Efficacy of Laser Debridement on Pain and Bacterial Load in Chronic Wounds: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy of Laser Debridement on Pain and Bacterial Load in Chronic Wounds (NCT03182582), a randomized na study. The primary outcome is Pain With Debridement.

2. Clinical Question

The study rationale links chronic-wound bacterial load with impaired healing and notes that pain during sharp debridement may cause distress. The stated purpose was to assess laser debridement in relation to bacterial load and patient distress. However, the primary outcome with posted numerical results is pain, not bacterial load. Numerical bacterial-load findings are not reported in the registry record.

The design is a randomized crossover: the registry describes treatment sequences in which participants received both procedures, with the order varying between the two listed groups. That makes the within-participant pain comparison central to the clinical question. The posted primary measure was taken immediately following the respective procedure on Day 1. The record does not provide enough detail to characterize how long each participant’s experience of pain was assessed beyond that stated measurement time.

3. Trial Design

This was a randomized, single-masked crossover study sponsored by Stanford University. The registry lists an enrollment of 22 and a completed status. Its listed conditions are open wounds, chronic venous hypertension with ulcer, and diabetic foot ulcer. The record gives no further description of the enrolled participants’ characteristics in the primary outcome entry.

The two procedures were Er:YAG laser debridement and scalpel/curette sharp debridement. The arm descriptions indicate that participants were assigned to treatment sequences: one sequence began with laser and then used sharp debridement, while the other began with sharp debridement and then used laser. Both procedures were described as continuing until punctate bleeding was visualized. The text of the arm descriptions is incomplete, so additional procedural details are not reported in the registry record.

A crossover design compares treatments within participants, which can reduce the influence of stable differences between people. It also makes the sequence and timing of treatments important to interpretation. The registry identifies the model as crossover and reports a paired t test, but details such as a washout period, period effects, and how possible carryover was handled are not reported in the registry record. The identity of the masked party is also not reported in the registry record.

The listed study dates are 2017-01-05 for start and 2017-03-17 for primary completion. The registry gives no sample-size justification or original design assumptions. Although enrollment is listed as 22 and each primary outcome group has 22 observations, the record does not clarify participant flow or missing observations beyond those posted group counts.

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.

Treatment 1

Treatment 2

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 With Debridement, measured over Day 1 of the respective procedure (immediately following).

The primary endpoint is pain with debridement, measured immediately after the respective procedure on Day 1. The registry describes using a Numerical Rating Scale, a variant of the Visual Analogue Scale, to record pain intensity. The scale runs from 0, representing no pain, to 10, representing the worst possible pain. The endpoint is summarized as a mean with a standard deviation for each procedure.

Patient-reported pain is used because the experience of pain is not directly observable in the way a physical measurement is. A numeric response gives participants a consistent way to report their perception, and a scale permits comparisons of group averages. In general, a mean describes the average reported score, while a standard deviation describes how spread out individual scores are around that average. Neither measure alone describes every participant’s experience.

The registry’s stated rationale is that pain during sharp debridement may cause distress and could contribute to inadequate debridement. The pain endpoint therefore addresses an immediate patient-reported experience relevant to the procedures being compared. It does not, by itself, measure wound healing, bacterial burden, or whether any difference is important to patients. A threshold for a clinically meaningful change in this pain scale is not reported in the registry record.

7. Results Posted in the Registry

• Sharp Debridement: mean 4.80 versus 3.00 on control; difference 1.80 (95% CI 0.50 to 3.10), standardized effect d = 0.82; z-test p = 0.007.

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.

Percent Change in Wound Size- Immediately Post-debridement

• 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:
  • Sharp Debridement: mean 63.40 versus 40.20 on control; difference 23.20 (95% CI -33.47 to 79.87), standardized effect d = 0.24; z-test p = 0.422.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Sharp Debridement and the control. The interval gives the range of effects that remain compatible with the data.

