, while the interval makes the uncertainty around that value visible.

The interval is not a range containing 95% of individual participants' scores. It describes uncertainty about the group-level mean difference under the calculation used. The arm standard deviations describe participant-to-participant spread; the confidence interval describes precision in the estimated contrast. Those are related but distinct concepts.

The primary confidence interval has a negative lower bound and a small positive upper bound. Its inclusion of zero means that the posted estimate does not precisely establish the direction of the average contrast. The interval also allows effects of different magnitudes, so the result should not be reduced to a simple statement that the groups were identical or that one preparation had a definite advantage.

Precision is affected by the amount of information in the data and by the variability of the outcome. The primary outcome has 42 participants in the lidocaine-alone arm and 44 in the bicarbonate arm. The registry does not report the original precision target, a minimum clinically important difference, or the trial's own sample-size justification. Without those details, the interval can be described statistically, but its practical importance cannot be determined from the registry record alone.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size display is a planning illustration based on the observed effect, not a report of the trial's original design assumptions. Its figures are participants per arm, not total events. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning row uses a stated fraction of the observed effect as the effect to detect. The trial's own original sample-size assumptions are not reported in the registry record.

The 80% power column gives the planned number of participants per arm for a hypothetical future study to have 80% power under those assumptions and for the effect specified in that row. In plain terms, power describes the chance that a study would identify an effect at the chosen significance threshold if that assumed effect were the true effect and the planning assumptions held. The 90% power column gives the corresponding per-arm planning number for 90% power. These are planning probabilities, not guarantees about an individual study's outcome.

For the primary outcome, planning for 100% of the observed effect gives 106 participants per arm for 80% power and 142 participants per arm for 90% power. Planning for 75% of the observed effect gives 188 participants per arm for 80% power and 251 participants per arm for 90% power. Planning for 50% of the observed effect gives 422 participants per arm for 80% power and 565 participants per arm for 90% power. Smaller effects require more participants to detect under the same assumptions, which is why the planning numbers rise as the assumed effect becomes smaller.

This is not observed power. It is a forward-looking illustration that uses the observed effect as its starting point; it does not measure the probability that the completed trial's result is correct. The sample-size figures are sensitive to the effect chosen for planning and should not be read as the trial's actual enrollment target or as evidence that the study was adequately or inadequately designed.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.630; pooled standard deviation σ = 1.632.
2. n = 2 × (1.96 + 0.842)² × 1.632² / -0.630² = 105.4, rounded up to 106 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.63                      # observed difference in means
sigma <- 1.63230920273499                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2288364)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 106 (80% power), 142 (90% power)
 75% of observed effect: n per arm = 188 (80% power), 251 (90% power)
 50% of observed effect: n per arm = 422 (80% power), 565 (90% power)
power.t.test: 106.3 
Simulated power at n = 106 per arm: 0.794 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists 10 outcome measures and 3 analyses, and it identifies nine secondary outcomes as posted. When several outcomes or analyses are examined, the chance of obtaining at least one apparently notable result can increase. Statistical plans commonly address this issue by specifying a primary outcome, an ordering of secondary outcomes, or an adjustment for multiple comparisons. The registry record does not report whether any such multiplicity strategy was planned or used.

The primary endpoint is identified as pain at the specified time before anesthetizing. That designation helps distinguish the main question from secondary measurements, but it does not reveal the full prespecified hierarchy or how the investigators intended to interpret multiple analyses. The registry does not report whether the posted outcome list reflects the complete set of outcomes planned before enrollment, whether any outcomes changed, or whether analyses were selected after looking at the results. Those matters are not reported in the registry record.

Missing-data handling is also not described. The primary outcome arm counts are 42 and 44, and the overall enrollment is 88, but the record does not give a participant flow account or explain whether all enrolled participants contributed an outcome measurement. It does not report the amount or reasons for missing primary or secondary scores, or whether any imputation or other missing-data procedure was used. The difference between enrollment and outcome counts cannot be interpreted as missingness without further information.

The record does not define an intention-to-treat, per-protocol, or other analysis population. It also does not report exclusions after randomization, protocol deviations, or how participants were handled if they did not receive their assigned preparation. Thus, the arm summaries describe the posted outcome data but cannot be confidently assigned to a particular analysis population based on the registry record alone.

These reporting gaps do not establish that multiplicity, missing data, or analysis-population procedures were handled incorrectly. They limit the ability to assess those procedures from the registry record. The p-values and confidence intervals should be interpreted as reported, with the absence of documented analysis details kept distinct from evidence that a particular method was or was not used.

15. 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.

The registry reports zero serious adverse events affecting participants in the lidocaine-alone group, with 42 participants at risk, and zero in the lidocaine-plus-sodium-bicarbonate group, with 44 participants at risk. It also reports zero other adverse events affecting participants in each group, using the same at-risk counts. These entries describe the posted event counts, not a guarantee that no event occurred outside the registry's definitions or reporting process.

The death entries are null rather than a reported count of zero. A null value should be read as not reported in the registry record, not as evidence that there were no deaths. The record does not provide details about adverse-event definitions, collection procedures, monitoring duration, or whether events were assessed as related to study treatment. It also does not list serious adverse-event terms.

Safety figures should be read in light of the number of participants at risk and the information the registry actually records. The figures alone cannot establish comparative safety or exclude uncommon events. They are a description of adverse-event reporting for this completed trial, not individualized medical advice.

