Photodynamic Therapy-Induced Immune Modulation: Part III: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Photodynamic Therapy-Induced Immune Modulation: Part III (NCT03643744), a randomized phase 1 study. The primary outcome is Changes in Photodynamic Therapy (PDT)-Induced Systemic Immunosuppression From Baseline With Celecoxib Treatment..

2. Clinical Question

3. Trial Design

This was a randomized, double-blind, parallel-group phase 1 study sponsored by Wright State University. The registry lists an enrollment of 12 and a terminated status. The record lists a start date of 2019-04-01 and a primary completion date of 2023-03-21. The reason for termination is not reported in the registry record.

The four groups were PDT + Celecoxib, PDT + Placebo, Control + Celecoxib, and Control + Placebo. Each group has a posted outcome sample size of 3. Participants in the photodynamic therapy groups received treatment with 5-aminolevulinic acid followed by blue light. Control subjects did not receive photodynamic therapy. Within each of those settings, the treatment comparison was celecoxib 200mg against placebo.

The registry describes the study as a proof-of-concept feasibility study. Its stated rationale was to investigate whether celecoxib could block immunosuppression associated with photodynamic therapy. The summary also describes earlier research observations concerning platelet-activating factor and reports that mouse studies at the sponsor institution motivated the COX-2 inhibitor hypothesis. These statements describe the study rationale; they do not establish what happened in the human trial.

The registry describes the first part of the study for subjects with actinic keratoses as lasting 12 days, with follow-up visits at 6 and 12 months and 6 research-office visits in total. For control subjects, the described study lasts 10 days and includes 4 visits. The primary outcome timeframe is Baseline and Day 7. Whether all planned visits and follow-up assessments were completed is 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

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 Changes in Photodynamic Therapy (PDT)-Induced Systemic Immunosuppression From Baseline With Celecoxib Treatment., measured over Baseline and Day 7.

The primary endpoint is the change in photodynamic therapy-induced systemic immunosuppression from baseline with celecoxib treatment. It is expressed as a percentage of the initial reaction area. Investigators measured inflammation after intradermal skin testing with candida and trichophyton antigens. The areas of induration were measured with calipers in cm2, and the baseline and Day 7 measurements were used to calculate the percentage of the initial reaction area.

This outcome uses a skin-test response as an indicator of systemic immune response. In the study rationale, the investigators were interested in whether photodynamic therapy was associated with suppression of that response and whether celecoxib might alter it. The endpoint is therefore a biological measure related to the proposed immune mechanism, rather than a direct measure of actinic keratosis treatment response or a patient-reported outcome.

The posted summaries report group means with standard errors. The PDT + Celecoxib mean was 152.0, with a standard error of 107.0; the PDT + Placebo mean was 78.0, with a standard error of 19.0. The corresponding control means were 206.0 with a standard error of 58.0 for Control + Celecoxib, and 170.0 with a standard error of 44.0 for Control + Placebo. Each outcome group had 3 participants. Confidence intervals for these group summaries are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it is a percentage measure based on reaction areas at baseline and Day 7. For a continuous outcome, a group mean describes the average observed measurement in that group. The posted means are 152.0 for PDT + Celecoxib, 78.0 for PDT + Placebo, 206.0 for Control + Celecoxib, and 170.0 for Control + Placebo. Each group has 3 participants. A mean is a concise summary, but it does not show the individual observations or whether the group contains unusually high or low values.

The registry reports standard errors alongside the means. In general, a standard error describes the uncertainty of an estimated mean across repeated samples under a statistical model; it is not the same as the variability among individual participants. The standard errors are 107.0, 19.0, 58.0, and 44.0 for the groups in the order. The registry does not provide standard deviations or individual-level measurements, so the within-group distribution cannot be evaluated from these summaries alone. A confidence interval would show a range of values compatible with the data and assumptions, but confidence intervals for the group means or comparisons are not reported in the registry record.

The sponsor reports ANOVA for each of the two celecoxib-versus-placebo comparisons. In general, analysis of variance is a method for comparing means while accounting for variability within groups. Its test result is commonly expressed as a p-value. The reported p-values are 0.530 for PDT + Celecoxib versus PDT + Placebo, and 0.727 for Control + Celecoxib versus Control + Placebo. A p-value describes how compatible the observed data are with a specified null model, conditional on the model assumptions. It is not the probability that the null hypothesis is true, and it does not measure the size of an effect.

The registry does not state the detailed ANOVA model, the exact test statistic, degrees of freedom, handling of covariates, or assumption checks. In general, ANOVA-based inference depends on the design and model being suitable for the data. Independence of observations and reasonable behavior of model residuals are among considerations in common forms of ANOVA. With 3 participants per group, evaluating distributional assumptions from summaries is especially limited. The record does not report whether assumptions were assessed or whether an alternative method was considered.

