Tetracaine Versus Lidocaine Gel for Anesthetic Effect and Comfort in Patients Undergoing LASIK: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Tetracaine Versus Lidocaine Gel for Anesthetic Effect and Comfort in Patients Undergoing LASIK (NCT01383200), a randomized phase 4 study. The primary outcome is Participants Score on Pain Scale.

2. Clinical Question

The study asked whether comfort after LASIK differed between eyes treated with tetracaine drops and eyes treated with lidocaine gel. Its primary question focused on sharp eye pain reported one hour after the operation, measured on a scale from 1 to 5. The registry describes 1 as no symptoms and 5 as severe discomfort, with intermediate values representing increasing discomfort.

The planned comparison is a within-participant eye comparison: each participant received both anesthetics, one in each eye. That design makes each participant their own pairing context, but the posted outcome summaries give separate eye-level means and standard deviations. The registry also describes comfort assessments at one hour and one day in its study summary; the posted primary endpoint is the one-hour pain score. A one-day primary result is not reported in the registry record.

3. Trial Design

The registry identifies this as a Phase 4, randomized, double-masked study, with enrollment of 11 and status listed as terminated. The recorded start is 2011-06 and the primary completion is 2011-10. The sponsor is the University of Miami. A reason for termination is not reported in the registry record.

The treatment assignment operated at the eye level. Each participant received tetracaine in one eye and lidocaine in the other; randomization determined which eye received which drug. The registry reports that five participants received tetracaine in the right eye and lidocaine in the left, while six received the reverse arrangement. The arm-level outcome summaries contain 11 eyes for tetracaine and 11 eyes for lidocaine. These are eye-level treatment groups, not separate groups of participants.

There is an important distinction between the randomized treatment arrangement and the registry's model label. The record labels the model as single group, although its description specifies randomized allocation of treatments between each participant's eyes. The record does not provide further details explaining that model classification. It also does not report the sequence-generation method beyond describing the eye assignment as random, or describe allocation concealment.

The record lists tetracaine drops and lidocaine gel as the interventions. Both were administered before LASIK according to the arm descriptions. The study summary says participants completed baseline comfort questions and were asked about eye comfort after surgery, but the posted primary outcome is specifically sharp pain at one hour. The registry's planned and actual analysis procedures, reasons for stopping, and details about deviations from the intended treatment schedule are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Five participants received tetracaine right eye and lidocaine left eye and six participants received lidocaine right eye and tetracaine left eye. A total of 22 eyes were analyzed for pain.

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 Participants Score on Pain Scale, measured over 1 hour (60minutes) post LASIK operation.

The primary endpoint is the mean score on a pain scale at 1 hour (60minutes) after LASIK. The question asked whether participants had sharp pain in the eye. The scale runs from 1 to 5: 1 means no symptoms, 2 slight discomfort, 3 mild discomfort, 4 moderate discomfort, and 5 severe discomfort. Higher values therefore represent more reported pain or discomfort.

A continuous score allows the comparison to describe average responses across treated eyes. The registry reports the mean and standard deviation for each treatment group. The mean describes the group's average score, while the standard deviation describes how much scores varied around that average. Both are useful: an average alone does not show whether individual responses were tightly clustered or more spread out.

The endpoint addresses pain at a specified postoperative time, rather than comfort at every time point or overall preference. Although the registry summary mentions additional comfort questions and a one-day assessment, the posted primary outcome is the one-hour pain score. Results for other outcomes or time points are not reported in the registry record. The record does not report a threshold defining a clinically important difference in this scale, so the numerical contrast cannot by itself establish whether a difference would matter to patients.

7. Results Posted in the Registry

• Lidocaine: mean 2.01 versus 1.95 on control; difference 0.06 (95% CI -0.65 to 0.77), standardized effect d = 0.07; z-test p = 0.868.

8. Statistical Interpretation

9. Statistical Methods Explained

The posted comparison concerns a continuous outcome summarized by means and standard deviations. A mean is the arithmetic average of the observed scale scores within a treatment group. A standard deviation describes the dispersion of observations around that mean. These quantities answer different questions: the mean locates the average response, while the standard deviation gives a sense of individual variability. In this study, the reported mean scores are 1.95 for tetracaine and 2.01 for lidocaine, with standard deviations of 0.75 and 0.93.

What does the mean difference represent?