Percent Change in Wound Size - 1 Week Post-debridement

• 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:
  • Sharp Debridement: mean -36.70 versus -20.80 on control; difference -15.90 (95% CI -56.34 to 24.54), standardized effect d = -0.23; z-test p = 0.441.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Sharp Debridement and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes include patient preference and change in wound size immediately after debridement and one week later. Numerical results are posted for the two wound-size comparisons, while numerical results for patient preference are not reported in the registry record. The wound-size estimates do not form a consistent directional pattern across the two assessment times, and their unadjusted intervals include no difference. They therefore do not provide a clear, precise secondary pattern that independently reinforces the primary pain finding.

These outcomes address different questions from immediate pain. Wound-size change is a measurement of wound dimensions at specified times, not a direct measure of pain, bacterial load, or longer-term healing. The registry gives the timeframes, means, standard deviations, and summary-based comparisons, but does not report a clinically meaningful threshold for wound-size change. The posted information consequently does not establish whether a particular numerical change would matter to patients.

Unadjusted secondary results carry less weight because several outcomes may be examined, increasing the chance that one comparison appears notable even when there is no underlying difference. In general, multiplicity procedures control the overall false-positive risk across a family of tests; no such adjustment is reported in the registry record. The record lists six outcome measures and one reported analysis, but does not explain how the full set of outcome comparisons was handled analytically.

The primary pain result should not be treated as confirmed by the secondary outcomes, nor should the secondary findings be interpreted as a substitute for the primary paired analysis. Their different measures, timeframes, and uncertainty make them complementary but limited context. The numerical bacterial-load result described in the study rationale is not reported in the registry record.

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

• Patient Preference
• Percent Change in Wound Size- Immediately Post-debridement
• Percent Change in Wound Size - 1 Week Post-debridement

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports a paired t test for the primary comparison. This method is suited to data in which the same participant contributes a measurement under each of two conditions. Rather than treating the two sets of scores as unrelated, a paired analysis focuses on each participant’s difference between conditions. In general, accounting for pairing can improve precision when measurements from the same person are correlated. The amount of that improvement depends on the within-person relationship between scores.

The record labels the study as a crossover and the sponsor’s analysis as paired. The posted group means and standard deviations, however, do not show the individual paired differences or their standard deviation. Without those data, a reader cannot independently reconstruct the paired estimate, its standard error, or its confidence interval. The reported p-value is therefore the available result from the registry’s paired analysis, while summary-based recalculations should be understood as a different and less design-specific comparison.

What does an unadjusted recalculation represent?

The recalculated mean difference is based on the posted summaries for the two procedure groups, with sharp debridement minus laser debridement as the direction of subtraction. It is a simple unadjusted comparison, not an attempt to reproduce all details of the sponsor’s analysis. In general, a standard error describes the sampling variability of an estimated contrast, and a test statistic compares the estimated contrast with that variability under a null hypothesis. The recalculated p-value of 0.007 is based on that summary-level approach; it does not use the unreported within-participant covariance.

Because the study is a crossover, the paired analysis is more directly connected to the design than an unpaired reconstruction. The difference between p = 0.003 in the registry and the recalculated p = 0.007 should not be interpreted as a contradiction in the findings. The methods use different information and assumptions. The record does not give enough detail to determine every element of the paired test implementation or whether other adjustments were made.

Why do standard deviations matter?

A standard deviation describes the spread of observed scores around a group mean. In general, larger spread makes an estimated mean less precise, all else being equal. In a paired study, however, separate group standard deviations do not tell the whole story: the variability of within-person differences also matters. Two treatment measurements may move together within individuals, and the paired analysis uses that relationship. It is not reported in the registry record, so it cannot be derived from the two marginal standard deviations alone.

Over-dispersion is a general concern when data vary more than a statistical model assumes. If a model understates variability, standard errors may be too small and intervals too narrow. The primary outcome is summarized with means and standard deviations, and the registry names a paired t test. No separate over-dispersion assessment is reported in the registry record. The posted summary does not allow a reader to assess the distribution of individual pain scores or paired differences.

What does the p-value say?

In general, a p-value measures how compatible observed data are with a specified null hypothesis, given a statistical model and its assumptions. It is not the probability that the null hypothesis is true, nor is it the probability that the observed result occurred by chance in an everyday sense. The reported p = 0.003 pertains to the paired t test of the primary comparison. It does not quantify the size of the pain difference, establish clinical importance, or account automatically for other outcomes tested in a study.