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

The posted primary results show a lower average pain score in the lidocaine-plus-sodium-bicarbonate group than in the lidocaine-alone group at the specified time immediately before anesthetizing. The estimated mean difference is -0.63 units. The confidence interval includes zero, and the unadjusted p-value is 0.076. Taken together, these results leave substantial uncertainty about the average difference: the estimate favors a lower score in the bicarbonate group, but the interval does not exclude no difference.

This is not the same as proving that the two preparations have identical effects. Failure to rule out zero does not demonstrate equivalence or noninferiority; those conclusions require an appropriate design, prespecified margin, and analysis. The registry record does not report an equivalence or noninferiority objective or margin. Nor does the p-value alone establish that a difference is unimportant or important to participants.

The trial addresses a narrow and clearly timed experience: pain at the beginning of local anesthetic injection before a percutaneous breast biopsy. It does not establish effects on pain during the biopsy, pain after the procedure, or other clinical outcomes. The secondary measurement at completion of skin anesthetizing is related but distinct. The registry does not report detailed results for every listed secondary outcome in the registry entries.

The trial enrolled 88 participants, and its primary arm counts are 42 and 44. This is the information base underlying the posted group summaries. A confidence interval communicates uncertainty in the average contrast, but it does not capture all limitations, including possible missing data, outcome measurement details, analysis choices, or generalizability. Several of those details are not reported in the registry record.

The results therefore support a measured description, not a treatment recommendation: average scores were lower in the bicarbonate arm in the posted primary summaries, while the estimate remains imprecise enough to include no average difference. They do not establish a definite advantage, a definite absence of an effect, or what any individual participant would experience. Interpretation should remain tied to the studied preparations, setting, outcome, and time point.

17. Why This Trial Matters Statistically

This trial offers a useful statistical example of why a point estimate, confidence interval, and p-value should be read together. The primary point estimate is in one direction, but the interval crosses zero and the unadjusted p-value is 0.076. Reporting only the direction of the estimate would hide uncertainty; reporting only whether a threshold was crossed would hide the size and range of effects compatible with the data.

The outcome is measured on a defined pain scale and at a specific procedural moment. That clarity makes it possible to distinguish the primary question from a related secondary pain measurement taken at a different time. It also illustrates why endpoint timing and definition are part of statistical interpretation, rather than merely descriptive details.

The record further illustrates the importance of distinguishing a completed trial's observed results from planning calculations. The sample-size illustrations use fractions of the observed effect and make assumptions about allocation, significance level, and approximation. They are not the original trial justification and do not provide observed power. Keeping these purposes separate prevents planning scenarios from being mistaken for evidence about the completed study's certainty.

Finally, the trial demonstrates how registry reporting shapes what can be evaluated. Randomization, masking, arm summaries, and adverse-event counts are documented, but details about the analysis plan, missing data, multiplicity, and participant flow are not. A careful statistical reading can describe the numerical results while also identifying where the record does not support stronger claims.

18. 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 endpoint is an immediate pain score at the start of anesthetizing. It is a specific, short-term measure and does not describe pain at other stages of the biopsy or later. The registry record does not report details about how the scale was administered, whether participants received instructions, or whether the measurement instrument had been validated in this setting.

The total enrollment was 88, with primary outcome counts of 42 and 44 in the two arms. The confidence interval crosses zero, indicating uncertainty around the estimated mean difference. The registry does not report a minimum clinically important difference, so the practical meaning of the point estimate and interval cannot be determined from a clinical threshold stated in the record.

Several features needed to evaluate conduct and analysis are not reported in the registry record. These include the randomization and allocation procedures, who was masked, how masking was maintained, the original sample-size justification, the detailed primary statistical plan, the analysis populations, and missing-data handling. The record also does not explain the relationship between the continuous secondary summary and the listed chi-squared analysis.

The registry lists multiple outcomes and analyses but does not report a multiplicity strategy or a full set of detailed numerical results for every listed secondary outcome. This limits interpretation of secondary findings and makes it difficult to assess whether all planned analyses are represented. The adverse-event counts are reported, but the death fields are null, and details about event definitions, ascertainment, and follow-up are not reported.

These limitations concern the scope of the available record and the precision of the evidence. They do not establish that the trial procedures were inadequate or that unreported procedures were absent. They do mean that conclusions should stay close to the reported population, preparations, outcome timing, and summary statistics.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Reducing Pain of Lidocaine Injection — NCT02288364.
• Registry record last updated 2016-04-15; status last verified 2016-02.
• Results first posted 2016-03-14.
• 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.

22. Record Summary

NCT02288364 is a completed Phase 4 randomized, double-masked, parallel-group trial sponsored by Duke University. It enrolled 88 participants and compared 1% lidocaine alone with 1% lidocaine plus 8.4% sodium bicarbonate before percutaneous breast needle core biopsy.

The primary outcome was pain immediately before anesthetizing, measured on a 0-to-10 scale. The mean scores were 1.19 for lidocaine alone and 0.56 for lidocaine plus sodium bicarbonate. The recalculated unadjusted mean difference was -0.63, with a 95% confidence interval from -1.326 to 0.066 and p = 0.076.

The estimate points toward a lower average score in the bicarbonate group, but the interval includes zero. The registry record does not report several details needed for fuller assessment, including the trial's original sample-size justification, detailed primary analysis plan, missing-data procedures, multiplicity strategy, and analysis-population definitions.