The reported contrast is the lidocaine mean minus the tetracaine mean. Its estimate is 0.06. A positive value means the lidocaine group's average score was higher in the posted summaries; because higher scale values denote more pain or discomfort, that direction corresponds to a slightly higher average score for lidocaine in this descriptive comparison. The estimate is not an adjusted effect and does not account for a within-person pairing in the recalculation.

For a paired-eye design, the comparison can use the fact that each participant received both treatments. In general, pairing helps account for characteristics shared by the two eyes of the same participant. A paired analysis works with within-participant treatment contrasts and their variability. Separate group means and standard deviations do not reveal the correlation between the two eyes' scores. Without the participant-level paired outcomes or a reported paired variance, that aspect of the design cannot be incorporated into a recalculation from the posted summaries. The registry does not report the investigators' analysis method.

What does a confidence interval express?

A confidence interval gives a range of values compatible with the estimate under the method's assumptions and sampling variability. The interval for the recalculated mean difference runs from -0.646 to 0.766. Because it includes zero, the summaries do not resolve the direction of the average difference. Its width also signals that the estimate is imprecise: a range of effects remains compatible with the data. A confidence interval is not a statement that a particular probability applies to the fixed true effect after the data have been observed.

How should the p-value be understood?

The unadjusted p-value is 0.868. In general, a p-value measures how unusual data at least as incompatible with a specified null model would be if that model and the analysis assumptions were correct. It is not the probability that the null model is true, and it does not measure the size or clinical importance of an effect. A large p-value does not establish that the treatments have equal effects. Interpretation should consider the estimated difference, its confidence interval, the design, and the limited information available about the actual analysis.

The recalculated contrast is explicitly unadjusted and uses posted summary statistics. The registry reports no sponsor analysis results in its analyses listing. Since the paired participant-level information and the investigators' statistical procedure are not reported, the recalculation is best understood as a descriptive statistical comparison rather than a substitute for a documented trial analysis. No discrepancy between a sponsor analysis and the recalculation is indicated in the registry record.

Why does dependence between eyes matter?

Two eyes from the same person may have related outcomes because they share participant-level characteristics. General statistical methods for independent groups assume observations are independent across groups. When observations are paired or clustered, ignoring dependence can misrepresent the uncertainty around a contrast. The appropriate analysis generally uses the pairing or a model that accounts for within-participant correlation. The required correlation information is not available in the posted summaries, and the registry does not report how dependence was handled in the investigators' analysis.

The record's label of single group does not remove the paired nature of the described treatment allocation. The design description says each participant received both drugs, whereas the outcome summaries list treatment groups by eye. Readers should keep those levels distinct: participants entered the study, while eyes received the respective treatments and contributed to the posted eye-level summaries.

What does the scale imply for interpretation?

The score is a bounded 1-to-5 scale with ordered descriptions from no symptoms to severe discomfort. The registry analyzes it as a continuous measure and reports means and standard deviations. In general, treating an ordered scale as continuous summarizes average score differences simply, but it does not show the full distribution of responses or how many participants selected each category. Category counts and individual paired responses are not reported in the registry record. The scale's bounded range also means that interpretation should remain tied to its defined scoring system rather than assuming a difference has a universal meaning.

No formal analysis plan, model specification, handling of missing outcome data, or prespecified threshold for meaningful difference is reported in the registry record. These omissions limit assessment of whether the recalculated method matches the intended analysis. They do not change the reported summaries, but they constrain the strength of conclusions that can be drawn from them.

10. Confidence Intervals and Precision

The recalculated mean difference is 0.06, with a 95% confidence interval from -0.646 to 0.766. This interval is the main guide to precision: it shows that the estimate is compatible with differences favoring either treatment, as well as a range of effect sizes around zero. The interval includes zero, so the posted summaries do not establish a directional difference under this unadjusted comparison.

The interval is relatively broad in relation to a point estimate close to zero. That means the estimate does not pin down the true average contrast closely. It is not enough to say that the observed averages are near each other; uncertainty must also be considered. The standard deviations, 0.75 for tetracaine and 0.93 for lidocaine, describe variation among the eye-level scores, but they do not give the paired variability directly.