The registry lists one reported analysis. Its fields do not include a paired effect estimate or confidence interval for the primary test. The absence of those quantities means the p-value alone cannot show the range of paired effects compatible with the analysis. The unadjusted summary-based estimate and interval offer a different view, but they are not replacements for the paired result.

What assumptions remain unclear?

A t test generally relies on assumptions about the distribution of the data being analyzed. For a paired t test, the relevant data are the participant-level differences. In general, the test is most straightforward to interpret when those differences are reasonably compatible with the model’s assumptions and observations are independent across participants. The registry does not report diagnostic checks, the distribution of paired differences, or a transformation or alternative method.

Crossover analyses can also be affected by period or sequence effects, and by carryover if an earlier procedure influences a later measurement. These are general design considerations, not evidence that such effects occurred in this trial. The registry does not report a washout period, an analysis of period or sequence effects, or a carryover assessment. Consequently, readers cannot evaluate those issues from the posted record.

11. Confidence Intervals and Precision

Precision concerns how much uncertainty surrounds an estimated treatment contrast. A confidence interval is a range of values compatible with the data and the method used, under its assumptions. In general, a narrower interval indicates greater precision, while a wider interval indicates that the data are compatible with a broader range of effects. An interval that includes no difference does not establish equivalence; it indicates that the analysis does not rule out no difference at the interval’s stated level.

The registry reports a paired-test p-value for pain but no paired effect estimate or confidence interval. The summary-based recalculation gives a mean difference of 1.8 units, sharp minus laser, with an interval whose lower limit is positive and upper limit is 3.098 units. This is an unadjusted reconstruction from the posted group summaries. It does not use the paired covariance and is not the confidence interval for the registry’s paired test. The confidence level for the recalculated interval is not stated in the record.

The distinction matters because a p-value and an interval answer related but different questions. The p-value indicates compatibility with a null hypothesis under the test, while the interval conveys a range of effect sizes under a specified method. A significant p-value does not by itself establish that the estimated difference is precise enough for a particular decision. The registry does not report a minimum clinically important difference for the pain scale, so statistical precision cannot be translated into a judgment about clinical importance.

The secondary wound-size recalculations have intervals that include no difference, reflecting uncertainty about those comparisons. The registry does not report confidence intervals for the paired pain result or numerical preference results. Missing paired estimates, interval confidence level details, and participant-level data limit independent assessment of precision.

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 planning figures are participants per arm, not total events. They are illustrations based on the observed effect, rather than a report of the trial’s original design calculation. The listed assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The assumed effect to detect is the stated fraction of the observed effect. The trial’s own sample-size justification and original design assumptions are not reported in the registry record.

For 80% power, the planning figure describes the number of participants per arm that would give an 80% chance of detecting the chosen effect under the stated assumptions, if that effect and the model assumptions were correct. The 90% power column uses the same interpretation but targets a greater chance of detecting that effect. These are planning calculations, not observed power. They do not describe the probability that the trial’s result is correct or the probability that a particular effect exists.

The rows consider planning for 100%, 75%, and 50% of the observed effect. For the primary pain comparison, the figures are 24 participants per arm for 80% power and 32 for 90% power when planning for 100% of the observed effect. Planning for 75% of the observed effect gives 42 and 56 participants per arm; planning for 50% gives 94 and 126. The smaller assumed effects require more participants because they are harder to distinguish from random variation.

These illustrations use a two-arm, equal-allocation normal approximation, whereas the trial is described as a crossover and its reported primary analysis is paired. They should therefore be read as standardized planning illustrations, not as a reconstruction of a suitable original design calculation for this crossover trial. The registry does not provide the assumptions or calculations used when the study was planned.