The study is randomized and double-blind according to the registry. Randomization is intended, in general, to reduce systematic differences between assigned groups, while blinding is intended to limit the influence of treatment knowledge on behavior or assessment. The record does not describe the randomization procedure, who was blinded, whether blinding was maintained, or how allocation was concealed. Those implementation details are not reported in the registry record.

The two sponsor-reported analyses address separate comparisons within the two treatment settings. They do not, on their own, test whether the celecoxib-placebo contrast differs according to photodynamic therapy status. A statistical interaction analysis would address that distinct question by assessing whether the treatment contrast varies across settings. Such an analysis is not reported in the registry record. The reported results also do not include an adjusted estimate or a confidence interval for either treatment contrast.

Some recalculations from posted summary statistics can be used to illustrate possible treatment differences or planning scenarios, but the registry record does not contain a recalculated two-arm estimate for this continuous endpoint. The posted analysis note indicates that values were missing or not estimable for a two-arm comparison. No recalculated p-value or comparison interval should therefore be substituted for the sponsor's reported analyses. Any sample-size illustration based on an observed effect would be a planning illustration only, not observed power and not evidence that the original study was designed with those assumptions. The registry record does not report the trial's own sample-size justification or a detailed statistical analysis plan.

General statistical interpretation also depends on distinguishing estimation from testing. A p-value alone does not convey the magnitude of a difference, the range of plausible values, or practical importance. An estimate and its confidence interval would generally help readers assess both direction and precision. Here, the group means and standard errors provide some descriptive information, but the absence of comparison estimates and confidence intervals leaves uncertainty about the treatment contrasts difficult to quantify. The small group sizes further limit how much can be inferred from the reported summaries.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("PDT + Celecoxib", "PDT + Placebo", "Control + Celecoxib", "Control + Placebo")
n   <- c(3, 3, 3, 3)
m   <- c(152, 78, 206, 170)
sp  <- c(107, 19, 58, 44)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  PDT + Celecoxib  3  152.000  185.329  -308.384  612.384
CARM  PDT + Placebo  3  78.000  32.909  -3.750  159.750
CARM  Control + Celecoxib  3  206.000  100.459  -43.554  455.554
CARM  Control + Placebo  3  170.000  76.210  -19.317  359.317

11. Analyses Reported by the Sponsor

The registry reports the sponsor's ANOVA p-values for the celecoxib-versus-placebo comparisons: 0.530 among participants receiving photodynamic therapy and 0.727 among control subjects not receiving photodynamic therapy. It does not report an ANOVA estimate or confidence interval for either contrast.

No recalculated two-arm estimate or p-value is available for comparison with the sponsor's analyses. The registry's posted analysis note says the values were missing or not estimable for a two-arm comparison of this continuous endpoint. Accordingly, there is no recalculated result to use as a numerical cross-check. The sponsor-reported analyses remain the available inferential results in the registry record; they should be interpreted alongside the group means, standard errors, and small group sizes.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures and reports no secondary outcomes. It does not provide a complete statistical analysis plan describing which outcomes or comparisons were designated as primary for inferential testing, or how multiple tests were to be handled. The record reports separate ANOVA p-values for the celecoxib-placebo comparisons in the photodynamic therapy and control settings. Whether any multiplicity adjustment was planned or applied is not reported in the registry record.

Multiplicity matters when several outcomes, time points, subgroups, or comparisons are tested. In general, conducting more tests can increase the chance of at least one seemingly notable result arising by chance, unless the analysis plan accounts for that testing. The posted record does not describe a family of tests or an adjustment method, so it is not possible to determine how the reported p-values fit into a broader testing strategy. The stated sample-size assumptions for planning illustrations do not establish the trial's own design rationale or testing plan.

The registry gives group sample sizes for the primary outcome, but does not explain the analysis population. It does not state whether the analyses included all randomized participants, whether any participants were excluded, or how deviations from assigned treatment were handled. The relationship between enrollment and the outcome analysis population is not described beyond the group counts in the posted summaries.

Missing-data procedures are also not reported. The record does not state whether any primary outcome measurements were missing, how missing measurements were handled, or whether sensitivity analyses were conducted. It does not provide participant flow or reasons for withdrawal. The study status is terminated, but the reason for termination and its effect, if any, on planned analyses or follow-up are not reported in the registry record. These omissions limit assessment of the completeness and robustness of the reported comparisons.

13. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry reports no serious adverse events in any of the four groups. Each group lists 3 participants at risk and 0 participants affected by serious adverse events. The recorded number of deaths is 0 in each group. The record also lists 0 participants affected by other, non-serious adverse events in each group.

These are counts from a small study, with 3 participants per group. A count of zero in these groups means that no events were recorded for the listed categories in the registry; it does not show that an event could not occur or establish a general safety profile. The record does not list serious adverse event terms, and the reason no terms are listed is not reported in the registry record. The posted safety counts should be interpreted as a description of events recorded during this study, not as a stand-alone assessment of risk.