Because treatment was assigned to opposite eyes within each participant, the correlation between eyes matters to a paired estimate's precision. The registry posts separate group summaries but not the paired score differences or the correlation needed to quantify that dependence. The confidence interval is therefore an unadjusted recalculation from posted summaries, not a documented sponsor-reported paired interval. The registry does not report a clinically important difference threshold for the scale, so the interval cannot be classified against such a threshold.

11. 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 figures are planning illustrations based on the observed effect, not the trial's original design assumptions. The registry does not report the original sample-size justification or assumptions. For this continuous outcome, the figures give participants per arm for the stated power levels; they are not total event counts. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario uses the stated fraction of the observed effect as the effect to detect.

The 80% power column describes the planned number of participants per arm under those assumptions for a design with an 80% chance of detecting the specified effect if that effect were true. The 90% power column gives the corresponding planning number for a design with a 90% chance under the same assumptions. These are design calculations, not evidence about the chance that the completed study found a real effect.

The rows illustrate planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. For example, planning for 75% of the observed effect gives 5,533 participants per arm for 80% power and 7,407 participants per arm for 90% power. The accompanying curve should be read as a visual representation of how the required sample size changes with the effect assumed for planning. Smaller effects are harder to distinguish from random variation and therefore require more participants under the stated assumptions.

These planning figures are not observed power. They do not describe the probability that the completed trial detected an effect, and they should not be used as a substitute for interpreting the confidence interval. The trial's original design rationale is not reported in the registry record.

12. 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 = 0.060; pooled standard deviation σ = 0.845.
2. n = 2 × (1.96 + 0.842)² × 0.845² / 0.060² = 3,112.1, rounded up to 3,113 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 <- 0.0599999999999998                      # observed difference in means
sigma <- 0.844807670419723                     # 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(1383200)
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 = 3,113 (80% power), 4,167 (90% power)
 75% of observed effect: n per arm = 5,533 (80% power), 7,407 (90% power)
 50% of observed effect: n per arm = 12,449 (80% power), 16,665 (90% power)
power.t.test: 3113 
Simulated power at n = 3,113 per arm: 0.804 (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.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure, the pain-scale score one hour after LASIK. It lists no posted secondary outcomes and no analyses in the analyses listing. The study summary mentions comfort questions and a one-day assessment, but results for those measures are not reported in the registry record. The record does not describe a multiplicity adjustment or explain whether any other outcomes or analyses were planned.

Multiplicity is a general concern when many outcomes, time points, or comparisons are examined: the chance of at least one apparently notable result can increase as the number of analyses grows. That general issue cannot be quantified for this study because the full set of planned analyses is not reported. The presence of one listed primary endpoint does not establish that no additional analyses were conducted.

Missing-data handling is also not reported. The registry reports 22 eyes analyzed for pain and gives 11 eyes in each treatment arm, but it does not describe whether any outcome observations were missing, how missing values were handled, or whether participants were excluded from the analysis. No intention-to-treat or per-protocol analysis population is defined in the posted results.

The record does not report a statistical analysis plan, a prespecified model, or a method for accounting for the paired eyes. It is therefore not possible to determine whether the recalculated unadjusted comparison matches the investigators' intended analysis. The trial's terminated status is recorded, but the reason and any relationship to outcome availability are not reported in the registry record.

14. 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 serious adverse events as zero affected in the group with tetracaine in the right eye and lidocaine in the left eye, among 5 at risk, and zero affected in the group with tetracaine in the left eye and lidocaine in the right eye, among 6 at risk. For other adverse events, it likewise reports zero affected among 5 at risk in the first group and zero affected among 6 at risk in the second group.

These figures describe the recorded groups and should be read alongside the small study enrollment. A record of zero affected does not prove that an event cannot occur; it indicates that none was recorded as affecting participants in these groups in the registry results. The registry does not report death counts, so deaths should not be interpreted as absent. Specific serious adverse event terms are not listed. The adverse-event information does not establish comparative safety beyond the limited observations recorded.

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

The posted results show close average pain scores at one hour: 1.95 for tetracaine-treated eyes and 2.01 for lidocaine-treated eyes. The unadjusted recalculated difference is 0.06, with a 95% confidence interval from -0.646 to 0.766 and an unadjusted p-value of 0.868. Those statistics describe the posted summaries; they do not establish that the treatments are equivalent or that either treatment is superior.