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 = 1.800; pooled standard deviation σ = 2.197.
2. n = 2 × (1.96 + 0.842)² × 2.197² / 1.800² = 23.4, rounded up to 24 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 <- 1.8                      # observed difference in means
sigma <- 2.19658826364888                     # 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(3182582)
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 = 24 (80% power), 32 (90% power)
 75% of observed effect: n per arm = 42 (80% power), 56 (90% power)
 50% of observed effect: n per arm = 94 (80% power), 126 (90% power)
power.t.test: 24.4 
Simulated power at n = 24 per arm: 0.796 (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. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary analysis as a paired t test, with p = 0.003. This approach matches the crossover structure because the comparison is based on measurements paired within participants. The posted analysis does not include a paired mean difference or confidence interval, so the estimated size and precision of that paired contrast cannot be read directly from the reported analysis.

The summary-based recalculation gives a mean difference of 1.8 units, with sharp minus laser as the direction, and p = 0.007. It uses the reported group means and standard deviations and does not recover the within-participant covariance. It is consequently an unadjusted, unpaired-style recalculation, not a replication of the paired t test. The different p-values are consistent with the analyses using different information; the registry does not mark a discrepancy.

The sponsor’s paired result is the relevant reported inferential analysis for the crossover comparison. The recalculation can help describe the group summaries, but should not be presented as the sponsor’s analysis or as evidence that the paired calculation is wrong. The registry does not provide the paired data needed to independently reproduce the sponsor’s test.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures and one reported analysis. The primary pain analysis is identified as a paired t test. It does not report a multiplicity adjustment, a hierarchy of tests, or a family of outcomes designated for formal inference. The registry also does not explain whether secondary outcomes were exploratory or how the chance of false-positive findings across outcomes was considered.

In general, when several hypotheses are tested, the chance of at least one apparently positive result can increase. Adjustment methods can account for that, but they may change p-values or confidence intervals and require a defined testing strategy. The posted secondary comparisons are unadjusted recalculations, so they should be considered exploratory rather than treated as confirmatory evidence. The primary paired p-value is reported, but the record does not state whether it was part of a broader multiplicity plan.

Handling of missing observations is not reported in the registry record. The posted group counts are 22 for each primary procedure, but this alone does not describe participant flow, missing outcome data, exclusions, or whether all randomized participants were included in the analysis. The analysis population—such as an intention-to-treat or per-protocol population—is not reported in the registry record. Methods for imputing missing data, if any, are also not reported in the registry record.

The crossover design raises additional questions about treatment sequence, period effects, and possible carryover. The registry identifies the design and the paired test but does not report how these features were handled, whether any washout was used, or whether participants were analyzed according to their randomized sequence. These are not claims that a problem occurred; they are details needed to assess the analysis fully. The original sample-size rationale, interim analyses, and complete statistical analysis plan are not reported in the registry record.

16. 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.

For laser debridement, the registry reports 22 participants at risk for serious adverse events and zero affected; it also reports 22 at risk for other adverse events and zero affected. For sharp debridement, it reports the same at-risk counts and zero affected for both serious and other adverse events. No deaths are reported in either group.

These figures describe events recorded in the registry for the groups and observation period represented in the results. They should not be read as proof that no adverse event could occur, or that the procedures have identical safety profiles. A zero count in a study of this size gives limited information about uncommon events, and the registry does not provide further detail on safety surveillance duration or event definitions in the posted data. The serious-event figures are therefore a description of what was recorded, not a general safety guarantee.

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

The primary posted result is a difference in average immediate pain scores between laser and sharp debridement. The group means were 3.0 and 4.8 units, respectively, and the sponsor-reported paired t test had p = 0.003. The summary-based recalculation also indicates a higher average score for sharp than laser, with a mean difference of 1.8 units. These figures describe the participants and procedures represented in the registry record; they do not mean every participant had the same response.

Statistical evidence of a difference is not the same as evidence that the difference is important to patients. The registry does not give a threshold for a clinically meaningful change on the pain scale. Nor does a p-value tell readers the probability that the treatment effect is true. It expresses compatibility with a null hypothesis under the selected analysis and its assumptions.

The posted results do not establish a difference in bacterial load: numerical bacterial-load results are not reported in the registry record. They also do not establish that one procedure improves wound healing. Wound-size outcomes were measured at immediate and one-week timeframes, but their recalculated comparisons are uncertain, and wound size is not itself a complete measure of healing. Longer-term outcomes are not described in the posted results.