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

The posted results describe a small randomized, double-blind study of celecoxib and placebo, with groups receiving photodynamic therapy and control groups not receiving it. The primary endpoint is a skin-test reaction-area measure from baseline to Day 7. The registry reports group means and standard errors and gives sponsor-reported ANOVA p-values for the two within-setting comparisons.

The summaries do not establish that celecoxib blocked photodynamic therapy-associated immunosuppression. Nor do they establish that celecoxib had no effect. The means are estimates from groups of 3 participants, and comparison confidence intervals and treatment-effect estimates are not reported. The p-values alone do not show the magnitude or precision of a treatment contrast.

The control groups provide a separate celecoxib-placebo comparison among subjects not receiving photodynamic therapy. However, the registry does not report an analysis testing whether the celecoxib-placebo contrast differs between people receiving photodynamic therapy and control subjects. That is a different question from either of the posted within-setting comparisons.

The study's stated purpose was proof of concept and feasibility. The endpoint is a biological measure of immune response, not a direct measure of clinical benefit. The record does not report a detailed analysis plan, missing-data methods, or the reason the study was terminated. The results therefore offer limited evidence for interpreting the proposed mechanism and should not be extended beyond the measured outcome and study groups.

15. Why This Trial Matters Statistically

This trial illustrates how a mechanistic research question can be represented by a measurable continuous endpoint. The investigators used skin-test reaction areas at baseline and Day 7 to examine a proposed immune response associated with photodynamic therapy. The record also separates the celecoxib-placebo comparison among participants receiving photodynamic therapy from the same treatment comparison among control subjects. Those design features make clear that a question about treatment within a setting is not identical to a question about whether treatment effects differ across settings.

The posted results also show why group means should be read together with measures of precision and sample size. Each outcome group contains 3 participants, and standard errors accompany the means. The registry does not post confidence intervals or comparison estimates, so readers have limited information about the precision of the treatment contrasts. A p-value cannot replace those quantities: it addresses compatibility with a statistical model, not effect size or clinical importance.

Finally, the record distinguishes a proof-of-concept study from a definitive evaluation. It presents a biologically motivated hypothesis and an early human comparison, but does not report enough statistical detail to reconstruct the analysis or assess the study's planning assumptions. The terminated status adds an important record-level uncertainty because the reason is not reported. Together, these features make the study useful for considering endpoint choice, small-sample inference, and the distinction between a mechanistic hypothesis and a demonstrated result.

16. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The principal limitation is the small number of participants in each group: the posted outcome summaries include 3 participants per group. This limits the stability of group means and makes it difficult to assess the distribution of measurements. The standard errors, especially 107.0 for the PDT + Celecoxib mean, indicate that the group estimate should not be treated as highly precise. Confidence intervals for the means and treatment comparisons are not reported.

The registry does not provide individual participant data, standard deviations, details of the ANOVA model, or assumption checks. It therefore does not permit an independent assessment of the observed outcome distribution or a full reconstruction of the sponsor's analysis. The record also does not report an interaction analysis addressing whether the celecoxib-placebo comparison differs between the photodynamic therapy and control settings.

The study status is terminated, but the reason for termination is not reported in the registry record. Participant flow, completion of planned visits, missing outcome data, and reasons for withdrawal are also not described. The record gives follow-up schedules for participants with actinic keratoses and control subjects, but does not report whether those visits or longer-term assessments were completed.

Additional limitations include the absence of a detailed sample-size justification and a complete statistical analysis plan. The registry does not report analysis populations, missing-data procedures, or whether multiplicity was addressed. These gaps make it harder to assess how the posted analyses relate to the original protocol and whether the reported results represent all planned analyses. The primary endpoint is a biological skin-test measure; the registry does not report a direct clinical outcome linked to the proposed mechanism.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Photodynamic Therapy-Induced Immune Modulation: Part III — NCT03643744.
• Registry record last updated 2024-12-19; status last verified 2024-12.
• Results first posted 2024-12-19.
• 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.

20. Record Summary

NCT03643744 is a randomized, double-blind, parallel-group phase 1 study sponsored by Wright State University. It enrolled 12 participants and is listed as terminated. The study compared celecoxib 200mg with placebo in participants receiving photodynamic therapy and in control subjects who did not receive photodynamic therapy.

The primary outcome measured change from baseline in a skin-test reaction-area response at Day 7, expressed as a percentage of the initial reaction area. Each group had 3 participants in the posted outcome summaries. The sponsor reported ANOVA p-values of 0.530 for the comparison within the photodynamic therapy groups and 0.727 for the comparison within the control groups. Comparison estimates and confidence intervals are not reported in the registry record. The reason for termination, missing-data methods, and detailed statistical plan are also not reported.