The confidence interval includes differences in both directions and is wide enough that meaningful uncertainty remains. The registry does not define a clinically important difference for the 1-to-5 scale. Without such a threshold, and without a documented paired analysis, the estimates cannot settle whether any possible contrast would matter in practice. The results also do not answer questions about comfort at one day, patient preference, or outcomes beyond the primary endpoint, because those results are not reported in the registry record.

The study has a paired-eye treatment arrangement: participants received one drug in each eye. The reported group summaries are eye-level, while the recalculation uses separate summary statistics and does not account for the unavailable within-participant correlation. This limits how closely the recalculation can represent an analysis that fully uses the randomized paired design. The registry's single-group model label and its within-participant treatment description should both be kept in view.

The results are bounded by the recorded enrollment and the study's terminated status. The registry does not report why the study was terminated, the original sample-size rationale, missing-data procedures, or the investigators' analysis plan. These gaps constrain interpretation, but they do not change what the posted numbers say: average scores were close in this dataset, and the estimated contrast remains imprecise. They do not warrant a medical recommendation or a categorical conclusion about anesthetic choice.

16. Why This Trial Matters Statistically

This trial illustrates why the unit of treatment and the unit of analysis need careful attention. Treatments were assigned to eyes, with both eyes from each participant receiving different anesthetics. That paired arrangement can be statistically useful because the two observations from one participant share context, but it also means the eye-level outcomes are not necessarily independent. Separate group means and standard deviations do not preserve the information needed to estimate the paired variability.

It also demonstrates the difference between a small point estimate and a precise estimate. The mean difference is 0.06, but its confidence interval extends from -0.646 to 0.766. A point estimate near zero alone cannot establish equivalence. Precision depends on the data and analysis, and the registry does not give a clinically important difference threshold against which to evaluate the interval.

The registry's single-group model label sits alongside a description of randomized treatment assignment between eyes. This is a useful reminder to read design labels together with the operational description. The registry reports the randomization of which eye received which drug, while the posted comparison is summarized by treatment arm. Statistical interpretation depends on recognizing this within-participant structure.

Finally, planning figures based on the observed effect are not the same as evidence of power in the completed study. Their large values reflect the difficulty of planning to detect a small effect under the stated assumptions. They do not repair uncertainty in the observed estimate, and they are not a substitute for a clearly reported analysis plan and paired outcome analysis.

17. 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 limitations are specific to the available record. Enrollment was 11 participants, and the primary endpoint summarizes 22 eyes. The paired-eye design means outcomes within a participant may be related, but the posted summaries do not report paired differences or the within-participant correlation. The recalculated contrast is unadjusted and cannot recover that missing paired information.

The registry labels the model as single group while describing randomized allocation of the two anesthetics between each participant's eyes. The record does not explain this difference in labeling. It also does not report the investigators' statistical analysis, the original sample-size rationale, or the reason the study was terminated. The record lists no analyses, and the posted secondary outcome count is zero.

The primary endpoint is a pain score at one hour. Although the study summary discusses comfort at one day and patient preference, corresponding results are not reported in the registry record. The registry also does not report a clinically important score difference, missing-data procedures, or the full distribution of scale responses. These omissions restrict assessment of clinical relevance, completeness, and whether the recalculation corresponds to the intended analysis.

The safety record shows no affected participants for the adverse-event categories reported, but deaths are not reported and no serious adverse-event terms are listed. With the limited enrollment and follow-up information recorded, these entries should be treated as a description of reported events, not as comprehensive evidence about risks.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Tetracaine Versus Lidocaine Gel for Anesthetic Effect and Comfort in Patients Undergoing LASIK — NCT01383200.
• Registry record last updated 2017-08-11; status last verified 2017-06.
• Results first posted 2015-04-01.
• 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.

21. Record Summary

The registry record describes a Phase 4, randomized, double-masked study sponsored by the University of Miami, with status listed as terminated. It compares 0.5% tetracaine drops with 2% lidocaine gel before LASIK. Each participant received one treatment in each eye, with random assignment of which eye received each drug.

The primary endpoint is the mean sharp-pain score one hour after LASIK on a scale from 1 to 5. The posted means are 1.95 for tetracaine and 2.01 for lidocaine. The unadjusted recalculated mean difference is 0.06, with a 95% confidence interval from -0.646 to 0.766 and an unadjusted p-value of 0.868. The registry does not report the investigators' analysis method, a reason for termination, or results for the one-day assessment mentioned in the study summary.