The crossover design and paired test are important to interpreting the pain comparison. The registry lacks the paired estimate and interval, as well as details needed to assess sequence, period, or carryover effects. The secondary outcomes are also subject to uncertainty and no multiplicity adjustment is reported. These limits mean the result is best understood as evidence of a difference in the recorded average pain scores in this trial, rather than a complete assessment of comparative clinical effects.

18. Why This Trial Matters Statistically

This trial illustrates why statistical interpretation should begin with the study design. A crossover study measures outcomes under both procedures within participants, so the within-person contrast—not just two separate group averages—is central to the analysis. The registry’s paired t test acknowledges that structure. The summary data alone cannot reproduce that analysis because they do not contain the association between each participant’s two measurements.

It also shows why an effect estimate and a p-value serve different purposes. The reported p-value gives evidence against a null hypothesis under the paired test, but does not quantify the paired difference or its precision. A recalculation from group summaries can provide a descriptive contrast, yet its assumptions differ from those of the reported paired analysis. Clear labeling of the methods prevents the two results from being mistaken for interchangeable calculations.

The registry also makes visible the boundary between statistical and clinical interpretation. Pain scores are patient-reported, and the scale gives a direct measure of the experience the study set out to assess. But statistical evidence alone cannot establish clinical importance without an interpretable effect estimate and a meaningful-change threshold. Secondary wound-size outcomes and the absence of posted bacterial-load results also show that the study rationale and the outcomes with numerical results are not identical.

Finally, the record illustrates the value of reporting paired estimates, confidence intervals, missing-data methods, multiplicity plans, and crossover-specific design details. Their absence does not negate the posted paired test, but it limits independent assessment of its precision and assumptions.

19. 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 outcome is measured immediately following the respective procedures on Day 1. It therefore addresses immediate reported pain, not pain over a longer period. The registry does not report a clinically meaningful threshold for interpreting score differences. The record also does not give participant-level paired data, a paired effect estimate, or a paired confidence interval, limiting independent assessment of the magnitude and precision of the primary result.

The crossover design makes treatment sequence, period effects, and carryover relevant considerations, but the registry does not report a washout period or analyses addressing those issues. Masking is described as single, but the identity of the masked party is not reported in the registry record. The available description does not explain whether participants, outcome assessors, or other personnel were masked.

The registry lists 22 observations in each primary group but does not report participant flow, missing-data methods, or the analysis population. It does not describe a multiplicity plan for the outcome measures. Numerical patient-preference results are not reported, and the bacterial-load result emphasized in the study rationale is not reported in the registry record.

The secondary wound-size assessments cover the immediate post-procedure period and one week following the respective procedure. These timeframes do not establish longer-term wound outcomes. The record does not report a threshold for meaningful wound-size change, and the summary comparisons are unadjusted. In addition, the original sample-size justification and the complete statistical analysis plan are not reported in the registry record. These limitations narrow what can be concluded from the posted results without invalidating the fact that the registry reports a paired primary analysis.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy of Laser Debridement on Pain and Bacterial Load in Chronic Wounds — NCT03182582.
• Registry record last updated 2020-03-30; status last verified 2020-03.
• Results first posted 2018-04-17.
• 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.

23. Record Summary

The registry describes a completed, randomized, single-masked crossover study sponsored by Stanford University, with enrollment of 22. It compares Er:YAG laser debridement with scalpel/curette sharp debridement in chronic wounds. The primary outcome is pain measured immediately after each procedure on a numeric scale from 0 to 10.

The posted mean pain scores are 3.0 for laser and 4.8 for sharp debridement. The registry reports a paired t test with p = 0.003. An unadjusted summary-based recalculation gives a mean difference of 1.8 units, sharp minus laser, but it does not reproduce the paired analysis. Secondary wound-size results are uncertain, and numerical patient-preference and bacterial-load results are not reported in the registry record. Details on missing data, multiplicity, and several crossover analysis considerations are also not reported.